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S352

p3. Anxiety disorders and anxiolytics

using IV administration of ethanol, in order to eliminate any bias

due to the act of drinking.

(P.3.0501 The antipanic effect of acute exertion and high

lactate levels on 35 CO2 challenge

in healthy

subjects

K. Schruers’, G. Esquivel’, H. Kuipers3, E. Griez2. ‘Maastricht

University, PMS Vijverdal, Academisch Angst Centrum,

Maastricht, The Netherlands; 2Maastricht University Psychiao

Neuropsychology, Maastricht, The Netherlands; 3Maastricht

University, Movement Sciences, Maastricht, The Netherlands

Objective: CO2 challenges elicit small but consistent increases

on panic scales in healthy subjects. Acute exertion, despite high

lactate levels, does not produce panic in Panic Disorder Patients.

Moreover, exercise may have a beneficial effect in PD when

performed chronically. The purpose of this study is to test the

possible antipanic effects of acute exertion in healthy volunteers

exposed to an inhalation of 35% CO2 challenge.

Method:

Twenty healthy subjects in a randomized separate

group design, performed exercise in a bicycle ergometer reaching

>6 mmol/l of blood lactate and a control condition of minimal

activity in the same fashion with no lactate elevation. After either

condition the subjects were asked to relax in an armchair for 3

minutes. To assess the reactivity to CO2, they were then asked

to fill-in the DSM-IV Panic Symptom List (PSL) and a Visual

Analogue Anxiety Scale (VAAS). Immediately afterwards, an

inhalation of a vital capacity using a mixture of 35% CO2/65% 02

through a mask was given. Finally, the subjects were asked to fill-

in the PSL and VAAS.

Results:

To analyze the effects of exercise versus the control

condition with the CO; challenge, the increases on PSL and VAAS

scores were determined for each subject, by the difference in the

‘post’ minus ‘pre’-CO2 inhalation. These scores showed a lower

PSL for the exercise group when compared to the controls. Scores

were 2.00 (13.91) for the exertion group and 8.50 (+6.20) for

the control group (two sample t-test, ~~0.02, two tailed). For the

VAAS, exertions versus control scores were 7.40 (113.99) and

13.3 (114.61), which were not significantly different (two sample

t-test, p=O. I, two tailed). There was no correlation between lactate

levels and PSL or VAAS scores.

Conclusion:

Acute exertion seemed to reduce the effects of a

CO2 challenge. Subjects under the exertion condition had lactate

levels comparable to those produced by lactate infusion but an

inhibitory rather than accumulative effect was seen, although this

cannot be attributed directly to lactate.

3 51 Results from a randomized, double-blind,

multicenter trial of sertaline in the treatment

of moderate-to-severe social phobia social

anxiety disorder)

M. Liebowitz’, N. DeMartinis2, K. Weihs3, H. Chung4, C. Clary4.

‘Nav York State Psychiatric Institute, New York, NY, USA.;

‘Farmington, CT, US.A.; 3 Washington DC, US.A.; 4Pfizer, Inc.,

Depression/Anxiety, New York, NY, US.A.

Background: The objective of the current study was to evaluate

the efficacy, tolerability, and quality of life improvement of pa-

tients treated with sertraline for generalized social phobia in U.S.

adults.

Method: After a 1 wk, single-blind, placebo lead-in period,

patients were randomized to 12 wk of double-blind treatment with

flexible dose of sertraline (5&200 mg) vs. placebo. Primary effi-

cacy outcomes were the Liebowitz Social Anxiety Scale (LSAS)

total score and the Clinical Global Impression-Improvement scale

(CGI-I) responder rate. Additional measures included the Quality

of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q),

Brief Social Phobia Scale (BSPS), the Sheehan Disability Inven-

tory (SDI), and the Endicott Work Productivity Index.

Results: 211

patients received sertraline (60.2% male, baseline

LSAS, 91.3 + 15.9; mean illness duration 21 yr), and 204 received

placebo (58.8% male, baseline LSAS, 93.9 + 16.0; mean illness

duration 22 yr). Study subjects had moderate-severe illness with

mean CGI-S score of 4.810.7. At week 12, the mean change

in LSAS Total Score was -35.0 vs. -24.2 for sertraline vs.

placebo, p<.OOl with a greater proportion of responders (CGI-

1~2: 55.6% vs. 29.5%; p<O.OOl). Similarly, there was a significant

improvement in the Q-LES-Q, (LS mean change from baseline

was -6.8 vs. -1.8, p<.OOl). Significant measures of change

in satisfaction in favor of sertraline were significant for mood,

work, social relationships, leisure time activities, daily function,

economic status, living situation, well being, and overall life satis-

faction. At LOCF-endpoint, 47% of sertraline subjects were CGI-I

responders compared to 26% of placebo subjects (p<.OOl) with a

significant reduction in LSAS total score compared to placebo (LS

mean change from baseline: -3 1.3 vs. -2 1.4; p<O.OOl). Sertraline

was significantly superior to placebo on most secondary efficacy

measures including the BSPS and the SDI. Sertraline was well-

tolerated, with 7.6% attrition due to adverse events compared to

a 2.9% attrition on placebo.

Conclusion:

The results of the current study confirm the

efficacy of sertraline in the treatment of generalized social phobia,

even in a study sample with high levels of severity.

Funded by Pfizer,Inc.

References

[l]

Randomized Controlled General Practice Trial of Sertraline, Exposure

Therapy and Combined Treatement in Generalized Social Phobia. Pages

23-30. Br J Psychiatry,

Blomhoff S, Haug TT, Hellstrom K, et al.

[2] Sertraline Treatment of Generalized Social Phobia: a 20 week, double

blind, placebo controlled study. Pages 275-28 1. Am J Psychiatry, Van

Ameringen M, Lane RM, Walker R, et al.

lP.3.052]

Addition of behaviour therapy enhances

treatment outcome of patients with obsessive-

compulsive disorder already responding to

medication

N. Tenney’ , G. Glas*, D. Denys’ , N. Van der Wee’, H.J.G.M. Van

Megen’, H.G.M. Westenberg’

’ University Medical Center

Utrecht,Psychiatry, Utrecht, The Netherlands: 2Zwolse Poort,

Psychiatry, Zwolle, The Netherlands

Introduction:

Numerous studies have shown that behaviour ther-

apy and serotonergic antidepressants are effective in the treatment

of OCD. Relatively few studies have investigated the combination

of behaviour therapy and pharmacotherapy. Generally, it is found

that this combination does not result in a greater reduction of

OCD-symptoms compared to monotherapy of either pharmaco-

therapy or behaviour therapy. However, in most studies pharma-

cological and behavioural treatment start simultaneously, therefore

no information exists with regard to the effectiveness of offering

treatment modalities sequentially. Appropriate pharmacological

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P.3. Anxie ty disorders and a nxiolytics

t r ia ls show an improvement o f about 30% to 50% reduc t ion

of symptoms in 60% to 80% of OCD pa t ien ts . We tes ted the

hypothesis that addition of behaviour therapy to patients already

responding to pharmacological treatment was beneficial.

Method

79 pa t ien ts with a p r imary d iagnos is o f OCD

(DSM-IV) who responded (response was defined as a reduction

of a t leas t 25% in symptoms as measured with the Y-BOCS) on a

twe lve weeks t rea tment with e i ther ven la fax ine or pa roxe t ine were

included (mean age 35.4 years; 70.9% female; illness duration

14.6 years; 79.7% treated for OCD before). During s ix months,

half of the patients received medication only, the other half

rece ived a combina t ion o f medica t ion and behaviour the rapy (16

weekly-sessions consis ting primarily of exposure with response

prevent ion) . Before pharmacologica l t rea tment , mean Y-BOCS

score for responders was 26 and after pharmacotherapy 15.8, a

reduc t ion of a lmos t 40% in symptoms .

Resul t s

Sixty-one patients completed this s tudy. Fifteen pa-

tients dropped out in the combination therapy group and three

patients in the medication only group. In the combination group

OCD-symptoms reduced with 41%, whereas in the medica t ion

only group symp toms increased with 18%. The results of the

repea ted measures ANOVA showed a main e ffec t fo r g roup

(F(1,59)=9.02,P=.004) and an interaction effect between time X

group (F(1,59)=19,27,P<.000). In contrast, no main effect for time

(F (1,59)=3.31,P=.074) was found.

When repeating this analysis for the total sample (com-

pleters and drop outs) again a main effect for group

(F(1,77)=6.07,P=.016), an interaction effect between time X

group (F(1,77)=13.69,P<.000) and no main effect for time (F

(1,77)=0.79,P=.375) was found.

Conc lus i on

These results clearly indicate that administration

of behaviour therapy to patients , who have benefited already

from a pharmacological intervention, enhances treatment effect

considerably.

References

[1] van B alkom, A. J. L. M., van O ppe n, P., Vermeu len, A. W. A., et

al (1994) A Meta-analysis on the Treatment of Obsessive-Compulsive

Disorder:A Comparison of Antidepressants, Behaviour, and Cognitive

Therapy. Clinical Psychology Review, 14, 3 5~38 1.

[2] Hohagen, E, W inkelmann, G., Rasche-Rauchle, H., et al (1998) Com-

bination of behaviour therapy with fluvoxamine in comparison with

bebaviour therapy and placebo. British Journal of Psychiatry, 173

(suppl.35), 71-78.

[3] Montgommery, S.A. (1996) Long term m anagement of obsessive-

compulsive disorder. International Clinical Psychopharmaeology, 11

(suppl 5),11-20.

•

Paroxetine effectively treats post-traumatic

stress disorder PTSD) in males

M.J. Friedman 1 E.M. Dube 2, K .L. Beebe 2, M . Truman 3.

1National Center fo r PTSD VA Medic al Center White River

Junction VT U.S.A .; 2GlaxoSmithKline Philadelphia US.A .;

3 GlaxoSmithKline Harlow Unite d Kingdom

Post-traumatic s tress disorder (PTSD ) is one of the most debil-

ita ting and difficult to treat anxiety disorders . Whereas gender

differences have been elucidated with depression and other anxiety

disorders , relatively little is known about the gender differences

in treatment response with PTSD. The firs t agent approved for

the treatment of PTSD, the SSRI sertraline, failed to demonstrate

e ffec t ive re l ie f o f overa l l o r core symptoms in males (Zolof t

prescribing information, 2001). Thus, the question arose as to

353

whether males and females differ in their response to antide-

pressants , or whether male patients with PTSD respond to this

class of agents . Paroxetine has also received the indication for

the treatment o f PTSD; patients treated with paroxetine have

shown significant response with a 12-week course of therapy

(Marshall e t a l, 2001). Data from three multicenter, double-blind,

placebo-controlled clinical tria ls with paroxetine are presented.

The da ta f rom 436 males d iagnosed with PTSD, 67 of whom

were exposed to war or combat, were ramd omize d to receive either

paroxetine or placebo for 12 weeks. Efficacy was measured using

the Cl in ic ian Adminis te red PTSD Sca le , ve rs ion 2 (CAPS-2) and

the Cl in ic ian ' s Globa l Impress ion of g loba l improvement (CGI-

I). Depressive symptoms were assessed with the Montomery-

Asberg Depress ion Ra t ing Sca le (MADRS), and Sheehan Dis -

ability Scale (SDS) was used to rate functional disability. By

week 12 (LOCF), overa l l PTSD symptoms on the CAPS-2 (ad j .

mean d iffe rence , 95% CI, -9 .19 (-14 .12 , -4 .27) P=0.0003) were

significantly reduced. In addition, the three symptom clusters

of re -experienc ing , ( -2 .13 (-3 .66 , -0 .59) P<0.01) , hypera rousa l ,

( -4 .18 (-6 .56 , -1 .80) P<.001) , and avoidance , ( -2 .72 (-4 .34 ,

-1.10) P=0.001) were s ignificantly improved with the treatment

of paroxetine compared to placebo. Moreo ver, patients receiving

paroxetine showed significant improvements in MADRS (adj.

mean d iffe rence -2 .93 (-4 .96 , -0 .90) P<0.005) , and SDS to ta l

scores (ad j . mean d iffe rence -1 .78 (-3 .31 , -0 .24) P<0.05) com-

pared with placebo. Response and remission rates (determined

by CAPS-2 and CGI criteria) were s ignificantly higher with

paroxetine than with placebo, and will a lso be presented. These

findings provide further support for the efficacy of paroxetine in

the treatment of PTSD. More importantly, they represent the most

robust results to date for the treatment of PTSD in males . Overall,

paroxetine was effective and well-tolerated in this large sample of

adult males with PTSD.

•

Anxiolytic activity of plants used in Brazilian

traditional medicine

M. Costa, M.M. Blanco, M.I.R. Carvalho-Freitas . U N E S P -

Universidade Estadual Paulista Departam ento de Farmacologia

Botucatu Brazil

Anxiety is the most frequently psychiatric disorder with a preva-

lence, estimates by DSM-III diagnosis , varying from 10 to 18%

in urban populations in Brazil (Almeida-Filho et a l. , 1997). In

spite of the role of several neurotransmitters in anxiety, the

mos t commonly employed medic ina l t rea tments fo r the common

clinical anxiety disorders are benzodiazepines and buspirone,

involvin g gabaergic and serotonergic system. Several problems

are assoc ia ted with the use of these drugs. A bout 25-3 0% of a l l

patients fail to respond, and tolerance and dependence may occur

with benzodiazepines, and buspirone had no beneficial actions

in severe anxiety. In this way, the evaluation of new compounds

could be hope to found safer alternative drugs.

The role of ethnopharmacology in natural product drug dis-

covery is well established (Heinrich and Gibbons, 2001). Based

on ethnopharmacological use as anxiolytic , essential oils (EO)

obtained from Cymbopogon citratus (DC) Stapf. (EOCc) and

Citrus aurantium L. (EOCa) were selected and evaluated in order

to investigate their activity on elevated plus-maze (EPM), one of

the most widely used animal models in preclinical research on

anxiety. EOCc and EOCa were administered orally (0,5 and 1

g /kg) to male a lb ino mice (30-40 g) 30 min before experimenta l