farmacos en personalidad

8112019 Farmacos en Personalidad

httpslidepdfcomreaderfullfarmacos-en-personalidad 124

Luis H Ripoll Joseph Triebwasser

Larry J Siever Evidence-Based Pharmacotherapy forPersonality Disorders

Abstract Patients with personality disorders are prescribed psychotropic medications with greater frequency than almost

any other diagnostic group Prescribing practices in these populations are often based on anecdotal evidence rather than

rigorous data Although evidence-based psychotherapy remains an integral part of treatment Axis II psychopathology is

increasingly conceptualized according to neurobiological substrates that correspond to speci1047297c psychopharmacological

strategies We summarize the best available evidence regarding medication treatment of personality disordered patients and

provide optimal strategies for evidence-based practice Most available evidence is concentrated around borderline and

schizotypal personality disorders with some additional evidence concerning the treatment of avoidant and antisocial

personality disorders Although maladaptive personality symptoms respond to antidepressants antipsychotics mood

stabilizers and other medications evidence-based pharmacotherapy is most useful in treating circumscribed symptom

domains and induces only partial improvement Most available evidence supports use of medication in reducing impulsivity

and aggression characteristic of borderline and antisocial psychopathology Efforts have also begun to reduce psychotic-like

symptoms and improve cognitive de1047297cits characteristic of schizotypy Indirect evidence is also provided for

psychopharmacological reduction of social anxiety central to avoidant personality disorder Evidence-based practice requires

attention to domains of expected clinical improvement associated with a medication relative to the potential risks The

development of future rational pharmacotherapy will require increased understanding of the neurobiological underpinnings

of personality disorders and their component dimensions Increasing efforts to translate personality theory and social

cognitive neuroscience into increasingly speci1047297c neurobiological substrates may provide more effective targets for

pharmacotherapy

(Reprinted with permission from International Journal of Neuropsychopharmacology 2011 141257 ndash1288)

INTRODUCTION

Personality disorders are de1047297nedbyan lsquoenduring

pattern of inner experience and behavior thathellip

isin1047298exible and pervasive across a broad range of personal and social situationsrsquo with symptomaticdisturbances in cognition affect impulsivity and interpersonal functioning leading to distress (APA1994) Until recently guidelines recommended sparing use of pharmacotherapy and expectationsremained guarded regarding expected bene1047297ts frommedications Since then distinctions between Axis Idisorders considered lsquo genetichellip biologicalhellip braindisordersrsquo treated with medications and Axis II dis-orders alternatively considered lsquopsychologicalrsquo and

therefore treated with psychotherapy has undergonea paradigm shift (Siever amp Davis 1991) In this at-

mosphere clinicians must rely on the most up-to-

date evidence-based practices for pharmacotherapy to be effective

Component dimensions of personality such as im-pulsivity or aggressiveness have demonstrable neuro-biologicalcorrelatesasshownviaavarietyofendocrineelectrophysiological and neuroimaging measures(Brambilla et al 2004 Goodman et al 2004Houston et al 2004 Juengling et al 2003 Levittet al 2004 Minzenberg et al 2006 New et al

1997 2004 Ogiso et al 1993 Oquendo et al

2005 Prossin et al 2010 Rusch et al 2003 Russ

focuspsychiatryonlineorg FOCUS Spring 2013 Vol XI No 2 225

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et al 1991 Simeon et al 1992 Soderstrom ampForesman 2004) Identifying neurobiological sub-strates of personality has allowed for increasingly speci1047297c pharmacotherapy Nevertheless improvementfrom effective pharmacotherapeutic interventions isoften transient andor restricted to several symptom

domains In the USA there are no FDA-approved medications for treating personality disorders Thuspharmacotherapy for personality disorders remainsoff-label and psychopharmacological strategies for evidence-based practices remain lacking

Themajorityofpsychopharmacologicalresearchon personality disorders has focused on borderlinepersonality disorder (BPD) In the most recenttreatment guidelines for BPD the AmericanPsychiatric Association (APA 2001) acknowl-edges that lsquopharmacotherapy has an importantadjunctive rolersquo along with lsquoextended psycho-

therapy to attain and maintain lasting improvementinhellip personality interpersonal problems and overallfunctioning rsquo Similarly others have described psy-chopharmacological treatment of BPD as resulting only in lsquoa mild degree of symptom relief rsquo (Paris2005) Moreover there remainsa dearth of evidence-based medication treatments for other personality disorders

Often pharmacotherapy for severe personality disorders is used to stabilize patientsrsquo symptomssuf 1047297ciently in order to facilitate psychosocial inter-ventions and foster re1047298ective functioning Close

communication between psychotherapists and psychopharmacologists remains crucial Althoughfunctional gains can be expected from medicationsthe magnitude and time-course vary There is littleevidence regarding distinctions between acute and maintenance pharmacotherapy or how long to

continue patients on a medication Empirical data on recurrence or relapse is similarly scarce There-fore evidence-based practices must be judged case-by-case weighing clinical risks and bene1047297ts

Clinicians canreferto accompanyingtables forthebest available evidence regarding pharmacotherapy for personality disorders (see Tables 1ndash4) This data

was compiled by searching the Medline database with the main combinations pharmacotherapy and each of the various DSM-IV personality disorder diagnoses In addition we paid particularly closeattention to randomized placebo-controlled trials

(along with some lower-level evidence if this type of evidence was severely limited) We focused onstudies published in the past 3 years since thepublication of the last World Federation of Societiesof Biological Psychiatry Guidelines for the BiologicalTreatment of Personality Disorders (Herpertz et al

2007) Additional research regarding medicationsfor treating impulsive aggression was found via a similar Medline search on impulsivity aggressionand pharmacotherapy

Unfortunately only a few novel trials of pharmaco-therapy for personality disorders have been published

Table 1 Schizotypal Personality Disorder (SPD)

Study Diagnosis N Medication(s) Dosage(s)

Design

duration Results in active drug group(s)

Koenigsberg

et al (2003)

SPD 25 males

and

females

Risperidone Started

at 025 mgd

titrated up to

2 mgd

Parallel

design

9 wk

Significantly lower scores on PANSS

negative and general symptom scales

by week 3 and positive symptoms by

week 7

McClureet al (2007b )

SPD 29 malesand

females

Guanfacine Titrated up to2 mgd within

first 2 wk

Paralleldesign

4 wk

After 4 wk greater improvements frombaseline in neuropsychological

measures of working memory (Modified

AX-Continuous Performance Task)

compared to placebo

McClure

et al (2010)

SPD 25 males

and

females

Pergolide 0025 mgd for

first 3 d then

005 mgd for 4 d

then 01 mgd for 1 wk


then 03 mgd

Parallel

design

4 wk

Greater improvement from baseline in

tasks measuring executive function

(Trail-Making Test Part B) verbal

memory (Word List Learning-

immediate and delayed recall) verbal

working memory (Letter Number Span)

long-term visuospatial memory

(Wechsler Memory Scale Visual

Reproduction Test) and visuospatial

working memory (Dot Test) comparedto placebo Dot findings were largely

driven by worsening in placebo group

PANSS Positive and Negative Symptom Scale

226 Spring 2013 Vol XI No 2 F O C U S T H E J O U R N A L O F L I F E L O N G L E A R N I N G I N P S Y C H I A T R Y

R IPOLL ET AL



during this recent period Several recent meta-analyses have been published in this time which we utilized to establish areas of consensus for evidence-basedpracticeandidentifygapsthatneed to be addressed with future research Many prior reviews cover only BPD but we expanded our scope to include all personality disorders Thus

we include a comprehensive summary of the bestcurrent evidence with commentary on recentconsensus and recommendations for evidence-based practices and future directions regarding pharmacotherapeutic strategies that have been in-

suf 1047297

ciently tested but appear promising for further research This situates this review as a nexuscompiling evidence-based practices for treating personality disorders for interested clinicians as

well as providing avenues for future psychophar-macological research

SCHIZOTYPAL PERSONALITY DISORDER

(SPD)

SPD is characterized by interpersonal de1047297citsand psychotic-like symptoms Like schizophrenia

Table 2 Antisocial Personality Disorder


Design


Sheard

(1971)

Inmates of

maximum security

prison with verbal

and physical

aggression whilein prison

12 males Lithium

carbonate

Lithium levels of

06ndash15 meql

mean dose

1200 mgd

Crossoversingle-

blind three

4-wk phases

Decrease in serious incidents of verbal

or physical aggression Improvements

in self-rated anger and tension

Single-blind Aggressive incidents

scored on basis of prison guardsrsquo

issuing of punitive tickets not by

psychiatristsrsquo ratings

Sheard

et al

(1976)

Prisoners

convicted of

lsquoserious

aggressive

crimesrsquo

80 males Lithium

carbonate

Lithium levels of

06ndash10 meql

mean lithium level

during last week

of medication

phase 089 meql

Parallel design

5 months with

first and

last months

medication

free and 3

months lithium

vs placebo

Decrease in violent infractions of prison

rules in lithium group

Lion

(1979)

lsquo All patients had

past histories of

temper outbursts

belligerenceassaultive

behaviour and

impulsiveness

had experienced

legal difficulties

and some

had committed

criminal actsrsquo

65 males

and females

Chlordiazepoxide

oxazepam

Chlordiazepoxide

100 mgd for 2 wk

then 200 mgd for

2 wk Oxazepam120 mgd for 2 wk

then 240 mgd

for 2wk

Parallel design

4 wk

Oxazepam superior to chlordiazepoxide

and placebo for indirect hostility

(Buss-Durkee Hostility Scale) anxiety

Barratt

et al

(1991)

Maximum security

prison inmates

with impulsive

aggression

while in prison

19 males Phenytoin 100 mgd or

300 mgd

Crossover design

three 4-wk

phases

Significant reduction in aggressive

acts at 300 mgd but not

100 mgd Improvements in

tension-anxiety and

depression-dejection at 300 mgd

but not anger-hostility

Barratt

et al

(1997)

Prison inmates

with aggression

while in prison

150 total but only

30 males with

primarily impulsive

aggression and

30 males with

primarily

pre-meditated

aggression included

in analysis (other

66 had mixture

of both types)

Phenytoin 300 mgd Crossover

design two

6-wk phases

Significant reduction in frequency

and intensity of aggressive acts

in impulsive aggressive group

but not pre-meditated aggressive

group


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Table 3 Borderline Personality Disorder (BPD)


Design


Rifkin et al

(1972)

EUCD (emotionally

unstable character

disorder

characterized by

rsquochronic maladaptivebehaviour patternshellip

poor acceptance of

reasonable authority

truancy poor

work history

manipulativenesshellip

with a core

psychopathological

disturbance of

depressive and

hypomanic mood

swings lasting hours

to daysrsquo)

21 (sex

distribution

not specified)

Lithium

carbonate

Dosed to levels

between 06ndash15

meql

Crossover

design

two 6-wk

phases

Mood swings and overall clinical

status judged better on lithium

Leone (1982) BPD 80 males and

females

Loxapine

succinate

chlorpromazine

Mean doses

loxapine

145 mgd

chlorpromazine

110 mgd

Parallel design but

not placebo-

controlled 6 wk

Both groups with significant

improvements Loxapine group

improved more especially in

depression and anger-hostility

Montgomery

amp Montgomery

(1982)

BPD DPD andor

HPD all hospitalized

after a suicidal act

with history of at

least 2 prior suicidal

acts

Not specified 30

males and

females

completed the

study 23 with

BPD 15 with

HPD and 2

with DPD

Depot

flupenthixol

20 mg IM every

4 wk

Parallel design

6 months

Flupenthixol group showed reduction

in number of suicidal acts

Montgomery

et al (1983)

BPD andor HPD all

hospitalized after

a suicidal act with

history of at least 2

prior suicidal acts

Not specified

38 male

and female

subjects

completed

30 with BPD and

12 with HPD

Mianserin 30 mg qhs Parallel design

6 months

Mianserin group showed less

suicidal acts but this did not

reach trend levels

Serban amp

Siegel (1984)

BPD SPD 52 males and

females

Thiothixene

haloperidol

Thiothexene began at

2 mgd then adjusted

up or down mean

dose 94 mgd

Haloperidol began at

08 mg bid then

adjusted dose up

or down mean

dose 3 mgd

Parallel design

but not

placebo-

controlled

3 months

Final drop-out rate unspecified

but 19 dropped out during

the first month 84 of all

subjects moderately to markedly

improved (mainly in cognitive

disturbance derealization ideas of

reference anxiety depression

Thiothixene superior to haloperidol

BPD vs SPD diagnoses did not

predict outcome

Goldberg

et al (1986)

BPD andor SPD

all subjects with

at least one

psychotic symptom

50 males and

females

Thiothixene Started at 5 mgd then

increased gradually to

maximum of 35 mgd

Parallel design

12 wk

48 drop-out rate Significant

improvement in ideas of reference

illusions phobic anxiety

psychoticism and obsessive-

compulsive symptoms but not

depression (SCL-90) Predictors of

response from pre-treatment MMPI

discussed in Goldberg et al (1986)

Soloff et al

(1986b )

BPD andor SPD 64 total with 28

BPD only 4 SPD

only and 32

Haloperidol

amitryptiline

Amitryptiline began

at 25 mgd then

titrated upward to

Parallel design

5 wk

Observer-rated measures did

not demonstrate significant

medication effects

(Continued)


R IPOLL ET AL



Table 3 Continued


Design


comorbid BPD and

SPD

mean final dose of

14762 mgd

Haloperidol began

at 2 mgd then

titrated upward tomean final dose of

724 mgd

Haloperidol superior to amitryptiline

in self-report measures of hostility

paranoia anxiety and depression

Little benefit from amitryptiline

even on depression Resultspresented again in Soloff et al

(1989) but outpatients deleted

from analyses (N 5 13)

Soloff et al

(1986c )

See above See above See above See above See above Haloperidol better than both

amitryptiline and placebo for overall

symptom severity Improvements

described as lsquomodest rsquo more

apparent in self-rated than

observer-rated measures

No differences between

amitryptiline and placebo

Soloff et al

(1986a

1987)

See above Papers analyse

paradoxical

response toamitryptiline

during study first

described in

Soloff et al

(1986b )

Compared 15

amitryptiline non-

responders

14 placebo

non-responders

13 amitryptiline

responders and

10 placebo

responders

Amitryptiline See above Mean final

amitryptiline1

nortryptiline bloodlevels were 246 ngml

for responders and

2459 ngml for non-

responders

See above Amitrypti line associated with

paradoxical increases in hostility

irritability impulsivity paranoiasuicide threats and demanding

and assaultive behaviour in

non-responders

Cowdry amp

Gardner

(1988)

BPD with lsquoprominent

behavioural

dyscontrolrsquo

16 females Alprazolam

carbamazepine

trifluoperazine

hydrochloride

tranylcypromine

sulfate

Mean doses of

alprazolam 47 mgd

carbamazepine

820 mgd

trifluoperazine

78 mgd and

tranylcypromine

40 mgd

Crossover design

each phase

lasting 6 wk

Tranylcypromine and carbamazepine

had lowest drop-out rates (25 and

33 respectively compared to

average 45) and were associated

with physician-rated improvements

Tranylcypromine also associated

with patient-rated improvements

Trifluoperazine completers showed

some improvements Carbamazepine

group showed improvement

especially in behavioural dyscontrol

(Gardner amp Cowdry 1986b )

Alprazolam group showed

worsening behavioural dyscontrol

(Cowdry amp Gardner 1988)3 subjects on carbamazepine

developed worsening melancholia

that remitted on discontinuation

(Gardner amp Cowdry 1986a )

Parsons et al

(1989)

BPD and atypical

depression

First sample of

subjects were

required to meet

5 BPD criteria

(N 5 40) second

sample met 4

Phenelzine

imipramine

Phenelzine titration to

60 mgd with

option to increase to

90 mgd if no

response by week 5

Imipramine titration

to 200 mgd with

Crossover

design two

6-wk phases

Greater proportion of subjects

responded to phenelzine than

imipramine Presence of BPD

symptoms was negative predictor

of response to imipramine in

subjects with 4 or more BPD

symptoms higher number

(Continued)


R IPOLL ET AL

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Table 3 Continued


Design


BPD criteria

(N 5 19)

option to increase

to 300 mgd if no

response by week 5

of symptoms predicted superiority

of phenelzine

Soloff et al

(1989)

Same as Soloff

et al (1986 b)

90 total with 35

lsquounstablersquo BPD

4 SPD and 51

lsquomixedrsquo BPD

and SPD

Same as Soloff

et al (1986b )

Same procedure as

Soloff et al (1986b )

Mean dose of

haloperidol was 48

mgd and mean dose

of amitryptiline was

1491 mgd on

day 35

Parallel design

5 wk

Significant differences between

haloperidol and placebo in global

functioning depression hostility

schizotypy and impulsivity

Differences between amitryptiline

and placebo limited to depressive

symptoms Final results of 4-year

study only analyzed data from

inpatients deleting data from

outpatients in prior reports

Links et al

(1990)

BPD 17 males and

females

Lithium

carbonate

desipramine

Not spe ci fi ed Cr ossover d es ig n

two 6-wk phases

No statistically significant effects on

depression Trend towards decrease

in anger and suicidality in lithium

group relative to desipramine

Therapistsrsquo perceptions favored

lithium over placebo Trendtowards favoring lithium over

desipramine Therapists did not find

desipramine superior to placebo

Soloff et al

(1993)

BPD 108 males and

females

Haloperidol

phenelzine


1 mgd then titrated

up to mean dose of

4 mgd Phenelzine

began at 15 mgd

then titrated up to

mean dose of 60

mgd

Parallel design

5 wk

Improvements observed with

haloperidol in Soloff et al

(1986a ndashc 19871989) were not

replicated Phenelzine associated

with improvements in depression

borderline symptoms anxiety

anger and hostility but not

atypical depressionhysteroid

dysphoria

Cornelius

et al (1993)

BPD 54 males and

females

Haloperidol

phenelzine

Haloperidol up to 6

mgd phenelzine upto 90 mgd Doses

generally did not

change from final

dose of prior 5-wk

acute phase

(Soloff et al 1993)

Parallel design

16 wk following 5-wk

acute phase

(Soloff et al

1993)

Drop-out rate during entire 22-wk

study acute phase (Soloff et al1993) and continuation was

73 (79108) Only benefit in

haloperidol group was decreased

irritability Haloperidol contributed

to worsening depression leaden

paralysis and hypersomnia

Phenelzine showed modest

efficacy on depression and

irritability but unpleasant activation

de la Fuente

amp Lotstra

(1994)

BPD 20 males and

females

Carbamazepine Dosed to obtain

therapeutic blood

levels

Parallel design

32 days

No significant benefit

Salzman

et al (1995)

BPD 27 males and

females

Fluoxet ine Started at 20 mgd

titrated up toa maximum of

60 mgd with mean

dose of 40 mgd

Parallel design

12 wk

Decrease in anger with fluoxetine

but high placebo response rateSubjects from outpatient sample

without Axis I comorbidity limiting

generalizability

Coccaro amp

Kavoussi

(1997)

All subjects had at

least one PD as

well as current

problems with

impulsive aggression

and irritability Most

frequent PD was

BPD

40 males and

females


and after end of 4th

week could be

increased to

40 mgd with further

increase to 60 mgd

possible after end of

8th week

Parallel design

12 wk

Reduction in irritability and

aggression subscales of OAS-M

Higher proportion of CGI

responders in fluoxetine group

relative to placebo

D-fenfluramine challenge of subset

of 15 subjects showed positive

correlation in fluoxetine-treated but

not placebo-treated subjects

(Continued)


R IPOLL ET AL



Table 3 Continued


Design


between improvement in OAS-M

subscales and pre-treatment

prolactin response (Coccaro

amp Kavoussi 1997)

Verkes et al

(1998)

Non-depressed

subjects who had

recently attempted

suicide for at least

the second time

81 met criteria

for a Cluster B PD

91 males and

females

Paroxet ine Started at 20 mgd

increased to

40 mgd after

1 wk

Parallel design

52 wk

79 (7291) dropped out prematurely

Significant efficacy in preventing

suicidal behaviour after controlling

for number of prior suicide

attempts Paroxetine more effective

in patients who met fewer than

15 Cluster B PD criteria Paroxetine

group did not differ from placebo

in depressed mood

hopelessness or anger

Battaglia

et al (1999)

Multiple suicide

attempters 85

had BPD

58 males and

females

Fluphenazine

decanoate

125 mg IM monthly

or 15 mg IM

monthly

Parallel design

but not placebo-

controlled

6 months

60 (3558) dropped out

prematurely Marked reduction in

self-harm behaviours but 125 mg

dose did not significantly differ from

15 mg dose According to authorslsquoThe lsquoultra-lowrsquo 15 mg dose was

chosen to represent the extreme

low end of possible

pharmacological effect for

fluphenazine treatment The

investigators believed that the

ethics review board would not

approve a study with the use of a

placebo in such a critically ill

group of patients

Hollander

et al (2001)

BPD 16 males and

females

Divalproex

sodium

Started at 250 mg qhs

increased gradually

to maintain valproate

levels of 80 mgml or

highest tolerable

dose Mean

endpoint valproate

level 6457 mgml

Parallel design

10 wk

50 (612) of medication group

and 100 (612) of placebo

group dropped out No statistically

significant benefits in ITT

analyses Among completers

significant improvements from

baseline in CGI and GAS ITT

data showed changes in expected

directions in BDI and AQ scores

Zanarini amp

Frankenburg

(2001)

BPD 28 females Olanzapine Started with

125 mgd then

titrated up to

mean dose of

533 mgd at

endpoint

Parallel design

6 months


prematurely Improvements in

olanzapine group in anxiety

paranoia angerhostility and

interpersonal sensitivity

subscales but not depression

subscale of SCL-90

Frankenburg

amp Zanarini

(2002)

BPD and bipolar

disorder type II

30 females Divalproex

sodium

Started at 250 mg bid

then titrated to target

serum levels of

50ndash100 mgl

Parallel design 6

months



medication group in

interpersonal sensitivity anger

hostility and overall aggression

Rinne et al

(2002)

BPD 38 females Fluvoxamine Began with 150 mgd

then titrated up to

a maximum of 250

mgd after 10th

week if insufficient

response

6-wk double-blind

placebo-controlled

phase followed by

6-wk singleblind

half-crossover

phase in which all

subjects received

fluvoxamine This

was followed by

Significant reduction in BPD

Severity Index rapid mood

shift subscale but not in

impulsivity or aggression

(Continued)


R IPOLL ET AL

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Table 3 Continued


Design


12-wk open label

study of

fluvoxamine

Hollander

et al (2003)

Cluster B PD IED or

PTSD with OAS-M

Aggression score

15

Males and females

Cluster B PD 96

with 55 BPD

13 NPD 10

AsPD 1 HPD

PD NOS 21) IED

116 PTSD 34

Divalproex

sodium

Began with 250 mg

bid then increased

by 250 mgd every

3ndash7d during first

3 wk Recommended

valproate levels were

80ndash120mgml by third

week Maximum dose

30 mgkgd

Parallel design

12 wk

44 (54124) divalproex group

and 39 (47122) placebo group

dropped out No differences in ITT

data sets when all subjects

included In Cluster B PD subjects

significant decreases in CGI

scores OAS-M irritability scores

and verbal assault and assault

against objects items of OAS-M

aggression scale in medication

group Secondary analysis

(Hollander et al 2005) revealed

improvements in impulsive

aggression in a subset of BPD

subjects and that high BIS

scores and high OAS-M

aggression scores predicted

better responses

Zanarini amp

Frankenburg

(2003)

BPD 30 females Ethyl-eicosa-

pentaenoic acid

(E-EPA)

500 mg b i d Pa ral le l d es ig n

8 wk

Better than placebo in reducing

aggression and severity of

depressive symptoms

Bogenschutz

amp Nurnberg

(2004)

BPD 40 males and

females

Olanzapine Started at 25 mgd

then increased by

25ndash5 mgdwk up to

10 mgd After week 8

dose could be further

increased to

maximum of 20 mgd

Most patients received

less than 10 mgd

Parallel design

12 wk

Superior to placebo on CGI

and CGI-BPD

Nickel et al

(2004)

BPD 31 females Topiramate Began with 50 mgd

then increased to

250 mgd by last

3 wk

Parallel design

8 wk

Significant improvements in

State-Anger Trait-Anger

Anger-Out and Anger-

Control subscales of STAXI

Philipsen

et al

(2004a )

BPD 22 females Clonidine 75 mg or l50 mg Crossov er design in

which each subject

received one 75 mg

dose and one

150 mg dose in

randomized

crossover fashion

during separate

episodes of lsquostrong

aversive inner

tension and urge

to commit

self-injurious

behaviourrsquo no

placebo-control

single-blind

Significant decreases in aversive

inner tension dissociative

symptoms suicidal ideation

and urges to commit

self-injurious behaviour

30ndash60 min after clonidine for

both doses Dose did not affect

response no placebo-control

Philipsen

et al (2004b )

BPD 9 females Naloxone

hydrochloride

04 mg IV administered

over 30 s

Crossover design in

which each subject

received one dose

of naloxone and

onedose of placebo

in randomized

Dissociative symptoms decreased

after both naloxone and placebo

but no difference between groups

(Continued)


R IPOLL ET AL



Table 3 Continued


Design


crossover fashion

during separate

acute dissociative

episodes

Simpson

et al (2004)

BPD 25 females Fluoxetine plus

concurrent DBT

Started at 20 mgd

increased to 40 mgd

at week 3

Parallel design

12 wk

No significant group differences

from pre-treatment to

post-treatment

Zanarini et al

(2004b )

BPD 45 females Fluoxetine

olanzapine and

olanzapine-

fluoxetine

combination

(OFC)

Fluoxetine started at

10 mgd with endpoint

mean dose of 15 mgd

Olanzapine started at


mean dose of 33 mgd

OFC started at

olanzapine 25 mgd

and fluoxetine 10 mgd

with endpoint mean

doses of 32 mgd and

127 mgd respectively

Parallel design but

not placebo-

controlled 8 wk

Olanzapine and OFC superior to

fluoxetine for depression and

impulsive aggression although

patients on fluoxetine improved

in both as well Weight gain

greater in olanzapine group than

fluoxetine or OFC groups

Nickel et al

(2005)

BPD 44 males Topiramate Began with 50 mgd

then increased to

250 mgd by last 3 wk

Parallel design

8 wk

Significant improvements for

medication group in State-Anger

Trait-Anger Anger-Out and

Anger-Control subscales of STAXI

Subsequent open-label follow-up

(Nickel amp Loew 2008)

demonstrated continued

benefits in topiramate group

in ITT analysis

Soler et al

(2005)

BPD 60 males and

females

Olanzapine with

concurrent DBT

Flexible dosing from 5ndash

20 mgd with mean

dose 883 mgd

Parallel design

12 wk

Olanzapine superior to placebo

for depression anxiety and


Tritt et al

(2005)

BPD 27 females Lamotrigine Started at 50 mgd then

increased to 100 mgd

during week 3

150 mgd during wk 4

and 5 and 200 mgd

during wk 6ndash8

Parallel design

8 wk

Significant improvement on


Anger-Out and Anger-Control

subscales of STAXI in

medication group

Nickel et al

(2006)

BPD 52 males and

females

Aripiprazole 15 mgd Parallel design

8 wk

Aripiprazole group evidenced

greater improvements in SCL-90

subscales of obsessive-compulsive

symptoms insecurity in social

contacts depression anxiety

hostility phobic anxiety paranoia

and psychoticism as well as

global psychological stress

Medication group also improved

on HAMD and HAMA as well asall subscales of the STAXI Less

selfinjurious behaviour

observed in medication group

Loew et al

(2006)


increasing to a target

dose of 200 mgd by

the 6th week

Parallel design

10 wk


medication group in SCL-90

subscales of somatization

symptoms interpersonal sensitivity

anxiety hostility phobic anxiety

and global stress but not in

obsessive-compulsive

depression paranoia or

psychoticism subscales

Medication group significantly

(Continued)


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patients SPD patients often demonstrate cognitivede1047297cits in working memory particularly sustained attention and executive functioning (Bergida ampLenzenweger 2006 McClure et al 2007a Parc ampMcTigue 1997) as well as signi1047297cant abnormalitiesin empathic understanding (Langdon amp Coltheart2004 Pickup 2006 Ripoll et al unpublished data)Unlike schizophrenic patients there is greater preservation of frontal volume in SPD (Siever ampDavis 2004)

Overall clinical trials for SPD have been com-plicated by comorbidity particularly with other personality disorders Most early RCTs on BPDalso included SPD patients (Goldberg et al 1986Serban amp Siegel 1984 Soloff et al 1986c ) be-cause both SPD and BPD were considered rooted in lsquoborderlinersquo schizophrenia but psychoticsymptoms in SPD and BPD are clinically distin-guishable

The conceptualization of SPD within theschizophrenia spectrum supports treatment withantipsychotic medications Antipsychotics appear

tobeusefulinthetreatmentofSPDparticularlyinterms of psychotic-like symptoms (Goldberg et al

1986 Koenigsberg e t a l 2003) Open-labelstudies have suggested a role for antidepressantsin treating self-injury psychotic-like and de-pressive symptomatology (Jensen amp Andersen1989 Markovitz et al 1991) but the evidence is

weaker Recent RCTs targeting cognitive de1047297citsin SPD compared performance on neuro-psychological tasks before and after treatment

with medication or placebo Both pergolidea dopaminergic agonist active at both the D1 and

D2 receptor (McClure et al 2010) and the nor-adrenergic a2A agonist guanfacine (McClure et al

2007b ) improved SPD patientsrsquo cognitive per-formance on distinct neuropsychological mea-sures Whether this improvement extends tooverall clinical functioning in SPD remains sub-

ject to future investigationIn sumSPDpatients respondto low-dose atypical

antipsychotics targeting psychotic-like symptomsand general functioning First-generation antipsy-

chotic medication and antidepressants may alsoplay a role although the evidence is not as reliableEvidence-based practice requires weighing risk of extrapyramidal side-effects or tardive dyskinesia against potential bene1047297ts Cognitive enhancementvia noradrenergic a2A or dopaminergic agonismmay be future avenues of research given that by analogy with schizophrenia the cognitive impair-ment in SPD may be responsible for the overalldysfunction observed in the disorder Researchefforts to understand neurobiological substratesof social cognitive dysfunction have heretofore

mainly focused on BPD and schizophrenia Be-cause SPD involves social isolation relationalparanoia and empathic de1047297cits research on phar-macotherapeutic effects on social cognition may also be fruitful

A NTISOCIAL PERSONALITY DISORDER

(A SPD)

Peer-reviewed trials of AsPD include studieson groups of individuals likely to have been antiso-cial based on histories of repeated violence and

Table 3 Continued


Design


Shafti amp

Shahveisi

(2010)

BPD 28 females

recruited shortly

after inpatient

psychiatric

admission andsubsequent 7d

washout

Olanzapine

haloperidol

Both medications began

at 25 mgd and

increased weekly by

25 mgd as needed or

tolerated toa maximum of 10

mgd by week 4

Doses at week 4 were

maintained for

remainder of study

Parallel design

but no placebo-

control 8 wk

Olanzapine group trended

towards greater

improvement in Bussndash

Durkee Hostility scores

Haloperidol trended towardsgreater improvement in

CGI scores No significant

between-group differences

Olanzapine group associated

with worsening metabolic

profile Higher rates of

extrapyramidal symptoms in

haloperidol group

AQ Aggression Questionnaire AsPD antis ocial personality disorder AvPD avoidant personality disorder BDI Beck Depression Inventory BPD borderline personality disorder CGI Clinical Global

ImpressionCGI-BPD ClinicalGlobal Impressionfor Borderline PersonalityDisorder DPDdependent personalitydisorder GASGlobalAssessmentScale HAMAHamilton Anxiety Scale HAMDHamilton

Depression Scale HPD histrionic personality disorder MMPI Minnesota Multiphasic Personality Inventory OAS-M Modified Overt Aggression Scale PANSS Positive and Negative Symptom Scale PD

personality disorder PTSD post-traumatic stress disorder SCL-90 Symptom Checklist-90 STAXI State-Trait Anger Expression Inventory ZAN-PBD Zanarini Rating Scale for Borderline Personality

Disorder


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criminality and an absence of other stated causes for these behaviours Lithium has been associated withdecreases in serious rule infractions in incarcerated males (Sheard 1971 Sheard et al 1976) Prisonerstreated with phenytoin committed fewer aggressiveacts and evidenced decreased tension-anxiety and depression-dejection (although not anger-hostility)and improvements in aggression appeared to belimited to impulsive (not pre-meditated) aggres-sion (Barratt et al 1991 1997) At presentevidenced-based pharmacotherapy for AsPD isrestricted to treatment of impulsive aggressionFuture neurobiological research in AsPD and psychopathy will probably increase our un-derstanding of the dysfunctional emotional em-pathy often seen in this disorder (Blair 2005) and

whether this may be susceptible to psychophar-macological intervention

BPD

Most RCTs on personality disorders focused onBPD which consists of several domains of dys-function affective instability impulsivity and an-ger transient psychotic or dissociative symptomsand intense unstable relationships (Lieb et al

2004 Zanarini et al 1990) BPD patients oftendemonstrate high comorbidity (Zanarini et al

2004a c ) and make numerous suicide attempts and parasuicidal gestures conferring signi1047297cantly higher risk for completed suicide (Welch amp Linehan2000)

Early studies employed a distinct nosology incharacterizing subjects some of whom actually had

what might be called BPD today (Rifkin et al 1972)In studies on suicidal or parasuicidal subjects themajority often have BPD (Battaglia et al 1999Montgomery amp Montgomery 1982 Montgomery et al 1983 Verkes et al 1998) Early studies oftenincluded combinations of BPD and SPD subjects(Goldberg et al 1986 Serban amp Siegel 1984 Soloff et al 1986c ) and studies recruiting a range of allpersonality disorders ultimately include BPD as themost frequent diagnosis (Coccaro amp Kavoussi

1997 Hollander et al 2003)Cliniciansshouldexercisecautioninattemptingtoapplyresearch1047297ndingstoseverelyillBPDpatientsasmany RCTs recruited only outpatients who further

were excluded if they expressed acute suicidality (Frankenburg amp Zanarini 2002 Tritt et al 2005Zanarini amp Frankenburg 2003 Zanarini et al

2004b ) or had made a recent suicide attempt(Bogenschutz amp Nurnberg 2004) In additionsmall sample sizes predominated and most studieslasted 3 months The few trials lasting $6 monthssuffered from high drop-out rates (Frankenburg amp

Zanarini 2002 Zanarini amp Frankenburg 2001) or concomitant recruitment of subjects without BPD(Battaglia et al 1999 Montgomery et al 1983Verkes et al 1998) Moreover RCTs with BPDsubjects appear to be prone to highplacebo responserates (Lieb et al 2004 Salzman et al 1995)meaning that open-label trial data should be inter-preted with caution

APA practice guidelines (APA 2001) recom-mended a symptom-targeted approach in pharma-cotherapy of BPD This leaves open the possibility for patients to improve in some but not all symptomdimensions Some clinicians have based their de-cision to implement polypharmacy on this butthere is actually little evidence as to the effectivenessof this strategy The only study on combined pharmacotherapy in BPD (Zanarini et al 2004b )found no superior ef 1047297cacy for combination treat-ment compared to one medication alone Using asfew medications as possible to target central areas of

clinical dysfunction together with evidence-based psychotherapy is usually the optimal treatmentstrategy In light of this although the 2001 guide-lines suggest a prominent role for serotonergicpharmacotherapy recent reviews have questioned this and instead emphasized anticonvulsants and antipsychotics (Abraham amp Calabrese 2008 Mercer et al 2009)

TRICYCLIC ANTIDEPRESSANTS (TCA S)

Disturbances of serotonin have been associated

with BPD impulsive aggression self-harm and suicidality (Coccaro et al 1995 Evenden 1999Malone et al 1996 Pitchot et al 2005) Low CSFlevels of serotonin metabolites have been associated

with suicide attempts and completion (Samuelssonet al 2006 Traskman et al 1981) impulsivityaggression (Mehlman et al 1994 Virkkunen et al

1994) lifetime aggressiveness and suicidal lethality (Placidi et al 2001) Impulsive aggression withsuicidality has been linked to blunted prolactinresponses to the serotonergic probe fen1047298uramine(Coccaro et al 1989) PET scans of personality-

disordered subjects high in impulsive aggressionhave demonstrated reduced response to fen1047298ur-amine in orbitofrontal ventromedial and cingulateregions (Siever et al 1999)

Nevertheless early research on TCAs for BPDproved disappointing (Montgomery et al 1983Soloff et al 1989) Amitryptiline has been associ-ated with paradoxical increases in suicidality para-noia and behavioural dysregulation attributed tolsquogeneralized disinhibition of cognitive and affec-tive controlsrsquo (Soloff et al 1986a 1987) Indeedborderline patients have dif 1047297culty cognitively


R IPOLL ET AL



resolving con1047298ict among stimulus dimensions(Posner et al 2002) and prefrontal hypofunctioncan be seen after a serotonergic stimulus in subjects

with prominent impulsive aggression (New et al

2002) Thus medications with adverse cognitivesequelae including anticholinergic side-effects may contribute to worsening impulsivity As mentioned in prior reviews the use of TCAs in treating BPD isdiscouraged (Abraham amp Calabrese 2008 Mercer et al 2009) Their use is also associated with po-tentially signi1047297cant risk of overdose

MONOAMINE OXIDASE INHIBITORS (MAOIS)

Despite hesitancyinprescribingMAOIstopatients with prominent impulsivity or self-injurious behav-iour some recommend these medications for BPDpatientswhocantakethemsafelyandreliablyInterestin MAOIs for BPD is rooted in their differential ef-1047297cacy for conditions such as hysteroid dysphoria or atypical depression viewed as being related to oneother and BPD (Kayser et al 1985 Liebowitz ampKlein 1981) In a crossover trial with multiplemedication phases only tranylcypromine was as-sociated with higher patient-rated improvementscores and completion rates (Cowdry amp Gardner1988)

Similarly relative prominence of BPD symptomspredicted superiority of phenelzine (Parsons et al

1989) Phenelzine is bene1047297cial in the treatment of hostility anxiety and borderline symptoms (Soloff et al 1993) In some patients it could cause un-

comfortable excitement and emotional reactivity (Cornelius et al 1993) Thus although there isevidence for their ef 1047297cacy many patients may nottolerate these medications Other associated risksof MAOIs include toxicity in overdose and po-tentially fatal hypertensive crises or serotoninsyndrome

SELECTIVE SEROTONIN REUPTAKE INHIBITORS

(SSRIS)

SSRIs are thought to potentiate serotonergicneuromodulation but demonstrate more favour-able side-effect pro1047297les Fluoxetine reduced anger in BPD independent of any antidepressant ef-fect (Salzman et al 1995) It also improved verbaland impulsive aggression irritability and overallfunctioning (Coccaro amp Kavoussi 1997) Simi-larly a RCT with paroxetine demonstrated ef 1047297cacy in preventing recurrent suicidal behaviour but nosigni1047297cant effect on depression hopelessness or anger (Verkes et al 1998) By contrast there waslittle added bene1047297t from 1047298uoxetine when added to

dialectical behavioural therapy (DBT) (Simpsonet al 2004)

On the other hand 1047298uvoxamine decreased af-fective lability but not scores of impulsivity or ag-gression (Rinne et al 2002) Although SSRIsdecrease impulsivity and aggression in BPD patients

with comorbid intermittent explosive disorder (IED Coccaro amp Kavoussi 1997 New et al 2004)data from BPD subjects without comorbid IED areinconsistent (Rinne et al 2002) Previous reviewshave emphasized that effect sizes for antidepressantpharmacotherapy vary widely between classes and trials (Ingenhoven et al 2010 Lieb et al 2010Mercer et al 2009) Nevertheless current evidence-based practice recommends use of SSRIs due topotential bene1047297ts on impulsive aggression that may outweigh associated risks There has been no evi-dence that antidepressants alleviate the chronicemptiness shameful self-concept and intrapsychicpain in BPD

FIRST-GENERATION ANTIPSYCHOTICS

An early interest in antipsychotic medications for treating BPD probably arose from a conception of BPD as a variant of schizophrenia (eg Deutsch1942) Antipsychotics have demonstrated partialef 1047297cacy re1047298ecting underlying abnormalities in do-paminergic signalling Borderline subjects demon-strate high levels of the dopamine metabolitehomovallinic acid in both plasma and cerebrospinal1047298uid (Siever et al unpublished data) Prior to more

widespread use of SSRIs antipsychotics demon-strated ef 1047297cacy in decreasing psychotic-like symptoms(Goldberg et al 1986 Soloff et al 1986b ) depression(Soloff et al 1986b ) irritability (Cornelius et al

1993) and general symptom severity (Cowdry ampGardner 1988 Soloff et al 1986b )

A recent Cochrane review suggests haloperidol isef 1047297cacious in reducing anger in BPD and treatment

with 1047298upenthixol decanoate reduced suicidal be-haviour (Lieb et al 2010) By contrast evidence for ef 1047297cacy of neuroleptics on affective symptomspsychosis and anxiety remains inconsistent The

dosage of antipsychotic medication for evidence-based treatment of BPD is usually lower thanschizophrenia High drop-out rates are noted and risk of extrapyramidal symptoms may further limitthe utility of neuroleptics

SECOND-GENERATION ANTIPSYCHOTICS

Classical neuroleptics have largely been superseded by atypical antipsychotics whose broader therapeuticbene1047297ts may be explained by activity beyond the D2

receptor As mentioned in prior reviews olanzapine


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has proven bene1047297cial in treatment of BPD patientsrsquoanxiety anger interpersonal sensitivity and para-noia but not depression (Zanarini amp Frankenburg2001) as well as improving general clinical func-tioning and BPD symptomatology (Bogenschutz ampNurnberg 2004) A recent large RCT demonstrated no effect of olanzapine on BPD symptoms (Schulzet al 2008) although the authors suggested thatpatients may have been underdosed A study comparing olanzapine to haloperidol showed nobetween-group differences except with respect toside-effects with more weight gain associated witholanzapine and more extra-pyramidal side-effects

with haloperidol (Shafti amp Shahveisi 2010) Adding 1047298uoxetine to olanzapine did not elicit

further bene1047297t except that subjects receiving bothmedications gained less weight than those receiving only olanzapine (Zanarini et al 2004b ) The addi-tion of olanzapine to DBT reduced depressionanxiety and impulsive aggression but the magni-

tude and timing of these bene1047297ts relative to DBT was dif 1047297cult to interpret (Soler et al 2005)

Aripiprazolehas a novelmechanismof action(partialagonist at the dopamine D2 receptor and serotonin 5-HT1A receptor antagonist at the 5-HT2A receptor) Itmay be more favourable than other atypicals withrespect to metabolic side-effects A longer half-lifemay be more effective for patients susceptible to non-adherence In non-suicidal BPD patients aripipra-zole was effective in reducing aggression anxietydepression psychosis interpersonal symptoms self-injurious behaviour and subjective distress There

were no signi1047297cant differences between groups in weight gain (Nickel et al 2006) An 18-month open-label follow-up showed sustained improvements and continued tolerability (Nickel et al 2007)

Previously open-label trials suggested possibleef 1047297cacy of ziprasidone in BPD patients during acute exacerbations (Pascual et al 2004 2006) Theside-effect and psychopharmacological pro1047297les of ziprasidone indicated lesser metabolic risks and an-tidepressant and anxiolytic effects thought to beindependent of antidopaminergic activity (Keck et al 1998 Tandon 2000 Wilner et al 2002)

Despite such promise a recent RCT with ziprasi-done was negative (Pascual et al 2008) Thusevidence-based practice supports use of aripiprazolebut not ziprasidone in treating BPD

In meta-analyses the class of antipsychotics had moderate effect in treating aggression but no sig-ni1047297cant effect on depression although aripiprazoleand olanzapine may be exceptions (Lieb et al 2010Mercer et al 2009) For aypicals metabolic side-effects may limit clinical utility Because 29-53of borderline patients ful1047297l criteria for an eating disorder at some point in their lives (Lieb et al

2004) and a signi1047297cant number suffer from obesity (Frankenburg amp Zanarini 2006) iatrogenic meta-bolic risks must be regarded as serious Althoughevidence-based practices have advanced in treating aggression associated with BPD chronic emptinessaffective lability and interpersonal dysfunction lack effective evidence-based medication treatments

MOOD STABILIZERS AND ANTICONVULSANTS

Due to BPD patientsrsquo affective dysregulation and comorbidity with bipolar disorder some have clas-si1047297ed BPD within the bipolar spectrum (Akiskal2004 Smith et al 2004) although most continue todistinguish between the two particularly withregard to interpersonal dysfunction (Bolton ampGunderson 1996 Henry et al 2001 Paris 2004)Mood stabilizers are indeed becoming a more in-tegral component of evidence-based treatmentpractices for BPD

Lithium is bene1047297cial in treating BPD particularly in terms of quieting affective instability (Links et al

1990 Rifkin et al 1972) Lithium toxicity andor non-compliance may be problematic due to BPDpatientsrsquo characteristic impulsive self-destructivebehaviour

However anticonvulsants are more often rec-ommended for treatment of rapid-cycling bipolar disorder the variant most closely resembling BPDCarbamazepine demonstrated lsquodramaticrsquo reductionsin behavioural dyscontrol and improvements inglobal functioning anxiety anger euphoria im-

pulsivity and suicidality but it was associated with worsening melancholic depression (Gardner ampCowdry 1986a b ) and therapeutic bene1047297ts could not be replicated in in-patients (de la Fuente ampLotstra 1994)

Although high drop-out rates were reported withdivalproex (Hollander et al 2001) it subsequently demonstrated bene1047297ts on interpersonal sensitivityanger and aggression in euthymic borderline wo-men with bipolar II (Frankenburg amp Zanarini2002) Divalproex reduced aggression irritabilityand overall disease severity in patients with Cluster

B personality disorders and prominent impulsiveaggression (Hollander et al 2003) Differentialtreatment response in Cluster B subjects was en-hanced by baseline trait impulsivity and state ag-gression although not affective instability (Hollander et al 2005)

Lamotrigine extends periods of euthymia in bi-polar patients (eg Goodwin et al 2004) Potentialbene1047297ts also include pro-cognitive activity as pre-viously demonstrated in normal volunteers(Aldenkamp et al 2002) Lamotrigine effectively reduced BPD patientsrsquo anger (Tritt et al 2005) and


R IPOLL ET AL



Table 4 Avoidant Personality Disorder (AvPD)

Study Diagnosis N M edication(s) Dosage(s)

Design

duration

Results in active drug

group(s)

Versiani et al

(1992)

Social

phobia

78 males and

females (percent

AvPD or

generalized

type not reported)

Moclobemide

phenelzine

Moclobemide started with

100 mg bid with flexible

dose increases after 4d

again after 4 wk and 5 wk

Mean dose 580 mgdPhenelzine started with



again after 4 wk 5 wk

Mean dose 675 mgd

Parallel design 16 wk

(with 8 additional wk

follow-up in which

half of each

medication groupgradually

switched to placebo

others continued on

last dosage)

Both agents better than

placebo in reducing

social anxiety and

improving social

function 82 responserate for moclobemide

group 91 for

phenelzine group

Moclobemide better

tolerated than

phenelzine

Van Vliet

et al (1994)

Social

phobia

30 males and

females (53

generalized

subtype)

Fluvoxamine 150 mgd Parallel design 12 wk Reduction of social and

general anxiety but not

phobic avoidance

Fahlen

(1995)

Social

phobia

63 males and

females (34 with

comorbid AvPD

1 with comorbidDPD)

Brofaromine Started at 50 mgd then

increased to 100 mgd in

2nd week and 150 mgd

in 3rd week

Parallel design 12 wk Improvement in social

anxiety More marked

improvements in

maladaptive personalitytraits 23 of subjects in

medication group with

comorbid AvPD and 1

DPD comorbid subject

no longer met criteria

Katzelnick

et al (1995)

Social

phobia

12 males and

females (percent

AvPD or

generalized type

not reported)

Sertral ine Began with 50 mgd with

flexible increases by

50 mg every 2 wk if no

clinical response to

maximum of 200 mg

Mean dose 1335 mgd at

endpoint

Parallel design 10 wk Reduction of social

anxiety bodily pain and

improvement in social

functioning 50 of

sertraline group rated

moderately or markedly

improved vs 9 of

placebo group

IMCTGMSPand

Katschnig

(1997)

Socialphobia

578 males andfemales (78

generalized type

49 comorbid

AvPD)

Moclobemide 300 mgd vs 600 mgd(after 4d of 300 mg initial

dose)

Parallel design 12 wk Reduction of social anxietyand improved social

functioning in 600 mg

group (47 responders

vs 34 in placebo

group) No differences

between groups with

without AvPD in

response but comorbid

AvPD patients

responded less to

placebo

Lott et al

(1997)

Social

phobia

102 males and

females

(percent

AvPD or

generalized type

not reported)

Brofaromine After 1ndash8 wk washout

started on 50 mgd with

flexible dosing to

maximum of 150 mgd

Parallel design 10 wk Reduction of social anxiety

but no significant effect

in social functioning

50 response rate vs

19 in placebo group

Noyes et al

(1997)

Social

phobia

583 males and

females (625

generalized

type

478

comorbid

AvPD)

Moclobemide Fixed dose comparison of

75 mgd vs 150 mgd vs

300 mgd vs 600 mgd

vs 900 mgd 75ndash150

mg d began with full

dose other groups began

with 150 mgd and

increased by 150 mg q4d

to target dosage

Parallel design 12 wk No improvement

independent of dose at

12 wk only at 8 wk

35 much improved but

high placebo response

rate As above no

difference between

groups withwithout

AvPD but less drug

(Continued)


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Table 4 Continued


Design

duration


group(s)

placebo difference in

comorbid AvPD patients

Heimberg

et al (1998)

Social

phobia

133 males and

females (707

generalized

type)

Phenelzine Began with 15 mgd with

increases to 30 mg after

4d then 45 mg after 8d

then 60 mg after 15d

Further flexible dose

increases possible after

4 wk to 75 mgd and after

5 wk to 90 mgd

Parallel design but

non-randomized

comparing

medication to group

cognitivebehavioural

therapy (CBT) or

supportive

educational

therapy or placebo

12 wk

Phenelzine and CBT better

than both comparison

conditions Phenelzine

effect earlier and on more

subscales 77 response

rate to phenelzine and 75

to CBT Phenelzine group

showed trend towards

greater relapse in subsequent

treatment-free follow-up

(Liebowitz et al 1999)

Schneier

et al (1998)

Social

phobia

77 males and

females (85

generalized

type 38

comorbid AvPD)

Moclobemide Began with 100 mg bid

flexibly dosed to

a maximum of 400 mg

bid Mean dose 728

mgd at endpoint

Parallel design 8 wk Reduction of 2 of 10

subscores of social

anxiety (total fear avoidance)

175 response rate vs

135 in placebo group

Stein et al

(1998)

Social

phobia

183 males and

females (100

generalized

subtype)

Paroxet ine Began with 20 mgd with

possible 10 mg increases

every 2 wk to a maximum

of 50 mgd Mean dose

366 mgd at endpoint


and improvement in

social functioning

Allgulander

(1999)

Social

phobia

99 males and

females

(percent

with comorbid

AvPD or

generalized type

not reported)



every week to maximum

of 50 mgd


and improvement in social

functioning 705 response

rate vs 83 in placebo

group Rate of response lower

amongst those with comorbid

dysthymia

Baldwin et al

(1999)

Social

phobia

290 males and

females

(percent with

comorbid AvPD

or generalized

type not reported)




of 50 mgd Mean dose

347 mgd at endpoint


and improvement in

social functioning 657

response rate vs 324

in placebo group

Stein et al

(1999)

Social

phobia

92 males and

females (913

generalized

type)

Fluvoxamine Began with 50 mgd with

further weekly 50 mgd


week 1 to maximum of

300 mgd Mean dose

202 mgd at endpoint


and improvement in



in placebo group

Blomhoff

et al (2001)

Social

phobia

387 males and

females (100

generalized

type)

Se rtr al in e B eg an wit h 50 mg d


after 4 wk if insufficient

improvement noted

Further dose escalationto 150 mgd allowed

after 8 or 12wk

Parallel design

comparing

sertraline1general

medical care

sertraline1

prolonged

exposure therapy

(PE) placebo1PE

and placebo1

general medical

care 24 wk

Sertraline and combined

sertralinePE groups

superior to placebo

groups in reduction of

social anxiety Greatest improvement in

combination group

though not significantly

different than sertraline

alone

van

Ameringen

et al (2001)

Social

phobia

204 males and

females (100

generalized

type 61

comorbid AvPD)


option to increase after 4

wk by 50 mg every 3 wk

to maximum of

200 mg d Mean dose

1467 mgd at endpoint


and improvement in


response rate vs 29 in

placebo group

(Continued)


R IPOLL ET AL



Table 4 Continued


Design

duration


group(s)

Liebowitz

et al (2002)

Social

phobia

384 males and

females (100

generalized

type)

Paroxet ine Fixed dose comparison of

20 mgd vs 40 mgd vs

60 mgd All groups

began with 20 mgd

increasing to 40 mgdafter 1 wk and to

60 mgd after 2 wk in

each respective group

Parallel design 12 wk Greatest improvement of

baseline social anxiety in

20 mg group Highest

response rate (based on

CGI) in 40 mg group

Stein et al

(2002)

Social

phobia

257 males and

females (100

generalized

type)

Par oxeti ne B eg an with 20 mgd

flexibly increased by 10

mg at 2 3 4 and 8 wk to

maximum of 50 mgd

Parallel design single-

blind 12-wk acute

phase with those

whose CGI

decreased by at least

2 entering 24-wk

double-blind

continuation

phase

Relapse in paroxetine

group 14 compared to

39 in placebo group

Davidson

et al(2004b )

Social

phobia

279 males and

females (100generalized

type)

Fluvoxamine CR Began with 100 mgd and

flexibly increased by50 mg every week to

maximum of 300 mgd

Mean dose 174 mgd


and improvement insocial functioning

Davidson

et al

(2004a )

Social

phobia

295 (100

generalized

type)

F lu oxeti ne B eg an with 10 mgd

increasing to 20 mgd on

day 8 to 30 mgd on day

15 and to 40 mgd on

day 29 Dose could be

further increased to

50ndash60 mgd on days

43 and 57 if insufficient

improvement

Parallel design

comparing

fluoxetine group

CBT fluoxetine1

group CBT placebo

placebo1group CBT

14 wk

All treatments superior to

placebo No differences

between treatments at

14 wk Combined

treatment without further

advantage

Lepola et al

(2004)

Social

phobia

372 males and

females(percent

with comorbid

AvPD or

generalized

type not

reported)

Paroxetine CR Began with 125 mgd for 2

wk with flexibleincreases by 125 mg


of 375 mgd Mean dose

323 mgd at endpoint


and improvement insocial functioning 57


in placebo group

Rickels et al

(2004)

Social

phobia

272 males and

females (100

generalized

type)

Venlafaxine ER Began with 75 mgd with

increase to 150 mg after

1 wk and possible further

increase to maximum of

225 mgd after at least

one more week


and improvement in

social functioning

Lader et al

(2004)

Social

phobia

839 males and


type)

Escitalopram

paroxetine

Escitalopram fixed dose

comparison of 5 mgd vs10 mgd vs 20 mgd

Paroxetine 20 mgd


with 24 wk continuation and

follow-up

Reduction of social anxiety

and improvement insocial functioning for all

doses of escitalopram

and paroxetine

Escitalopram 20 mgd

superior to paroxetine

20 mgd

Allgulander

et al (2004)

Social

phobia

434 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine

Venlafaxine ER Began with

75 mgd with flexible

increases by 75 mg after

1 wk and after 3 wk to

maximum of 225 mgd

Parallel design 12 wk Both venlafaxine and

paroxetine groups

similarly efficacious in

reducing social anxiety

and improvement in

(Continued)


R IPOLL ET AL

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an 18-month follow-up demonstrated maintenanceof this anti-aggressive effect (Leiberich et al 2008)More recently BPD patients without comorbid bipolar disorder but with prominent affective in-stability demonstrated reduced affective lability and

impulsivity but no change in other BPD symp-toms when treated with lamotrigine (Reich et al

2009) Documented effects on impulsivity angerand affective lability in BPD thus make lamo-trigine an attractive pharmacotherapeutic option

Table 4 Continued


Design

duration


group(s)


endpoint Paroxetine

Began with 20 mgd with

flexible increases by 10

mg every week tomaximum of 50 mgd


endpoint

social functioning

Possibly more rapid

effect of venlafaxine

Kasper et al

(2005)

Social

phobia

358 males and

females (100

generalized

type)

Escitalopram Began with 10 mgd with

possible increase to 20

mgd after 4 6 or 8 wk

for unsatisfactory

response Mean dose

176 mgd at endpoint


and improvement in



placebo group

Liebowitz

et al

(2005b )

Social

phobia

271 males and

females (100

generalized

type)

Venlafaxine ER Began with 75 mgd for first

week with increase to

150 mg in 2nd week and

to maximum of 225 mg in

3rd week if clinicallyindicated


and improvement in



placebo group

Liebowitz

et al

(2005a )

Social

phobia

413 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine


75 mgd-225 mgd with

flexible 75 mg increases

each week to maximum



Paroxetine Began with


10 mg increases to

maximum of 50 mgd

Mean dose 46 mgd at

endpoint


and improvement in

social functioning

compared with placebo

for both medication

groups Both medications

equally efficacious

566 response rate for

venlafaxine 625 for

paroxetine and 361

for placebo group

Stein et al(2005)

Socialphobia


generalized

type)

Venlafaxine Comparison of low-dose(fixed) to higher-dose

(flexible) All began with

75 mgd and if

randomized to higher-

dose increased to 150

mgd after first week

with further flexible

increase to 225 mgd

after 2nd week

Parallel design 24 wk Reduction in social phobiaand improvement in

social functioning in both

dosage groups 31

remission rate for both

venlafaxine groups

combined vs 16 in

placebo group

Montgomery

et al (2005)

Social

phobia

517 males and

females (100

generalized

type)

Escitalopram During open-label phase

began with 10 mgd with


mgd at wk 2 4 or 8 CGI

responders entered

relapse prevention phase

with last dose continued

for remainder

12-wk open-label

phase followed by

24-wk fixed-

dose relapse

prevention

(parallel design

double-blind RCT)

Relapse rate 22 vs 50

in placebo group Median

time to relapse was 407d

vs 144d for placebo

group No direct

comparison made

between doses

For abbreviations in table see notes to Table 3


R IPOLL ET AL



Nevertheless the latter study reported higher ratesof skin rash than reported elsewhere Due to thislife-threatening risk clinicians should monitor patients closely and titrate the dose slowly

Although topiramatersquos utility in bipolar disorder is controversial it is ef 1047297cacious for BPD Top-iramate reduced anger in female BPD subjects(Nickel et al 2004) and a similar RCT reported thiseffect in males with BPD (Nickel et al 2005) A separate RCT conducted with female BPD patientstaking topiramate also demonstrated improve-ments in somatization anxiety health-related quality of life overall stress interpersonal sensi-tivity hostility and other facets of interpersonalfunctioning (Loew et al 2006) Although no drop-outs were due to side-effects cognitive impairmentreduced appetite and weight loss were commonly reported

Open-labelfollow-upstudiestotheseinitialRCTsdemonstrated maintenance of therapeutic gains and

additional weight loss associated with topiramateand the authors therefore encouraged longer-termuse (Loew amp Nickel 2008 Nickel amp Loew2008) The authors admit that the patients studied

were not the most severe Because cognitive side-effects of topiramate may more adversely affect se-verely impulsive or suicidal BPD patients a carefulriskbene1047297t analysis should be undertaken beforeprescribing

Overall mood stabilizers and anticonvulsants areeffective in treating BPD particularly symptoms of impulsivity and aggression As a class they also

demonstrate a moderate effect in treating depressionin BPD (Ingenhoven et al 2010 Mercer et al

2009) Although they are an important componentof evidence-based practice patients should beclosely monitored because some may not toleratethese medications The relatively slow titrationschedules and the necessity of drawing plasma levels to reach an optimal dose may limit clinicaleffectiveness particularly in a population oftencharacterized by impulsive non-compliance Al-though impulsivity and aggression appear to re-spond to treatment there is little evidence of any

effect from mood stabilizers in improving in-terpersonal dysfunction or disturbances of iden-tity Future research should focus more closely onthese domains

OTHER MEDICATIONS

Although there have been case reports of im-provement in BPD patients treated with alprazolam(Faltus 1984) theclass of benzodiazepines has beenassociated with disinhibition worsening impulsiv-ity suicidal ideation and behavioural dyscontrol in

BPD (Cowdry amp Gardner 1988) Benzodiazepinesare vehemently discouraged due to these risks as

well as elevated risks of dependence Patients may abuse benzodiazepines to self-medicate intrapsychicpain interfering with progress in psychotherapy and adversely affecting cognition

The omega-3 fatty acid ethyl-eicosapentaenoicacid (E-EPA) decreased aggression and depressioninwomenwithmoderatetosevereBPD(ZanariniampFrankenburg 2003) A similar anti-aggressive effect

was observedin two other RCTswithhealthy subjects(Hamazaki et al 1996 2002) Omega-3 fatty acidsmay act by inhibiting protein kinase C a mechanismthought to be involved in lithium and valproic acid pharmacotherapy (Peet amp Stokes 2005)

Clonidine a presynaptic a2 noradrenergic ago-nist has been studied in a trial comparing two dosesgiven to BPD patients amidst states of lsquoacute aver-sive inner tensionrsquo Although tension dissociativesymptoms self-injurious urges and suicidal idea-

tion decreased for both doses there was no differ-ence between the two doses (Philipsen et al 2004a )Ziegenhorn et al (2009) conducted an RCT of clonidine with BPD subjects with prominentsymptoms of hyperarousal Most of them thereforealso met criteria for comorbid PTSD which limited generalizability of 1047297ndings In the total sample clo-nidine treatment improved hyperarousal subjectivequality of sleep and anxiety but not borderline-speci1047297c symptoms and these bene1047297ts were not seenin the minuscule non-PTSD subsample Althoughclonidine and similar agents have been ef 1047297cacious in

the treatment of PTSD (eg Southwick et al 1999Strawn amp Geracioti 2008) their role in treating BPD remains unclear

A subset of borderline patients engage in self-injurious behaviour or more indirect forms of self-destructiveness (eg bulimia substance abuse)

which may re1047298ect disturbances in endogenousopioids Some BPD patients become disinhibited and aggressive after receiving opiate medications(Saper 2000) and morphine administration in-creased self-injurious behaviour in one patient withBPD (Thurauf amp Washeim 2000) Naloxone used

during acute states of aversive tension and dissoci-ation in BPD demonstrated no signi1047297cant bene1047297t(Philipsen et al 2004b ) Naltrexone has been used successfully in open-label trials to treat self-harm(Griengl et al 2001 McGee 1997 Roth et al

1996) and dissociation (Bohus et al 1999) There-fore evidence for treatment of BPD with medicationsacting upon opioid receptors remains inconsistentTreatment with full agonists or antagonists may becomplicated by differences between chronic effectson post-synaptic receptor density on the one handand distinct acute effects of receptor agonism or


R IPOLL ET AL

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F L

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T

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P U

B L

I C A T

I O

N

S



antagonism ontheother (Prossin et al 2010Stanley ampSiever 2010) The potential for abuse of full opioid agonists may pose too great a risk for an effectivetreatment For both these reasons future trials withpartial opioid agonists may be more effective in re-ducing self-injury interpersonal dysfunction and intrapsychic pain

A VOIDANT PERSONALITY DISORDER

(A VPD)

AvPD is a common personality disorder (Loranger et al 1994) existing as a comorbid condition in upto one-third of all patients with anxiety disorders(Alden et al 2002) Up to 56 of AvPD patientscontinue to meet criteria after 2 years (Skodol et al

2005) Nevertheless distinguishing between thisand generalized social phobia has been dif 1047297cult dueto similarities in diagnostic criteria as well as fre-quently reported comorbidity No neurobiological

evidence indicates how the aetiology and psychopa-thology of AvPD differs from social phobia

At present clinicians should lsquoextrapolate from data which are primarily related to anxiety disordershellipto apply treatment strategieshellip that have primarily been developed for social phobia rsquo (Herpertz et al

2007) Evidence-based treatment for AvPD would thereby include venlafaxine and SSRIs as 1047297rst-lineagents A potential caveat is mentioned for sertra-line if symptoms began in childhood or adoles-cence in which case lesser ef 1047297cacy was reported (van Ameringen et al 2004) Gabapentin (Pande

et al 1999) and pregabalin (Pande et al 2004)have also demonstrated ef 1047297cacy in social phobiaSecond-line agents would include reversible MAOIsbrofaromine and moclobemide for which there ispresently less robust evidence and the irreversibleMAOI phenelzine which entails risk of serious side-effects

OTHER PERSONALITY DISORDERSMALADAPTIVE TRAITS

Pharmacological research is strikingly absent from

other personality disorders In these cases medicationis particularly indicated in the treatment of comorbid Axis I disorders particularly mood and anxiety dis-orders that frequently co-occur with narcissistichistrionic and dependent personality disordersSSRIs may be of particular clinical bene1047297t relative toTCAs given their more favourable side-effect pro1047297leand the possibility of an independent effect on per-sonality factors (Ekselius amp von Knorring 1998Reich et al 2002) With the advent of thenext DSMa greater emphasis on a dimensional diagnostic ap-proach to personality disorders will probably cast

greater importance upon pharmacotherapeutic inter-ventions targeting dimensions common to a variety of current Axis II diagnoses

One such dimension of personality dysfunction isimpulsive aggression Recent trials with levetir-acetamand oxcarbazepinefor impulsive aggressionrecruited individuals with IED without signi1047297cantcomorbidity (eg Mattes 2005 2008) whileother trials recruited subjects with personality disorders and a history of impulsive aggression (eg Coccaro et al 2009 Hollander et al 2003)Coccaro et al (2009) found an anti-aggressiveeffect of 1047298uoxetine in patients with IED and per-sonality disorders Several anticonvulsants (mostnotably divalproex oxcarbazepine and phenyt-oin) have also demonstrated evidence in treating impulsive aggression across diagnoses (Huband et al 2010)

FUTURE DIRECTIONS

Although the past two decades of research haveushered a paradigm shift in personality disordersmost research has been limited to BPD and SPDFuture research should be directed towards thetreatment of other Axis II diagnoses and dimen-sions of dysfunction across diagnoses Althoughresearch has made great strides towards under-standing impulsivity and aggression similar neu-robiological substrates should be sought for other dimensionsofpersonalityOnlybyclarifyingthesegaps in the evidence base can clinicians anticipate

more effective evidence-based psychopharmaco-logical practices for the treatment of personality disorders

FurthereffortstounderstandtowhatextentAvPDdiffers from generalized social phobia are warrantedThis may require understanding distinctions be-tween these diagnoses in neurobiology of fear and socialinhibitionandinthedevelopmentaltrajectory of each disorder For SPD the effects of pro-cognitive interventions should be evaluated withrespect to social isolation and overall function-ing More comprehensive efforts are needed to

understand the underlying neurobiology of SPDto improve evidence-based practices Further char-acterization of the interpersonal dysfunction and cognitive sensory-gating abnormalities seen in SPD

will probably improve the effect of treatment ongeneral functioning Efforts at understanding theneurobiology of schizophrenia and its prodrome willalso assist in de1047297ning targets for pharmacotherapyClarifying the respective roles of genes and envi-ronment in shaping the course of the schizophrenia spectrum will also uncover future pharmacother-apeutic targets


R IPOLL ET AL



Within BPD research has detailed more extensiveevidence-based practices for treating impulsive ag-gression Anticonvulsants and atypical anti-psychotics areacquiring more prominentroles in thetreatment of BPD relative to SSRIs Neverthelessgreaterserotonergicspeci1047297citywillprobablyimprovethe ef 1047297cacy of treatments For example selective5-HT2A antagonism but not 5-HT2C antagonismhas been shown to decrease impulsivity (Higginset al 2003 Winstanley et al 2004)

Futureresearch will also focus on treating affectiveinstability intrapsychic pain dissociation and in-terpersonal dysfunction associated with BPD BPDhas been conceptualized as related to disturbed at-tachment (Fonagy amp Luyten 2009) and dysfunc-tional representations of self and other (Bender ampSkodol 2007) with other symptoms seen as se-quelae to this core feature Oxytocin vasopressinand opioids may therefore be of particular rele-vance for treating BPD (Stanley amp Siever 2010)

given the developmental role of these neuro-peptides in attachment and the relationship be-tween attachment security and stable socialcognitive representations of self and other (Fonagy amp Luyten 2009) Although these domains havebeen exclusively treated with psychotherapy re-search in the neurobiology of af 1047297liative behaviour (eg Depue amp Morrone-Strupinsky 2005) as well asself-injury and dissociation (Mauchnik amp Schmahl2010) may eventually provide novel pharmacother-apeutic targets

For all personality disorders integrating psycho-

pharmacology with neurobiological effects of psy-chotherapy may produce synergistic and long-lasting bene1047297ts Evidence-based practice continues to recom-mend an approach that includes both psychotherapy and pharmacotherapy Although experienced therapistsrsquo contributions to personality theory and empirical research often continue to be at odds withone another future research should attempt toconnect theory with empirically-validated psycho-pharmacological targets By understanding the neu-robiology underlying increasingly complex behaviorpharmacotherapy can be optimized and targeted to

personality dimensions previously considered sus-ceptible only to psychotherapy

R E F E R E N C E S

Abraham PF Calabrese JR (2008) Evidence-based pharmacologic treatment of

borderline personality disorder a shift from SSRIs to anticonvulsants and atypical

antipsychotics Journal of Affective Disorders 111 21ndash30

Akiskal HS (2004) Demystifying borderline personality critique of the concept

and unorthodox reflections on its natural kinship with the bipolar spectrum Acta

Psychiatrica Scandinavica 110 401ndash407

Alden LE Paosa JM Taylor CT Ryder AG (2002) Avoidant personality disorder

current status and future directions Journal of Personality Disorders 16 1ndash29

Aldenkamp AP Arends J Boorsma HPR Diepman L et al (2002) Randomized

double-blind parallel-group study comparing cognitive effects of a low-dose

lamotrigine with valproate and placebo in healthy volunteers Epilepsia 43 19ndash26

Allgulander C (1999) Paroxetine in social anxiety disorder a randomized

placebo-controlled study Acta Psychiatrica Scandinavica 100 193ndash198

Allgulander C Mangano R Zhang J Dahl AA et al (2004) Efficacy of venlafaxine

ER in patients with social anxiety disorder a double-blind placebo-controlled

parallel-group comparison with paroxetine Human Psychopharmacology 19

387ndash396

APA (1994) Diagnostic and Statistical Manual of Mental Disorders 4th edn

Washington DC American Psychiatric Association

APA (2001) Practice guideline for the treatment of patients with borderline per-sonality disorder American Journalof Psychiatry 158 (October supplement) 1ndash52

Baldwin D Bobes J Stein DJ Scharwachter I et al (1999) Paroxetine in social

phobiasocial anxiety disorder Randomised double-blind placebo-controlled

study Paroxetine Study British Journal of Psychiatry 175 120ndash126

Barratt ES Kent TA Bryant SG Felthous AR (1991) A controlled trial of phenytoin

in impulsive aggression Journal of Clinical Psychopharmacology 11 388ndash389

Barratt ES Stanford MS Felthous AR Kent TA (1997) The effects of phenytoin on

impulsive and pre-meditated aggression a controlled study Journal of Clinical

Psychopharmacology 17 341ndash349

Battaglia J Wolff TK Wagner-Johnson DS Rush AJ et al (1999) Structured

diagnostic assessment and depot fluphenazine treatment of multiple suicide

attempters in the emergency department International Clinical Psychopharma-

cology 14 361ndash372

Bender DS Skodol AE (2007) Borderline personality as a self-other representa-

tional disturbance Journal of Personality Disorders 21 500ndash517

Bergida H Lenzenweger MF (2006) Schizotypy and sustained attention con-

firming evidence from an adult community sample Journal of Abnormal Psychol- ogy 115 545ndash551

Blair RJR (2005) Responding to the emotions of others dissociating forms of

empathy through the study of typical and psychiatric populations Consciousness

and Cognition 14 698ndash718

Blomhoff S Haug TT Hellstrom K Holme I et al (2001) Randomised controlled

general practice trial of sertraline exposure therapy and combined treatment in

generalised social phobia British Journal of Psychiatry 179 23ndash30

Bogenschutz MP Nurnberg PH (2004) Olanzapine vs placebo in the treatment of

borderline personality disorder Journal of Clinical Psychiatry 65 104ndash109

Bohus MJ Landwehrmeyer GB Stiglmayr CE Limberger MF et al (1999)

Naltrexone in the treatment of dissociative symptoms in patients with borderline

personality disorder an open-label trial Journal of Clinical Psychiatry 60598ndash603

Bolton S Gunderson JG (1996) Distinguishing borderline personality disorder

from bipolar disorder differential diagnosis and implications American Journal of

Psychiatry 153 1202ndash1207

Brambilla P Soloff PH Sala M Nicoletti MA et al (2004) Anatomical MRI

study of borderline personality disorder patients Psychiatry Research 131125ndash133

Coccaro EF Kavoussi RJ (1997) Fluoxetine and impulsive aggressive behavior in

personality-disordered subjects Archives of General Psychiatry 54 1081ndash1088

Coccaro EF Kavoussi RJ Hauger RL (1995) Physiological responses to

d-fenfluramine and ipsapirone challenge correlate with indices of aggression in

males with personality disorder International Clinical Psychopharmacology 10

177ndash179

Coccaro EF Lee RJ Kavoussi RJ (2009) A double-blind randomized placebo-

controlled trial of fluoxetine in patients with intermittent explosive disorder Jour-

nal of Clinical Psychiatry 70 653ndash662

Coccaro EF Siever LJ Klar HM Maurer G et al (1989) Serotonergic studies

in patients with affective and personality disorders correlates with suicidal

and impulsive aggressive behavior Archives of General Psychiatry 46 587ndash599

Cornelius JR Soloff PH Perel JM Ulrich RF (1993) Continuation pharmacother-

apy of borderline personality disorder with haloperidol and phenelzine American

Journal of Psychiatry 150 1843ndash1848

Cowdry RW Gardner DL (1988) Pharmacotherapy of borderline personality dis-order alprazolam carbamazepine trifluoperazine and tranylcypromine

Archives of General Psychiatry 45 111ndash119

Davidson J Yaryura-Tobias J DuPont R Stallings L et al (2004b ) Fluvoxamine-

controlled release formulation for the treatment of generalized social anxiety

disorder Journal of Clinical Psychopharmacology 24 118ndash125

Davidson JR Foa EB Huppert JD Keefe FJ et al (2004a ) Fluoxetine compre-

hensive cognitive behavioral therapy and placebo in generalized social phobia


de la Fuente JM Lotstra F (1994) A trial of carbamazepine in borderline person-

ality disorder European Neuropsychopharmacology 4 479ndash486

Depue RA Morrone-Strupinsky JV (2005) A neurobehavioral model of affiliative

bonding implications for conceptualizing a human trait of affiliation Behavioral

and Brain Sciences 28 313ndash395

Deutsch H (1942) Some forms of emotional disturbance and their relationship to

schizophrenia Psychoanalytic Quarterly 11 301ndash321


R IPOLL ET AL

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F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Ekselius L von Knorring L (1998) Personality disorder comorbidity with major

depression and response to treatment with sertraline or citalopram International

Clinical Psychopharmacology 13 205ndash211

Evenden J (1999) Impulsivity a discussion of clinical and experimental findings

Journal of Psychopharmacology 13 180ndash192

Fahlen T (1995) Personality traits in social phobia II changes during drug

treatment Journal of Clinical Psychiatry 56 569ndash573

Faltus FJ (1984) The positive effect of alprazolam in the treatment of three

patients with borderline personality disorder American Journal of Psychiatry

141 802ndash803

Fonagy P Luyten P (2009) A developmental mentalization-based approach to

the understanding and treatment of borderline personality disorder Development and Psychopathology 21 1355ndash1381

Frankenburg FR Zanarini MC (2002) Divalproex sodium treatment of women

with borderline personality disorder and bipolar II disorder a double-blind

placebo-controlled pilot study Journal of Clinical Psychiatry 63 442ndash446

Frankenburg FR Zanarini MC (2006) Obesity and obesity-related illnesses in

borderline patients Journal of Personality Disorders 20 71ndash80

Gardner DL Cowdry RW (1986a ) Development of melancholia during carbama-

zepine treatment in borderline personality disorder Journal of Clinical Psycho-

pharmacology 6 236ndash239

Gardner DL Cowdry RW (1986b ) Positive effectsof carbamazepineon behavioral

dyscontrolin borderlinepersonalitydisorder American Journal of Psychiatry 143

519ndash522

Goldberg SC Schulz SC Schulz PM Resnick RJ et al (1986) Borderline and

schizotypal personality disorders treated with low-dose thiothixene vs placebo


Goodman M New A Siever L (2004) Trauma genes and the neurobiology of

personality disorders Annals of the New York Academy of Sciences 1032104ndash116

GoodwinGM Bowden CLCalabrese JRGrunzeH etal (2004) A pooled analysis

of 2 placebo-controlled18-month trials of lamotrigine andlithium maintenance in

bipolar I disorder Journal of Clinical Psychiatry 65 432ndash441

Griengl H Sendera A Dantendorfer K (2001) Naltrexone as a treatment of

self-injurious behavior ndash a case report Acta Psychiatrica Scandinavica 103

234ndash236

Hamazaki T Sawazaki S Itomura M Asaoka E et al (1996) The effect of

docosahexaenoic acid on aggression in young adults A placebo-controlled

double-blind study Journal of Clinical Investigation 97 1129ndash1133

Hamazaki T Thienprasert A Kheovichai K Samuhaseneetoo S et al (2002) The

effect of docosahexaenoic acidon aggression in elderly Thaisubjects ndash a placebo-

controlled double-blind study Nutritional Neuroscience 5 37ndash41

Heimberg RG Liebowitz MR Hope DA Schneier FR et al (1998) Cognitive

behavioral group therapy vs phenelzine therapy for social phobia 12-week out-

come Archives of General Psychiatry 55 1133ndash1141

Henry C Mitropoulou V New AS Koenigsberg HW et al (2001) Affectiveinstability and impulsivity in borderline personality and bipolar II disor-

ders similarities and differences Journal of Psychiatric Research 35

307 ndash312

Herpertz SC Zanarini M Schulz CS Siever L et al (2007) World Federation of

Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of

Personality Disorders World Journal of Biological Psychiatry 8 212ndash244

Higgins GA Enderlin M Haman M Fletcher PJ (2003) The 5-HT2A receptor

antagonist M100907 attenuates motor and lsquo impulsive-typersquo behaviours pro-

duced by NMDA receptor antagonism Psychopharmacology (Berlin) 170

309ndash319

Hollander E Allen A Lopez RP Bienstock CA et al (2001) A preliminary double-

blind placebo-controlled trial of divalproex sodium in borderline personality dis-

order Journal of Clinical Psychiatry 62 199ndash203

Hollander E Swann AC Coccaro EF Jiang P et al (2005) Impact of trait impul-

sivity and state aggression on divalproex vs placebo response in borderline

personality disorder American Journal of Psychiatry 162 621ndash624

Hollander E Tracy KA Swann AC Coccaro EF et al (2003) Divalproex in thetreatment of impulsive aggression efficacy in cluster B personality disorders

Neuropsychopharmacology 28 1185ndash1197

Houston RJ Bauer LO Hesselbrock VM (2004) Effects of borderline personality

disorder features and a family history of alcohol or drug dependence on P300 in

adolescents International Journal of rsquo Psychophysiology 53 57ndash70

Huband N FerriterM Nathan R Jones H (2010) Antiepileptics foraggression and

associated impulsivity Cochrane Database for Systematic Reviews Issue 2 Art

No CD003499

IMCTGMSP Katschnig H (1997) The International Multicenter Clinical Trial Group

on Moclobemide in Social Phobia Moclobemide in social phobia a double-blind

placebo-controlled clinical study European Archives of Psychiatry and Clinical

Neuroscience 247 71ndash80

Ingenhoven T Lafay P Rinne T Passchier J et al (2010) Effectiveness of

pharmacotherapy for severe personality disorders meta-analyses of randomized

controlled trials Journal of Clinical Psychiatry 71 14ndash25

Jensen HV Andersen J (1989) An open noncomparative study of amoxapine in

borderline disorders Acta Psychiatrica Scandinavica 79 89ndash93

Juengling FD Schmahl C Hesslinger B Ebert D et al (2003) Positron emission

tomography in female patients with borderline personality disorder Journal of

Psychiatric Research 37 109ndash115

Kasper S Stein DJ Loft H Nil R (2005) Escitalogram in the treatment of social

anxiety disorder randomised placebo-controlled flexible-dosage study British


Katzelnick DJ Kobak KA Greist JH Jefferson JW et al (1995) Sertraline for

social phobia a double-blind placebo-controlled crossover study American


Kayser A Robinson DS Nies A Howard D (1985) Respons to phenelzine amongdepressed patients with features of hysteroid dysphoria American Journal of


Keck P Buffenstein A Ferguson J Feighner J et al (1998) Ziprasidone 40 and

120 mgday in the acute exacerbation of schizophrenia and schizoaffective dis-

order a 4-week placebo-controlled trial Psychopharmacology 140 173ndash184

Koenigsberg HW Reynolds D Goodman M New AS et al (2003) Risperidone in

the treatment of schizotypal personality disorder Journal of Clinical Psychiatry

64 628ndash634

Lader M Stender K Burger V Nil R (2004) Efficacy and tolerability of escitalo-

pram in 12- and 24-week treatment of social anxiety disorder randomised

double-blind placebo-controlled fixed-dose study Depression and Anxiety 19

241ndash248

Langdon R Coltheart M (2004) Recognition of metaphor and irony in young

adults the impact of schizotypal personality traits Psychiatry Research 125

9ndash20

Leiberich P Nickel MK Tritt K Pedrosa Gil F (2008) Lamotrigine treatment of

aggression in female borderline patients part II an 18-month follow-up Journal of Psychopharmacology 22 805ndash808

Leone NF (1982) Response of borderline patients to loxapine and chlorproma-

zine Journal of Clinical Psychiatry 43 148ndash150

Lepola U Bergtholdt B St Lambert J Davy KL et al (2004) Controlled-release

paroxetine in the treatment of patients with social anxiety disorder Journal of

Clinical Psychiatry 65 222ndash229

Levitt JJ Westin CF Nestor PG Estepar RS et al (2004) Shape of caudate

nucleus and its cognitive correlates in neuroleptic-naiumlve schizotypal personality

disorder Biological Psychiatry 55 177ndash184

Lieb K Vollm B Rucker G Timmer A et al (2010) Pharmacotherapy for border-

linepersonalitydisorder Cochranesystematic review of randomized trials British


Lieb K ZanariniMC Schmahl CLinehanMM etal (2004) Borderlinepersonality

disorder Lancet 364 453ndash461

Liebowitz MR Gelenberg AJ Munjack D (2005a ) Venlafaxine extended release

vs placebo and paroxetine in social anxiety disorder Archives of General Psy-

chiatry 62 190ndash198Liebowitz MR Heimberg RG Schneier FR Hope DA et al (1999) Cognitive-

behavioral group therapy versus phenelzine in social phobia long-term outcome

Depression and Anxiety 10 89ndash98

Liebowitz MR Klein DF (1981) Interrelationship of hysteroid dysphoria and bor-

derline personality disorder Psychiatric Clinics of North America 4 67ndash87

Liebowitz MR Mangano RM Bradwejn J Asnis G et al (2005b ) A randomized

controlled trial of venlafaxine extended release in generalized social anxiety

disorder Journal of Clinical Psychiatry 66 238ndash247

Liebowitz MR Stein MB Tancer M Carpenter D et al (2002) A randomized

double-blind fixed-dose comparison of paroxetine and placebo in the treat-

ment of generalized social anxiety disorder Journal of Clinical Psychiatry 63

66ndash74

Links PS Steiner M Boiago I Irwin D (1990) Lithium therapy for borderline

patients preliminary findings Journal of Personality Disorders 4 173ndash181

Lion JR (1979) Benzodiazepines in the treatment of aggressive patients Journal

of Clinical Psychiatry 40 70ndash71

Loew TH Nickel MK (2008) Topiramate treatment of women with borderlinepersonality disorder part II an open 18-month follow-up Journal of Clinical


Loew TH Nickel MK Muehlbacher M Kaplan P et al (2006) Topiramate treat-

ment of women with borderline personality disorder a double-blind placebo-

controlled study Journal of Clinical Psychopharmacology 26 61ndash66

Loranger AW Sartorius N Andreoli A Berger P et al (1994) The international

personality disorders examination The world health organizationalcohol drug

abuse and mental health administration international pilot study of personality

disorders Archives of General Psychiatry 51 215ndash224

Lott M Greist JH Jefferson JW Kobak KA et al (1997) Brofaromine for social

phobia a multicenter placebo-controlled double-blind study Journal of Clinical

Psychophamacology 17 255ndash260

Malone KM Corbitt EM Li S Mann JJ (1996) Prolactin response to fenfluramine

and suicide attempt lethality in major depression British Journal of Psychiatry

168 324ndash329


R IPOLL ET AL



Markovitz PJ Calabrese JR Schulz SC Meltzer HY (1991) Fluoxetine in the

treatment of borderline and schizotypal personality disorders American Journal

of Psychiatry 148 1064ndash1067

Mattes JA (2005) Oxcarbazepine in patients with impulsive aggression

a double-blind placebo-controlled trial Journal of Clinical Psychopharmacology

25 575ndash579

Mattes JA (2008) Levetiracetam in patients with impulsive aggression a double-

blind placebo-controlled trial Journal of Clinical Psychiatry 69 310ndash315

Mauchnik J Schmahl C (2010) The latest neuroimaging findings in borderline

personality disorder Current Psychiatry Reports 12 46ndash55

McClure MM Barch DM Romero MJ Minzenberg MJ et al (2007b ) The effects

of guanfacine on context-processing abnormalities in schizotypal personalitydisorder Biological Psychiatry 61 1157ndash1160

McClure MM Harvey PD Goodman M Triebwasser J et al (2010) Pergolide

treatment of cognitive deficits associated with schizotypal personality disorder

continued evidence of the importance of the dopamine system in the schizophre-

nia spectrum Neuropsychopharmacology 35 1356ndash1362

McClure MM Romero MJ Bowie CR Reichenberg A etal (2007a ) Visual-spatial

learning and memory in schizotypal personality disorder continued evidence for

the importance of working memory in the schizophrenia spectrum Archives of

Clinical Neuropsychology 22 109ndash116

McGee MD (1997) Cessation of self-mutilation in a patient with borderline per-

sonalitydisordertreated withnaltrexoneJournalof ClinicalPsychiatry 5832ndash33

Mehlman PT Higley JD Faucher I Lilly AA et al (1994) Low CSF 5-HIAA

concentrations andsevere aggression andimpairedimpulsecontrol in nonhuman

primates American Journal of Psychiatry 151 1485ndash1491

Mercer D Douglass AB Links PS (2009) Meta-analyses of mood stabilizers

antidepressants and antipsychotics in the treatment of borderline personality

disorder effectiveness for depression and anger symptoms Journal of Person- ality Disorders 23 156ndash174

Minzenberg MJ Grossman R New AS Mitropoulou V et al (2006) Blunted

hormone responses to ipsapirone are associated with trait impulsivity in person-

ality disorder patients Neuropsychopharmacology 31 197ndash203

Montgomery SA Montgomery D (1982) Pharmacological prevention of suicidal

behavior Journal of Affective Disorders 4 291ndash298

Montgomery SA Nil R Durr-Pal N Loft H et al (2005) A 24-week randomized

double-blind placebo-controlled study of escitalopram for the prevention of gen-

eralized social anxiety disorder Journal of Clinical Psychiatry 66 1270ndash1278

Montgomery SA Roy D Montgomery DB (1983) The prevention of recurrent

suicidal acts British Journal of Clinical Pharmacology 15 183Sndash188S

New AS Hazlett EA Buchsbaum MS Goodman M et al (2002) Blunted pre-

frontal cortical 18fluorodeoxyglucose positron emission tomography response to

meta-chlorophenylpiperazine in impulsive aggression Archives of General Psy-

chiatry 59 621ndash629

New AS Trestman R Mitropoulou V Benishay DS et al (1997) Serotonergic

function and self-injurious behavior in personality disorder patients Psychiatry Research 69 17ndash26

New AS Trestman R Mitropoulou V Goodman M et al (2004) Low prolactin

response to fenfluramine in impulsive aggression Journal of Psychiatric Re-

search 38 223ndash230

Nickel MK Loew TH (2008) Treatment of aggression with topiramate in male

borderline patients part II 18-month follow-up European Psychiatry 23 115ndash

117

Nickel MK Loew TH Pedrosa Gil F (2007) Aripiprazole in treatment of border-

line patients part II an 18-month follow-up Psychopharmacology 191 1023ndash

1026

Nickel MK Muehlbacher M Nickel C Kettler C et al (2006) Aripiprazole in the

treatment of patients with borderline personality disorder a double-blind

placebo-controlled study American Journal of Psychiatry 163 833ndash838

Nickel MK Nickel C Kaplan P Lahmann C et al (2005) Treatment of aggression

with topiramate in male borderline patients a double-blind placebo-controlled

study Biological Psychiatry 57 495ndash499

Nickel MK Nickel C Mitterlehner FO Tritt K et al (2004) Topiramate treatment of aggression in female borderline personality disorder patients a double-blind

placebo-controlled study Journal of Clinical Psychiatry 65 1515ndash1519

Noyes R Moroz G Davidson JR Liebowitz MR et al (1997) Moclobemide in

social phobia a controlled dose-response trial Journal of Clinical Psychophar-

macology 17 247ndash254

Ogiso Y Moriya N Ikuta N Maher-Nishizono A et al (1993) Relationship be-

tween clinical symptoms and EEG findings in borderline personality disorder

Japanese Journal of Psychiatry and Neurology 47 37ndash46

Oquendo MA Krunic A Parsey RV Milak M et al (2005) Positron emission

tomography of regional brain metabolic responses to a serotonergic challenge

in major depressive disorder with and without borderline personality disorder


Pande AC Davidson JR Jefferson JW Janney CA et al (1999) Treatment of

social phobia with gabapentin a placebo-controlled study Journal of Clinical


Pande AC Feltner DE Jefferson JW Davidson JR et al (2004) Efficacy of the

novel anxiolytic pregabalin in social anxiety disorder Journal of Clinical Psycho-


Parc S McTigue K (1997) Working memory and the syndromes of schizotypal

personality Schizophrenia Research 29 213ndash220

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disorder from bipolar spectrum disorders Harvard Review of Psychiatry 1 2

140ndash145

Paris J (2005) Borderline personality disorder Canadian Medical Association

Journal 172 1579ndash1583

Parsons B Quitkin FM McGrath PJ Stewart JW et al (1989) Phenelzine

imipramine and placebo in borderline patients meeting criteria for atypical de-pression Psychopharmacological Bulletin 25 524ndash534

Pascual JC Oller S Soler J Barrachina J et al (2004) Ziprasidone in the acute

treatment of borderline personality disorder in psychiatric emergency services

Journal of Clinical Psychiatry 65 1281ndash1283

Pascual JC Madre M Soler J Barrachina J et al (2006) Injectable atypical

antipsychotics for agitation in borderline personality disorder Pharmacopsychia-

try 39 117ndash118

Pascual JCSoler J PuigdemontD Perez-EgeaR etal (2008) Ziprasidone in the

treatment of borderline personality disorder a double-blind placebo-controlled

randomized study Journal of Clinical Psychiatry 69 603ndash608

Peet M Stokes C (2005) Omega-3 fatty acids in the treatment of psychiatric

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Philipsen A Richter H Schmahl C Peters J et al (2004a ) Clonidine in acute

aversive inner tension and self-injurious behavior in female patients with border-

line personality disorder Journal of Clinical Psychiatry 65 1414ndash1419

Philipsen A Schmahl C Lieb K (2004b ) Naloxone in the treatment of acute

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Pickup GJ (2006) Theory of mind and its relation to schizotypy Cognitive Neu-

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Pitchot W Hansenne M Pinto E Reggers J etal (2005) 5-Hydroxytryptamine1A

receptors major depression and suicidal behavior Biological Psychiatry 58

854ndash858

Placidi GP Oquendo MA Malone KM Huang YY et al (2001) Aggressivity

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Posner MI Rothbart MK Vizueta N Levy KN et al (2002) Attentional mecha-

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Prossin AR Love TM Koeppe RA Zubieta JK et al (2010) Dysregulation of

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treatment of affective instability in borderline personality disorder International Clinical Psychopharmacology 24 270ndash275

Reich J (2002) Drug treatment of personality disorder traits Psychiatric Annals

32 590ndash596

Rickels K Mangano R KhanA (2004) A double-blindplacebo-controlled studyof

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519ndash523

Rinne T van den Brink W Wouters L van Dyck R (2002) SSRI treatment of

borderline personality disorder a randomized placebo-controlled clinical trial for

female patients with borderline personality disorder American Journal of Psy-


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233ndash237

Rusch N van Elst LT Ludaescher P Wilke M et al (2003) A voxel-basedmorphometric MRI study in female patients with borderline personality disorder

Neuroimage 20 385ndash392

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pain insensitivity in self-injurious borderline patients Psychiatry Research 89

201ndash214

Salzman C WolfsonAN Schatzberg A Looper J etal (1995) Effectsof fluoxetine

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Samuelsson M Jokinen J Nordstrom AL Nordstrom P (2006) CSF 5-HIAA

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Saper JR (2000) Borderline personality opioids and naltrexone Headache 40

765ndash766

Schneier FR Gortz D Campeas R Fallon B et al (1998) Placebo-controlled trial

of moclobemide in social phobia British Journal of Psychiatry 172 70ndash77


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Schulz SC Zanarini MC Bateman A Bohus M et al (2008) Olanzapine for the

treatment of borderline personality disorder variable-dose 12-week random-

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485ndash492

Serban G Siegel S (1984) Response of borderline and schizotypal patients to

small doses of thiothixene and haloperidol American Journal of Psychiatry 141

1455ndash1458

Shafti SS Shahveisi B (2010) Olanzapine vs haloperidol in the management of

borderline personality disorder a randomized double-blind trial Journal of Clin-

ical Psychopharmacology 30 44ndash47

Sheard MH (1971) Effect of lithium on human aggression Nature 230 113ndash114

Sheard MH Marini JL Bridges CI Wagner E (1976) The effect of lithium onimpulsive aggressive behavior in man American Journal of Psychiatry 133

1409ndash1413

Siever LJ Buchsbaum MS New AS Spiegel-Cohen J et al (1999) D L-

fenfluramine response in impulsive personality disorder assessed with [18F]

fluorodeoxyglucose positron emission tomography Neuropsychopharmacology

20 413ndash423

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disorders American Journal of Psychiatry 148 1647ndash1658

Siever LJ Davis KL (2004) The pathophysiology of schizophrenia disorders

perspectives from the spectrum American Journal of Psychiatry 161 398ndash413

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sonality disorders psychological and biological correlates American Journal of


Simpson EB Yen S Costello E Rosen K et al (2004) Combined dialectical

behavior therapy and fluoxetine in the treatment of borderline personality disor-

der Journal of Clinical Psychiatry 65 379ndash385

Skodol AE Gunderson JG Shea MT McGlashan TH et al (2005) The collabo-rative longitudinal personality disorders study (CLPS) overview and implications

Journal of Personality Disorders 19 487ndash504

Smith DJ Muir WJ Blackwood DH (2004) Is borderline personality disorder part

of the bipolar spectrum Harvard Review of Psychiatry 12 133ndash139

Soderstrom H Foresman A (2004) Elevated triiodothyronine in psychopathy ndash

possible physiological mechanisms Journal of NeuralTransmission 111739ndash744

Soler J PascualJC CampinsJ BarrachinaJ etal (2005)Double-blindplacebo-

controlled study of dialectical behavior therapy plus olanzapine for border-

line personality disorder American Journal of Psychiatry 162 1221ndash1224

Soloff PH Cornelius J George A Nathan S et al (1993) Efficacy of phenelzine

and haloperidol in borderline personality disorder Archives of General Psychiatry

50 377ndash385

Soloff PH George A Nathan RS Schulz PM et al (1986a ) Paradoxical effects

of amitryptiline on borderline patients American Journal of Psychiatry 143 1603ndash

1605

Soloff PH George A Nathan RS Schulz PM et al (1986b ) Amitryptiline and

haloperidol in unstable and schizotypal borderline disorders Psychopharmacol-

ogy Bulletin 22 177ndash182

Soloff PH George A Nathan RS Schulz PM et al (1986c ) Progress in

pharmacotherapy of borderline disorders Archives of General Psychiatry

43 691ndash697

Soloff PH George A Nathan RS Schulz PM etal (1987) Behavioral dyscontrol in

borderline patients treated with amitryptiline Psychopharmacology Bulletin 23

177ndash181

Soloff PH George A Nathan RS Schulz PM et al (1989) Amitryptiline vs

haloperidol in borderlines final outcomes and predictors of response Journal


Southwick SM Bremner JD Rasmusson A Morgan CA et al (1999) Role of

norepinephrine in the pathophysiology and treatment of posttraumatic stress


Stanley B Siever LJ (2010) Theinterpersonal dimension of borderline personality

disorder toward a neuropeptide model American Journal of Psychiatry 167

24ndash39

Stein DJ Versiani M Hair T Kumar R (2002) Efficacy of paroxetine for relapse

preventionin social anxiety disorder Archives of General Psychiatry 591111ndash1118

Stein MB Fyer AJ Davidson JR Pollack MH etal (1999) Fluvoxamine treatment

of social phobia (social anxiety disorder) a double-blind placebo-controlled

study American Journal of Psychiatry 156 756ndash760

Stein MB Liebowitz MR Lydiard RB Pitts CD et al (1998) Paroxetine treatment

of gereralized social phobia (social anxiety disorder) a randomized controlled

trial Journal of the American Medical Association 280 708ndash713

Stein MB Pollack MH Bystritsky A Kelsey JE et al (2005) Efficacy of low

and higher dose extended-release venlafaxine in generalized social anxiety

disorder a 6-month randomized controlled trial Psychopharmalogy 177

280ndash288

Strawn JR Geracioti TD (2008) Noradrenergic dysfunction and the psycho-

pharmacology of posttraumatic stress disorder Depression and Anxiety 25

260ndash271

Tandon R (2000) Introduction ziprasidone appears to offer important therapeutic

and tolerability advantages over conventional and some novel antipsychotics

British Journal of Clinical Pharmacology 49(Suppl 1) 1Sndash3S

Thurauf NJ Washeim HA (2000) The effects of exogenous analgesia in a patient

with borderline personality disorder (BPD) and severe self-injurious behavior

European Journal of Pain 4 107ndash109

Traskman L Asberg M Bertilsson L Sjostrand L (1981) Monoamine metabolitesin CSF and suicidal behavior Archives of General Psychiatry 38 631ndash636

Tritt K Nickel C Lahmann C Leiberich PK et al (2005) Lamotrigine treatment of

aggression in female borderline patients a randomized double-blind placebo-

controlled study Journal of Psychopharmacology 19 287ndash291

van Ameringen M Oakman J Mancini C Pipe B et al (2004) Predictors of

response in generalized social phobia effect of age of onset Journal of Clinical


van Ameringen MA Lane RM Walker JR Bowen RC et al (2001) Sertraline

treatment of generalized social phobia a 20ndashweek doubleblind placebo-

controlled study American Journal of Psychiatry 158 275ndash281

van Vliet IM den Boer JA Westenberg HG (1994) Psychopharmacological treat-

ment of social phobia a double blind placebo controlled study with fluvoxamine

Psychopharmacology (Berlin) 115 128ndash134

Verkes RJ van der Mast RC Hengeveld MW Tuyl JP et al (1998) Reduction by

paroxetine of suicidal behavior in patients with repeated suicide attempts but not

major depression American Journal of Psychiatry 155 543ndash547

Versiani M Nardi AE Mundim FD Alves AB et al (1992) Pharmacotherapy of social phobia A controlled study with moclobemide and phenelzine British Jour-

nal of Psychiatry 161 353ndash360

Virkkunen M Raw lings R Tokola R Polan d RE et al (1994) CSF biochemis-

tries glucose metabolism and diurnal activity rhythms in alcoholic violent

offenders fire setters and healthy volunteers Archives of General Psychiatry

51 20ndash27

Welch SS Linehan MM (2002) High-risk situations associated with parasuicide

and drug use in borderline personality disorder Journal of Personality Disorders

16 561ndash569

Wilner KD Anziano RJ Johnson AC Miceli JJ et al (2002) The anxiolytic effect

of the novel antipsychotic ziprasidone compared with diazepam in subjects

anxious before dental surgery Journal of Clinical Psychopharmacology 22

206ndash210

Winstanley CA Theobald DE Dalley JW Glennon JC et al (2004) 5-HT2A and

5-HT2C receptor antagonists have opposing effects on a measure of impulsivity

Interactions with global 5-HT depletion Psychopharmacology (Berlin) 176

376ndash385

Zanarini MC Frankenburg FR (2001) Olanzapine treatment of female borderline

personality disorderpatients a double-blindplacebo-controlled pilot study Jour-


Zanarini MC Frankenburg FR (2003) Omega-3 fatty acid treatment of women

with borderline personality disorder a double-blind placebo-controlled pilot


Zanarini MC Frankenburg FR Hennen J Reich DB et al (2004a ) Axis I

comorbidity of borderline personality disorder Description of six-year course

and prediction to time-to-remission American Journal of Psychiatry 161

2108ndash2114

Zanarini MC Frankenburg FR Parachini EA (2004b ) A preliminary randomized

trial of fluoxetine olanzapine and the olanzapine-fluoxetine combination in

women with borderline personality disorder Journal of Clinical Psychiatry 7

903ndash907

Zanarini MC Frankenburg FR Vujanovic AA Hennen J et al (2004c ) Axis II


and prediction to time-to-remission Acta Psychiatrica Scandinavica 110

416ndash420

Zanarini MC Gunderson JG Frankenburg FR Chauncey DL (1990) Discriminat-

ing borderline personality disorder from other axis II disorders American Journal


Ziegenhorn AA Roepke S Schommer NC Merkl A et al (2009) Clonidine

improves hyperarousal in borderline personality disorder with or without

comorbid post-traumatic stress disorder a randomized double-blind

placebo-controlled trial Journal of Clinical Psychopharmacology 29

170ndash173

R IPOLL ET AL



et al 1991 Simeon et al 1992 Soderstrom ampForesman 2004) Identifying neurobiological sub-strates of personality has allowed for increasingly speci1047297c pharmacotherapy Nevertheless improvementfrom effective pharmacotherapeutic interventions isoften transient andor restricted to several symptom

domains In the USA there are no FDA-approved medications for treating personality disorders Thuspharmacotherapy for personality disorders remainsoff-label and psychopharmacological strategies for evidence-based practices remain lacking

Themajorityofpsychopharmacologicalresearchon personality disorders has focused on borderlinepersonality disorder (BPD) In the most recenttreatment guidelines for BPD the AmericanPsychiatric Association (APA 2001) acknowl-edges that lsquopharmacotherapy has an importantadjunctive rolersquo along with lsquoextended psycho-

therapy to attain and maintain lasting improvementinhellip personality interpersonal problems and overallfunctioning rsquo Similarly others have described psy-chopharmacological treatment of BPD as resulting only in lsquoa mild degree of symptom relief rsquo (Paris2005) Moreover there remainsa dearth of evidence-based medication treatments for other personality disorders

Often pharmacotherapy for severe personality disorders is used to stabilize patientsrsquo symptomssuf 1047297ciently in order to facilitate psychosocial inter-ventions and foster re1047298ective functioning Close

communication between psychotherapists and psychopharmacologists remains crucial Althoughfunctional gains can be expected from medicationsthe magnitude and time-course vary There is littleevidence regarding distinctions between acute and maintenance pharmacotherapy or how long to

continue patients on a medication Empirical data on recurrence or relapse is similarly scarce There-fore evidence-based practices must be judged case-by-case weighing clinical risks and bene1047297ts

Clinicians canreferto accompanyingtables forthebest available evidence regarding pharmacotherapy for personality disorders (see Tables 1ndash4) This data

was compiled by searching the Medline database with the main combinations pharmacotherapy and each of the various DSM-IV personality disorder diagnoses In addition we paid particularly closeattention to randomized placebo-controlled trials

(along with some lower-level evidence if this type of evidence was severely limited) We focused onstudies published in the past 3 years since thepublication of the last World Federation of Societiesof Biological Psychiatry Guidelines for the BiologicalTreatment of Personality Disorders (Herpertz et al

2007) Additional research regarding medicationsfor treating impulsive aggression was found via a similar Medline search on impulsivity aggressionand pharmacotherapy

Unfortunately only a few novel trials of pharmaco-therapy for personality disorders have been published

Table 1 Schizotypal Personality Disorder (SPD)


Design


Koenigsberg

et al (2003)

SPD 25 males

and

females

Risperidone Started

at 025 mgd

titrated up to

2 mgd

Parallel

design

9 wk

Significantly lower scores on PANSS

negative and general symptom scales

by week 3 and positive symptoms by

week 7

McClureet al (2007b )

SPD 29 malesand

females

Guanfacine Titrated up to2 mgd within

first 2 wk

Paralleldesign

4 wk

After 4 wk greater improvements frombaseline in neuropsychological

measures of working memory (Modified

AX-Continuous Performance Task)

compared to placebo

McClure

et al (2010)

SPD 25 males

and

females

Pergolide 0025 mgd for

first 3 d then

005 mgd for 4 d



then 03 mgd

Parallel

design

4 wk

Greater improvement from baseline in

tasks measuring executive function

(Trail-Making Test Part B) verbal

memory (Word List Learning-

immediate and delayed recall) verbal

working memory (Letter Number Span)

long-term visuospatial memory

(Wechsler Memory Scale Visual

Reproduction Test) and visuospatial

working memory (Dot Test) comparedto placebo Dot findings were largely

driven by worsening in placebo group

PANSS Positive and Negative Symptom Scale


R IPOLL ET AL





suf 1047297




(SPD)




Design


Sheard

(1971)

Inmates of

maximum security

prison with verbal

and physical


12 males Lithium

carbonate

Lithium levels of

06ndash15 meql

mean dose

1200 mgd

Crossoversingle-

blind three

4-wk phases








Sheard

et al

(1976)

Prisoners

convicted of

lsquoserious

aggressive

crimesrsquo

80 males Lithium

carbonate

Lithium levels of

06ndash10 meql

mean lithium level

during last week

of medication

phase 089 meql

Parallel design

5 months with

first and

last months

medication

free and 3

months lithium

vs placebo



Lion

(1979)


past histories of

temper outbursts


behaviour and

impulsiveness

had experienced

legal difficulties

and some

had committed

criminal actsrsquo

65 males

and females

Chlordiazepoxide

oxazepam

Chlordiazepoxide

100 mgd for 2 wk

then 200 mgd for


then 240 mgd

for 2wk

Parallel design

4 wk




Barratt

et al

(1991)

Maximum security

prison inmates

with impulsive

aggression

while in prison


300 mgd

Crossover design

three 4-wk

phases




tension-anxiety and



Barratt

et al

(1997)

Prison inmates

with aggression

while in prison

150 total but only

30 males with

primarily impulsive

aggression and

30 males with

primarily

pre-meditated

aggression included

in analysis (other

66 had mixture

of both types)


design two

6-wk phases





group


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





Design


Rifkin et al

(1972)

EUCD (emotionally

unstable character

disorder

characterized by


poor acceptance of


truancy poor

work history


with a core

psychopathological

disturbance of

depressive and

hypomanic mood


to daysrsquo)

21 (sex

distribution

not specified)

Lithium

carbonate

Dosed to levels

between 06ndash15

meql

Crossover

design

two 6-wk

phases




females

Loxapine

succinate

chlorpromazine

Mean doses

loxapine

145 mgd

chlorpromazine

110 mgd

Parallel design but

not placebo-

controlled 6 wk





Montgomery

amp Montgomery

(1982)

BPD DPD andor



with history of at


acts

Not specified 30

males and

females

completed the

study 23 with

BPD 15 with

HPD and 2

with DPD

Depot

flupenthixol

20 mg IM every

4 wk

Parallel design

6 months



Montgomery

et al (1983)

BPD andor HPD all

hospitalized after

a suicidal act with


prior suicidal acts

Not specified

38 male

and female

subjects

completed

30 with BPD and

12 with HPD


6 months



reach trend levels

Serban amp

Siegel (1984)


females

Thiothixene

haloperidol


2 mgd then adjusted

up or down mean

dose 94 mgd


08 mg bid then

adjusted dose up

or down mean

dose 3 mgd

Parallel design

but not

placebo-

controlled

3 months










predict outcome

Goldberg

et al (1986)

BPD andor SPD

all subjects with

at least one

psychotic symptom

50 males and

females



maximum of 35 mgd

Parallel design

12 wk









Soloff et al

(1986b )


BPD only 4 SPD

only and 32

Haloperidol

amitryptiline

Amitryptiline began

at 25 mgd then

titrated upward to

Parallel design

5 wk



medication effects

(Continued)


R IPOLL ET AL



Table 3 Continued


Design


comorbid BPD and

SPD

mean final dose of

14762 mgd

Haloperidol began

at 2 mgd then


724 mgd








Soloff et al

(1986c )









Soloff et al

(1986a

1987)


paradoxical


during study first

described in

Soloff et al

(1986b )

Compared 15

amitryptiline non-

responders

14 placebo

non-responders

13 amitryptiline

responders and

10 placebo

responders


amitryptiline1


for responders and

2459 ngml for non-

responders





non-responders

Cowdry amp

Gardner

(1988)


behavioural

dyscontrolrsquo


carbamazepine

trifluoperazine

hydrochloride

tranylcypromine

sulfate

Mean doses of

alprazolam 47 mgd

carbamazepine

820 mgd

trifluoperazine

78 mgd and

tranylcypromine

40 mgd

Crossover design

each phase

lasting 6 wk



















Parsons et al

(1989)

BPD and atypical

depression

First sample of

subjects were

required to meet

5 BPD criteria

(N 5 40) second

sample met 4

Phenelzine

imipramine


60 mgd with


90 mgd if no

response by week 5


to 200 mgd with

Crossover

design two

6-wk phases








(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 3 Continued


Design


BPD criteria

(N 5 19)

option to increase

to 300 mgd if no

response by week 5


of phenelzine

Soloff et al

(1989)

Same as Soloff

et al (1986 b)

90 total with 35


4 SPD and 51

lsquomixedrsquo BPD

and SPD

Same as Soloff

et al (1986b )

Same procedure as


Mean dose of

haloperidol was 48

mgd and mean dose


1491 mgd on

day 35

Parallel design

5 wk











Links et al

(1990)

BPD 17 males and

females

Lithium

carbonate

desipramine


two 6-wk phases









Soloff et al

(1993)

BPD 108 males and

females

Haloperidol

phenelzine


1 mgd then titrated

up to mean dose of

4 mgd Phenelzine

began at 15 mgd

then titrated up to

mean dose of 60

mgd

Parallel design

5 wk









dysphoria

Cornelius

et al (1993)

BPD 54 males and

females

Haloperidol

phenelzine

Haloperidol up to 6


generally did not

change from final

dose of prior 5-wk

acute phase

(Soloff et al 1993)

Parallel design


acute phase

(Soloff et al

1993)











de la Fuente

amp Lotstra

(1994)

BPD 20 males and

females


therapeutic blood

levels

Parallel design

32 days


Salzman

et al (1995)

BPD 27 males and

females



60 mgd with mean

dose of 40 mgd

Parallel design

12 wk




generalizability

Coccaro amp

Kavoussi

(1997)

All subjects had at

least one PD as

well as current

problems with



frequent PD was

BPD

40 males and

females



week could be

increased to

40 mgd with further

increase to 60 mgd


8th week

Parallel design

12 wk





relative to placebo





(Continued)


R IPOLL ET AL



Table 3 Continued


Design





amp Kavoussi 1997)

Verkes et al

(1998)

Non-depressed

subjects who had

recently attempted


the second time

81 met criteria

for a Cluster B PD

91 males and

females


increased to

40 mgd after

1 wk

Parallel design

52 wk









in depressed mood


Battaglia

et al (1999)

Multiple suicide

attempters 85

had BPD

58 males and

females

Fluphenazine

decanoate

125 mg IM monthly

or 15 mg IM

monthly

Parallel design

but not placebo-

controlled

6 months







low end of possible







group of patients

Hollander

et al (2001)

BPD 16 males and

females

Divalproex

sodium


increased gradually



highest tolerable

dose Mean

endpoint valproate

level 6457 mgml

Parallel design

10 wk










Zanarini amp

Frankenburg

(2001)


125 mgd then

titrated up to

mean dose of

533 mgd at

endpoint

Parallel design

6 months







subscale of SCL-90

Frankenburg

amp Zanarini

(2002)

BPD and bipolar

disorder type II


sodium



serum levels of

50ndash100 mgl

Parallel design 6

months



medication group in



Rinne et al

(2002)


then titrated up to

a maximum of 250

mgd after 10th


response

6-wk double-blind

placebo-controlled

phase followed by

6-wk singleblind

half-crossover

phase in which all

subjects received

fluvoxamine This

was followed by





(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 3 Continued


Design


12-wk open label

study of

fluvoxamine

Hollander

et al (2003)

Cluster B PD IED or

PTSD with OAS-M

Aggression score

15

Males and females

Cluster B PD 96

with 55 BPD

13 NPD 10

AsPD 1 HPD

PD NOS 21) IED

116 PTSD 34

Divalproex

sodium

Began with 250 mg

bid then increased

by 250 mgd every


3 wk Recommended



week Maximum dose

30 mgkgd

Parallel design

12 wk


















better responses

Zanarini amp

Frankenburg

(2003)


pentaenoic acid

(E-EPA)


8 wk



depressive symptoms

Bogenschutz

amp Nurnberg

(2004)

BPD 40 males and

females


then increased by


10 mgd After week 8


increased to

maximum of 20 mgd


less than 10 mgd

Parallel design

12 wk


and CGI-BPD

Nickel et al

(2004)


then increased to

250 mgd by last

3 wk

Parallel design

8 wk





Philipsen

et al

(2004a )


which each subject

received one 75 mg

dose and one

150 mg dose in

randomized

crossover fashion

during separate


aversive inner

tension and urge

to commit

self-injurious

behaviourrsquo no

placebo-control

single-blind




and urges to commit





Philipsen

et al (2004b )


hydrochloride


over 30 s

Crossover design in

which each subject

received one dose

of naloxone and

onedose of placebo

in randomized




(Continued)


R IPOLL ET AL



Table 3 Continued


Design


crossover fashion

during separate

acute dissociative

episodes

Simpson

et al (2004)


concurrent DBT

Started at 20 mgd

increased to 40 mgd

at week 3

Parallel design

12 wk



post-treatment

Zanarini et al

(2004b )


olanzapine and

olanzapine-

fluoxetine

combination

(OFC)



mean dose of 15 mgd



mean dose of 33 mgd

OFC started at

olanzapine 25 mgd


with endpoint mean

doses of 32 mgd and


Parallel design but

not placebo-

controlled 8 wk








Nickel et al

(2005)


then increased to


Parallel design

8 wk









in ITT analysis

Soler et al

(2005)

BPD 60 males and

females

Olanzapine with

concurrent DBT


20 mgd with mean

dose 883 mgd

Parallel design

12 wk




Tritt et al

(2005)



during week 3

150 mgd during wk 4

and 5 and 200 mgd

during wk 6ndash8

Parallel design

8 wk





medication group

Nickel et al

(2006)

BPD 52 males and

females


8 wk













Loew et al

(2006)



dose of 200 mgd by

the 6th week

Parallel design

10 wk











(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



















(A SPD)


Table 3 Continued


Design


Shafti amp

Shahveisi

(2010)

BPD 28 females

recruited shortly

after inpatient

psychiatric


washout

Olanzapine

haloperidol


at 25 mgd and

increased weekly by

25 mgd as needed or


mgd by week 4


maintained for

remainder of study

Parallel design

but no placebo-

control 8 wk


towards greater










haloperidol group





Disorder


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





BPD




















R IPOLL ET AL












(SSRIS)
















R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S























R IPOLL ET AL





Design

duration


group(s)

Versiani et al

(1992)

Social

phobia

78 males and

females (percent

AvPD or

generalized

type not reported)

Moclobemide

phenelzine









Mean dose 675 mgd



follow-up in which

half of each


switched to placebo

others continued on

last dosage)


placebo in reducing

social anxiety and

improving social


group 91 for

phenelzine group

Moclobemide better

tolerated than

phenelzine

Van Vliet

et al (1994)

Social

phobia

30 males and

females (53

generalized

subtype)



phobic avoidance

Fahlen

(1995)

Social

phobia

63 males and

females (34 with

comorbid AvPD

1 with comorbidDPD)




in 3rd week


anxiety More marked

improvements in



comorbid AvPD and 1



Katzelnick

et al (1995)

Social

phobia

12 males and

females (percent

AvPD or

generalized type

not reported)





maximum of 200 mg


endpoint




functioning 50 of



improved vs 9 of

placebo group

IMCTGMSPand

Katschnig

(1997)

Socialphobia


generalized type

49 comorbid

AvPD)


dose)




vs 34 in placebo


between groups with

without AvPD in


AvPD patients

responded less to

placebo

Lott et al

(1997)

Social

phobia

102 males and

females

(percent

AvPD or

generalized type

not reported)



flexible dosing to

maximum of 150 mgd




50 response rate vs

19 in placebo group

Noyes et al

(1997)

Social

phobia

583 males and

females (625

generalized

type

478

comorbid

AvPD)



300 mgd vs 600 mgd




with 150 mgd and


to target dosage



12 wk only at 8 wk



rate As above no

difference between

groups withwithout

AvPD but less drug

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 4 Continued


Design

duration


group(s)



Heimberg

et al (1998)

Social

phobia

133 males and

females (707

generalized

type)








5 wk to 90 mgd

Parallel design but

non-randomized

comparing

medication to group


therapy (CBT) or

supportive

educational

therapy or placebo

12 wk












Schneier

et al (1998)

Social

phobia

77 males and

females (85

generalized

type 38

comorbid AvPD)


flexibly dosed to

a maximum of 400 mg

bid Mean dose 728

mgd at endpoint


subscores of social




Stein et al

(1998)

Social

phobia

183 males and

females (100

generalized

subtype)




of 50 mgd Mean dose

366 mgd at endpoint


and improvement in

social functioning

Allgulander

(1999)

Social

phobia

99 males and

females

(percent

with comorbid

AvPD or

generalized type

not reported)




of 50 mgd







dysthymia

Baldwin et al

(1999)

Social

phobia

290 males and

females

(percent with

comorbid AvPD

or generalized

type not reported)




of 50 mgd Mean dose

347 mgd at endpoint


and improvement in



in placebo group

Stein et al

(1999)

Social

phobia

92 males and

females (913

generalized

type)





300 mgd Mean dose

202 mgd at endpoint


and improvement in



in placebo group

Blomhoff

et al (2001)

Social

phobia

387 males and

females (100

generalized

type)




improvement noted


after 8 or 12wk

Parallel design

comparing

sertraline1general

medical care

sertraline1

prolonged

exposure therapy

(PE) placebo1PE

and placebo1

general medical

care 24 wk


sertralinePE groups

superior to placebo



combination group



alone

van

Ameringen

et al (2001)

Social

phobia

204 males and

females (100

generalized

type 61

comorbid AvPD)




to maximum of

200 mg d Mean dose



and improvement in



placebo group

(Continued)


R IPOLL ET AL



Table 4 Continued


Design

duration


group(s)

Liebowitz

et al (2002)

Social

phobia

384 males and

females (100

generalized

type)


20 mgd vs 40 mgd vs

60 mgd All groups

began with 20 mgd






20 mg group Highest


CGI) in 40 mg group

Stein et al

(2002)

Social

phobia

257 males and

females (100

generalized

type)




maximum of 50 mgd


blind 12-wk acute

phase with those

whose CGI


2 entering 24-wk

double-blind

continuation

phase



39 in placebo group

Davidson

et al(2004b )

Social

phobia

279 males and


type)



maximum of 300 mgd

Mean dose 174 mgd



Davidson

et al

(2004a )

Social

phobia

295 (100

generalized

type)




15 and to 40 mgd on





improvement

Parallel design

comparing

fluoxetine group

CBT fluoxetine1

group CBT placebo

placebo1group CBT

14 wk




14 wk Combined


advantage

Lepola et al

(2004)

Social

phobia

372 males and

females(percent

with comorbid

AvPD or

generalized

type not

reported)





323 mgd at endpoint




in placebo group

Rickels et al

(2004)

Social

phobia

272 males and

females (100

generalized

type)






one more week


and improvement in

social functioning

Lader et al

(2004)

Social

phobia

839 males and


type)

Escitalopram

paroxetine



Paroxetine 20 mgd



follow-up




and paroxetine

Escitalopram 20 mgd


20 mgd

Allgulander

et al (2004)

Social

phobia

434 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine





maximum of 225 mgd


paroxetine groups



and improvement in

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






Table 4 Continued


Design

duration


group(s)


endpoint Paroxetine





endpoint

social functioning

Possibly more rapid


Kasper et al

(2005)

Social

phobia

358 males and

females (100

generalized

type)




for unsatisfactory

response Mean dose

176 mgd at endpoint


and improvement in



placebo group

Liebowitz

et al

(2005b )

Social

phobia

271 males and

females (100

generalized

type)







and improvement in



placebo group

Liebowitz

et al

(2005a )

Social

phobia

413 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine


75 mgd-225 mgd with







10 mg increases to

maximum of 50 mgd

Mean dose 46 mgd at

endpoint


and improvement in

social functioning


for both medication


equally efficacious


venlafaxine 625 for

paroxetine and 361

for placebo group

Stein et al(2005)

Socialphobia


generalized

type)



75 mgd and if





increase to 225 mgd

after 2nd week



dosage groups 31


venlafaxine groups

combined vs 16 in

placebo group

Montgomery

et al (2005)

Social

phobia

517 males and

females (100

generalized

type)





responders entered



for remainder

12-wk open-label

phase followed by

24-wk fixed-

dose relapse

prevention

(parallel design

double-blind RCT)




vs 144d for placebo

group No direct

comparison made

between doses



R IPOLL ET AL












OTHER MEDICATIONS














R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





(A VPD)












FUTURE DIRECTIONS







R IPOLL ET AL









R E F E R E N C E S

















387ndash396









































177ndash179


























R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S












141 802ndash803













519ndash522











234ndash236












307 ndash312







309ndash319














No CD003499


























64 628ndash634




241ndash248



9ndash20





























66ndash74



















168 324ndash329


R IPOLL ET AL








25 575ndash579












































117



1026





























140ndash145










try 39 117ndash118















854ndash858













32 590ndash596






519ndash523







233ndash237





201ndash214








765ndash766




R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






485ndash492



1455ndash1458






1409ndash1413




20 413ndash423






















50 377ndash385



1605






43 691ndash697



177ndash181









24ndash39












280ndash288



260ndash271




























51 20ndash27



16 561ndash569




206ndash210




376ndash385










2108ndash2114




903ndash907




416ndash420








170ndash173

R IPOLL ET AL





suf 1047297




(SPD)




Design


Sheard

(1971)

Inmates of

maximum security

prison with verbal

and physical


12 males Lithium

carbonate

Lithium levels of

06ndash15 meql

mean dose

1200 mgd

Crossoversingle-

blind three

4-wk phases








Sheard

et al

(1976)

Prisoners

convicted of

lsquoserious

aggressive

crimesrsquo

80 males Lithium

carbonate

Lithium levels of

06ndash10 meql

mean lithium level

during last week

of medication

phase 089 meql

Parallel design

5 months with

first and

last months

medication

free and 3

months lithium

vs placebo



Lion

(1979)


past histories of

temper outbursts


behaviour and

impulsiveness

had experienced

legal difficulties

and some

had committed

criminal actsrsquo

65 males

and females

Chlordiazepoxide

oxazepam

Chlordiazepoxide

100 mgd for 2 wk

then 200 mgd for


then 240 mgd

for 2wk

Parallel design

4 wk




Barratt

et al

(1991)

Maximum security

prison inmates

with impulsive

aggression

while in prison


300 mgd

Crossover design

three 4-wk

phases




tension-anxiety and



Barratt

et al

(1997)

Prison inmates

with aggression

while in prison

150 total but only

30 males with

primarily impulsive

aggression and

30 males with

primarily

pre-meditated

aggression included

in analysis (other

66 had mixture

of both types)


design two

6-wk phases





group


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





Design


Rifkin et al

(1972)

EUCD (emotionally

unstable character

disorder

characterized by


poor acceptance of


truancy poor

work history


with a core

psychopathological

disturbance of

depressive and

hypomanic mood


to daysrsquo)

21 (sex

distribution

not specified)

Lithium

carbonate

Dosed to levels

between 06ndash15

meql

Crossover

design

two 6-wk

phases




females

Loxapine

succinate

chlorpromazine

Mean doses

loxapine

145 mgd

chlorpromazine

110 mgd

Parallel design but

not placebo-

controlled 6 wk





Montgomery

amp Montgomery

(1982)

BPD DPD andor



with history of at


acts

Not specified 30

males and

females

completed the

study 23 with

BPD 15 with

HPD and 2

with DPD

Depot

flupenthixol

20 mg IM every

4 wk

Parallel design

6 months



Montgomery

et al (1983)

BPD andor HPD all

hospitalized after

a suicidal act with


prior suicidal acts

Not specified

38 male

and female

subjects

completed

30 with BPD and

12 with HPD


6 months



reach trend levels

Serban amp

Siegel (1984)


females

Thiothixene

haloperidol


2 mgd then adjusted

up or down mean

dose 94 mgd


08 mg bid then

adjusted dose up

or down mean

dose 3 mgd

Parallel design

but not

placebo-

controlled

3 months










predict outcome

Goldberg

et al (1986)

BPD andor SPD

all subjects with

at least one

psychotic symptom

50 males and

females



maximum of 35 mgd

Parallel design

12 wk









Soloff et al

(1986b )


BPD only 4 SPD

only and 32

Haloperidol

amitryptiline

Amitryptiline began

at 25 mgd then

titrated upward to

Parallel design

5 wk



medication effects

(Continued)


R IPOLL ET AL



Table 3 Continued


Design


comorbid BPD and

SPD

mean final dose of

14762 mgd

Haloperidol began

at 2 mgd then


724 mgd








Soloff et al

(1986c )









Soloff et al

(1986a

1987)


paradoxical


during study first

described in

Soloff et al

(1986b )

Compared 15

amitryptiline non-

responders

14 placebo

non-responders

13 amitryptiline

responders and

10 placebo

responders


amitryptiline1


for responders and

2459 ngml for non-

responders





non-responders

Cowdry amp

Gardner

(1988)


behavioural

dyscontrolrsquo


carbamazepine

trifluoperazine

hydrochloride

tranylcypromine

sulfate

Mean doses of

alprazolam 47 mgd

carbamazepine

820 mgd

trifluoperazine

78 mgd and

tranylcypromine

40 mgd

Crossover design

each phase

lasting 6 wk



















Parsons et al

(1989)

BPD and atypical

depression

First sample of

subjects were

required to meet

5 BPD criteria

(N 5 40) second

sample met 4

Phenelzine

imipramine


60 mgd with


90 mgd if no

response by week 5


to 200 mgd with

Crossover

design two

6-wk phases








(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 3 Continued


Design


BPD criteria

(N 5 19)

option to increase

to 300 mgd if no

response by week 5


of phenelzine

Soloff et al

(1989)

Same as Soloff

et al (1986 b)

90 total with 35


4 SPD and 51

lsquomixedrsquo BPD

and SPD

Same as Soloff

et al (1986b )

Same procedure as


Mean dose of

haloperidol was 48

mgd and mean dose


1491 mgd on

day 35

Parallel design

5 wk











Links et al

(1990)

BPD 17 males and

females

Lithium

carbonate

desipramine


two 6-wk phases









Soloff et al

(1993)

BPD 108 males and

females

Haloperidol

phenelzine


1 mgd then titrated

up to mean dose of

4 mgd Phenelzine

began at 15 mgd

then titrated up to

mean dose of 60

mgd

Parallel design

5 wk









dysphoria

Cornelius

et al (1993)

BPD 54 males and

females

Haloperidol

phenelzine

Haloperidol up to 6


generally did not

change from final

dose of prior 5-wk

acute phase

(Soloff et al 1993)

Parallel design


acute phase

(Soloff et al

1993)











de la Fuente

amp Lotstra

(1994)

BPD 20 males and

females


therapeutic blood

levels

Parallel design

32 days


Salzman

et al (1995)

BPD 27 males and

females



60 mgd with mean

dose of 40 mgd

Parallel design

12 wk




generalizability

Coccaro amp

Kavoussi

(1997)

All subjects had at

least one PD as

well as current

problems with



frequent PD was

BPD

40 males and

females



week could be

increased to

40 mgd with further

increase to 60 mgd


8th week

Parallel design

12 wk





relative to placebo





(Continued)


R IPOLL ET AL



Table 3 Continued


Design





amp Kavoussi 1997)

Verkes et al

(1998)

Non-depressed

subjects who had

recently attempted


the second time

81 met criteria

for a Cluster B PD

91 males and

females


increased to

40 mgd after

1 wk

Parallel design

52 wk









in depressed mood


Battaglia

et al (1999)

Multiple suicide

attempters 85

had BPD

58 males and

females

Fluphenazine

decanoate

125 mg IM monthly

or 15 mg IM

monthly

Parallel design

but not placebo-

controlled

6 months







low end of possible







group of patients

Hollander

et al (2001)

BPD 16 males and

females

Divalproex

sodium


increased gradually



highest tolerable

dose Mean

endpoint valproate

level 6457 mgml

Parallel design

10 wk










Zanarini amp

Frankenburg

(2001)


125 mgd then

titrated up to

mean dose of

533 mgd at

endpoint

Parallel design

6 months







subscale of SCL-90

Frankenburg

amp Zanarini

(2002)

BPD and bipolar

disorder type II


sodium



serum levels of

50ndash100 mgl

Parallel design 6

months



medication group in



Rinne et al

(2002)


then titrated up to

a maximum of 250

mgd after 10th


response

6-wk double-blind

placebo-controlled

phase followed by

6-wk singleblind

half-crossover

phase in which all

subjects received

fluvoxamine This

was followed by





(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 3 Continued


Design


12-wk open label

study of

fluvoxamine

Hollander

et al (2003)

Cluster B PD IED or

PTSD with OAS-M

Aggression score

15

Males and females

Cluster B PD 96

with 55 BPD

13 NPD 10

AsPD 1 HPD

PD NOS 21) IED

116 PTSD 34

Divalproex

sodium

Began with 250 mg

bid then increased

by 250 mgd every


3 wk Recommended



week Maximum dose

30 mgkgd

Parallel design

12 wk


















better responses

Zanarini amp

Frankenburg

(2003)


pentaenoic acid

(E-EPA)


8 wk



depressive symptoms

Bogenschutz

amp Nurnberg

(2004)

BPD 40 males and

females


then increased by


10 mgd After week 8


increased to

maximum of 20 mgd


less than 10 mgd

Parallel design

12 wk


and CGI-BPD

Nickel et al

(2004)


then increased to

250 mgd by last

3 wk

Parallel design

8 wk





Philipsen

et al

(2004a )


which each subject

received one 75 mg

dose and one

150 mg dose in

randomized

crossover fashion

during separate


aversive inner

tension and urge

to commit

self-injurious

behaviourrsquo no

placebo-control

single-blind




and urges to commit





Philipsen

et al (2004b )


hydrochloride


over 30 s

Crossover design in

which each subject

received one dose

of naloxone and

onedose of placebo

in randomized




(Continued)


R IPOLL ET AL



Table 3 Continued


Design


crossover fashion

during separate

acute dissociative

episodes

Simpson

et al (2004)


concurrent DBT

Started at 20 mgd

increased to 40 mgd

at week 3

Parallel design

12 wk



post-treatment

Zanarini et al

(2004b )


olanzapine and

olanzapine-

fluoxetine

combination

(OFC)



mean dose of 15 mgd



mean dose of 33 mgd

OFC started at

olanzapine 25 mgd


with endpoint mean

doses of 32 mgd and


Parallel design but

not placebo-

controlled 8 wk








Nickel et al

(2005)


then increased to


Parallel design

8 wk









in ITT analysis

Soler et al

(2005)

BPD 60 males and

females

Olanzapine with

concurrent DBT


20 mgd with mean

dose 883 mgd

Parallel design

12 wk




Tritt et al

(2005)



during week 3

150 mgd during wk 4

and 5 and 200 mgd

during wk 6ndash8

Parallel design

8 wk





medication group

Nickel et al

(2006)

BPD 52 males and

females


8 wk













Loew et al

(2006)



dose of 200 mgd by

the 6th week

Parallel design

10 wk











(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



















(A SPD)


Table 3 Continued


Design


Shafti amp

Shahveisi

(2010)

BPD 28 females

recruited shortly

after inpatient

psychiatric


washout

Olanzapine

haloperidol


at 25 mgd and

increased weekly by

25 mgd as needed or


mgd by week 4


maintained for

remainder of study

Parallel design

but no placebo-

control 8 wk


towards greater










haloperidol group





Disorder


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





BPD




















R IPOLL ET AL












(SSRIS)
















R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S























R IPOLL ET AL





Design

duration


group(s)

Versiani et al

(1992)

Social

phobia

78 males and

females (percent

AvPD or

generalized

type not reported)

Moclobemide

phenelzine









Mean dose 675 mgd



follow-up in which

half of each


switched to placebo

others continued on

last dosage)


placebo in reducing

social anxiety and

improving social


group 91 for

phenelzine group

Moclobemide better

tolerated than

phenelzine

Van Vliet

et al (1994)

Social

phobia

30 males and

females (53

generalized

subtype)



phobic avoidance

Fahlen

(1995)

Social

phobia

63 males and

females (34 with

comorbid AvPD

1 with comorbidDPD)




in 3rd week


anxiety More marked

improvements in



comorbid AvPD and 1



Katzelnick

et al (1995)

Social

phobia

12 males and

females (percent

AvPD or

generalized type

not reported)





maximum of 200 mg


endpoint




functioning 50 of



improved vs 9 of

placebo group

IMCTGMSPand

Katschnig

(1997)

Socialphobia


generalized type

49 comorbid

AvPD)


dose)




vs 34 in placebo


between groups with

without AvPD in


AvPD patients

responded less to

placebo

Lott et al

(1997)

Social

phobia

102 males and

females

(percent

AvPD or

generalized type

not reported)



flexible dosing to

maximum of 150 mgd




50 response rate vs

19 in placebo group

Noyes et al

(1997)

Social

phobia

583 males and

females (625

generalized

type

478

comorbid

AvPD)



300 mgd vs 600 mgd




with 150 mgd and


to target dosage



12 wk only at 8 wk



rate As above no

difference between

groups withwithout

AvPD but less drug

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 4 Continued


Design

duration


group(s)



Heimberg

et al (1998)

Social

phobia

133 males and

females (707

generalized

type)








5 wk to 90 mgd

Parallel design but

non-randomized

comparing

medication to group


therapy (CBT) or

supportive

educational

therapy or placebo

12 wk












Schneier

et al (1998)

Social

phobia

77 males and

females (85

generalized

type 38

comorbid AvPD)


flexibly dosed to

a maximum of 400 mg

bid Mean dose 728

mgd at endpoint


subscores of social




Stein et al

(1998)

Social

phobia

183 males and

females (100

generalized

subtype)




of 50 mgd Mean dose

366 mgd at endpoint


and improvement in

social functioning

Allgulander

(1999)

Social

phobia

99 males and

females

(percent

with comorbid

AvPD or

generalized type

not reported)




of 50 mgd







dysthymia

Baldwin et al

(1999)

Social

phobia

290 males and

females

(percent with

comorbid AvPD

or generalized

type not reported)




of 50 mgd Mean dose

347 mgd at endpoint


and improvement in



in placebo group

Stein et al

(1999)

Social

phobia

92 males and

females (913

generalized

type)





300 mgd Mean dose

202 mgd at endpoint


and improvement in



in placebo group

Blomhoff

et al (2001)

Social

phobia

387 males and

females (100

generalized

type)




improvement noted


after 8 or 12wk

Parallel design

comparing

sertraline1general

medical care

sertraline1

prolonged

exposure therapy

(PE) placebo1PE

and placebo1

general medical

care 24 wk


sertralinePE groups

superior to placebo



combination group



alone

van

Ameringen

et al (2001)

Social

phobia

204 males and

females (100

generalized

type 61

comorbid AvPD)




to maximum of

200 mg d Mean dose



and improvement in



placebo group

(Continued)


R IPOLL ET AL



Table 4 Continued


Design

duration


group(s)

Liebowitz

et al (2002)

Social

phobia

384 males and

females (100

generalized

type)


20 mgd vs 40 mgd vs

60 mgd All groups

began with 20 mgd






20 mg group Highest


CGI) in 40 mg group

Stein et al

(2002)

Social

phobia

257 males and

females (100

generalized

type)




maximum of 50 mgd


blind 12-wk acute

phase with those

whose CGI


2 entering 24-wk

double-blind

continuation

phase



39 in placebo group

Davidson

et al(2004b )

Social

phobia

279 males and


type)



maximum of 300 mgd

Mean dose 174 mgd



Davidson

et al

(2004a )

Social

phobia

295 (100

generalized

type)




15 and to 40 mgd on





improvement

Parallel design

comparing

fluoxetine group

CBT fluoxetine1

group CBT placebo

placebo1group CBT

14 wk




14 wk Combined


advantage

Lepola et al

(2004)

Social

phobia

372 males and

females(percent

with comorbid

AvPD or

generalized

type not

reported)





323 mgd at endpoint




in placebo group

Rickels et al

(2004)

Social

phobia

272 males and

females (100

generalized

type)






one more week


and improvement in

social functioning

Lader et al

(2004)

Social

phobia

839 males and


type)

Escitalopram

paroxetine



Paroxetine 20 mgd



follow-up




and paroxetine

Escitalopram 20 mgd


20 mgd

Allgulander

et al (2004)

Social

phobia

434 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine





maximum of 225 mgd


paroxetine groups



and improvement in

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






Table 4 Continued


Design

duration


group(s)


endpoint Paroxetine





endpoint

social functioning

Possibly more rapid


Kasper et al

(2005)

Social

phobia

358 males and

females (100

generalized

type)




for unsatisfactory

response Mean dose

176 mgd at endpoint


and improvement in



placebo group

Liebowitz

et al

(2005b )

Social

phobia

271 males and

females (100

generalized

type)







and improvement in



placebo group

Liebowitz

et al

(2005a )

Social

phobia

413 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine


75 mgd-225 mgd with







10 mg increases to

maximum of 50 mgd

Mean dose 46 mgd at

endpoint


and improvement in

social functioning


for both medication


equally efficacious


venlafaxine 625 for

paroxetine and 361

for placebo group

Stein et al(2005)

Socialphobia


generalized

type)



75 mgd and if





increase to 225 mgd

after 2nd week



dosage groups 31


venlafaxine groups

combined vs 16 in

placebo group

Montgomery

et al (2005)

Social

phobia

517 males and

females (100

generalized

type)





responders entered



for remainder

12-wk open-label

phase followed by

24-wk fixed-

dose relapse

prevention

(parallel design

double-blind RCT)




vs 144d for placebo

group No direct

comparison made

between doses



R IPOLL ET AL












OTHER MEDICATIONS














R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





(A VPD)












FUTURE DIRECTIONS







R IPOLL ET AL









R E F E R E N C E S

















387ndash396









































177ndash179


























R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S












141 802ndash803













519ndash522











234ndash236












307 ndash312







309ndash319














No CD003499


























64 628ndash634




241ndash248



9ndash20





























66ndash74



















168 324ndash329


R IPOLL ET AL








25 575ndash579












































117



1026





























140ndash145










try 39 117ndash118















854ndash858













32 590ndash596






519ndash523







233ndash237





201ndash214








765ndash766




R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






485ndash492



1455ndash1458






1409ndash1413




20 413ndash423






















50 377ndash385



1605






43 691ndash697



177ndash181









24ndash39












280ndash288



260ndash271




























51 20ndash27



16 561ndash569




206ndash210




376ndash385










2108ndash2114




903ndash907




416ndash420








170ndash173

R IPOLL ET AL





Design


Rifkin et al

(1972)

EUCD (emotionally

unstable character

disorder

characterized by


poor acceptance of


truancy poor

work history


with a core

psychopathological

disturbance of

depressive and

hypomanic mood


to daysrsquo)

21 (sex

distribution

not specified)

Lithium

carbonate

Dosed to levels

between 06ndash15

meql

Crossover

design

two 6-wk

phases




females

Loxapine

succinate

chlorpromazine

Mean doses

loxapine

145 mgd

chlorpromazine

110 mgd

Parallel design but

not placebo-

controlled 6 wk





Montgomery

amp Montgomery

(1982)

BPD DPD andor



with history of at


acts

Not specified 30

males and

females

completed the

study 23 with

BPD 15 with

HPD and 2

with DPD

Depot

flupenthixol

20 mg IM every

4 wk

Parallel design

6 months



Montgomery

et al (1983)

BPD andor HPD all

hospitalized after

a suicidal act with


prior suicidal acts

Not specified

38 male

and female

subjects

completed

30 with BPD and

12 with HPD


6 months



reach trend levels

Serban amp

Siegel (1984)


females

Thiothixene

haloperidol


2 mgd then adjusted

up or down mean

dose 94 mgd


08 mg bid then

adjusted dose up

or down mean

dose 3 mgd

Parallel design

but not

placebo-

controlled

3 months










predict outcome

Goldberg

et al (1986)

BPD andor SPD

all subjects with

at least one

psychotic symptom

50 males and

females



maximum of 35 mgd

Parallel design

12 wk









Soloff et al

(1986b )


BPD only 4 SPD

only and 32

Haloperidol

amitryptiline

Amitryptiline began

at 25 mgd then

titrated upward to

Parallel design

5 wk



medication effects

(Continued)


R IPOLL ET AL



Table 3 Continued


Design


comorbid BPD and

SPD

mean final dose of

14762 mgd

Haloperidol began

at 2 mgd then


724 mgd








Soloff et al

(1986c )









Soloff et al

(1986a

1987)


paradoxical


during study first

described in

Soloff et al

(1986b )

Compared 15

amitryptiline non-

responders

14 placebo

non-responders

13 amitryptiline

responders and

10 placebo

responders


amitryptiline1


for responders and

2459 ngml for non-

responders





non-responders

Cowdry amp

Gardner

(1988)


behavioural

dyscontrolrsquo


carbamazepine

trifluoperazine

hydrochloride

tranylcypromine

sulfate

Mean doses of

alprazolam 47 mgd

carbamazepine

820 mgd

trifluoperazine

78 mgd and

tranylcypromine

40 mgd

Crossover design

each phase

lasting 6 wk



















Parsons et al

(1989)

BPD and atypical

depression

First sample of

subjects were

required to meet

5 BPD criteria

(N 5 40) second

sample met 4

Phenelzine

imipramine


60 mgd with


90 mgd if no

response by week 5


to 200 mgd with

Crossover

design two

6-wk phases








(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 3 Continued


Design


BPD criteria

(N 5 19)

option to increase

to 300 mgd if no

response by week 5


of phenelzine

Soloff et al

(1989)

Same as Soloff

et al (1986 b)

90 total with 35


4 SPD and 51

lsquomixedrsquo BPD

and SPD

Same as Soloff

et al (1986b )

Same procedure as


Mean dose of

haloperidol was 48

mgd and mean dose


1491 mgd on

day 35

Parallel design

5 wk











Links et al

(1990)

BPD 17 males and

females

Lithium

carbonate

desipramine


two 6-wk phases









Soloff et al

(1993)

BPD 108 males and

females

Haloperidol

phenelzine


1 mgd then titrated

up to mean dose of

4 mgd Phenelzine

began at 15 mgd

then titrated up to

mean dose of 60

mgd

Parallel design

5 wk









dysphoria

Cornelius

et al (1993)

BPD 54 males and

females

Haloperidol

phenelzine

Haloperidol up to 6


generally did not

change from final

dose of prior 5-wk

acute phase

(Soloff et al 1993)

Parallel design


acute phase

(Soloff et al

1993)











de la Fuente

amp Lotstra

(1994)

BPD 20 males and

females


therapeutic blood

levels

Parallel design

32 days


Salzman

et al (1995)

BPD 27 males and

females



60 mgd with mean

dose of 40 mgd

Parallel design

12 wk




generalizability

Coccaro amp

Kavoussi

(1997)

All subjects had at

least one PD as

well as current

problems with



frequent PD was

BPD

40 males and

females



week could be

increased to

40 mgd with further

increase to 60 mgd


8th week

Parallel design

12 wk





relative to placebo





(Continued)


R IPOLL ET AL



Table 3 Continued


Design





amp Kavoussi 1997)

Verkes et al

(1998)

Non-depressed

subjects who had

recently attempted


the second time

81 met criteria

for a Cluster B PD

91 males and

females


increased to

40 mgd after

1 wk

Parallel design

52 wk









in depressed mood


Battaglia

et al (1999)

Multiple suicide

attempters 85

had BPD

58 males and

females

Fluphenazine

decanoate

125 mg IM monthly

or 15 mg IM

monthly

Parallel design

but not placebo-

controlled

6 months







low end of possible







group of patients

Hollander

et al (2001)

BPD 16 males and

females

Divalproex

sodium


increased gradually



highest tolerable

dose Mean

endpoint valproate

level 6457 mgml

Parallel design

10 wk










Zanarini amp

Frankenburg

(2001)


125 mgd then

titrated up to

mean dose of

533 mgd at

endpoint

Parallel design

6 months







subscale of SCL-90

Frankenburg

amp Zanarini

(2002)

BPD and bipolar

disorder type II


sodium



serum levels of

50ndash100 mgl

Parallel design 6

months



medication group in



Rinne et al

(2002)


then titrated up to

a maximum of 250

mgd after 10th


response

6-wk double-blind

placebo-controlled

phase followed by

6-wk singleblind

half-crossover

phase in which all

subjects received

fluvoxamine This

was followed by





(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 3 Continued


Design


12-wk open label

study of

fluvoxamine

Hollander

et al (2003)

Cluster B PD IED or

PTSD with OAS-M

Aggression score

15

Males and females

Cluster B PD 96

with 55 BPD

13 NPD 10

AsPD 1 HPD

PD NOS 21) IED

116 PTSD 34

Divalproex

sodium

Began with 250 mg

bid then increased

by 250 mgd every


3 wk Recommended



week Maximum dose

30 mgkgd

Parallel design

12 wk


















better responses

Zanarini amp

Frankenburg

(2003)


pentaenoic acid

(E-EPA)


8 wk



depressive symptoms

Bogenschutz

amp Nurnberg

(2004)

BPD 40 males and

females


then increased by


10 mgd After week 8


increased to

maximum of 20 mgd


less than 10 mgd

Parallel design

12 wk


and CGI-BPD

Nickel et al

(2004)


then increased to

250 mgd by last

3 wk

Parallel design

8 wk





Philipsen

et al

(2004a )


which each subject

received one 75 mg

dose and one

150 mg dose in

randomized

crossover fashion

during separate


aversive inner

tension and urge

to commit

self-injurious

behaviourrsquo no

placebo-control

single-blind




and urges to commit





Philipsen

et al (2004b )


hydrochloride


over 30 s

Crossover design in

which each subject

received one dose

of naloxone and

onedose of placebo

in randomized




(Continued)


R IPOLL ET AL



Table 3 Continued


Design


crossover fashion

during separate

acute dissociative

episodes

Simpson

et al (2004)


concurrent DBT

Started at 20 mgd

increased to 40 mgd

at week 3

Parallel design

12 wk



post-treatment

Zanarini et al

(2004b )


olanzapine and

olanzapine-

fluoxetine

combination

(OFC)



mean dose of 15 mgd



mean dose of 33 mgd

OFC started at

olanzapine 25 mgd


with endpoint mean

doses of 32 mgd and


Parallel design but

not placebo-

controlled 8 wk








Nickel et al

(2005)


then increased to


Parallel design

8 wk









in ITT analysis

Soler et al

(2005)

BPD 60 males and

females

Olanzapine with

concurrent DBT


20 mgd with mean

dose 883 mgd

Parallel design

12 wk




Tritt et al

(2005)



during week 3

150 mgd during wk 4

and 5 and 200 mgd

during wk 6ndash8

Parallel design

8 wk





medication group

Nickel et al

(2006)

BPD 52 males and

females


8 wk













Loew et al

(2006)



dose of 200 mgd by

the 6th week

Parallel design

10 wk











(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



















(A SPD)


Table 3 Continued


Design


Shafti amp

Shahveisi

(2010)

BPD 28 females

recruited shortly

after inpatient

psychiatric


washout

Olanzapine

haloperidol


at 25 mgd and

increased weekly by

25 mgd as needed or


mgd by week 4


maintained for

remainder of study

Parallel design

but no placebo-

control 8 wk


towards greater










haloperidol group





Disorder


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





BPD




















R IPOLL ET AL












(SSRIS)
















R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S























R IPOLL ET AL





Design

duration


group(s)

Versiani et al

(1992)

Social

phobia

78 males and

females (percent

AvPD or

generalized

type not reported)

Moclobemide

phenelzine









Mean dose 675 mgd



follow-up in which

half of each


switched to placebo

others continued on

last dosage)


placebo in reducing

social anxiety and

improving social


group 91 for

phenelzine group

Moclobemide better

tolerated than

phenelzine

Van Vliet

et al (1994)

Social

phobia

30 males and

females (53

generalized

subtype)



phobic avoidance

Fahlen

(1995)

Social

phobia

63 males and

females (34 with

comorbid AvPD

1 with comorbidDPD)




in 3rd week


anxiety More marked

improvements in



comorbid AvPD and 1



Katzelnick

et al (1995)

Social

phobia

12 males and

females (percent

AvPD or

generalized type

not reported)





maximum of 200 mg


endpoint




functioning 50 of



improved vs 9 of

placebo group

IMCTGMSPand

Katschnig

(1997)

Socialphobia


generalized type

49 comorbid

AvPD)


dose)




vs 34 in placebo


between groups with

without AvPD in


AvPD patients

responded less to

placebo

Lott et al

(1997)

Social

phobia

102 males and

females

(percent

AvPD or

generalized type

not reported)



flexible dosing to

maximum of 150 mgd




50 response rate vs

19 in placebo group

Noyes et al

(1997)

Social

phobia

583 males and

females (625

generalized

type

478

comorbid

AvPD)



300 mgd vs 600 mgd




with 150 mgd and


to target dosage



12 wk only at 8 wk



rate As above no

difference between

groups withwithout

AvPD but less drug

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 4 Continued


Design

duration


group(s)



Heimberg

et al (1998)

Social

phobia

133 males and

females (707

generalized

type)








5 wk to 90 mgd

Parallel design but

non-randomized

comparing

medication to group


therapy (CBT) or

supportive

educational

therapy or placebo

12 wk












Schneier

et al (1998)

Social

phobia

77 males and

females (85

generalized

type 38

comorbid AvPD)


flexibly dosed to

a maximum of 400 mg

bid Mean dose 728

mgd at endpoint


subscores of social




Stein et al

(1998)

Social

phobia

183 males and

females (100

generalized

subtype)




of 50 mgd Mean dose

366 mgd at endpoint


and improvement in

social functioning

Allgulander

(1999)

Social

phobia

99 males and

females

(percent

with comorbid

AvPD or

generalized type

not reported)




of 50 mgd







dysthymia

Baldwin et al

(1999)

Social

phobia

290 males and

females

(percent with

comorbid AvPD

or generalized

type not reported)




of 50 mgd Mean dose

347 mgd at endpoint


and improvement in



in placebo group

Stein et al

(1999)

Social

phobia

92 males and

females (913

generalized

type)





300 mgd Mean dose

202 mgd at endpoint


and improvement in



in placebo group

Blomhoff

et al (2001)

Social

phobia

387 males and

females (100

generalized

type)




improvement noted


after 8 or 12wk

Parallel design

comparing

sertraline1general

medical care

sertraline1

prolonged

exposure therapy

(PE) placebo1PE

and placebo1

general medical

care 24 wk


sertralinePE groups

superior to placebo



combination group



alone

van

Ameringen

et al (2001)

Social

phobia

204 males and

females (100

generalized

type 61

comorbid AvPD)




to maximum of

200 mg d Mean dose



and improvement in



placebo group

(Continued)


R IPOLL ET AL



Table 4 Continued


Design

duration


group(s)

Liebowitz

et al (2002)

Social

phobia

384 males and

females (100

generalized

type)


20 mgd vs 40 mgd vs

60 mgd All groups

began with 20 mgd






20 mg group Highest


CGI) in 40 mg group

Stein et al

(2002)

Social

phobia

257 males and

females (100

generalized

type)




maximum of 50 mgd


blind 12-wk acute

phase with those

whose CGI


2 entering 24-wk

double-blind

continuation

phase



39 in placebo group

Davidson

et al(2004b )

Social

phobia

279 males and


type)



maximum of 300 mgd

Mean dose 174 mgd



Davidson

et al

(2004a )

Social

phobia

295 (100

generalized

type)




15 and to 40 mgd on





improvement

Parallel design

comparing

fluoxetine group

CBT fluoxetine1

group CBT placebo

placebo1group CBT

14 wk




14 wk Combined


advantage

Lepola et al

(2004)

Social

phobia

372 males and

females(percent

with comorbid

AvPD or

generalized

type not

reported)





323 mgd at endpoint




in placebo group

Rickels et al

(2004)

Social

phobia

272 males and

females (100

generalized

type)






one more week


and improvement in

social functioning

Lader et al

(2004)

Social

phobia

839 males and


type)

Escitalopram

paroxetine



Paroxetine 20 mgd



follow-up




and paroxetine

Escitalopram 20 mgd


20 mgd

Allgulander

et al (2004)

Social

phobia

434 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine





maximum of 225 mgd


paroxetine groups



and improvement in

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






Table 4 Continued


Design

duration


group(s)


endpoint Paroxetine





endpoint

social functioning

Possibly more rapid


Kasper et al

(2005)

Social

phobia

358 males and

females (100

generalized

type)




for unsatisfactory

response Mean dose

176 mgd at endpoint


and improvement in



placebo group

Liebowitz

et al

(2005b )

Social

phobia

271 males and

females (100

generalized

type)







and improvement in



placebo group

Liebowitz

et al

(2005a )

Social

phobia

413 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine


75 mgd-225 mgd with







10 mg increases to

maximum of 50 mgd

Mean dose 46 mgd at

endpoint


and improvement in

social functioning


for both medication


equally efficacious


venlafaxine 625 for

paroxetine and 361

for placebo group

Stein et al(2005)

Socialphobia


generalized

type)



75 mgd and if





increase to 225 mgd

after 2nd week



dosage groups 31


venlafaxine groups

combined vs 16 in

placebo group

Montgomery

et al (2005)

Social

phobia

517 males and

females (100

generalized

type)





responders entered



for remainder

12-wk open-label

phase followed by

24-wk fixed-

dose relapse

prevention

(parallel design

double-blind RCT)




vs 144d for placebo

group No direct

comparison made

between doses



R IPOLL ET AL












OTHER MEDICATIONS














R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





(A VPD)












FUTURE DIRECTIONS







R IPOLL ET AL









R E F E R E N C E S

















387ndash396









































177ndash179


























R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S












141 802ndash803













519ndash522











234ndash236












307 ndash312







309ndash319














No CD003499


























64 628ndash634




241ndash248



9ndash20





























66ndash74



















168 324ndash329


R IPOLL ET AL








25 575ndash579












































117



1026





























140ndash145










try 39 117ndash118















854ndash858













32 590ndash596






519ndash523







233ndash237





201ndash214








765ndash766




R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






485ndash492



1455ndash1458






1409ndash1413




20 413ndash423






















50 377ndash385



1605






43 691ndash697



177ndash181









24ndash39












280ndash288



260ndash271




























51 20ndash27



16 561ndash569




206ndash210




376ndash385










2108ndash2114




903ndash907




416ndash420








170ndash173

R IPOLL ET AL



Table 3 Continued


Design


comorbid BPD and

SPD

mean final dose of

14762 mgd

Haloperidol began

at 2 mgd then


724 mgd








Soloff et al

(1986c )









Soloff et al

(1986a

1987)


paradoxical


during study first

described in

Soloff et al

(1986b )

Compared 15

amitryptiline non-

responders

14 placebo

non-responders

13 amitryptiline

responders and

10 placebo

responders


amitryptiline1


for responders and

2459 ngml for non-

responders





non-responders

Cowdry amp

Gardner

(1988)


behavioural

dyscontrolrsquo


carbamazepine

trifluoperazine

hydrochloride

tranylcypromine

sulfate

Mean doses of

alprazolam 47 mgd

carbamazepine

820 mgd

trifluoperazine

78 mgd and

tranylcypromine

40 mgd

Crossover design

each phase

lasting 6 wk



















Parsons et al

(1989)

BPD and atypical

depression

First sample of

subjects were

required to meet

5 BPD criteria

(N 5 40) second

sample met 4

Phenelzine

imipramine


60 mgd with


90 mgd if no

response by week 5


to 200 mgd with

Crossover

design two

6-wk phases








(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 3 Continued


Design


BPD criteria

(N 5 19)

option to increase

to 300 mgd if no

response by week 5


of phenelzine

Soloff et al

(1989)

Same as Soloff

et al (1986 b)

90 total with 35


4 SPD and 51

lsquomixedrsquo BPD

and SPD

Same as Soloff

et al (1986b )

Same procedure as


Mean dose of

haloperidol was 48

mgd and mean dose


1491 mgd on

day 35

Parallel design

5 wk











Links et al

(1990)

BPD 17 males and

females

Lithium

carbonate

desipramine


two 6-wk phases









Soloff et al

(1993)

BPD 108 males and

females

Haloperidol

phenelzine


1 mgd then titrated

up to mean dose of

4 mgd Phenelzine

began at 15 mgd

then titrated up to

mean dose of 60

mgd

Parallel design

5 wk









dysphoria

Cornelius

et al (1993)

BPD 54 males and

females

Haloperidol

phenelzine

Haloperidol up to 6


generally did not

change from final

dose of prior 5-wk

acute phase

(Soloff et al 1993)

Parallel design


acute phase

(Soloff et al

1993)











de la Fuente

amp Lotstra

(1994)

BPD 20 males and

females


therapeutic blood

levels

Parallel design

32 days


Salzman

et al (1995)

BPD 27 males and

females



60 mgd with mean

dose of 40 mgd

Parallel design

12 wk




generalizability

Coccaro amp

Kavoussi

(1997)

All subjects had at

least one PD as

well as current

problems with



frequent PD was

BPD

40 males and

females



week could be

increased to

40 mgd with further

increase to 60 mgd


8th week

Parallel design

12 wk





relative to placebo





(Continued)


R IPOLL ET AL



Table 3 Continued


Design





amp Kavoussi 1997)

Verkes et al

(1998)

Non-depressed

subjects who had

recently attempted


the second time

81 met criteria

for a Cluster B PD

91 males and

females


increased to

40 mgd after

1 wk

Parallel design

52 wk









in depressed mood


Battaglia

et al (1999)

Multiple suicide

attempters 85

had BPD

58 males and

females

Fluphenazine

decanoate

125 mg IM monthly

or 15 mg IM

monthly

Parallel design

but not placebo-

controlled

6 months







low end of possible







group of patients

Hollander

et al (2001)

BPD 16 males and

females

Divalproex

sodium


increased gradually



highest tolerable

dose Mean

endpoint valproate

level 6457 mgml

Parallel design

10 wk










Zanarini amp

Frankenburg

(2001)


125 mgd then

titrated up to

mean dose of

533 mgd at

endpoint

Parallel design

6 months







subscale of SCL-90

Frankenburg

amp Zanarini

(2002)

BPD and bipolar

disorder type II


sodium



serum levels of

50ndash100 mgl

Parallel design 6

months



medication group in



Rinne et al

(2002)


then titrated up to

a maximum of 250

mgd after 10th


response

6-wk double-blind

placebo-controlled

phase followed by

6-wk singleblind

half-crossover

phase in which all

subjects received

fluvoxamine This

was followed by





(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 3 Continued


Design


12-wk open label

study of

fluvoxamine

Hollander

et al (2003)

Cluster B PD IED or

PTSD with OAS-M

Aggression score

15

Males and females

Cluster B PD 96

with 55 BPD

13 NPD 10

AsPD 1 HPD

PD NOS 21) IED

116 PTSD 34

Divalproex

sodium

Began with 250 mg

bid then increased

by 250 mgd every


3 wk Recommended



week Maximum dose

30 mgkgd

Parallel design

12 wk


















better responses

Zanarini amp

Frankenburg

(2003)


pentaenoic acid

(E-EPA)


8 wk



depressive symptoms

Bogenschutz

amp Nurnberg

(2004)

BPD 40 males and

females


then increased by


10 mgd After week 8


increased to

maximum of 20 mgd


less than 10 mgd

Parallel design

12 wk


and CGI-BPD

Nickel et al

(2004)


then increased to

250 mgd by last

3 wk

Parallel design

8 wk





Philipsen

et al

(2004a )


which each subject

received one 75 mg

dose and one

150 mg dose in

randomized

crossover fashion

during separate


aversive inner

tension and urge

to commit

self-injurious

behaviourrsquo no

placebo-control

single-blind




and urges to commit





Philipsen

et al (2004b )


hydrochloride


over 30 s

Crossover design in

which each subject

received one dose

of naloxone and

onedose of placebo

in randomized




(Continued)


R IPOLL ET AL



Table 3 Continued


Design


crossover fashion

during separate

acute dissociative

episodes

Simpson

et al (2004)


concurrent DBT

Started at 20 mgd

increased to 40 mgd

at week 3

Parallel design

12 wk



post-treatment

Zanarini et al

(2004b )


olanzapine and

olanzapine-

fluoxetine

combination

(OFC)



mean dose of 15 mgd



mean dose of 33 mgd

OFC started at

olanzapine 25 mgd


with endpoint mean

doses of 32 mgd and


Parallel design but

not placebo-

controlled 8 wk








Nickel et al

(2005)


then increased to


Parallel design

8 wk









in ITT analysis

Soler et al

(2005)

BPD 60 males and

females

Olanzapine with

concurrent DBT


20 mgd with mean

dose 883 mgd

Parallel design

12 wk




Tritt et al

(2005)



during week 3

150 mgd during wk 4

and 5 and 200 mgd

during wk 6ndash8

Parallel design

8 wk





medication group

Nickel et al

(2006)

BPD 52 males and

females


8 wk













Loew et al

(2006)



dose of 200 mgd by

the 6th week

Parallel design

10 wk











(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



















(A SPD)


Table 3 Continued


Design


Shafti amp

Shahveisi

(2010)

BPD 28 females

recruited shortly

after inpatient

psychiatric


washout

Olanzapine

haloperidol


at 25 mgd and

increased weekly by

25 mgd as needed or


mgd by week 4


maintained for

remainder of study

Parallel design

but no placebo-

control 8 wk


towards greater










haloperidol group





Disorder


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





BPD




















R IPOLL ET AL












(SSRIS)
















R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S























R IPOLL ET AL





Design

duration


group(s)

Versiani et al

(1992)

Social

phobia

78 males and

females (percent

AvPD or

generalized

type not reported)

Moclobemide

phenelzine









Mean dose 675 mgd



follow-up in which

half of each


switched to placebo

others continued on

last dosage)


placebo in reducing

social anxiety and

improving social


group 91 for

phenelzine group

Moclobemide better

tolerated than

phenelzine

Van Vliet

et al (1994)

Social

phobia

30 males and

females (53

generalized

subtype)



phobic avoidance

Fahlen

(1995)

Social

phobia

63 males and

females (34 with

comorbid AvPD

1 with comorbidDPD)




in 3rd week


anxiety More marked

improvements in



comorbid AvPD and 1



Katzelnick

et al (1995)

Social

phobia

12 males and

females (percent

AvPD or

generalized type

not reported)





maximum of 200 mg


endpoint




functioning 50 of



improved vs 9 of

placebo group

IMCTGMSPand

Katschnig

(1997)

Socialphobia


generalized type

49 comorbid

AvPD)


dose)




vs 34 in placebo


between groups with

without AvPD in


AvPD patients

responded less to

placebo

Lott et al

(1997)

Social

phobia

102 males and

females

(percent

AvPD or

generalized type

not reported)



flexible dosing to

maximum of 150 mgd




50 response rate vs

19 in placebo group

Noyes et al

(1997)

Social

phobia

583 males and

females (625

generalized

type

478

comorbid

AvPD)



300 mgd vs 600 mgd




with 150 mgd and


to target dosage



12 wk only at 8 wk



rate As above no

difference between

groups withwithout

AvPD but less drug

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 4 Continued


Design

duration


group(s)



Heimberg

et al (1998)

Social

phobia

133 males and

females (707

generalized

type)








5 wk to 90 mgd

Parallel design but

non-randomized

comparing

medication to group


therapy (CBT) or

supportive

educational

therapy or placebo

12 wk












Schneier

et al (1998)

Social

phobia

77 males and

females (85

generalized

type 38

comorbid AvPD)


flexibly dosed to

a maximum of 400 mg

bid Mean dose 728

mgd at endpoint


subscores of social




Stein et al

(1998)

Social

phobia

183 males and

females (100

generalized

subtype)




of 50 mgd Mean dose

366 mgd at endpoint


and improvement in

social functioning

Allgulander

(1999)

Social

phobia

99 males and

females

(percent

with comorbid

AvPD or

generalized type

not reported)




of 50 mgd







dysthymia

Baldwin et al

(1999)

Social

phobia

290 males and

females

(percent with

comorbid AvPD

or generalized

type not reported)




of 50 mgd Mean dose

347 mgd at endpoint


and improvement in



in placebo group

Stein et al

(1999)

Social

phobia

92 males and

females (913

generalized

type)





300 mgd Mean dose

202 mgd at endpoint


and improvement in



in placebo group

Blomhoff

et al (2001)

Social

phobia

387 males and

females (100

generalized

type)




improvement noted


after 8 or 12wk

Parallel design

comparing

sertraline1general

medical care

sertraline1

prolonged

exposure therapy

(PE) placebo1PE

and placebo1

general medical

care 24 wk


sertralinePE groups

superior to placebo



combination group



alone

van

Ameringen

et al (2001)

Social

phobia

204 males and

females (100

generalized

type 61

comorbid AvPD)




to maximum of

200 mg d Mean dose



and improvement in



placebo group

(Continued)


R IPOLL ET AL



Table 4 Continued


Design

duration


group(s)

Liebowitz

et al (2002)

Social

phobia

384 males and

females (100

generalized

type)


20 mgd vs 40 mgd vs

60 mgd All groups

began with 20 mgd






20 mg group Highest


CGI) in 40 mg group

Stein et al

(2002)

Social

phobia

257 males and

females (100

generalized

type)




maximum of 50 mgd


blind 12-wk acute

phase with those

whose CGI


2 entering 24-wk

double-blind

continuation

phase



39 in placebo group

Davidson

et al(2004b )

Social

phobia

279 males and


type)



maximum of 300 mgd

Mean dose 174 mgd



Davidson

et al

(2004a )

Social

phobia

295 (100

generalized

type)




15 and to 40 mgd on





improvement

Parallel design

comparing

fluoxetine group

CBT fluoxetine1

group CBT placebo

placebo1group CBT

14 wk




14 wk Combined


advantage

Lepola et al

(2004)

Social

phobia

372 males and

females(percent

with comorbid

AvPD or

generalized

type not

reported)





323 mgd at endpoint




in placebo group

Rickels et al

(2004)

Social

phobia

272 males and

females (100

generalized

type)






one more week


and improvement in

social functioning

Lader et al

(2004)

Social

phobia

839 males and


type)

Escitalopram

paroxetine



Paroxetine 20 mgd



follow-up




and paroxetine

Escitalopram 20 mgd


20 mgd

Allgulander

et al (2004)

Social

phobia

434 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine





maximum of 225 mgd


paroxetine groups



and improvement in

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






Table 4 Continued


Design

duration


group(s)


endpoint Paroxetine





endpoint

social functioning

Possibly more rapid


Kasper et al

(2005)

Social

phobia

358 males and

females (100

generalized

type)




for unsatisfactory

response Mean dose

176 mgd at endpoint


and improvement in



placebo group

Liebowitz

et al

(2005b )

Social

phobia

271 males and

females (100

generalized

type)







and improvement in



placebo group

Liebowitz

et al

(2005a )

Social

phobia

413 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine


75 mgd-225 mgd with







10 mg increases to

maximum of 50 mgd

Mean dose 46 mgd at

endpoint


and improvement in

social functioning


for both medication


equally efficacious


venlafaxine 625 for

paroxetine and 361

for placebo group

Stein et al(2005)

Socialphobia


generalized

type)



75 mgd and if





increase to 225 mgd

after 2nd week



dosage groups 31


venlafaxine groups

combined vs 16 in

placebo group

Montgomery

et al (2005)

Social

phobia

517 males and

females (100

generalized

type)





responders entered



for remainder

12-wk open-label

phase followed by

24-wk fixed-

dose relapse

prevention

(parallel design

double-blind RCT)




vs 144d for placebo

group No direct

comparison made

between doses



R IPOLL ET AL












OTHER MEDICATIONS














R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





(A VPD)












FUTURE DIRECTIONS







R IPOLL ET AL









R E F E R E N C E S

















387ndash396









































177ndash179


























R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S












141 802ndash803













519ndash522











234ndash236












307 ndash312







309ndash319














No CD003499


























64 628ndash634




241ndash248



9ndash20





























66ndash74



















168 324ndash329


R IPOLL ET AL








25 575ndash579












































117



1026





























140ndash145










try 39 117ndash118















854ndash858













32 590ndash596






519ndash523







233ndash237





201ndash214








765ndash766




R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






485ndash492



1455ndash1458






1409ndash1413




20 413ndash423






















50 377ndash385



1605






43 691ndash697



177ndash181









24ndash39












280ndash288



260ndash271




























51 20ndash27



16 561ndash569




206ndash210




376ndash385










2108ndash2114




903ndash907




416ndash420








170ndash173

R IPOLL ET AL



Table 3 Continued


Design


BPD criteria

(N 5 19)

option to increase

to 300 mgd if no

response by week 5


of phenelzine

Soloff et al

(1989)

Same as Soloff

et al (1986 b)

90 total with 35


4 SPD and 51

lsquomixedrsquo BPD

and SPD

Same as Soloff

et al (1986b )

Same procedure as


Mean dose of

haloperidol was 48

mgd and mean dose


1491 mgd on

day 35

Parallel design

5 wk











Links et al

(1990)

BPD 17 males and

females

Lithium

carbonate

desipramine


two 6-wk phases









Soloff et al

(1993)

BPD 108 males and

females

Haloperidol

phenelzine


1 mgd then titrated

up to mean dose of

4 mgd Phenelzine

began at 15 mgd

then titrated up to

mean dose of 60

mgd

Parallel design

5 wk









dysphoria

Cornelius

et al (1993)

BPD 54 males and

females

Haloperidol

phenelzine

Haloperidol up to 6


generally did not

change from final

dose of prior 5-wk

acute phase

(Soloff et al 1993)

Parallel design


acute phase

(Soloff et al

1993)











de la Fuente

amp Lotstra

(1994)

BPD 20 males and

females


therapeutic blood

levels

Parallel design

32 days


Salzman

et al (1995)

BPD 27 males and

females



60 mgd with mean

dose of 40 mgd

Parallel design

12 wk




generalizability

Coccaro amp

Kavoussi

(1997)

All subjects had at

least one PD as

well as current

problems with



frequent PD was

BPD

40 males and

females



week could be

increased to

40 mgd with further

increase to 60 mgd


8th week

Parallel design

12 wk





relative to placebo





(Continued)


R IPOLL ET AL



Table 3 Continued


Design





amp Kavoussi 1997)

Verkes et al

(1998)

Non-depressed

subjects who had

recently attempted


the second time

81 met criteria

for a Cluster B PD

91 males and

females


increased to

40 mgd after

1 wk

Parallel design

52 wk









in depressed mood


Battaglia

et al (1999)

Multiple suicide

attempters 85

had BPD

58 males and

females

Fluphenazine

decanoate

125 mg IM monthly

or 15 mg IM

monthly

Parallel design

but not placebo-

controlled

6 months







low end of possible







group of patients

Hollander

et al (2001)

BPD 16 males and

females

Divalproex

sodium


increased gradually



highest tolerable

dose Mean

endpoint valproate

level 6457 mgml

Parallel design

10 wk










Zanarini amp

Frankenburg

(2001)


125 mgd then

titrated up to

mean dose of

533 mgd at

endpoint

Parallel design

6 months







subscale of SCL-90

Frankenburg

amp Zanarini

(2002)

BPD and bipolar

disorder type II


sodium



serum levels of

50ndash100 mgl

Parallel design 6

months



medication group in



Rinne et al

(2002)


then titrated up to

a maximum of 250

mgd after 10th


response

6-wk double-blind

placebo-controlled

phase followed by

6-wk singleblind

half-crossover

phase in which all

subjects received

fluvoxamine This

was followed by





(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 3 Continued


Design


12-wk open label

study of

fluvoxamine

Hollander

et al (2003)

Cluster B PD IED or

PTSD with OAS-M

Aggression score

15

Males and females

Cluster B PD 96

with 55 BPD

13 NPD 10

AsPD 1 HPD

PD NOS 21) IED

116 PTSD 34

Divalproex

sodium

Began with 250 mg

bid then increased

by 250 mgd every


3 wk Recommended



week Maximum dose

30 mgkgd

Parallel design

12 wk


















better responses

Zanarini amp

Frankenburg

(2003)


pentaenoic acid

(E-EPA)


8 wk



depressive symptoms

Bogenschutz

amp Nurnberg

(2004)

BPD 40 males and

females


then increased by


10 mgd After week 8


increased to

maximum of 20 mgd


less than 10 mgd

Parallel design

12 wk


and CGI-BPD

Nickel et al

(2004)


then increased to

250 mgd by last

3 wk

Parallel design

8 wk





Philipsen

et al

(2004a )


which each subject

received one 75 mg

dose and one

150 mg dose in

randomized

crossover fashion

during separate


aversive inner

tension and urge

to commit

self-injurious

behaviourrsquo no

placebo-control

single-blind




and urges to commit





Philipsen

et al (2004b )


hydrochloride


over 30 s

Crossover design in

which each subject

received one dose

of naloxone and

onedose of placebo

in randomized




(Continued)


R IPOLL ET AL



Table 3 Continued


Design


crossover fashion

during separate

acute dissociative

episodes

Simpson

et al (2004)


concurrent DBT

Started at 20 mgd

increased to 40 mgd

at week 3

Parallel design

12 wk



post-treatment

Zanarini et al

(2004b )


olanzapine and

olanzapine-

fluoxetine

combination

(OFC)



mean dose of 15 mgd



mean dose of 33 mgd

OFC started at

olanzapine 25 mgd


with endpoint mean

doses of 32 mgd and


Parallel design but

not placebo-

controlled 8 wk








Nickel et al

(2005)


then increased to


Parallel design

8 wk









in ITT analysis

Soler et al

(2005)

BPD 60 males and

females

Olanzapine with

concurrent DBT


20 mgd with mean

dose 883 mgd

Parallel design

12 wk




Tritt et al

(2005)



during week 3

150 mgd during wk 4

and 5 and 200 mgd

during wk 6ndash8

Parallel design

8 wk





medication group

Nickel et al

(2006)

BPD 52 males and

females


8 wk













Loew et al

(2006)



dose of 200 mgd by

the 6th week

Parallel design

10 wk











(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



















(A SPD)


Table 3 Continued


Design


Shafti amp

Shahveisi

(2010)

BPD 28 females

recruited shortly

after inpatient

psychiatric


washout

Olanzapine

haloperidol


at 25 mgd and

increased weekly by

25 mgd as needed or


mgd by week 4


maintained for

remainder of study

Parallel design

but no placebo-

control 8 wk


towards greater










haloperidol group





Disorder


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





BPD




















R IPOLL ET AL












(SSRIS)
















R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S























R IPOLL ET AL





Design

duration


group(s)

Versiani et al

(1992)

Social

phobia

78 males and

females (percent

AvPD or

generalized

type not reported)

Moclobemide

phenelzine









Mean dose 675 mgd



follow-up in which

half of each


switched to placebo

others continued on

last dosage)


placebo in reducing

social anxiety and

improving social


group 91 for

phenelzine group

Moclobemide better

tolerated than

phenelzine

Van Vliet

et al (1994)

Social

phobia

30 males and

females (53

generalized

subtype)



phobic avoidance

Fahlen

(1995)

Social

phobia

63 males and

females (34 with

comorbid AvPD

1 with comorbidDPD)




in 3rd week


anxiety More marked

improvements in



comorbid AvPD and 1



Katzelnick

et al (1995)

Social

phobia

12 males and

females (percent

AvPD or

generalized type

not reported)





maximum of 200 mg


endpoint




functioning 50 of



improved vs 9 of

placebo group

IMCTGMSPand

Katschnig

(1997)

Socialphobia


generalized type

49 comorbid

AvPD)


dose)




vs 34 in placebo


between groups with

without AvPD in


AvPD patients

responded less to

placebo

Lott et al

(1997)

Social

phobia

102 males and

females

(percent

AvPD or

generalized type

not reported)



flexible dosing to

maximum of 150 mgd




50 response rate vs

19 in placebo group

Noyes et al

(1997)

Social

phobia

583 males and

females (625

generalized

type

478

comorbid

AvPD)



300 mgd vs 600 mgd




with 150 mgd and


to target dosage



12 wk only at 8 wk



rate As above no

difference between

groups withwithout

AvPD but less drug

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 4 Continued


Design

duration


group(s)



Heimberg

et al (1998)

Social

phobia

133 males and

females (707

generalized

type)








5 wk to 90 mgd

Parallel design but

non-randomized

comparing

medication to group


therapy (CBT) or

supportive

educational

therapy or placebo

12 wk












Schneier

et al (1998)

Social

phobia

77 males and

females (85

generalized

type 38

comorbid AvPD)


flexibly dosed to

a maximum of 400 mg

bid Mean dose 728

mgd at endpoint


subscores of social




Stein et al

(1998)

Social

phobia

183 males and

females (100

generalized

subtype)




of 50 mgd Mean dose

366 mgd at endpoint


and improvement in

social functioning

Allgulander

(1999)

Social

phobia

99 males and

females

(percent

with comorbid

AvPD or

generalized type

not reported)




of 50 mgd







dysthymia

Baldwin et al

(1999)

Social

phobia

290 males and

females

(percent with

comorbid AvPD

or generalized

type not reported)




of 50 mgd Mean dose

347 mgd at endpoint


and improvement in



in placebo group

Stein et al

(1999)

Social

phobia

92 males and

females (913

generalized

type)





300 mgd Mean dose

202 mgd at endpoint


and improvement in



in placebo group

Blomhoff

et al (2001)

Social

phobia

387 males and

females (100

generalized

type)




improvement noted


after 8 or 12wk

Parallel design

comparing

sertraline1general

medical care

sertraline1

prolonged

exposure therapy

(PE) placebo1PE

and placebo1

general medical

care 24 wk


sertralinePE groups

superior to placebo



combination group



alone

van

Ameringen

et al (2001)

Social

phobia

204 males and

females (100

generalized

type 61

comorbid AvPD)




to maximum of

200 mg d Mean dose



and improvement in



placebo group

(Continued)


R IPOLL ET AL



Table 4 Continued


Design

duration


group(s)

Liebowitz

et al (2002)

Social

phobia

384 males and

females (100

generalized

type)


20 mgd vs 40 mgd vs

60 mgd All groups

began with 20 mgd






20 mg group Highest


CGI) in 40 mg group

Stein et al

(2002)

Social

phobia

257 males and

females (100

generalized

type)




maximum of 50 mgd


blind 12-wk acute

phase with those

whose CGI


2 entering 24-wk

double-blind

continuation

phase



39 in placebo group

Davidson

et al(2004b )

Social

phobia

279 males and


type)



maximum of 300 mgd

Mean dose 174 mgd



Davidson

et al

(2004a )

Social

phobia

295 (100

generalized

type)




15 and to 40 mgd on





improvement

Parallel design

comparing

fluoxetine group

CBT fluoxetine1

group CBT placebo

placebo1group CBT

14 wk




14 wk Combined


advantage

Lepola et al

(2004)

Social

phobia

372 males and

females(percent

with comorbid

AvPD or

generalized

type not

reported)





323 mgd at endpoint




in placebo group

Rickels et al

(2004)

Social

phobia

272 males and

females (100

generalized

type)






one more week


and improvement in

social functioning

Lader et al

(2004)

Social

phobia

839 males and


type)

Escitalopram

paroxetine



Paroxetine 20 mgd



follow-up




and paroxetine

Escitalopram 20 mgd


20 mgd

Allgulander

et al (2004)

Social

phobia

434 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine





maximum of 225 mgd


paroxetine groups



and improvement in

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






Table 4 Continued


Design

duration


group(s)


endpoint Paroxetine





endpoint

social functioning

Possibly more rapid


Kasper et al

(2005)

Social

phobia

358 males and

females (100

generalized

type)




for unsatisfactory

response Mean dose

176 mgd at endpoint


and improvement in



placebo group

Liebowitz

et al

(2005b )

Social

phobia

271 males and

females (100

generalized

type)







and improvement in



placebo group

Liebowitz

et al

(2005a )

Social

phobia

413 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine


75 mgd-225 mgd with







10 mg increases to

maximum of 50 mgd

Mean dose 46 mgd at

endpoint


and improvement in

social functioning


for both medication


equally efficacious


venlafaxine 625 for

paroxetine and 361

for placebo group

Stein et al(2005)

Socialphobia


generalized

type)



75 mgd and if





increase to 225 mgd

after 2nd week



dosage groups 31


venlafaxine groups

combined vs 16 in

placebo group

Montgomery

et al (2005)

Social

phobia

517 males and

females (100

generalized

type)





responders entered



for remainder

12-wk open-label

phase followed by

24-wk fixed-

dose relapse

prevention

(parallel design

double-blind RCT)




vs 144d for placebo

group No direct

comparison made

between doses



R IPOLL ET AL












OTHER MEDICATIONS














R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





(A VPD)












FUTURE DIRECTIONS







R IPOLL ET AL









R E F E R E N C E S

















387ndash396









































177ndash179


























R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S












141 802ndash803













519ndash522











234ndash236












307 ndash312







309ndash319














No CD003499


























64 628ndash634




241ndash248



9ndash20





























66ndash74



















168 324ndash329


R IPOLL ET AL








25 575ndash579












































117



1026





























140ndash145










try 39 117ndash118















854ndash858













32 590ndash596






519ndash523







233ndash237





201ndash214








765ndash766




R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






485ndash492



1455ndash1458






1409ndash1413




20 413ndash423






















50 377ndash385



1605






43 691ndash697



177ndash181









24ndash39












280ndash288



260ndash271




























51 20ndash27



16 561ndash569




206ndash210




376ndash385










2108ndash2114




903ndash907




416ndash420








170ndash173

R IPOLL ET AL



Table 3 Continued


Design





amp Kavoussi 1997)

Verkes et al

(1998)

Non-depressed

subjects who had

recently attempted


the second time

81 met criteria

for a Cluster B PD

91 males and

females


increased to

40 mgd after

1 wk

Parallel design

52 wk









in depressed mood


Battaglia

et al (1999)

Multiple suicide

attempters 85

had BPD

58 males and

females

Fluphenazine

decanoate

125 mg IM monthly

or 15 mg IM

monthly

Parallel design

but not placebo-

controlled

6 months







low end of possible







group of patients

Hollander

et al (2001)

BPD 16 males and

females

Divalproex

sodium


increased gradually



highest tolerable

dose Mean

endpoint valproate

level 6457 mgml

Parallel design

10 wk










Zanarini amp

Frankenburg

(2001)


125 mgd then

titrated up to

mean dose of

533 mgd at

endpoint

Parallel design

6 months







subscale of SCL-90

Frankenburg

amp Zanarini

(2002)

BPD and bipolar

disorder type II


sodium



serum levels of

50ndash100 mgl

Parallel design 6

months



medication group in



Rinne et al

(2002)


then titrated up to

a maximum of 250

mgd after 10th


response

6-wk double-blind

placebo-controlled

phase followed by

6-wk singleblind

half-crossover

phase in which all

subjects received

fluvoxamine This

was followed by





(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 3 Continued


Design


12-wk open label

study of

fluvoxamine

Hollander

et al (2003)

Cluster B PD IED or

PTSD with OAS-M

Aggression score

15

Males and females

Cluster B PD 96

with 55 BPD

13 NPD 10

AsPD 1 HPD

PD NOS 21) IED

116 PTSD 34

Divalproex

sodium

Began with 250 mg

bid then increased

by 250 mgd every


3 wk Recommended



week Maximum dose

30 mgkgd

Parallel design

12 wk


















better responses

Zanarini amp

Frankenburg

(2003)


pentaenoic acid

(E-EPA)


8 wk



depressive symptoms

Bogenschutz

amp Nurnberg

(2004)

BPD 40 males and

females


then increased by


10 mgd After week 8


increased to

maximum of 20 mgd


less than 10 mgd

Parallel design

12 wk


and CGI-BPD

Nickel et al

(2004)


then increased to

250 mgd by last

3 wk

Parallel design

8 wk





Philipsen

et al

(2004a )


which each subject

received one 75 mg

dose and one

150 mg dose in

randomized

crossover fashion

during separate


aversive inner

tension and urge

to commit

self-injurious

behaviourrsquo no

placebo-control

single-blind




and urges to commit





Philipsen

et al (2004b )


hydrochloride


over 30 s

Crossover design in

which each subject

received one dose

of naloxone and

onedose of placebo

in randomized




(Continued)


R IPOLL ET AL



Table 3 Continued


Design


crossover fashion

during separate

acute dissociative

episodes

Simpson

et al (2004)


concurrent DBT

Started at 20 mgd

increased to 40 mgd

at week 3

Parallel design

12 wk



post-treatment

Zanarini et al

(2004b )


olanzapine and

olanzapine-

fluoxetine

combination

(OFC)



mean dose of 15 mgd



mean dose of 33 mgd

OFC started at

olanzapine 25 mgd


with endpoint mean

doses of 32 mgd and


Parallel design but

not placebo-

controlled 8 wk








Nickel et al

(2005)


then increased to


Parallel design

8 wk









in ITT analysis

Soler et al

(2005)

BPD 60 males and

females

Olanzapine with

concurrent DBT


20 mgd with mean

dose 883 mgd

Parallel design

12 wk




Tritt et al

(2005)



during week 3

150 mgd during wk 4

and 5 and 200 mgd

during wk 6ndash8

Parallel design

8 wk





medication group

Nickel et al

(2006)

BPD 52 males and

females


8 wk













Loew et al

(2006)



dose of 200 mgd by

the 6th week

Parallel design

10 wk











(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



















(A SPD)


Table 3 Continued


Design


Shafti amp

Shahveisi

(2010)

BPD 28 females

recruited shortly

after inpatient

psychiatric


washout

Olanzapine

haloperidol


at 25 mgd and

increased weekly by

25 mgd as needed or


mgd by week 4


maintained for

remainder of study

Parallel design

but no placebo-

control 8 wk


towards greater










haloperidol group





Disorder


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





BPD




















R IPOLL ET AL












(SSRIS)
















R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S























R IPOLL ET AL





Design

duration


group(s)

Versiani et al

(1992)

Social

phobia

78 males and

females (percent

AvPD or

generalized

type not reported)

Moclobemide

phenelzine









Mean dose 675 mgd



follow-up in which

half of each


switched to placebo

others continued on

last dosage)


placebo in reducing

social anxiety and

improving social


group 91 for

phenelzine group

Moclobemide better

tolerated than

phenelzine

Van Vliet

et al (1994)

Social

phobia

30 males and

females (53

generalized

subtype)



phobic avoidance

Fahlen

(1995)

Social

phobia

63 males and

females (34 with

comorbid AvPD

1 with comorbidDPD)




in 3rd week


anxiety More marked

improvements in



comorbid AvPD and 1



Katzelnick

et al (1995)

Social

phobia

12 males and

females (percent

AvPD or

generalized type

not reported)





maximum of 200 mg


endpoint




functioning 50 of



improved vs 9 of

placebo group

IMCTGMSPand

Katschnig

(1997)

Socialphobia


generalized type

49 comorbid

AvPD)


dose)




vs 34 in placebo


between groups with

without AvPD in


AvPD patients

responded less to

placebo

Lott et al

(1997)

Social

phobia

102 males and

females

(percent

AvPD or

generalized type

not reported)



flexible dosing to

maximum of 150 mgd




50 response rate vs

19 in placebo group

Noyes et al

(1997)

Social

phobia

583 males and

females (625

generalized

type

478

comorbid

AvPD)



300 mgd vs 600 mgd




with 150 mgd and


to target dosage



12 wk only at 8 wk



rate As above no

difference between

groups withwithout

AvPD but less drug

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 4 Continued


Design

duration


group(s)



Heimberg

et al (1998)

Social

phobia

133 males and

females (707

generalized

type)








5 wk to 90 mgd

Parallel design but

non-randomized

comparing

medication to group


therapy (CBT) or

supportive

educational

therapy or placebo

12 wk












Schneier

et al (1998)

Social

phobia

77 males and

females (85

generalized

type 38

comorbid AvPD)


flexibly dosed to

a maximum of 400 mg

bid Mean dose 728

mgd at endpoint


subscores of social




Stein et al

(1998)

Social

phobia

183 males and

females (100

generalized

subtype)




of 50 mgd Mean dose

366 mgd at endpoint


and improvement in

social functioning

Allgulander

(1999)

Social

phobia

99 males and

females

(percent

with comorbid

AvPD or

generalized type

not reported)




of 50 mgd







dysthymia

Baldwin et al

(1999)

Social

phobia

290 males and

females

(percent with

comorbid AvPD

or generalized

type not reported)




of 50 mgd Mean dose

347 mgd at endpoint


and improvement in



in placebo group

Stein et al

(1999)

Social

phobia

92 males and

females (913

generalized

type)





300 mgd Mean dose

202 mgd at endpoint


and improvement in



in placebo group

Blomhoff

et al (2001)

Social

phobia

387 males and

females (100

generalized

type)




improvement noted


after 8 or 12wk

Parallel design

comparing

sertraline1general

medical care

sertraline1

prolonged

exposure therapy

(PE) placebo1PE

and placebo1

general medical

care 24 wk


sertralinePE groups

superior to placebo



combination group



alone

van

Ameringen

et al (2001)

Social

phobia

204 males and

females (100

generalized

type 61

comorbid AvPD)




to maximum of

200 mg d Mean dose



and improvement in



placebo group

(Continued)


R IPOLL ET AL



Table 4 Continued


Design

duration


group(s)

Liebowitz

et al (2002)

Social

phobia

384 males and

females (100

generalized

type)


20 mgd vs 40 mgd vs

60 mgd All groups

began with 20 mgd






20 mg group Highest


CGI) in 40 mg group

Stein et al

(2002)

Social

phobia

257 males and

females (100

generalized

type)




maximum of 50 mgd


blind 12-wk acute

phase with those

whose CGI


2 entering 24-wk

double-blind

continuation

phase



39 in placebo group

Davidson

et al(2004b )

Social

phobia

279 males and


type)



maximum of 300 mgd

Mean dose 174 mgd



Davidson

et al

(2004a )

Social

phobia

295 (100

generalized

type)




15 and to 40 mgd on





improvement

Parallel design

comparing

fluoxetine group

CBT fluoxetine1

group CBT placebo

placebo1group CBT

14 wk




14 wk Combined


advantage

Lepola et al

(2004)

Social

phobia

372 males and

females(percent

with comorbid

AvPD or

generalized

type not

reported)





323 mgd at endpoint




in placebo group

Rickels et al

(2004)

Social

phobia

272 males and

females (100

generalized

type)






one more week


and improvement in

social functioning

Lader et al

(2004)

Social

phobia

839 males and


type)

Escitalopram

paroxetine



Paroxetine 20 mgd



follow-up




and paroxetine

Escitalopram 20 mgd


20 mgd

Allgulander

et al (2004)

Social

phobia

434 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine





maximum of 225 mgd


paroxetine groups



and improvement in

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






Table 4 Continued


Design

duration


group(s)


endpoint Paroxetine





endpoint

social functioning

Possibly more rapid


Kasper et al

(2005)

Social

phobia

358 males and

females (100

generalized

type)




for unsatisfactory

response Mean dose

176 mgd at endpoint


and improvement in



placebo group

Liebowitz

et al

(2005b )

Social

phobia

271 males and

females (100

generalized

type)







and improvement in



placebo group

Liebowitz

et al

(2005a )

Social

phobia

413 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine


75 mgd-225 mgd with







10 mg increases to

maximum of 50 mgd

Mean dose 46 mgd at

endpoint


and improvement in

social functioning


for both medication


equally efficacious


venlafaxine 625 for

paroxetine and 361

for placebo group

Stein et al(2005)

Socialphobia


generalized

type)



75 mgd and if





increase to 225 mgd

after 2nd week



dosage groups 31


venlafaxine groups

combined vs 16 in

placebo group

Montgomery

et al (2005)

Social

phobia

517 males and

females (100

generalized

type)





responders entered



for remainder

12-wk open-label

phase followed by

24-wk fixed-

dose relapse

prevention

(parallel design

double-blind RCT)




vs 144d for placebo

group No direct

comparison made

between doses



R IPOLL ET AL












OTHER MEDICATIONS














R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





(A VPD)












FUTURE DIRECTIONS







R IPOLL ET AL









R E F E R E N C E S

















387ndash396









































177ndash179


























R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S












141 802ndash803













519ndash522











234ndash236












307 ndash312







309ndash319














No CD003499


























64 628ndash634




241ndash248



9ndash20





























66ndash74



















168 324ndash329


R IPOLL ET AL








25 575ndash579












































117



1026





























140ndash145










try 39 117ndash118















854ndash858













32 590ndash596






519ndash523







233ndash237





201ndash214








765ndash766




R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






485ndash492



1455ndash1458






1409ndash1413




20 413ndash423






















50 377ndash385



1605






43 691ndash697



177ndash181









24ndash39












280ndash288



260ndash271




























51 20ndash27



16 561ndash569




206ndash210




376ndash385










2108ndash2114




903ndash907




416ndash420








170ndash173

R IPOLL ET AL



Table 3 Continued


Design


12-wk open label

study of

fluvoxamine

Hollander

et al (2003)

Cluster B PD IED or

PTSD with OAS-M

Aggression score

15

Males and females

Cluster B PD 96

with 55 BPD

13 NPD 10

AsPD 1 HPD

PD NOS 21) IED

116 PTSD 34

Divalproex

sodium

Began with 250 mg

bid then increased

by 250 mgd every


3 wk Recommended



week Maximum dose

30 mgkgd

Parallel design

12 wk


















better responses

Zanarini amp

Frankenburg

(2003)


pentaenoic acid

(E-EPA)


8 wk



depressive symptoms

Bogenschutz

amp Nurnberg

(2004)

BPD 40 males and

females


then increased by


10 mgd After week 8


increased to

maximum of 20 mgd


less than 10 mgd

Parallel design

12 wk


and CGI-BPD

Nickel et al

(2004)


then increased to

250 mgd by last

3 wk

Parallel design

8 wk





Philipsen

et al

(2004a )


which each subject

received one 75 mg

dose and one

150 mg dose in

randomized

crossover fashion

during separate


aversive inner

tension and urge

to commit

self-injurious

behaviourrsquo no

placebo-control

single-blind




and urges to commit





Philipsen

et al (2004b )


hydrochloride


over 30 s

Crossover design in

which each subject

received one dose

of naloxone and

onedose of placebo

in randomized




(Continued)


R IPOLL ET AL



Table 3 Continued


Design


crossover fashion

during separate

acute dissociative

episodes

Simpson

et al (2004)


concurrent DBT

Started at 20 mgd

increased to 40 mgd

at week 3

Parallel design

12 wk



post-treatment

Zanarini et al

(2004b )


olanzapine and

olanzapine-

fluoxetine

combination

(OFC)



mean dose of 15 mgd



mean dose of 33 mgd

OFC started at

olanzapine 25 mgd


with endpoint mean

doses of 32 mgd and


Parallel design but

not placebo-

controlled 8 wk








Nickel et al

(2005)


then increased to


Parallel design

8 wk









in ITT analysis

Soler et al

(2005)

BPD 60 males and

females

Olanzapine with

concurrent DBT


20 mgd with mean

dose 883 mgd

Parallel design

12 wk




Tritt et al

(2005)



during week 3

150 mgd during wk 4

and 5 and 200 mgd

during wk 6ndash8

Parallel design

8 wk





medication group

Nickel et al

(2006)

BPD 52 males and

females


8 wk













Loew et al

(2006)



dose of 200 mgd by

the 6th week

Parallel design

10 wk











(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



















(A SPD)


Table 3 Continued


Design


Shafti amp

Shahveisi

(2010)

BPD 28 females

recruited shortly

after inpatient

psychiatric


washout

Olanzapine

haloperidol


at 25 mgd and

increased weekly by

25 mgd as needed or


mgd by week 4


maintained for

remainder of study

Parallel design

but no placebo-

control 8 wk


towards greater










haloperidol group





Disorder


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





BPD




















R IPOLL ET AL












(SSRIS)
















R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S























R IPOLL ET AL





Design

duration


group(s)

Versiani et al

(1992)

Social

phobia

78 males and

females (percent

AvPD or

generalized

type not reported)

Moclobemide

phenelzine









Mean dose 675 mgd



follow-up in which

half of each


switched to placebo

others continued on

last dosage)


placebo in reducing

social anxiety and

improving social


group 91 for

phenelzine group

Moclobemide better

tolerated than

phenelzine

Van Vliet

et al (1994)

Social

phobia

30 males and

females (53

generalized

subtype)



phobic avoidance

Fahlen

(1995)

Social

phobia

63 males and

females (34 with

comorbid AvPD

1 with comorbidDPD)




in 3rd week


anxiety More marked

improvements in



comorbid AvPD and 1



Katzelnick

et al (1995)

Social

phobia

12 males and

females (percent

AvPD or

generalized type

not reported)





maximum of 200 mg


endpoint




functioning 50 of



improved vs 9 of

placebo group

IMCTGMSPand

Katschnig

(1997)

Socialphobia


generalized type

49 comorbid

AvPD)


dose)




vs 34 in placebo


between groups with

without AvPD in


AvPD patients

responded less to

placebo

Lott et al

(1997)

Social

phobia

102 males and

females

(percent

AvPD or

generalized type

not reported)



flexible dosing to

maximum of 150 mgd




50 response rate vs

19 in placebo group

Noyes et al

(1997)

Social

phobia

583 males and

females (625

generalized

type

478

comorbid

AvPD)



300 mgd vs 600 mgd




with 150 mgd and


to target dosage



12 wk only at 8 wk



rate As above no

difference between

groups withwithout

AvPD but less drug

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 4 Continued


Design

duration


group(s)



Heimberg

et al (1998)

Social

phobia

133 males and

females (707

generalized

type)








5 wk to 90 mgd

Parallel design but

non-randomized

comparing

medication to group


therapy (CBT) or

supportive

educational

therapy or placebo

12 wk












Schneier

et al (1998)

Social

phobia

77 males and

females (85

generalized

type 38

comorbid AvPD)


flexibly dosed to

a maximum of 400 mg

bid Mean dose 728

mgd at endpoint


subscores of social




Stein et al

(1998)

Social

phobia

183 males and

females (100

generalized

subtype)




of 50 mgd Mean dose

366 mgd at endpoint


and improvement in

social functioning

Allgulander

(1999)

Social

phobia

99 males and

females

(percent

with comorbid

AvPD or

generalized type

not reported)




of 50 mgd







dysthymia

Baldwin et al

(1999)

Social

phobia

290 males and

females

(percent with

comorbid AvPD

or generalized

type not reported)




of 50 mgd Mean dose

347 mgd at endpoint


and improvement in



in placebo group

Stein et al

(1999)

Social

phobia

92 males and

females (913

generalized

type)





300 mgd Mean dose

202 mgd at endpoint


and improvement in



in placebo group

Blomhoff

et al (2001)

Social

phobia

387 males and

females (100

generalized

type)




improvement noted


after 8 or 12wk

Parallel design

comparing

sertraline1general

medical care

sertraline1

prolonged

exposure therapy

(PE) placebo1PE

and placebo1

general medical

care 24 wk


sertralinePE groups

superior to placebo



combination group



alone

van

Ameringen

et al (2001)

Social

phobia

204 males and

females (100

generalized

type 61

comorbid AvPD)




to maximum of

200 mg d Mean dose



and improvement in



placebo group

(Continued)


R IPOLL ET AL



Table 4 Continued


Design

duration


group(s)

Liebowitz

et al (2002)

Social

phobia

384 males and

females (100

generalized

type)


20 mgd vs 40 mgd vs

60 mgd All groups

began with 20 mgd






20 mg group Highest


CGI) in 40 mg group

Stein et al

(2002)

Social

phobia

257 males and

females (100

generalized

type)




maximum of 50 mgd


blind 12-wk acute

phase with those

whose CGI


2 entering 24-wk

double-blind

continuation

phase



39 in placebo group

Davidson

et al(2004b )

Social

phobia

279 males and


type)



maximum of 300 mgd

Mean dose 174 mgd



Davidson

et al

(2004a )

Social

phobia

295 (100

generalized

type)




15 and to 40 mgd on





improvement

Parallel design

comparing

fluoxetine group

CBT fluoxetine1

group CBT placebo

placebo1group CBT

14 wk




14 wk Combined


advantage

Lepola et al

(2004)

Social

phobia

372 males and

females(percent

with comorbid

AvPD or

generalized

type not

reported)





323 mgd at endpoint




in placebo group

Rickels et al

(2004)

Social

phobia

272 males and

females (100

generalized

type)






one more week


and improvement in

social functioning

Lader et al

(2004)

Social

phobia

839 males and


type)

Escitalopram

paroxetine



Paroxetine 20 mgd



follow-up




and paroxetine

Escitalopram 20 mgd


20 mgd

Allgulander

et al (2004)

Social

phobia

434 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine





maximum of 225 mgd


paroxetine groups



and improvement in

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






Table 4 Continued


Design

duration


group(s)


endpoint Paroxetine





endpoint

social functioning

Possibly more rapid


Kasper et al

(2005)

Social

phobia

358 males and

females (100

generalized

type)




for unsatisfactory

response Mean dose

176 mgd at endpoint


and improvement in



placebo group

Liebowitz

et al

(2005b )

Social

phobia

271 males and

females (100

generalized

type)







and improvement in



placebo group

Liebowitz

et al

(2005a )

Social

phobia

413 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine


75 mgd-225 mgd with







10 mg increases to

maximum of 50 mgd

Mean dose 46 mgd at

endpoint


and improvement in

social functioning


for both medication


equally efficacious


venlafaxine 625 for

paroxetine and 361

for placebo group

Stein et al(2005)

Socialphobia


generalized

type)



75 mgd and if





increase to 225 mgd

after 2nd week



dosage groups 31


venlafaxine groups

combined vs 16 in

placebo group

Montgomery

et al (2005)

Social

phobia

517 males and

females (100

generalized

type)





responders entered



for remainder

12-wk open-label

phase followed by

24-wk fixed-

dose relapse

prevention

(parallel design

double-blind RCT)




vs 144d for placebo

group No direct

comparison made

between doses



R IPOLL ET AL












OTHER MEDICATIONS














R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





(A VPD)












FUTURE DIRECTIONS







R IPOLL ET AL









R E F E R E N C E S

















387ndash396









































177ndash179


























R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S












141 802ndash803













519ndash522











234ndash236












307 ndash312







309ndash319














No CD003499


























64 628ndash634




241ndash248



9ndash20





























66ndash74



















168 324ndash329


R IPOLL ET AL








25 575ndash579












































117



1026





























140ndash145










try 39 117ndash118















854ndash858













32 590ndash596






519ndash523







233ndash237





201ndash214








765ndash766




R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






485ndash492



1455ndash1458






1409ndash1413




20 413ndash423






















50 377ndash385



1605






43 691ndash697



177ndash181









24ndash39












280ndash288



260ndash271




























51 20ndash27



16 561ndash569




206ndash210




376ndash385










2108ndash2114




903ndash907




416ndash420








170ndash173

R IPOLL ET AL



Table 3 Continued


Design


crossover fashion

during separate

acute dissociative

episodes

Simpson

et al (2004)


concurrent DBT

Started at 20 mgd

increased to 40 mgd

at week 3

Parallel design

12 wk



post-treatment

Zanarini et al

(2004b )


olanzapine and

olanzapine-

fluoxetine

combination

(OFC)



mean dose of 15 mgd



mean dose of 33 mgd

OFC started at

olanzapine 25 mgd


with endpoint mean

doses of 32 mgd and


Parallel design but

not placebo-

controlled 8 wk








Nickel et al

(2005)


then increased to


Parallel design

8 wk









in ITT analysis

Soler et al

(2005)

BPD 60 males and

females

Olanzapine with

concurrent DBT


20 mgd with mean

dose 883 mgd

Parallel design

12 wk




Tritt et al

(2005)



during week 3

150 mgd during wk 4

and 5 and 200 mgd

during wk 6ndash8

Parallel design

8 wk





medication group

Nickel et al

(2006)

BPD 52 males and

females


8 wk













Loew et al

(2006)



dose of 200 mgd by

the 6th week

Parallel design

10 wk











(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



















(A SPD)


Table 3 Continued


Design


Shafti amp

Shahveisi

(2010)

BPD 28 females

recruited shortly

after inpatient

psychiatric


washout

Olanzapine

haloperidol


at 25 mgd and

increased weekly by

25 mgd as needed or


mgd by week 4


maintained for

remainder of study

Parallel design

but no placebo-

control 8 wk


towards greater










haloperidol group





Disorder


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





BPD




















R IPOLL ET AL












(SSRIS)
















R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S























R IPOLL ET AL





Design

duration


group(s)

Versiani et al

(1992)

Social

phobia

78 males and

females (percent

AvPD or

generalized

type not reported)

Moclobemide

phenelzine









Mean dose 675 mgd



follow-up in which

half of each


switched to placebo

others continued on

last dosage)


placebo in reducing

social anxiety and

improving social


group 91 for

phenelzine group

Moclobemide better

tolerated than

phenelzine

Van Vliet

et al (1994)

Social

phobia

30 males and

females (53

generalized

subtype)



phobic avoidance

Fahlen

(1995)

Social

phobia

63 males and

females (34 with

comorbid AvPD

1 with comorbidDPD)




in 3rd week


anxiety More marked

improvements in



comorbid AvPD and 1



Katzelnick

et al (1995)

Social

phobia

12 males and

females (percent

AvPD or

generalized type

not reported)





maximum of 200 mg


endpoint




functioning 50 of



improved vs 9 of

placebo group

IMCTGMSPand

Katschnig

(1997)

Socialphobia


generalized type

49 comorbid

AvPD)


dose)




vs 34 in placebo


between groups with

without AvPD in


AvPD patients

responded less to

placebo

Lott et al

(1997)

Social

phobia

102 males and

females

(percent

AvPD or

generalized type

not reported)



flexible dosing to

maximum of 150 mgd




50 response rate vs

19 in placebo group

Noyes et al

(1997)

Social

phobia

583 males and

females (625

generalized

type

478

comorbid

AvPD)



300 mgd vs 600 mgd




with 150 mgd and


to target dosage



12 wk only at 8 wk



rate As above no

difference between

groups withwithout

AvPD but less drug

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 4 Continued


Design

duration


group(s)



Heimberg

et al (1998)

Social

phobia

133 males and

females (707

generalized

type)








5 wk to 90 mgd

Parallel design but

non-randomized

comparing

medication to group


therapy (CBT) or

supportive

educational

therapy or placebo

12 wk












Schneier

et al (1998)

Social

phobia

77 males and

females (85

generalized

type 38

comorbid AvPD)


flexibly dosed to

a maximum of 400 mg

bid Mean dose 728

mgd at endpoint


subscores of social




Stein et al

(1998)

Social

phobia

183 males and

females (100

generalized

subtype)




of 50 mgd Mean dose

366 mgd at endpoint


and improvement in

social functioning

Allgulander

(1999)

Social

phobia

99 males and

females

(percent

with comorbid

AvPD or

generalized type

not reported)




of 50 mgd







dysthymia

Baldwin et al

(1999)

Social

phobia

290 males and

females

(percent with

comorbid AvPD

or generalized

type not reported)




of 50 mgd Mean dose

347 mgd at endpoint


and improvement in



in placebo group

Stein et al

(1999)

Social

phobia

92 males and

females (913

generalized

type)





300 mgd Mean dose

202 mgd at endpoint


and improvement in



in placebo group

Blomhoff

et al (2001)

Social

phobia

387 males and

females (100

generalized

type)




improvement noted


after 8 or 12wk

Parallel design

comparing

sertraline1general

medical care

sertraline1

prolonged

exposure therapy

(PE) placebo1PE

and placebo1

general medical

care 24 wk


sertralinePE groups

superior to placebo



combination group



alone

van

Ameringen

et al (2001)

Social

phobia

204 males and

females (100

generalized

type 61

comorbid AvPD)




to maximum of

200 mg d Mean dose



and improvement in



placebo group

(Continued)


R IPOLL ET AL



Table 4 Continued


Design

duration


group(s)

Liebowitz

et al (2002)

Social

phobia

384 males and

females (100

generalized

type)


20 mgd vs 40 mgd vs

60 mgd All groups

began with 20 mgd






20 mg group Highest


CGI) in 40 mg group

Stein et al

(2002)

Social

phobia

257 males and

females (100

generalized

type)




maximum of 50 mgd


blind 12-wk acute

phase with those

whose CGI


2 entering 24-wk

double-blind

continuation

phase



39 in placebo group

Davidson

et al(2004b )

Social

phobia

279 males and


type)



maximum of 300 mgd

Mean dose 174 mgd



Davidson

et al

(2004a )

Social

phobia

295 (100

generalized

type)




15 and to 40 mgd on





improvement

Parallel design

comparing

fluoxetine group

CBT fluoxetine1

group CBT placebo

placebo1group CBT

14 wk




14 wk Combined


advantage

Lepola et al

(2004)

Social

phobia

372 males and

females(percent

with comorbid

AvPD or

generalized

type not

reported)





323 mgd at endpoint




in placebo group

Rickels et al

(2004)

Social

phobia

272 males and

females (100

generalized

type)






one more week


and improvement in

social functioning

Lader et al

(2004)

Social

phobia

839 males and


type)

Escitalopram

paroxetine



Paroxetine 20 mgd



follow-up




and paroxetine

Escitalopram 20 mgd


20 mgd

Allgulander

et al (2004)

Social

phobia

434 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine





maximum of 225 mgd


paroxetine groups



and improvement in

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






Table 4 Continued


Design

duration


group(s)


endpoint Paroxetine





endpoint

social functioning

Possibly more rapid


Kasper et al

(2005)

Social

phobia

358 males and

females (100

generalized

type)




for unsatisfactory

response Mean dose

176 mgd at endpoint


and improvement in



placebo group

Liebowitz

et al

(2005b )

Social

phobia

271 males and

females (100

generalized

type)







and improvement in



placebo group

Liebowitz

et al

(2005a )

Social

phobia

413 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine


75 mgd-225 mgd with







10 mg increases to

maximum of 50 mgd

Mean dose 46 mgd at

endpoint


and improvement in

social functioning


for both medication


equally efficacious


venlafaxine 625 for

paroxetine and 361

for placebo group

Stein et al(2005)

Socialphobia


generalized

type)



75 mgd and if





increase to 225 mgd

after 2nd week



dosage groups 31


venlafaxine groups

combined vs 16 in

placebo group

Montgomery

et al (2005)

Social

phobia

517 males and

females (100

generalized

type)





responders entered



for remainder

12-wk open-label

phase followed by

24-wk fixed-

dose relapse

prevention

(parallel design

double-blind RCT)




vs 144d for placebo

group No direct

comparison made

between doses



R IPOLL ET AL












OTHER MEDICATIONS














R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





(A VPD)












FUTURE DIRECTIONS







R IPOLL ET AL









R E F E R E N C E S

















387ndash396









































177ndash179


























R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S












141 802ndash803













519ndash522











234ndash236












307 ndash312







309ndash319














No CD003499


























64 628ndash634




241ndash248



9ndash20





























66ndash74



















168 324ndash329


R IPOLL ET AL








25 575ndash579












































117



1026





























140ndash145










try 39 117ndash118















854ndash858













32 590ndash596






519ndash523







233ndash237





201ndash214








765ndash766




R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






485ndash492



1455ndash1458






1409ndash1413




20 413ndash423






















50 377ndash385



1605






43 691ndash697



177ndash181









24ndash39












280ndash288



260ndash271




























51 20ndash27



16 561ndash569




206ndash210




376ndash385










2108ndash2114




903ndash907




416ndash420








170ndash173

R IPOLL ET AL



















(A SPD)


Table 3 Continued


Design


Shafti amp

Shahveisi

(2010)

BPD 28 females

recruited shortly

after inpatient

psychiatric


washout

Olanzapine

haloperidol


at 25 mgd and

increased weekly by

25 mgd as needed or


mgd by week 4


maintained for

remainder of study

Parallel design

but no placebo-

control 8 wk


towards greater










haloperidol group





Disorder


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





BPD




















R IPOLL ET AL












(SSRIS)
















R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S























R IPOLL ET AL





Design

duration


group(s)

Versiani et al

(1992)

Social

phobia

78 males and

females (percent

AvPD or

generalized

type not reported)

Moclobemide

phenelzine









Mean dose 675 mgd



follow-up in which

half of each


switched to placebo

others continued on

last dosage)


placebo in reducing

social anxiety and

improving social


group 91 for

phenelzine group

Moclobemide better

tolerated than

phenelzine

Van Vliet

et al (1994)

Social

phobia

30 males and

females (53

generalized

subtype)



phobic avoidance

Fahlen

(1995)

Social

phobia

63 males and

females (34 with

comorbid AvPD

1 with comorbidDPD)




in 3rd week


anxiety More marked

improvements in



comorbid AvPD and 1



Katzelnick

et al (1995)

Social

phobia

12 males and

females (percent

AvPD or

generalized type

not reported)





maximum of 200 mg


endpoint




functioning 50 of



improved vs 9 of

placebo group

IMCTGMSPand

Katschnig

(1997)

Socialphobia


generalized type

49 comorbid

AvPD)


dose)




vs 34 in placebo


between groups with

without AvPD in


AvPD patients

responded less to

placebo

Lott et al

(1997)

Social

phobia

102 males and

females

(percent

AvPD or

generalized type

not reported)



flexible dosing to

maximum of 150 mgd




50 response rate vs

19 in placebo group

Noyes et al

(1997)

Social

phobia

583 males and

females (625

generalized

type

478

comorbid

AvPD)



300 mgd vs 600 mgd




with 150 mgd and


to target dosage



12 wk only at 8 wk



rate As above no

difference between

groups withwithout

AvPD but less drug

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 4 Continued


Design

duration


group(s)



Heimberg

et al (1998)

Social

phobia

133 males and

females (707

generalized

type)








5 wk to 90 mgd

Parallel design but

non-randomized

comparing

medication to group


therapy (CBT) or

supportive

educational

therapy or placebo

12 wk












Schneier

et al (1998)

Social

phobia

77 males and

females (85

generalized

type 38

comorbid AvPD)


flexibly dosed to

a maximum of 400 mg

bid Mean dose 728

mgd at endpoint


subscores of social




Stein et al

(1998)

Social

phobia

183 males and

females (100

generalized

subtype)




of 50 mgd Mean dose

366 mgd at endpoint


and improvement in

social functioning

Allgulander

(1999)

Social

phobia

99 males and

females

(percent

with comorbid

AvPD or

generalized type

not reported)




of 50 mgd







dysthymia

Baldwin et al

(1999)

Social

phobia

290 males and

females

(percent with

comorbid AvPD

or generalized

type not reported)




of 50 mgd Mean dose

347 mgd at endpoint


and improvement in



in placebo group

Stein et al

(1999)

Social

phobia

92 males and

females (913

generalized

type)





300 mgd Mean dose

202 mgd at endpoint


and improvement in



in placebo group

Blomhoff

et al (2001)

Social

phobia

387 males and

females (100

generalized

type)




improvement noted


after 8 or 12wk

Parallel design

comparing

sertraline1general

medical care

sertraline1

prolonged

exposure therapy

(PE) placebo1PE

and placebo1

general medical

care 24 wk


sertralinePE groups

superior to placebo



combination group



alone

van

Ameringen

et al (2001)

Social

phobia

204 males and

females (100

generalized

type 61

comorbid AvPD)




to maximum of

200 mg d Mean dose



and improvement in



placebo group

(Continued)


R IPOLL ET AL



Table 4 Continued


Design

duration


group(s)

Liebowitz

et al (2002)

Social

phobia

384 males and

females (100

generalized

type)


20 mgd vs 40 mgd vs

60 mgd All groups

began with 20 mgd






20 mg group Highest


CGI) in 40 mg group

Stein et al

(2002)

Social

phobia

257 males and

females (100

generalized

type)




maximum of 50 mgd


blind 12-wk acute

phase with those

whose CGI


2 entering 24-wk

double-blind

continuation

phase



39 in placebo group

Davidson

et al(2004b )

Social

phobia

279 males and


type)



maximum of 300 mgd

Mean dose 174 mgd



Davidson

et al

(2004a )

Social

phobia

295 (100

generalized

type)




15 and to 40 mgd on





improvement

Parallel design

comparing

fluoxetine group

CBT fluoxetine1

group CBT placebo

placebo1group CBT

14 wk




14 wk Combined


advantage

Lepola et al

(2004)

Social

phobia

372 males and

females(percent

with comorbid

AvPD or

generalized

type not

reported)





323 mgd at endpoint




in placebo group

Rickels et al

(2004)

Social

phobia

272 males and

females (100

generalized

type)






one more week


and improvement in

social functioning

Lader et al

(2004)

Social

phobia

839 males and


type)

Escitalopram

paroxetine



Paroxetine 20 mgd



follow-up




and paroxetine

Escitalopram 20 mgd


20 mgd

Allgulander

et al (2004)

Social

phobia

434 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine





maximum of 225 mgd


paroxetine groups



and improvement in

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






Table 4 Continued


Design

duration


group(s)


endpoint Paroxetine





endpoint

social functioning

Possibly more rapid


Kasper et al

(2005)

Social

phobia

358 males and

females (100

generalized

type)




for unsatisfactory

response Mean dose

176 mgd at endpoint


and improvement in



placebo group

Liebowitz

et al

(2005b )

Social

phobia

271 males and

females (100

generalized

type)







and improvement in



placebo group

Liebowitz

et al

(2005a )

Social

phobia

413 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine


75 mgd-225 mgd with







10 mg increases to

maximum of 50 mgd

Mean dose 46 mgd at

endpoint


and improvement in

social functioning


for both medication


equally efficacious


venlafaxine 625 for

paroxetine and 361

for placebo group

Stein et al(2005)

Socialphobia


generalized

type)



75 mgd and if





increase to 225 mgd

after 2nd week



dosage groups 31


venlafaxine groups

combined vs 16 in

placebo group

Montgomery

et al (2005)

Social

phobia

517 males and

females (100

generalized

type)





responders entered



for remainder

12-wk open-label

phase followed by

24-wk fixed-

dose relapse

prevention

(parallel design

double-blind RCT)




vs 144d for placebo

group No direct

comparison made

between doses



R IPOLL ET AL












OTHER MEDICATIONS














R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





(A VPD)












FUTURE DIRECTIONS







R IPOLL ET AL









R E F E R E N C E S

















387ndash396









































177ndash179


























R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S












141 802ndash803













519ndash522











234ndash236












307 ndash312







309ndash319














No CD003499


























64 628ndash634




241ndash248



9ndash20





























66ndash74



















168 324ndash329


R IPOLL ET AL








25 575ndash579












































117



1026





























140ndash145










try 39 117ndash118















854ndash858













32 590ndash596






519ndash523







233ndash237





201ndash214








765ndash766




R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






485ndash492



1455ndash1458






1409ndash1413




20 413ndash423






















50 377ndash385



1605






43 691ndash697



177ndash181









24ndash39












280ndash288



260ndash271




























51 20ndash27



16 561ndash569




206ndash210




376ndash385










2108ndash2114




903ndash907




416ndash420








170ndash173

R IPOLL ET AL





BPD




















R IPOLL ET AL












(SSRIS)
















R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S























R IPOLL ET AL





Design

duration


group(s)

Versiani et al

(1992)

Social

phobia

78 males and

females (percent

AvPD or

generalized

type not reported)

Moclobemide

phenelzine









Mean dose 675 mgd



follow-up in which

half of each


switched to placebo

others continued on

last dosage)


placebo in reducing

social anxiety and

improving social


group 91 for

phenelzine group

Moclobemide better

tolerated than

phenelzine

Van Vliet

et al (1994)

Social

phobia

30 males and

females (53

generalized

subtype)



phobic avoidance

Fahlen

(1995)

Social

phobia

63 males and

females (34 with

comorbid AvPD

1 with comorbidDPD)




in 3rd week


anxiety More marked

improvements in



comorbid AvPD and 1



Katzelnick

et al (1995)

Social

phobia

12 males and

females (percent

AvPD or

generalized type

not reported)





maximum of 200 mg


endpoint




functioning 50 of



improved vs 9 of

placebo group

IMCTGMSPand

Katschnig

(1997)

Socialphobia


generalized type

49 comorbid

AvPD)


dose)




vs 34 in placebo


between groups with

without AvPD in


AvPD patients

responded less to

placebo

Lott et al

(1997)

Social

phobia

102 males and

females

(percent

AvPD or

generalized type

not reported)



flexible dosing to

maximum of 150 mgd




50 response rate vs

19 in placebo group

Noyes et al

(1997)

Social

phobia

583 males and

females (625

generalized

type

478

comorbid

AvPD)



300 mgd vs 600 mgd




with 150 mgd and


to target dosage



12 wk only at 8 wk



rate As above no

difference between

groups withwithout

AvPD but less drug

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 4 Continued


Design

duration


group(s)



Heimberg

et al (1998)

Social

phobia

133 males and

females (707

generalized

type)








5 wk to 90 mgd

Parallel design but

non-randomized

comparing

medication to group


therapy (CBT) or

supportive

educational

therapy or placebo

12 wk












Schneier

et al (1998)

Social

phobia

77 males and

females (85

generalized

type 38

comorbid AvPD)


flexibly dosed to

a maximum of 400 mg

bid Mean dose 728

mgd at endpoint


subscores of social




Stein et al

(1998)

Social

phobia

183 males and

females (100

generalized

subtype)




of 50 mgd Mean dose

366 mgd at endpoint


and improvement in

social functioning

Allgulander

(1999)

Social

phobia

99 males and

females

(percent

with comorbid

AvPD or

generalized type

not reported)




of 50 mgd







dysthymia

Baldwin et al

(1999)

Social

phobia

290 males and

females

(percent with

comorbid AvPD

or generalized

type not reported)




of 50 mgd Mean dose

347 mgd at endpoint


and improvement in



in placebo group

Stein et al

(1999)

Social

phobia

92 males and

females (913

generalized

type)





300 mgd Mean dose

202 mgd at endpoint


and improvement in



in placebo group

Blomhoff

et al (2001)

Social

phobia

387 males and

females (100

generalized

type)




improvement noted


after 8 or 12wk

Parallel design

comparing

sertraline1general

medical care

sertraline1

prolonged

exposure therapy

(PE) placebo1PE

and placebo1

general medical

care 24 wk


sertralinePE groups

superior to placebo



combination group



alone

van

Ameringen

et al (2001)

Social

phobia

204 males and

females (100

generalized

type 61

comorbid AvPD)




to maximum of

200 mg d Mean dose



and improvement in



placebo group

(Continued)


R IPOLL ET AL



Table 4 Continued


Design

duration


group(s)

Liebowitz

et al (2002)

Social

phobia

384 males and

females (100

generalized

type)


20 mgd vs 40 mgd vs

60 mgd All groups

began with 20 mgd






20 mg group Highest


CGI) in 40 mg group

Stein et al

(2002)

Social

phobia

257 males and

females (100

generalized

type)




maximum of 50 mgd


blind 12-wk acute

phase with those

whose CGI


2 entering 24-wk

double-blind

continuation

phase



39 in placebo group

Davidson

et al(2004b )

Social

phobia

279 males and


type)



maximum of 300 mgd

Mean dose 174 mgd



Davidson

et al

(2004a )

Social

phobia

295 (100

generalized

type)




15 and to 40 mgd on





improvement

Parallel design

comparing

fluoxetine group

CBT fluoxetine1

group CBT placebo

placebo1group CBT

14 wk




14 wk Combined


advantage

Lepola et al

(2004)

Social

phobia

372 males and

females(percent

with comorbid

AvPD or

generalized

type not

reported)





323 mgd at endpoint




in placebo group

Rickels et al

(2004)

Social

phobia

272 males and

females (100

generalized

type)






one more week


and improvement in

social functioning

Lader et al

(2004)

Social

phobia

839 males and


type)

Escitalopram

paroxetine



Paroxetine 20 mgd



follow-up




and paroxetine

Escitalopram 20 mgd


20 mgd

Allgulander

et al (2004)

Social

phobia

434 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine





maximum of 225 mgd


paroxetine groups



and improvement in

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






Table 4 Continued


Design

duration


group(s)


endpoint Paroxetine





endpoint

social functioning

Possibly more rapid


Kasper et al

(2005)

Social

phobia

358 males and

females (100

generalized

type)




for unsatisfactory

response Mean dose

176 mgd at endpoint


and improvement in



placebo group

Liebowitz

et al

(2005b )

Social

phobia

271 males and

females (100

generalized

type)







and improvement in



placebo group

Liebowitz

et al

(2005a )

Social

phobia

413 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine


75 mgd-225 mgd with







10 mg increases to

maximum of 50 mgd

Mean dose 46 mgd at

endpoint


and improvement in

social functioning


for both medication


equally efficacious


venlafaxine 625 for

paroxetine and 361

for placebo group

Stein et al(2005)

Socialphobia


generalized

type)



75 mgd and if





increase to 225 mgd

after 2nd week



dosage groups 31


venlafaxine groups

combined vs 16 in

placebo group

Montgomery

et al (2005)

Social

phobia

517 males and

females (100

generalized

type)





responders entered



for remainder

12-wk open-label

phase followed by

24-wk fixed-

dose relapse

prevention

(parallel design

double-blind RCT)




vs 144d for placebo

group No direct

comparison made

between doses



R IPOLL ET AL












OTHER MEDICATIONS














R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





(A VPD)












FUTURE DIRECTIONS







R IPOLL ET AL









R E F E R E N C E S

















387ndash396









































177ndash179


























R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S












141 802ndash803













519ndash522











234ndash236












307 ndash312







309ndash319














No CD003499


























64 628ndash634




241ndash248



9ndash20





























66ndash74



















168 324ndash329


R IPOLL ET AL








25 575ndash579












































117



1026





























140ndash145










try 39 117ndash118















854ndash858













32 590ndash596






519ndash523







233ndash237





201ndash214








765ndash766




R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






485ndash492



1455ndash1458






1409ndash1413




20 413ndash423






















50 377ndash385



1605






43 691ndash697



177ndash181









24ndash39












280ndash288



260ndash271




























51 20ndash27



16 561ndash569




206ndash210




376ndash385










2108ndash2114




903ndash907




416ndash420








170ndash173

R IPOLL ET AL












(SSRIS)
















R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S























R IPOLL ET AL





Design

duration


group(s)

Versiani et al

(1992)

Social

phobia

78 males and

females (percent

AvPD or

generalized

type not reported)

Moclobemide

phenelzine









Mean dose 675 mgd



follow-up in which

half of each


switched to placebo

others continued on

last dosage)


placebo in reducing

social anxiety and

improving social


group 91 for

phenelzine group

Moclobemide better

tolerated than

phenelzine

Van Vliet

et al (1994)

Social

phobia

30 males and

females (53

generalized

subtype)



phobic avoidance

Fahlen

(1995)

Social

phobia

63 males and

females (34 with

comorbid AvPD

1 with comorbidDPD)




in 3rd week


anxiety More marked

improvements in



comorbid AvPD and 1



Katzelnick

et al (1995)

Social

phobia

12 males and

females (percent

AvPD or

generalized type

not reported)





maximum of 200 mg


endpoint




functioning 50 of



improved vs 9 of

placebo group

IMCTGMSPand

Katschnig

(1997)

Socialphobia


generalized type

49 comorbid

AvPD)


dose)




vs 34 in placebo


between groups with

without AvPD in


AvPD patients

responded less to

placebo

Lott et al

(1997)

Social

phobia

102 males and

females

(percent

AvPD or

generalized type

not reported)



flexible dosing to

maximum of 150 mgd




50 response rate vs

19 in placebo group

Noyes et al

(1997)

Social

phobia

583 males and

females (625

generalized

type

478

comorbid

AvPD)



300 mgd vs 600 mgd




with 150 mgd and


to target dosage



12 wk only at 8 wk



rate As above no

difference between

groups withwithout

AvPD but less drug

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 4 Continued


Design

duration


group(s)



Heimberg

et al (1998)

Social

phobia

133 males and

females (707

generalized

type)








5 wk to 90 mgd

Parallel design but

non-randomized

comparing

medication to group


therapy (CBT) or

supportive

educational

therapy or placebo

12 wk












Schneier

et al (1998)

Social

phobia

77 males and

females (85

generalized

type 38

comorbid AvPD)


flexibly dosed to

a maximum of 400 mg

bid Mean dose 728

mgd at endpoint


subscores of social




Stein et al

(1998)

Social

phobia

183 males and

females (100

generalized

subtype)




of 50 mgd Mean dose

366 mgd at endpoint


and improvement in

social functioning

Allgulander

(1999)

Social

phobia

99 males and

females

(percent

with comorbid

AvPD or

generalized type

not reported)




of 50 mgd







dysthymia

Baldwin et al

(1999)

Social

phobia

290 males and

females

(percent with

comorbid AvPD

or generalized

type not reported)




of 50 mgd Mean dose

347 mgd at endpoint


and improvement in



in placebo group

Stein et al

(1999)

Social

phobia

92 males and

females (913

generalized

type)





300 mgd Mean dose

202 mgd at endpoint


and improvement in



in placebo group

Blomhoff

et al (2001)

Social

phobia

387 males and

females (100

generalized

type)




improvement noted


after 8 or 12wk

Parallel design

comparing

sertraline1general

medical care

sertraline1

prolonged

exposure therapy

(PE) placebo1PE

and placebo1

general medical

care 24 wk


sertralinePE groups

superior to placebo



combination group



alone

van

Ameringen

et al (2001)

Social

phobia

204 males and

females (100

generalized

type 61

comorbid AvPD)




to maximum of

200 mg d Mean dose



and improvement in



placebo group

(Continued)


R IPOLL ET AL



Table 4 Continued


Design

duration


group(s)

Liebowitz

et al (2002)

Social

phobia

384 males and

females (100

generalized

type)


20 mgd vs 40 mgd vs

60 mgd All groups

began with 20 mgd






20 mg group Highest


CGI) in 40 mg group

Stein et al

(2002)

Social

phobia

257 males and

females (100

generalized

type)




maximum of 50 mgd


blind 12-wk acute

phase with those

whose CGI


2 entering 24-wk

double-blind

continuation

phase



39 in placebo group

Davidson

et al(2004b )

Social

phobia

279 males and


type)



maximum of 300 mgd

Mean dose 174 mgd



Davidson

et al

(2004a )

Social

phobia

295 (100

generalized

type)




15 and to 40 mgd on





improvement

Parallel design

comparing

fluoxetine group

CBT fluoxetine1

group CBT placebo

placebo1group CBT

14 wk




14 wk Combined


advantage

Lepola et al

(2004)

Social

phobia

372 males and

females(percent

with comorbid

AvPD or

generalized

type not

reported)





323 mgd at endpoint




in placebo group

Rickels et al

(2004)

Social

phobia

272 males and

females (100

generalized

type)






one more week


and improvement in

social functioning

Lader et al

(2004)

Social

phobia

839 males and


type)

Escitalopram

paroxetine



Paroxetine 20 mgd



follow-up




and paroxetine

Escitalopram 20 mgd


20 mgd

Allgulander

et al (2004)

Social

phobia

434 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine





maximum of 225 mgd


paroxetine groups



and improvement in

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






Table 4 Continued


Design

duration


group(s)


endpoint Paroxetine





endpoint

social functioning

Possibly more rapid


Kasper et al

(2005)

Social

phobia

358 males and

females (100

generalized

type)




for unsatisfactory

response Mean dose

176 mgd at endpoint


and improvement in



placebo group

Liebowitz

et al

(2005b )

Social

phobia

271 males and

females (100

generalized

type)







and improvement in



placebo group

Liebowitz

et al

(2005a )

Social

phobia

413 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine


75 mgd-225 mgd with







10 mg increases to

maximum of 50 mgd

Mean dose 46 mgd at

endpoint


and improvement in

social functioning


for both medication


equally efficacious


venlafaxine 625 for

paroxetine and 361

for placebo group

Stein et al(2005)

Socialphobia


generalized

type)



75 mgd and if





increase to 225 mgd

after 2nd week



dosage groups 31


venlafaxine groups

combined vs 16 in

placebo group

Montgomery

et al (2005)

Social

phobia

517 males and

females (100

generalized

type)





responders entered



for remainder

12-wk open-label

phase followed by

24-wk fixed-

dose relapse

prevention

(parallel design

double-blind RCT)




vs 144d for placebo

group No direct

comparison made

between doses



R IPOLL ET AL












OTHER MEDICATIONS














R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





(A VPD)












FUTURE DIRECTIONS







R IPOLL ET AL









R E F E R E N C E S

















387ndash396









































177ndash179


























R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S












141 802ndash803













519ndash522











234ndash236












307 ndash312







309ndash319














No CD003499


























64 628ndash634




241ndash248



9ndash20





























66ndash74



















168 324ndash329


R IPOLL ET AL








25 575ndash579












































117



1026





























140ndash145










try 39 117ndash118















854ndash858













32 590ndash596






519ndash523







233ndash237





201ndash214








765ndash766




R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






485ndash492



1455ndash1458






1409ndash1413




20 413ndash423






















50 377ndash385



1605






43 691ndash697



177ndash181









24ndash39












280ndash288



260ndash271




























51 20ndash27



16 561ndash569




206ndash210




376ndash385










2108ndash2114




903ndash907




416ndash420








170ndash173

R IPOLL ET AL























R IPOLL ET AL





Design

duration


group(s)

Versiani et al

(1992)

Social

phobia

78 males and

females (percent

AvPD or

generalized

type not reported)

Moclobemide

phenelzine









Mean dose 675 mgd



follow-up in which

half of each


switched to placebo

others continued on

last dosage)


placebo in reducing

social anxiety and

improving social


group 91 for

phenelzine group

Moclobemide better

tolerated than

phenelzine

Van Vliet

et al (1994)

Social

phobia

30 males and

females (53

generalized

subtype)



phobic avoidance

Fahlen

(1995)

Social

phobia

63 males and

females (34 with

comorbid AvPD

1 with comorbidDPD)




in 3rd week


anxiety More marked

improvements in



comorbid AvPD and 1



Katzelnick

et al (1995)

Social

phobia

12 males and

females (percent

AvPD or

generalized type

not reported)





maximum of 200 mg


endpoint




functioning 50 of



improved vs 9 of

placebo group

IMCTGMSPand

Katschnig

(1997)

Socialphobia


generalized type

49 comorbid

AvPD)


dose)




vs 34 in placebo


between groups with

without AvPD in


AvPD patients

responded less to

placebo

Lott et al

(1997)

Social

phobia

102 males and

females

(percent

AvPD or

generalized type

not reported)



flexible dosing to

maximum of 150 mgd




50 response rate vs

19 in placebo group

Noyes et al

(1997)

Social

phobia

583 males and

females (625

generalized

type

478

comorbid

AvPD)



300 mgd vs 600 mgd




with 150 mgd and


to target dosage



12 wk only at 8 wk



rate As above no

difference between

groups withwithout

AvPD but less drug

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 4 Continued


Design

duration


group(s)



Heimberg

et al (1998)

Social

phobia

133 males and

females (707

generalized

type)








5 wk to 90 mgd

Parallel design but

non-randomized

comparing

medication to group


therapy (CBT) or

supportive

educational

therapy or placebo

12 wk












Schneier

et al (1998)

Social

phobia

77 males and

females (85

generalized

type 38

comorbid AvPD)


flexibly dosed to

a maximum of 400 mg

bid Mean dose 728

mgd at endpoint


subscores of social




Stein et al

(1998)

Social

phobia

183 males and

females (100

generalized

subtype)




of 50 mgd Mean dose

366 mgd at endpoint


and improvement in

social functioning

Allgulander

(1999)

Social

phobia

99 males and

females

(percent

with comorbid

AvPD or

generalized type

not reported)




of 50 mgd







dysthymia

Baldwin et al

(1999)

Social

phobia

290 males and

females

(percent with

comorbid AvPD

or generalized

type not reported)




of 50 mgd Mean dose

347 mgd at endpoint


and improvement in



in placebo group

Stein et al

(1999)

Social

phobia

92 males and

females (913

generalized

type)





300 mgd Mean dose

202 mgd at endpoint


and improvement in



in placebo group

Blomhoff

et al (2001)

Social

phobia

387 males and

females (100

generalized

type)




improvement noted


after 8 or 12wk

Parallel design

comparing

sertraline1general

medical care

sertraline1

prolonged

exposure therapy

(PE) placebo1PE

and placebo1

general medical

care 24 wk


sertralinePE groups

superior to placebo



combination group



alone

van

Ameringen

et al (2001)

Social

phobia

204 males and

females (100

generalized

type 61

comorbid AvPD)




to maximum of

200 mg d Mean dose



and improvement in



placebo group

(Continued)


R IPOLL ET AL



Table 4 Continued


Design

duration


group(s)

Liebowitz

et al (2002)

Social

phobia

384 males and

females (100

generalized

type)


20 mgd vs 40 mgd vs

60 mgd All groups

began with 20 mgd






20 mg group Highest


CGI) in 40 mg group

Stein et al

(2002)

Social

phobia

257 males and

females (100

generalized

type)




maximum of 50 mgd


blind 12-wk acute

phase with those

whose CGI


2 entering 24-wk

double-blind

continuation

phase



39 in placebo group

Davidson

et al(2004b )

Social

phobia

279 males and


type)



maximum of 300 mgd

Mean dose 174 mgd



Davidson

et al

(2004a )

Social

phobia

295 (100

generalized

type)




15 and to 40 mgd on





improvement

Parallel design

comparing

fluoxetine group

CBT fluoxetine1

group CBT placebo

placebo1group CBT

14 wk




14 wk Combined


advantage

Lepola et al

(2004)

Social

phobia

372 males and

females(percent

with comorbid

AvPD or

generalized

type not

reported)





323 mgd at endpoint




in placebo group

Rickels et al

(2004)

Social

phobia

272 males and

females (100

generalized

type)






one more week


and improvement in

social functioning

Lader et al

(2004)

Social

phobia

839 males and


type)

Escitalopram

paroxetine



Paroxetine 20 mgd



follow-up




and paroxetine

Escitalopram 20 mgd


20 mgd

Allgulander

et al (2004)

Social

phobia

434 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine





maximum of 225 mgd


paroxetine groups



and improvement in

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






Table 4 Continued


Design

duration


group(s)


endpoint Paroxetine





endpoint

social functioning

Possibly more rapid


Kasper et al

(2005)

Social

phobia

358 males and

females (100

generalized

type)




for unsatisfactory

response Mean dose

176 mgd at endpoint


and improvement in



placebo group

Liebowitz

et al

(2005b )

Social

phobia

271 males and

females (100

generalized

type)







and improvement in



placebo group

Liebowitz

et al

(2005a )

Social

phobia

413 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine


75 mgd-225 mgd with







10 mg increases to

maximum of 50 mgd

Mean dose 46 mgd at

endpoint


and improvement in

social functioning


for both medication


equally efficacious


venlafaxine 625 for

paroxetine and 361

for placebo group

Stein et al(2005)

Socialphobia


generalized

type)



75 mgd and if





increase to 225 mgd

after 2nd week



dosage groups 31


venlafaxine groups

combined vs 16 in

placebo group

Montgomery

et al (2005)

Social

phobia

517 males and

females (100

generalized

type)





responders entered



for remainder

12-wk open-label

phase followed by

24-wk fixed-

dose relapse

prevention

(parallel design

double-blind RCT)




vs 144d for placebo

group No direct

comparison made

between doses



R IPOLL ET AL












OTHER MEDICATIONS














R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





(A VPD)












FUTURE DIRECTIONS







R IPOLL ET AL









R E F E R E N C E S

















387ndash396









































177ndash179


























R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S












141 802ndash803













519ndash522











234ndash236












307 ndash312







309ndash319














No CD003499


























64 628ndash634




241ndash248



9ndash20





























66ndash74



















168 324ndash329


R IPOLL ET AL








25 575ndash579












































117



1026





























140ndash145










try 39 117ndash118















854ndash858













32 590ndash596






519ndash523







233ndash237





201ndash214








765ndash766




R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






485ndash492



1455ndash1458






1409ndash1413




20 413ndash423






















50 377ndash385



1605






43 691ndash697



177ndash181









24ndash39












280ndash288



260ndash271




























51 20ndash27



16 561ndash569




206ndash210




376ndash385










2108ndash2114




903ndash907




416ndash420








170ndash173

R IPOLL ET AL





Design

duration


group(s)

Versiani et al

(1992)

Social

phobia

78 males and

females (percent

AvPD or

generalized

type not reported)

Moclobemide

phenelzine









Mean dose 675 mgd



follow-up in which

half of each


switched to placebo

others continued on

last dosage)


placebo in reducing

social anxiety and

improving social


group 91 for

phenelzine group

Moclobemide better

tolerated than

phenelzine

Van Vliet

et al (1994)

Social

phobia

30 males and

females (53

generalized

subtype)



phobic avoidance

Fahlen

(1995)

Social

phobia

63 males and

females (34 with

comorbid AvPD

1 with comorbidDPD)




in 3rd week


anxiety More marked

improvements in



comorbid AvPD and 1



Katzelnick

et al (1995)

Social

phobia

12 males and

females (percent

AvPD or

generalized type

not reported)





maximum of 200 mg


endpoint




functioning 50 of



improved vs 9 of

placebo group

IMCTGMSPand

Katschnig

(1997)

Socialphobia


generalized type

49 comorbid

AvPD)


dose)




vs 34 in placebo


between groups with

without AvPD in


AvPD patients

responded less to

placebo

Lott et al

(1997)

Social

phobia

102 males and

females

(percent

AvPD or

generalized type

not reported)



flexible dosing to

maximum of 150 mgd




50 response rate vs

19 in placebo group

Noyes et al

(1997)

Social

phobia

583 males and

females (625

generalized

type

478

comorbid

AvPD)



300 mgd vs 600 mgd




with 150 mgd and


to target dosage



12 wk only at 8 wk



rate As above no

difference between

groups withwithout

AvPD but less drug

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S



Table 4 Continued


Design

duration


group(s)



Heimberg

et al (1998)

Social

phobia

133 males and

females (707

generalized

type)








5 wk to 90 mgd

Parallel design but

non-randomized

comparing

medication to group


therapy (CBT) or

supportive

educational

therapy or placebo

12 wk












Schneier

et al (1998)

Social

phobia

77 males and

females (85

generalized

type 38

comorbid AvPD)


flexibly dosed to

a maximum of 400 mg

bid Mean dose 728

mgd at endpoint


subscores of social




Stein et al

(1998)

Social

phobia

183 males and

females (100

generalized

subtype)




of 50 mgd Mean dose

366 mgd at endpoint


and improvement in

social functioning

Allgulander

(1999)

Social

phobia

99 males and

females

(percent

with comorbid

AvPD or

generalized type

not reported)




of 50 mgd







dysthymia

Baldwin et al

(1999)

Social

phobia

290 males and

females

(percent with

comorbid AvPD

or generalized

type not reported)




of 50 mgd Mean dose

347 mgd at endpoint


and improvement in



in placebo group

Stein et al

(1999)

Social

phobia

92 males and

females (913

generalized

type)





300 mgd Mean dose

202 mgd at endpoint


and improvement in



in placebo group

Blomhoff

et al (2001)

Social

phobia

387 males and

females (100

generalized

type)




improvement noted


after 8 or 12wk

Parallel design

comparing

sertraline1general

medical care

sertraline1

prolonged

exposure therapy

(PE) placebo1PE

and placebo1

general medical

care 24 wk


sertralinePE groups

superior to placebo



combination group



alone

van

Ameringen

et al (2001)

Social

phobia

204 males and

females (100

generalized

type 61

comorbid AvPD)




to maximum of

200 mg d Mean dose



and improvement in



placebo group

(Continued)


R IPOLL ET AL



Table 4 Continued


Design

duration


group(s)

Liebowitz

et al (2002)

Social

phobia

384 males and

females (100

generalized

type)


20 mgd vs 40 mgd vs

60 mgd All groups

began with 20 mgd






20 mg group Highest


CGI) in 40 mg group

Stein et al

(2002)

Social

phobia

257 males and

females (100

generalized

type)




maximum of 50 mgd


blind 12-wk acute

phase with those

whose CGI


2 entering 24-wk

double-blind

continuation

phase



39 in placebo group

Davidson

et al(2004b )

Social

phobia

279 males and


type)



maximum of 300 mgd

Mean dose 174 mgd



Davidson

et al

(2004a )

Social

phobia

295 (100

generalized

type)




15 and to 40 mgd on





improvement

Parallel design

comparing

fluoxetine group

CBT fluoxetine1

group CBT placebo

placebo1group CBT

14 wk




14 wk Combined


advantage

Lepola et al

(2004)

Social

phobia

372 males and

females(percent

with comorbid

AvPD or

generalized

type not

reported)





323 mgd at endpoint




in placebo group

Rickels et al

(2004)

Social

phobia

272 males and

females (100

generalized

type)






one more week


and improvement in

social functioning

Lader et al

(2004)

Social

phobia

839 males and


type)

Escitalopram

paroxetine



Paroxetine 20 mgd



follow-up




and paroxetine

Escitalopram 20 mgd


20 mgd

Allgulander

et al (2004)

Social

phobia

434 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine





maximum of 225 mgd


paroxetine groups



and improvement in

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






Table 4 Continued


Design

duration


group(s)


endpoint Paroxetine





endpoint

social functioning

Possibly more rapid


Kasper et al

(2005)

Social

phobia

358 males and

females (100

generalized

type)




for unsatisfactory

response Mean dose

176 mgd at endpoint


and improvement in



placebo group

Liebowitz

et al

(2005b )

Social

phobia

271 males and

females (100

generalized

type)







and improvement in



placebo group

Liebowitz

et al

(2005a )

Social

phobia

413 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine


75 mgd-225 mgd with







10 mg increases to

maximum of 50 mgd

Mean dose 46 mgd at

endpoint


and improvement in

social functioning


for both medication


equally efficacious


venlafaxine 625 for

paroxetine and 361

for placebo group

Stein et al(2005)

Socialphobia


generalized

type)



75 mgd and if





increase to 225 mgd

after 2nd week



dosage groups 31


venlafaxine groups

combined vs 16 in

placebo group

Montgomery

et al (2005)

Social

phobia

517 males and

females (100

generalized

type)





responders entered



for remainder

12-wk open-label

phase followed by

24-wk fixed-

dose relapse

prevention

(parallel design

double-blind RCT)




vs 144d for placebo

group No direct

comparison made

between doses



R IPOLL ET AL












OTHER MEDICATIONS














R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





(A VPD)












FUTURE DIRECTIONS







R IPOLL ET AL









R E F E R E N C E S

















387ndash396









































177ndash179


























R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S












141 802ndash803













519ndash522











234ndash236












307 ndash312







309ndash319














No CD003499


























64 628ndash634




241ndash248



9ndash20





























66ndash74



















168 324ndash329


R IPOLL ET AL








25 575ndash579












































117



1026





























140ndash145










try 39 117ndash118















854ndash858













32 590ndash596






519ndash523







233ndash237





201ndash214








765ndash766




R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






485ndash492



1455ndash1458






1409ndash1413




20 413ndash423






















50 377ndash385



1605






43 691ndash697



177ndash181









24ndash39












280ndash288



260ndash271




























51 20ndash27



16 561ndash569




206ndash210




376ndash385










2108ndash2114




903ndash907




416ndash420








170ndash173

R IPOLL ET AL



Table 4 Continued


Design

duration


group(s)



Heimberg

et al (1998)

Social

phobia

133 males and

females (707

generalized

type)








5 wk to 90 mgd

Parallel design but

non-randomized

comparing

medication to group


therapy (CBT) or

supportive

educational

therapy or placebo

12 wk












Schneier

et al (1998)

Social

phobia

77 males and

females (85

generalized

type 38

comorbid AvPD)


flexibly dosed to

a maximum of 400 mg

bid Mean dose 728

mgd at endpoint


subscores of social




Stein et al

(1998)

Social

phobia

183 males and

females (100

generalized

subtype)




of 50 mgd Mean dose

366 mgd at endpoint


and improvement in

social functioning

Allgulander

(1999)

Social

phobia

99 males and

females

(percent

with comorbid

AvPD or

generalized type

not reported)




of 50 mgd







dysthymia

Baldwin et al

(1999)

Social

phobia

290 males and

females

(percent with

comorbid AvPD

or generalized

type not reported)




of 50 mgd Mean dose

347 mgd at endpoint


and improvement in



in placebo group

Stein et al

(1999)

Social

phobia

92 males and

females (913

generalized

type)





300 mgd Mean dose

202 mgd at endpoint


and improvement in



in placebo group

Blomhoff

et al (2001)

Social

phobia

387 males and

females (100

generalized

type)




improvement noted


after 8 or 12wk

Parallel design

comparing

sertraline1general

medical care

sertraline1

prolonged

exposure therapy

(PE) placebo1PE

and placebo1

general medical

care 24 wk


sertralinePE groups

superior to placebo



combination group



alone

van

Ameringen

et al (2001)

Social

phobia

204 males and

females (100

generalized

type 61

comorbid AvPD)




to maximum of

200 mg d Mean dose



and improvement in



placebo group

(Continued)


R IPOLL ET AL



Table 4 Continued


Design

duration


group(s)

Liebowitz

et al (2002)

Social

phobia

384 males and

females (100

generalized

type)


20 mgd vs 40 mgd vs

60 mgd All groups

began with 20 mgd






20 mg group Highest


CGI) in 40 mg group

Stein et al

(2002)

Social

phobia

257 males and

females (100

generalized

type)




maximum of 50 mgd


blind 12-wk acute

phase with those

whose CGI


2 entering 24-wk

double-blind

continuation

phase



39 in placebo group

Davidson

et al(2004b )

Social

phobia

279 males and


type)



maximum of 300 mgd

Mean dose 174 mgd



Davidson

et al

(2004a )

Social

phobia

295 (100

generalized

type)




15 and to 40 mgd on





improvement

Parallel design

comparing

fluoxetine group

CBT fluoxetine1

group CBT placebo

placebo1group CBT

14 wk




14 wk Combined


advantage

Lepola et al

(2004)

Social

phobia

372 males and

females(percent

with comorbid

AvPD or

generalized

type not

reported)





323 mgd at endpoint




in placebo group

Rickels et al

(2004)

Social

phobia

272 males and

females (100

generalized

type)






one more week


and improvement in

social functioning

Lader et al

(2004)

Social

phobia

839 males and


type)

Escitalopram

paroxetine



Paroxetine 20 mgd



follow-up




and paroxetine

Escitalopram 20 mgd


20 mgd

Allgulander

et al (2004)

Social

phobia

434 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine





maximum of 225 mgd


paroxetine groups



and improvement in

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






Table 4 Continued


Design

duration


group(s)


endpoint Paroxetine





endpoint

social functioning

Possibly more rapid


Kasper et al

(2005)

Social

phobia

358 males and

females (100

generalized

type)




for unsatisfactory

response Mean dose

176 mgd at endpoint


and improvement in



placebo group

Liebowitz

et al

(2005b )

Social

phobia

271 males and

females (100

generalized

type)







and improvement in



placebo group

Liebowitz

et al

(2005a )

Social

phobia

413 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine


75 mgd-225 mgd with







10 mg increases to

maximum of 50 mgd

Mean dose 46 mgd at

endpoint


and improvement in

social functioning


for both medication


equally efficacious


venlafaxine 625 for

paroxetine and 361

for placebo group

Stein et al(2005)

Socialphobia


generalized

type)



75 mgd and if





increase to 225 mgd

after 2nd week



dosage groups 31


venlafaxine groups

combined vs 16 in

placebo group

Montgomery

et al (2005)

Social

phobia

517 males and

females (100

generalized

type)





responders entered



for remainder

12-wk open-label

phase followed by

24-wk fixed-

dose relapse

prevention

(parallel design

double-blind RCT)




vs 144d for placebo

group No direct

comparison made

between doses



R IPOLL ET AL












OTHER MEDICATIONS














R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





(A VPD)












FUTURE DIRECTIONS







R IPOLL ET AL









R E F E R E N C E S

















387ndash396









































177ndash179


























R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S












141 802ndash803













519ndash522











234ndash236












307 ndash312







309ndash319














No CD003499


























64 628ndash634




241ndash248



9ndash20





























66ndash74



















168 324ndash329


R IPOLL ET AL








25 575ndash579












































117



1026





























140ndash145










try 39 117ndash118















854ndash858













32 590ndash596






519ndash523







233ndash237





201ndash214








765ndash766




R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






485ndash492



1455ndash1458






1409ndash1413




20 413ndash423






















50 377ndash385



1605






43 691ndash697



177ndash181









24ndash39












280ndash288



260ndash271




























51 20ndash27



16 561ndash569




206ndash210




376ndash385










2108ndash2114




903ndash907




416ndash420








170ndash173

R IPOLL ET AL



Table 4 Continued


Design

duration


group(s)

Liebowitz

et al (2002)

Social

phobia

384 males and

females (100

generalized

type)


20 mgd vs 40 mgd vs

60 mgd All groups

began with 20 mgd






20 mg group Highest


CGI) in 40 mg group

Stein et al

(2002)

Social

phobia

257 males and

females (100

generalized

type)




maximum of 50 mgd


blind 12-wk acute

phase with those

whose CGI


2 entering 24-wk

double-blind

continuation

phase



39 in placebo group

Davidson

et al(2004b )

Social

phobia

279 males and


type)



maximum of 300 mgd

Mean dose 174 mgd



Davidson

et al

(2004a )

Social

phobia

295 (100

generalized

type)




15 and to 40 mgd on





improvement

Parallel design

comparing

fluoxetine group

CBT fluoxetine1

group CBT placebo

placebo1group CBT

14 wk




14 wk Combined


advantage

Lepola et al

(2004)

Social

phobia

372 males and

females(percent

with comorbid

AvPD or

generalized

type not

reported)





323 mgd at endpoint




in placebo group

Rickels et al

(2004)

Social

phobia

272 males and

females (100

generalized

type)






one more week


and improvement in

social functioning

Lader et al

(2004)

Social

phobia

839 males and


type)

Escitalopram

paroxetine



Paroxetine 20 mgd



follow-up




and paroxetine

Escitalopram 20 mgd


20 mgd

Allgulander

et al (2004)

Social

phobia

434 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine





maximum of 225 mgd


paroxetine groups



and improvement in

(Continued)


R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






Table 4 Continued


Design

duration


group(s)


endpoint Paroxetine





endpoint

social functioning

Possibly more rapid


Kasper et al

(2005)

Social

phobia

358 males and

females (100

generalized

type)




for unsatisfactory

response Mean dose

176 mgd at endpoint


and improvement in



placebo group

Liebowitz

et al

(2005b )

Social

phobia

271 males and

females (100

generalized

type)







and improvement in



placebo group

Liebowitz

et al

(2005a )

Social

phobia

413 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine


75 mgd-225 mgd with







10 mg increases to

maximum of 50 mgd

Mean dose 46 mgd at

endpoint


and improvement in

social functioning


for both medication


equally efficacious


venlafaxine 625 for

paroxetine and 361

for placebo group

Stein et al(2005)

Socialphobia


generalized

type)



75 mgd and if





increase to 225 mgd

after 2nd week



dosage groups 31


venlafaxine groups

combined vs 16 in

placebo group

Montgomery

et al (2005)

Social

phobia

517 males and

females (100

generalized

type)





responders entered



for remainder

12-wk open-label

phase followed by

24-wk fixed-

dose relapse

prevention

(parallel design

double-blind RCT)




vs 144d for placebo

group No direct

comparison made

between doses



R IPOLL ET AL












OTHER MEDICATIONS














R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





(A VPD)












FUTURE DIRECTIONS







R IPOLL ET AL









R E F E R E N C E S

















387ndash396









































177ndash179


























R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S












141 802ndash803













519ndash522











234ndash236












307 ndash312







309ndash319














No CD003499


























64 628ndash634




241ndash248



9ndash20





























66ndash74



















168 324ndash329


R IPOLL ET AL








25 575ndash579












































117



1026





























140ndash145










try 39 117ndash118















854ndash858













32 590ndash596






519ndash523







233ndash237





201ndash214








765ndash766




R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






485ndash492



1455ndash1458






1409ndash1413




20 413ndash423






















50 377ndash385



1605






43 691ndash697



177ndash181









24ndash39












280ndash288



260ndash271




























51 20ndash27



16 561ndash569




206ndash210




376ndash385










2108ndash2114




903ndash907




416ndash420








170ndash173

R IPOLL ET AL






Table 4 Continued


Design

duration


group(s)


endpoint Paroxetine





endpoint

social functioning

Possibly more rapid


Kasper et al

(2005)

Social

phobia

358 males and

females (100

generalized

type)




for unsatisfactory

response Mean dose

176 mgd at endpoint


and improvement in



placebo group

Liebowitz

et al

(2005b )

Social

phobia

271 males and

females (100

generalized

type)







and improvement in



placebo group

Liebowitz

et al

(2005a )

Social

phobia

413 males and

females (100

generalized

type)

Venlafaxine

ER

paroxetine


75 mgd-225 mgd with







10 mg increases to

maximum of 50 mgd

Mean dose 46 mgd at

endpoint


and improvement in

social functioning


for both medication


equally efficacious


venlafaxine 625 for

paroxetine and 361

for placebo group

Stein et al(2005)

Socialphobia


generalized

type)



75 mgd and if





increase to 225 mgd

after 2nd week



dosage groups 31


venlafaxine groups

combined vs 16 in

placebo group

Montgomery

et al (2005)

Social

phobia

517 males and

females (100

generalized

type)





responders entered



for remainder

12-wk open-label

phase followed by

24-wk fixed-

dose relapse

prevention

(parallel design

double-blind RCT)




vs 144d for placebo

group No direct

comparison made

between doses



R IPOLL ET AL












OTHER MEDICATIONS














R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





(A VPD)












FUTURE DIRECTIONS







R IPOLL ET AL









R E F E R E N C E S

















387ndash396









































177ndash179


























R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S












141 802ndash803













519ndash522











234ndash236












307 ndash312







309ndash319














No CD003499


























64 628ndash634




241ndash248



9ndash20





























66ndash74



















168 324ndash329


R IPOLL ET AL








25 575ndash579












































117



1026





























140ndash145










try 39 117ndash118















854ndash858













32 590ndash596






519ndash523







233ndash237





201ndash214








765ndash766




R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






485ndash492



1455ndash1458






1409ndash1413




20 413ndash423






















50 377ndash385



1605






43 691ndash697



177ndash181









24ndash39












280ndash288



260ndash271




























51 20ndash27



16 561ndash569




206ndash210




376ndash385










2108ndash2114




903ndash907




416ndash420








170ndash173

R IPOLL ET AL












OTHER MEDICATIONS














R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S





(A VPD)












FUTURE DIRECTIONS







R IPOLL ET AL









R E F E R E N C E S

















387ndash396









































177ndash179


























R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S












141 802ndash803













519ndash522











234ndash236












307 ndash312







309ndash319














No CD003499


























64 628ndash634




241ndash248



9ndash20





























66ndash74



















168 324ndash329


R IPOLL ET AL








25 575ndash579












































117



1026





























140ndash145










try 39 117ndash118















854ndash858













32 590ndash596






519ndash523







233ndash237





201ndash214








765ndash766




R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






485ndash492



1455ndash1458






1409ndash1413




20 413ndash423






















50 377ndash385



1605






43 691ndash697



177ndash181









24ndash39












280ndash288



260ndash271




























51 20ndash27



16 561ndash569




206ndash210




376ndash385










2108ndash2114




903ndash907




416ndash420








170ndash173

R IPOLL ET AL





(A VPD)












FUTURE DIRECTIONS







R IPOLL ET AL









R E F E R E N C E S

















387ndash396









































177ndash179


























R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S












141 802ndash803













519ndash522











234ndash236












307 ndash312







309ndash319














No CD003499


























64 628ndash634




241ndash248



9ndash20





























66ndash74



















168 324ndash329


R IPOLL ET AL








25 575ndash579












































117



1026





























140ndash145










try 39 117ndash118















854ndash858













32 590ndash596






519ndash523







233ndash237





201ndash214








765ndash766




R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






485ndash492



1455ndash1458






1409ndash1413




20 413ndash423






















50 377ndash385



1605






43 691ndash697



177ndash181









24ndash39












280ndash288



260ndash271




























51 20ndash27



16 561ndash569




206ndash210




376ndash385










2108ndash2114




903ndash907




416ndash420








170ndash173

R IPOLL ET AL









R E F E R E N C E S

















387ndash396









































177ndash179


























R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S












141 802ndash803













519ndash522











234ndash236












307 ndash312







309ndash319














No CD003499


























64 628ndash634




241ndash248



9ndash20





























66ndash74



















168 324ndash329


R IPOLL ET AL








25 575ndash579












































117



1026





























140ndash145










try 39 117ndash118















854ndash858













32 590ndash596






519ndash523







233ndash237





201ndash214








765ndash766




R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






485ndash492



1455ndash1458






1409ndash1413




20 413ndash423






















50 377ndash385



1605






43 691ndash697



177ndash181









24ndash39












280ndash288



260ndash271




























51 20ndash27



16 561ndash569




206ndash210




376ndash385










2108ndash2114




903ndash907




416ndash420








170ndash173

R IPOLL ET AL












141 802ndash803













519ndash522











234ndash236












307 ndash312







309ndash319














No CD003499


























64 628ndash634




241ndash248



9ndash20





























66ndash74



















168 324ndash329


R IPOLL ET AL








25 575ndash579












































117



1026





























140ndash145










try 39 117ndash118















854ndash858













32 590ndash596






519ndash523







233ndash237





201ndash214








765ndash766




R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






485ndash492



1455ndash1458






1409ndash1413




20 413ndash423






















50 377ndash385



1605






43 691ndash697



177ndash181









24ndash39












280ndash288



260ndash271




























51 20ndash27



16 561ndash569




206ndash210




376ndash385










2108ndash2114




903ndash907




416ndash420








170ndash173

R IPOLL ET AL








25 575ndash579












































117



1026





























140ndash145










try 39 117ndash118















854ndash858













32 590ndash596






519ndash523







233ndash237





201ndash214








765ndash766




R IPOLL ET AL

I N

F L

U E N

T

I A L

P U

B L

I C A T

I O

N

S






485ndash492



1455ndash1458






1409ndash1413




20 413ndash423






















50 377ndash385



1605






43 691ndash697



177ndash181









24ndash39












280ndash288



260ndash271




























51 20ndash27



16 561ndash569




206ndash210




376ndash385










2108ndash2114




903ndash907




416ndash420








170ndash173

R IPOLL ET AL






485ndash492



1455ndash1458






1409ndash1413




20 413ndash423






















50 377ndash385



1605






43 691ndash697



177ndash181









24ndash39












280ndash288



260ndash271




























51 20ndash27



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