POST-TRAUMATIC STRESS DISORDER
Comorbidity and Treatment
Thomas A. Mellman, M.D.Thomas A. Mellman, M.D.
Howard University, Washington DC Howard University, Washington DC
Major Teaching Points
• PTSD develops in a substantial minority of individuals PTSD develops in a substantial minority of individuals exposed to severe traumaexposed to severe trauma
• PTSD is highly comorbid with other psychiatric PTSD is highly comorbid with other psychiatric disordersdisorders
• SSRI medications have FDA approval for PTSD and SSRI medications have FDA approval for PTSD and efficacy for some PTSD subpopulationsefficacy for some PTSD subpopulations
• Other antidepressants, new generation antipsychotic Other antidepressants, new generation antipsychotic medications, noradrenergic antagonists, and mood medications, noradrenergic antagonists, and mood stabilizers have a role in treating some PTSD casesstabilizers have a role in treating some PTSD cases
• Cognitive behavioral therapy is an important Cognitive behavioral therapy is an important evidence-based intervention for PTSD evidence-based intervention for PTSD
Pre-Lecture ExamQuestion 2
True or False:
1. All individuals exposed to severely threatening trauma will develop PTSD.
Pre-Lecture ExamQuestion 3
True or False:
1. Cortisol activity in chronic PTSD is similar to major depression.
Question 4
1. The psychosocial PTSD treatment with the strongest evidence for efficacy is:
A. EDMR
B. Breathing relaxation
C. Exposure
D. Thought-stopping
Question 5
1. The weakest evidence for efficacy for PTSD is for which class of pharmacological agents:
A. SSRI’s
B. TCA’s
C. MAOI’s
D. Benzodiazepines
E. Risperidone
Overview
I.I. EpidemiologyEpidemiology
II.II. DiagnosisDiagnosis
III.III. Psychiatric ComorbidityPsychiatric Comorbidity
IV.IV. TreatmentTreatment
Post-Traumatic Stress Disorder (PTSD)
Lifetime prevalence in community of 1% to 14%, Lifetime prevalence in community of 1% to 14%, recent estimates from NCS of 7-8% recent estimates from NCS of 7-8%
PTSD is associated with sexual abuse, physical PTSD is associated with sexual abuse, physical assault, military combat, torture, accidental assault, military combat, torture, accidental trauma, natural or man-made disasters, diagnosis trauma, natural or man-made disasters, diagnosis of threatening illnessof threatening illness
American Psychiatric Association, 1994Kessler et al., ’95, 05
POST-TRAUMATIC STRESS DISORDER
A characteristic set of symptoms following A characteristic set of symptoms following exposure to extreme traumatic stressexposure to extreme traumatic stress
1.1. experience, witness, or confronted with experience, witness, or confronted with actual or threatened death or injuryactual or threatened death or injury
2.2. Response involves intense fear, Response involves intense fear, helplessness, or horrorhelplessness, or horror
Duration more than one monthDuration more than one monthSignificant functional impairmentSignificant functional impairment
POST-TRAUMATIC STRESS DISORDER
Re-experiencing symptoms (need 1)Re-experiencing symptoms (need 1)
1.1. intrusive recollectionsintrusive recollections
2.2. trauma-related nightmarestrauma-related nightmares
3.3. flashbacksflashbacks
4.4. psychological distress with reminderspsychological distress with reminders
5.5. physiologic reactivity with remindersphysiologic reactivity with reminders
POST-TRAUMATIC STRESS DISORDER
Avoidance symptoms (need 3)Avoidance symptoms (need 3)
1.1. avoid thoughts/feelings/conversationsavoid thoughts/feelings/conversations
2.2. avoid activities, places, peopleavoid activities, places, people
3.3. inability to rememberinability to remember
4.4. diminished interestdiminished interest
5.5. feelings of detachmentfeelings of detachment
6.6. restricted affectrestricted affect
7.7. foreshortened futureforeshortened future
POST-TRAUMATIC STRESS DISORDER
Arousal symptoms (need 2)Arousal symptoms (need 2)
1.1. impaired sleep initiation/maintenanceimpaired sleep initiation/maintenance
2.2. irritabilityirritability
3.3. concentrationconcentration
4.4. hypervigilancehypervigilance
5.5. exaggerated startleexaggerated startle
PTSD
Associated Features
1.1. Alcohol/drug problemsAlcohol/drug problems
2.2. Aggression/violenceAggression/violence
3.3. Suicidal ideation, intent, attemptsSuicidal ideation, intent, attempts
4.4. DissociationDissociation
5.5. DistancingDistancing
6.6. Problems at workProblems at work
7.7. Marital problemsMarital problems
8.8. HomelessnessHomelessness
Lifetime Prevalence of DSM-III-RMajor Psychiatric Disorders
NCS Data
Mood DisordersMood Disorders
Major depressive episodeMajor depressive episode 17.117.1DysthymiaDysthymia 6.46.4Manic episodeManic episode 1.61.6
Anxiety DisordersAnxiety DisordersSocial phobiaSocial phobia 13.313.3Simple phobiaSimple phobia 11.311.3PTSDPTSD 7.87.8Agoraphobia without panicAgoraphobia without panic 5.35.3GADGAD 5.15.1Panic disorderPanic disorder 3.53.5
Substance Use DisordersSubstance Use DisordersAlcohol abuse/dependenceAlcohol abuse/dependence 23.523.5Drug abuse/dependenceDrug abuse/dependence 11.911.9
Adapted from: Kessler et al. Arch Gen Psychiatry. 1994;51:8–19.Adapted from: Kessler et al. Arch Gen Psychiatry. 1994;51:8–19.Kessler et al. Arch Gen Psychiatry. 1995;52:1048–1060.Kessler et al. Arch Gen Psychiatry. 1995;52:1048–1060.
%%
PTSD Risks of Specific Traumas
in the US PopulationP
erc
enta
ge
Pe
rcen
tag
e
Natural Natural DisasterDisaster
RapeRapeCombatCombatCriminalCriminalAssaultAssault
MenMen
WomenWomen
Kessler RC et al. Kessler RC et al. Arch Gen PsychiatryArch Gen Psychiatry. 1995;52:1048–1060.. 1995;52:1048–1060.
N/AN/A
PTSD
Risk Factors for PTSD
Severity of trauma (i.e., threat, duration, injury, loss)Severity of trauma (i.e., threat, duration, injury, loss)
Prior traumaPrior trauma
GenderGender
Prior mood and/or anxiety disordersPrior mood and/or anxiety disorders
Family history of mood or anxiety disordersFamily history of mood or anxiety disorders
Low EducationLow Education
PTSD
Rates Related to Specific TraumasP
erc
enta
ge
Pe
rcen
tag
e
Natural Natural DisasterDisaster
RapeRapeCombatCombatCriminalCriminalAssaultAssault
MenMen
WomenWomen
Kessler RC et al. Kessler RC et al. Arch Gen PsychiatryArch Gen Psychiatry. 1995;52:1048–1060.. 1995;52:1048–1060.
00
2525
5050
7575
100100
11 22 33 44 55 66 77 1010
PTSD
Persistence Over Time
Kessler RC et al. Kessler RC et al. Arch Gen PsychiatryArch Gen Psychiatry. 1995;52:1048–1060.. 1995;52:1048–1060.
YearsYears
% W
ith
ou
t R
eco
very
% W
ith
ou
t R
eco
very
(Untreated Group)(Untreated Group)
PTSD
Function and Quality of LifeIn VietnamVeterans With and Without PTSD
Pe
rcen
tP
erc
ent
Not Not WorkingWorking
PhysicalPhysicalLimitationLimitation
ReducedReducedWell-Well-BeingBeing
Fair orFair orPoorPoor
HealthHealth
Zatzick DF et al. Zatzick DF et al. Am J PsychiatryAm J Psychiatry. 1997;154:1690–1695.. 1997;154:1690–1695.
Violent Violent BehaviorBehaviorPast YearPast Year
PTSDPTSD
Non-PTSDNon-PTSD
DepressionDepression 48 48 1212 48481919
ManiaMania 12 12 11 6611
Panic DisorderPanic Disorder 7 7 22 131344
Social PhobiaSocial Phobia 28 28 1111 28281414
GADGAD 17 17 33 151566
Alcohol Abuse/DependencyAlcohol Abuse/Dependency 52 52 3434 28281313
Substance Abuse/DependencySubstance Abuse/Dependency 34 34 1515 272788
Any DiagnosisAny Diagnosis 88 88 5555 79794646
Kessler RC et al. Kessler RC et al. Arch Gen PsychiatryArch Gen Psychiatry. 1995;52:1048–1060.. 1995;52:1048–1060.
Lifetime Rates (%)Lifetime Rates (%)
Men Men Women Women
PTSD Non-PTSD PTSD Non-PTSDPTSD Non-PTSD PTSD Non-PTSD
PTSD
Psychiatric Comorbidity
Comorbidity in PTSDNational Comorbidity Study
1 Other Diagnoses 2 Other Diagnoses 3 Other Diagnoses No Other Diagnosis
1 Other Diagnoses 2 Other Diagnoses 3 Other Diagnoses No Other Diagnosis
MEN
WOMEN
0
20
40
60
80
PTSD
Impact of Comorbid PTSD in Subjects With Other Anxiety Disorders
(%)
Ra
tes
(%)
Ra
tes
38
48
30
6
30
21
AlcoholAlcoholProblemsProblems
HospitalizedHospitalizedAttemptedAttemptedSuicideSuicide
Anxiety DisorderAnxiety DisorderWith PTSDWith PTSD
Anxiety DisorderAnxiety DisorderWithout PTSDWithout PTSD
Warshaw MG et al. Warshaw MG et al. Am J PsychiatryAm J Psychiatry. 1993;150:1512–1516.. 1993;150:1512–1516.
DIAGNOSTIC SPECTRADIAGNOSTIC SPECTRA
PTSDPTSD
DepressionDepression
PanicPanicDisorderDisorder
DissociationDissociation
SubstanceSubstanceUseUse
DisordersDisorders
PersonalityPersonalityDisorderDisorder
PsychosisPsychosis
SomatizationSomatizationObsessiveObsessive
CompulsiveCompulsiveDisorderDisorder
PTSD
Model Sequence of Comorbidity
PTSDSubstance
AbuseGAD
MDDPANIC
AgeAge 2323 2424 2525 3030
Davidson JR et al. Davidson JR et al. Compr PsychiatryCompr Psychiatry. 1990;31:162–170.. 1990;31:162–170.Mellman TA et al. Mellman TA et al. Am J PsychiatryAm J Psychiatry. 1992;149:1568–. 1992;149:1568–1574.1574.
Disability--->Disability--->
Lifetime History of Suicidal Attempts by Anxiety Disorder
20
2523 23
33
16
0
4
0
5
10
15
20
25
30
35
Panic(n=86)
Pan/Ag(n=111)
Agora(n=22)
Social(n=158)
PTSD(n=170)
GAD(n=127)
MAD(n=12)
GenPop
General US population lifetime rates of suicide attempts range from 2.9% to 4.6%.General US population lifetime rates of suicide attempts range from 2.9% to 4.6%.
Kessler RC, Kessler RC, Archives of General PsychiatryArchives of General Psychiatry. 1999; Moscicki EK, . 1999; Moscicki EK, Yale Journal of Biology and Yale Journal of Biology and MedicineMedicine. 1988. 1988
%
Disability Weights (Rating Scale)
psych
osis
blindnes
s
parap
legia
opioid
dep
enden
ce
seve
re d
epre
ssio
n
anore
xia
nervo
sa
PTSD
agora
phobia
bipola
r dis
order
moder
ate
depre
ssio
n
panic
dis
order
border
line
PD0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
Score
Sanderson K and Andrews G, Australian and New Zealand Jnl of Psych 2001
640 36
PTSD
Impact of Treatment on Recovery
Kessler RC et al. Kessler RC et al. Arch Gen PsychiatryArch Gen Psychiatry. 1995;52:1048–1060.. 1995;52:1048–1060.
TreatedTreated
UntreatedUntreated
Median Months to RecoveryMedian Months to Recovery
(N = 459)(N = 459)
PTSD
Treatment Options
PsychotherapyPsychotherapy
PharmacotherapyPharmacotherapy
Combined treatmentsCombined treatments
PTSD
Considerations for Psychotherapy
1.1. Capacity to tolerate distress with Capacity to tolerate distress with exposureexposure
2.2. Motivation/preferenceMotivation/preference
3.3. Ability to participate and follow Ability to participate and follow structurestructure
4.4. Problems with interpersonal Problems with interpersonal adjustmentadjustment
Cognitive Restructuring and Combination Treatments
Study Population Comparison Results
Marks et al., 1998
87 civilian trauma victims
Relaxation vs E vs cognitive restructuring (CR) vs combination
All superior to relaxation
Resick et al. 2002
120 F, sexual assault
Cognitive processing Tx (CPT) (elements of CR and E) vs E vs minimal contact
CPT = E > MC CPT superior for guilt
Monson et al., 2007
60 Male veterans
Cognitive processing CPT vs Present Centered (PC)
CPT superior to PC
EXPOSURE STUDIES
Study Population Comparison Results
Keane et al., 1989 24 Vietnam veterans
E vs WL
Exposure group more improved, especially re-experiencing
Foa et al., 2005 179 Women civilian trauma
E vs E+CR vs WL E superior effective with all Sx clusters
Schnurr et al., 2007
Women veterans
E vs PC E superior to PC
*E = exposure-based treatment WL = wait list control SIT = stress inoculation training
PTSD
Treatment of PTSD by Exposureand/or Cognitive Restructuring
Marks I et al. Marks I et al. Arch Gen PsychiatryArch Gen Psychiatry. 1998;55:317–325.. 1998;55:317–325.
IES
Sco
res
IES
Sco
res
TreatmentTreatment1 mo1 mo 3 mos3 mos 6 mos6 mos
r = relaxationr = relaxationc = cognitive restructuringc = cognitive restructuringe = prolonged exposuree = prolonged exposureec = e + cec = e + crr
cc
ecec
ee
Follow UpFollow Up
Conclusions of the IOM report on the Treatment of PTSD (2007)
““The evidence is sufficient to conclude The evidence is sufficient to conclude the efficacy of (psychotherapy that the efficacy of (psychotherapy that utilize) exposure therapies in the utilize) exposure therapies in the treatment of PTSD” (PE, CPT)treatment of PTSD” (PE, CPT)
PHARMACOTHERAPYNeurobiological factorsNeurobiological factors
Evidence of efficacyEvidence of efficacy
What respondsWhat respondsPTSDPTSDrelated pathologyrelated pathology
Who respondsWho respondsType of traumaType of traumacomorbiditycomorbiditygendergender
PTSD: Neurobiological Alterations of Memory Processing
Greater physiologic reactivity to trauma-related stimuli Greater physiologic reactivity to trauma-related stimuli
Selective attention to trauma stimuliSelective attention to trauma stimuli
Fragmentary trauma narrativesFragmentary trauma narratives
Deficits in standard tests of verbal memoryDeficits in standard tests of verbal memory
Suggested abnormalities from structural and functional brain imaging Suggested abnormalities from structural and functional brain imaging
PTSD: Hormones and Neurotransmitters
Cortisol: reduced secretion and increased sensitivity Cortisol: reduced secretion and increased sensitivity to feedback inhibition with PTSD (to feedback inhibition with PTSD (Yehuda et al., 1993)Yehuda et al., 1993)
Role of noradrenergic activity in fear-enhanced Role of noradrenergic activity in fear-enhanced learning (learning (Cahill, 1997Cahill, 1997))
Noradrenergic and serotonergic probes stimulate Noradrenergic and serotonergic probes stimulate panic and flashback symptoms in combat-related panic and flashback symptoms in combat-related PTSD (PTSD (Southwick et al., 1997)Southwick et al., 1997)
Ross et al., 1994; Mellman et al., 1997, 2002, Breslau et al., 2004
PTSD: Dysregulated sleep SubjectiveSubjective
Trauma-related nightmaresTrauma-related nightmares
Insomnia/nonrestorative sleepInsomnia/nonrestorative sleep
Objective (EEG findings)Objective (EEG findings)
Mixed findings regarding sleep maintenance and Mixed findings regarding sleep maintenance and duration duration
Increased REM density/ Disrupted REM sleep Increased REM density/ Disrupted REM sleep continuity continuity
Increased motor activityIncreased motor activity
AIMS OF PHARMACOTHERAPY
Reduce core symptomsReduce core symptoms
Reduce associated symptomsReduce associated symptoms
Facilitate other therapyFacilitate other therapy
Medication Treatment for PTSD: Nature of the Evidence
At least 7 published RCTs supporting efficacy of At least 7 published RCTs supporting efficacy of SSRIs for acute Rx of PTSDSSRIs for acute Rx of PTSD
Mean N participants = 236.3 (range: 47-551)Mean N participants = 236.3 (range: 47-551)
FDA approval for sertraline (’99), paroxetine (’01)FDA approval for sertraline (’99), paroxetine (’01)
Maintenance efficacy established for sertraline for Maintenance efficacy established for sertraline for up to 52 weeks up to 52 weeks (Davidson et al. ‘01)(Davidson et al. ‘01)
Improvement in all 3 sx clusters and QOL Improvement in all 3 sx clusters and QOL measures, treatments safemeasures, treatments safe
Medication Treatment for PTSD: Nature of the Evidence
Additional RCTs not demonstrating Additional RCTs not demonstrating benefit for SSRIs. Some are benefit for SSRIs. Some are underpowered. The one large and well underpowered. The one large and well designed negative study featured designed negative study featured male combat veterans with chronic male combat veterans with chronic PTSD treated in VA settings PTSD treated in VA settings (Friedman et al., 2007)(Friedman et al., 2007)
Medication Treatment for PTSD: Nature of the Evidence
Efficacy supported by smaller RCTsEfficacy supported by smaller RCTs
TCAs, MAOIs, TCAs, MAOIs, lamotrigine; adjunctive lamotrigine; adjunctive olanzapine and risperidone, prazosin for olanzapine and risperidone, prazosin for sleep disturbancessleep disturbances
Efficacy Efficacy notnot supported by trials supported by trials
benzodiazepinesbenzodiazepines
Benefits suggested in open trialsBenefits suggested in open trials
Other SSRIs, Novel APs, AEDs, trazodone, Other SSRIs, Novel APs, AEDs, trazodone, nefazodone, noradrenergic nefazodone, noradrenergic suppressor/antagonists suppressor/antagonists
Medication Treatment for PTSD:Recommendations
11stst Line Line
SSRIs (sertraline, paroxetine, SSRIs (sertraline, paroxetine, fluoxetine) fluoxetine)
22ndnd Line Line
other novel and traditional ADs; other novel and traditional ADs; noradrenergic agents; noradrenergic agents; anticonvulsant/mood stabilizers; novel anticonvulsant/mood stabilizers; novel AP medicationsAP medications
Not recommendedNot recommended
traditional APs, benzodiazepines*traditional APs, benzodiazepines*
Friedman et al., 2000
DOES COMORBID PERSONALITY DISORDER AFFECT THE RESPONSE TO
AN SSRI?
0
25
50
75
FLUFLU PBOPBO
PDPD No PDNo PD
FLUFLU PBOPBOp=0.002p=0.002 nsns
DOES COMORBID DEPRESSION AFFECT THE RESPONSE TO AN SSRI?
0
10
20
30
40
50
60
70
MDD No MDD
FluoxetinePlacebo
p=0.003p=0.003 nsns
6060
00
Brady KT et al. Brady KT et al. J Clin Psychiatry.J Clin Psychiatry. 1995;56:502–505. 1995;56:502–505.
IES
IES
Sc
ore
Sc
ore
PTSD Treatment With SSRIs
Open-Label Sertraline in Comorbid PTSDand Alcoholism
PrePre PostPost
IESIES
PrePre PostPost
Alcohol UseAlcohol Use
140140
00
Sta
nd
ard
Sta
nd
ard
Drin
ks/W
eekD
rink
s/Week
(n = 9)(n = 9)
00
1010
3030FluoxetineFluoxetine
Davidson JR et al. Davidson JR et al. Int Clin PsychopharmacolInt Clin Psychopharmacol. 1997;12:291–296.. 1997;12:291–296.
Fin
al D
TS
Fin
al D
TS
PTSD Treatment With SSRIs
Effect of Fluoxetine in Symptom Clusters
2020
PP = 0.02 = 0.02
IntrusiveIntrusive
PP = 0.08 = 0.08
AvoidantAvoidant
PP = 0.01 = 0.01
NumbingNumbing
PP = 0.01 = 0.01
HyperarousalHyperarousal
PlaceboPlacebo
6.76.7
13.513.5
3.03.0
6.36.3 6.26.2
15.115.1
9.09.0
17.317.3
Total (N = 53)Total (N = 53)
EFFECT OF FLUOXETINE ON QUALITY OF LIFE (SF36) IN PTSD:
Pre- to Post-Treatment
0
25
50
75
100
FLU PBO FLU PBO
Davidson et al., 1997 Davidson et al., 1997
General HealthGeneral Health Mental HealthMental Health
PrePre PostPost PrePre PrePre PrePrePostPost PostPost PostPost
p=0.006p=0.006 nsns
IMPROVEMENT IN DISABILITY:Fluoxetine vs Placebo
0
5
10
15
Total Work Family Social/Leisure
FluoxetinePlacebo
p=0.02p=0.02 p=0.02p=0.02 p=0.02p=0.02 p=0.01p=0.01
Davidson et al., 1997 Davidson et al., 1997
WHICH SYMPTOMS RESPOND TO AN SSRI?
0
1
2
RIR PhysDistress
Detach Numbing Concn Startle
FluoxetinePlacebo
P=0.006P=0.006 P=0.01P=0.01 P=0.02P=0.02 P=0.02P=0.02 P=0.005P=0.005 P=0.002P=0.002
Davidson et al., 1997 Davidson et al., 1997
SEQUENCE OF SYMPTOM IMPROVEMENT WITH FLUOXETINE
(SIP)Week
4 8 12
Startle ** * **
Concentration ** **
Intrusive recollections ** **
Physiological symptoms ** **
Estrangement *
Numbing *
*p<0.05 *p<0.01
SEQUENCE OF SYMPTOM IMPROVEMENT WITH FLUOXETINE
(DTS)Week
2 4 6 8 10 12
Hypervigilance ** *** *** * ** ***
Poor concentration ** *** *** * *** **
Upset by reminders * * * *
Estrangement ** ** * ** **
Anhedonia * **
Avoid thoughts * *
Foreshortened future *
*p<0.05 **p<0.01 ***p<0.001
Davidson et al., 1997 Davidson et al., 1997
4040
100100
00
2020
8080
FluoxetineFluoxetine
van der Kolk BA, Fisler RE. van der Kolk BA, Fisler RE. Prim CarePrim Care. 1993;20:417–. 1993;20:417–432.432.
CA
PS
C
AP
S
To
tal S
co
reT
ota
l Sc
ore
Effect of Trauma PopulationEffect of Trauma Population
PTSD Treatment With SSRIs
Effect of Fluoxetine
PlaceboPlacebo
PrePre PostPost
6060
Trauma Clinic (n = 23)Trauma Clinic (n = 23)
PrePre PostPost PrePre PostPost
VA (n = 24)VA (n = 24)
PrePre PostPost
Sertraline vs Placebo in Non-Combat-related PTSD
-40
-35
-30
-25
-20
-15
-10
-5
0
0 2 4 6 8
SertralinePlacebo
WeekWeek
Brady et al.. JAMA 2000Brady et al.. JAMA 2000
ADVANTAGES AND DISADVANTAGES OF
SSRIs
Advantages Disadvantages
Effective on all PTSD symptoms
Unproven in Combat Veterans
Abuse-free GI, sexual, activating side effects
Once daily Medication interactions
Alprazolam (n = 10)Alprazolam (n = 10)
Braun P et al. Braun P et al. J Clin PsychiatryJ Clin Psychiatry. 1990;51:236–238.. 1990;51:236–238.
IES
IES
30.930.9
Effect of AlprazolamEffect of Alprazolam
26.626.630.030.0
28.828.8
PTSD
Treatment With Benzodiazepines
2020
4040
00
Placebo (n = 10)Placebo (n = 10)
1010
3030
PrePre PostPost PrePre PostPost
ADVANTAGES AND DISADVANTAGES OF BZDs
Advantages Disadvantages
Acute relief of non-specific anxiety
No evidence of efficacy for PTSD
Possible disinhbition
Possible dependence
AmitriptylineAmitriptyline
PlaceboPlacebo
Davidson J et al. Davidson J et al. Arch Gen PsychiatryArch Gen Psychiatry..1990;47:259-266.1990;47:259-266.
% R
esp
on
der
s%
Res
po
nd
ers
4747
Studies Comparing Amitriptyline and Imipramine With PlaceboStudies Comparing Amitriptyline and Imipramine With Placebo
n = 22n = 22
1919
6565
2828
PTSD
Treatment With Tricyclics
5050
100100
00n = 18n = 18 n = 18n = 18n = 23n = 23
ImipramineImipramine
PlaceboPlacebo
Kosten TR et al. Kosten TR et al. J Nerv Ment DisJ Nerv Ment Dis..1991;179:366–370.1991;179:366–370.
ADVANTAGES AND DISADVANTAGES OF TCAs
Advantages Disadvantages
Effective in PTSD Numerous side effects
Abuse-free Poorly tolerated
Once daily Dangerous in overdose
Hypnotic effects Wide dose range
Kosten TR et al.Kosten TR et al.J Nerv Ment DisJ Nerv Ment Dis..1991;179:366–370.1991;179:366–370.
Studies Comparing Phenelzine and Brofaromine With PlaceboStudies Comparing Phenelzine and Brofaromine With Placebo
PTSD
Treatment With MAOIs
PhenelzinePhenelzinePlaceboPlacebo
% R
esp
on
der
s%
Res
po
nd
ers 6868
n = 19n = 19
2828
6060
39395050
100100
00n = 18n = 18
BrofaromineBrofarominePlaceboPlacebo
2626
5555
n = 55n = 55 n = 58n = 58 n = 22n = 22 n = 23n = 23
BrofaromineBrofarominePlaceboPlacebo
Baker DG et al.Baker DG et al.PsychopharmacologyPsychopharmacology.. 1995;122:386–389. 1995;122:386–389.
Katz RJ et al.Katz RJ et al.AnxietyAnxiety..1994–95;1:169–174.1994–95;1:169–174.
ADVANTAGES AND DISADVANTAGES OF MAOIs
Advantages Disadvantages
Effective in PTSD Numerous side effects
Poor tolerance
Dietary & other restrictions
May be particularly useful in complex cases
Dangerous in overdose
Antipsychotic Medications• Support for risperidone as add on Rx (Bartzokis et al.,
2005; Reich et al., 2004
• olanzapine 1 small study supporting adjunct efficacy, benefit to sleep (Stein et al., 2002)
• Traditional Antipsychotic medications “not recommended” – (Friedman et al. ISTSS Treatment Guidelines, 2000)
Mood Stabilizers• Carbamazepine
– Open clinical trial: decreased intrusions, flashbacks, insomnia, irritability, impulsivity, and violent behavior (Lipper et al., Psychosomatics, 1986)
• Valproic acid – Open trial: decreased hyperarousal and avoidance
(Stein, J Clin Psych, 1995)
• Lamotrigine– Small controlled trial: decreased re-experiencing,
numbing and avoidance (Hertzberg et al., Biol Psychiatry, 1999)
Medication Treatments for Traumatic Nightmares (None are FDA
approved for indication)
Prazosin (controlled trial)Prazosin (controlled trial)11
Cyproheptadine Cyproheptadine —— (positive results, open label; pilot (positive results, open label; pilot placebo-controlled study,negative)placebo-controlled study,negative)2,32,3
TrazodoneTrazodone44
Nefazodone Nefazodone —— (changes in qualitative features of dream (changes in qualitative features of dream recall)recall)55
Clonidine/guanfacine Clonidine/guanfacine —— (have been used in children) (have been used in children)6,76,7
Novel antipsychotics (adjunct use improves sleep)Novel antipsychotics (adjunct use improves sleep)88
5.Mellman TA, et al. Depress Anxiety. 1999;9:146-148. 6.Kinzie JD, et al. J Nerv Ment Dis. 1994;182:585-587.7. Horrigan JP, JAA CAP. 1996;35:975-976.8. Stein MB et al., Am J Psychiatry. 2002; 159:1777-1779
1. Raskind MA, et al. A J Psychiatry. 2002;160:371-3. 2. Brophy MH. Mil Med. 1991;156:100-101.3. Jacobs-Rebhun S, et al. Am J Psych. 2000;157:1525-64. Ashford, Miller. 1996.
PTSD
Summary
1.1. PTSD is commonPTSD is common
Usually chronicUsually chronic
Presentations varyPresentations vary
Comorbidity is the ruleComorbidity is the rule
2.2. Comprehensive assessment of patients is Comprehensive assessment of patients is critical to develop an individualized critical to develop an individualized treatment plantreatment plan
3.3. Treatment often involves multiple Treatment often involves multiple modalitiesmodalities
CONCLUSIONS
PTSD prevalent and PTSD prevalent and treatabletreatable disorder disorder
CBT effectiveCBT effective
Antidepressant agents effectiveAntidepressant agents effective
SSRI, MAOI, TCASSRI, MAOI, TCA
Combined CBT & pharmacotherapy Combined CBT & pharmacotherapy trial neededtrial needed
Few Are Treated
% untreated 50% 90% 75% 80% 50% 30%
PTSD: Unmet Medical Need
0
2
4
6
8
10
12
14
16
18
% Lifetime Prevalence
Untreated
Treated
Depression Social phobia
PTSD GAD Panic disorder
OCD
Question 2
True or False:
1. All individuals exposed to severely threatening trauma will develop PTSD.
Question 4
1. The psychosocial PTSD treatment with the strongest evidence for efficacy is:
A. EDMR
B. Breathing relaxation
C. Exposure
D. Thought-stopping
Question 5
1. The weakest evidence for efficacy for PTSD is for which class of pharmacological agents:
A. SSRI’s
B. TCA’s
C. MAOI’s
D. Benzodiazepines
E. Risperidone