- Email: [email protected]
P.3.029 Efficacy of sertraline in improving quality of life and functioning in generalized anxiety disorder (GAD)
I?3. Anxiety
disorders
poteutiated startle in response to a threat stimulus is expressed as a chauge from baseline startle amplitude to startle amplitude in the threat condition The aim of the present study was to examiue the auxiolytic aud sedative effects of LY354740 in humaus using the fear poteutiated startle reflex paradigm. Forty-seven healthy meu aud women participated in the study. All participants were required to have a body mass index betweeu 19 aud 28 kglm2, aud to have 110 clinically significant abnormalities in EKG, lab chemistry, or medical examination Participants were also excluded if they met criteria for auy psychiatric disorder (as determiued using DMS-IV SCID), had a history of drug or alcohol abuse, or had small baseline startle reflexes (meau of less thau 50 iV over uiue startle responses). Participants who met all entry criteria received single doses of placebo (N=16), 20 mg LY354740 (N=15) or 200 mg LY354740 (N=13). Testing consisted of au assessment of baseline startle. Patients were theu giveu study drug. After 3 hours, this was followed by a test of threat of au electric shock aud darkness (fear poteutiated startle test). LY354740 did uot affect baseline startle. Cousisteut with previous results, startle was iucreased by threat of shock aud darkness. The degree of startle poteutiatiou during threat was siguificautly less in LY354740treated participants, thau in placebo-treated participants, resulting in a siguificaut Treatment x Couditiou iuteractiou, F( 1,42)=4.5, pi.04. Additionally, the overall level of anxiety during the test was lower in the LY354047-treated patieuts, compared to the placebo group, F(1,42)=5.702, piO.02 without developmeut of sedation These results are comparable to those observed in the rat model of fear poteutiated startle. In summary, LY354740 treatment was associated with reduced expression of fear poteutiated startle in response to a threat signal without affecting baseline startle response. Additionally, subjective data suggest that LY354740 reduced the overall anxiety level associated with participation in au experiment where uupleasaut shocks were administered. LY35470 appears to be associated with au auxiolytic profile in humans without being sedating.
lp.3.0281 Evaluation profile compared
of
of the cognitive and psychomotor a novel anxiolytic, LY54434-4, to lorazepam in normal volunteers
.I. Boyle’, L. Trick’, S. Soo-ampou’ I. Hindmarch’ ’ University of Surrey, Centre, Guildford, United Kingdom; Neuroscience, Indianapolis, US.A.
, S. Lilley’ , L. Leviue2, HPRU Medical Research 2Eli Lilly & Company,
Objective: LY544344 is the iuactive peptidyl prodrug form of the highly poteut aud selective mGlu2 agonist, LY354740. LY354740 is a novel pharmacological compound, which has previously beeu showu to demonstrate auxiolytic aud autipauic properties in a variety of auimal models (Schoepp et al., 1999). The curreut study was designed to evaluate the effects of repeated doses of LY544344 at a low (7.5 mg) aud supra-high (40 mg) dose compared with lorazepam (J,ZP) aud placebo 011 cognitive, psychomotor aud road driving parameters. Methods: 24 male aud female healthy volunteers (18-35 years) were raudomised, double-blind, to a four-way crossover study, with at least a 3-day washout betweeu treatments. A standard battery of cognitive aud psychomotor tests was administered 2 aud 4 hours post-dose, iucludiug on-the-road car driving. Results: Repeated measures ANOVAs demo&rated that LZP significantly impaired perfonnauce compared to LY544344 7.5 aud 40 mg 011 Choice Reaction Time: Recognition (piO.OOOl),
and
anxiolytics
S365
Motor (p=O.O006 aud 0.0003, respectively) aud Total reaction time (piO.0001); Compensatory Tracking (piO.0001); Rapid Visual Iufonnatiou Processing (piO.0001); Steinberg’ s Short-tenn Memory Scamring Test (p=O.O013 aud p=O.O144, respectively) aud Immediate aud Delayed recall of words (piO.0001). In addition LZP siguificautly impaired on-the-road driving perfonnauce as measured by Brake Reaction Time (piO.0001) compared to LY544344 7.5 aud 40 mg. In contrast, LY544344 7.5 aud 40 mg did uot significantly affect cognitive fuuctiou, psychomotor perfonnauce or driving ability compared to placebo 011 auy of the measures tested. Conclusions: Psychological tests are considered as aualogues of real-life behaviour, since perfonnauce chauges cau reflect the poteutial impainneut of the activities of daily living (Hiudmarch, 1988). This study clearly demonstrates that LZP, a 1,4beuzodiazepiue, impairs cognitive functioning, psychomotor perfonnauce aud car driving ability. More specifically, LZP impairs the cognitive aud motor compoueuts of response to novel stimuli, reduces tracking accuracy, has a detrimental effect 011 the ability to remail1 vigilaut, disrupts working memory aud produces trausieut auterograde amnesia. In contrast, LY544344 at both low aud suprahigh dose displays a distinct behavioural aud cognitive profile to LZP with 110 evidence for impainneut 011 cognition, atteutiou, memory or psychomotor perfonnauce. References [l]
[2]
Hindmarch, I. (1988) A Pharmacological Profile of Fluoxetine and Other Antidepressants on Aspects of Skilled Performance and Car Handling Ability’ , British Journal of Psychiatry,l53: S99-S104. Schoepp, D.D., Mom, J.A., Marek, G.J., Aghajanian, G. and Moghaddam, B. (1999) LY354740: A Systemically Active mGlu2/mGlu3 Receptor Agonist, CNS Drug Reviews, 5: l-12.
lP.3.0291
Efficacy life and disorder
of sertraline functioning (GAD)
in improving in generalized
quality anxiety
of
I. Sjodiu’ , S.P. Kutcher2, A. Raviudrau3, T. Burt4. ‘Psykiatriska Kliniken Universitetsjukhuset, Psychiatry, Linkoping, Sweden; 2Dalhousie University, Psychiatry, Nova Scotia, Canada; 3Royal Ottawa Hospital, Psychiatry & Psychopharmacology, Ottawa, Canada; 4qfzel;Inc., Depression/Anxiety, New York City, US.A. Objective: GAD is a chrouic ilhless associated with significant impainneut in quality of life (QoL) aud fuuctiouiug. Though comorbidity is frequent, community surveys indicate that eveu “pure” GAD results in fuuctioual impainneut that is similar to major depression The goal of this iuvestigatiou was to evaluate effect of short-tenn treatment with sertraliue 011 QoL aud work productivity in GAD. Methods: Adult outpatients were eligible who met DSM-IV criteria for GAD with a minimum HAM-A total score= 18 (anxiety aud teusiou items eachh2). After completion of a single-blind placebo lead-in period patients were randomized to 12 weeks of double-blind treatment with placebo (N=l88; female, 5 1%; meau age, 42 years; baseline HAM-A, 25) or flexible doses (SO&l50 mg) of sertraliiie (N=l82; female, 59%; meaii age, 40 years; baseline HAM-A, 25). Outcomes included the Quality of Life, Eujoymeut, aud Satisfaction scale (Q-LES-Q), the Eudicott Work Productivity impainneut scale (EWP-impainneut), aud a lo-point visual aualogue scale measuring perceived state of health @‘AShealth). Nonnal QoL was defined as a Q-LES-Q score withiu 10% of commuiiity iionns.
S366
P3.
Anxiety
disorders
Results: At baseline, 11.8% of patieuts reported normal Q-LES-Q scores, while 41.2% had markedly abnormal QoL (QLES-Q =2 standard deviatious below the community uorm meau). Treatment with sertraliue resulted in siguificautly greater improvemeut thau placebo 011 the Q-LES-Q (+9.0 11.0 vs. +2.410.9; p i O.OOOl), the EWP-impairment score (-9.211.3 vs. -2.511.4; p i O.OOOl), aud the VAS-health scale (+1.710.2 vs. +0.810.1; p i 0.0001). Improvement in QoL occurred early (siguificaut by first assessment at week 6), aud was cousisteut across all scale items 011 both the Q-LES-Q aud the EWP-impairment scale. Rates of QoL uonnalizatiou 011 sertraliue were progressively higher among study completers (5 l%), responders (66%), aud remitters (HAM-A =7: 71%). Iuterestiugly, a regression analysis found improvement in depressive symptoms (MADRS-change score) to be the ouly clinically meauiugful predictor of improved QoL (partial R2~0.322, piO.001). Conclusion: Sertraliue treatment resulted in siguificaut aud rapid improvement in QoL aud fuuctioual impainneut. Source of Funding: PfizerJuc. References [l]
R.C. Kessler, R.L. Dupont, I? Berglund, H.U. Wittchen, Impairment in pure and comorbid generalized anxiety disorder and major depression at 12 months in two national surveys, Am J Psychiatry 156(1999) pp. 1915-1923.
m P3
030
A polymorphism gene (BHTTLPR) patients
study of serotonin in Korean social
transporter phobia
KS. Oh’, H.K. Yoou2, M.S. Lee3 Y.C. Shiu2. ‘Kanglmk Samsung hospital, Sungkyunkwan &iversity, Psychiatry, Seoul, Republic of Korea; 2Kanglmk Samsung Hospital, Psychiatry, Seoul, Republic of Korea; 3College of Medicine,Korea University, Psychiatry, Seoul, Republic of Korea Serotouergic system have beeu reported to be implicated in the pathogeuesis of anxiety disorders. Polymorphism of serotouiu transporter geue (5-HTTLPR) could be associated with serotouergic fuuctiou variability in social phobia. The authors conducted au comparing study using 5-HTTLPR polymorphism comparing 30 social phobia patients aud 30 age, sex matched uonnal controls in Korea. Fresh bloods were obtained, aud PCR aud RFLP analysis were applied for detecting the polymorphism of 5-HTTLPR gene. We could find three differeut genotypes (l/s, l/l, s/s) of 5-HTTLPR. Niueteeu patients (63.3%) showed l/s type, uiue patients (30.0%) showed s/s type, aud ouly 2 patients (6.7%) showed l/l type. Among 30 uonnal controls, uiue (30.0%) showed l/s type, twenty (66.7%) showed s/s type, aud ouly oue (3.3%) showed l/l type. Our results showed that Korean social phobia patients showed higher proportiou of l/s type wheu compared with uonnal controls. The more systematized studies ueeded to iuvestigate the meauiug of the differeut genotypes in Korean social phobia patients. References [l]
[2]
Greenberg BD, Tolliver TJ, Haung SJ, Li Q, Bengel D, Murphy DL (1999): Genetic variation in the serotonin transporter gene affects serotonin uptake in human blood platelets. Am J Med Genet Neuropsychiatr Genet 88/l 83-87. Ohm K, Suzuki Y, Ochiai M, Tsukamoto T, Tani K (1999): A variable number tandem repeat of the serotonin transporter gene and anxiety disorders. Progress Neuro-Psychophamacol BIOL PSYCHIATRY 23/l: 55-65.
and
anxiolytics
Ip.3.0311 A comparative moclobemide, of PTSD
study of fluoxetine, and tianeptine in the
treatment
E. &der’ ,o. Tura12, T. Aker’ ‘Kocaeli University, Psychological Trauma Centel; Kocaeli, Turkey; 2Kocaeli University, Psychiatry Department, Kocaeli, Turkey Objective: Although autidepressaut drugs have beeu proveu as au effective treatment for PTSD, there are a few comparative studies of autidepressauts that are acting 011 differeut ueurotrausmitters. The maiu aim of this study is to compare the efficacy of differeut class of autidepressaut drugs 011 the PTSD. Methods: After au iufonned couseut the patieuts, who met DSM-IV criteria for PTSD, randomly assigned to flexible doses of fluoxetiue, moclobemide, or tiaueptiue. During this open label study, the patients were uot allowed to take auother psychotropic drug or to participate in a structured psychotherapy. After the first assessment the other assessments were perfonned at the cud of the weeks 2,4, 8, aud 12 using CAPS, CGI-S aud CGI-I. Chauges in the total score of CAPS aud subscale scores of symptom clusters (re-experience, avoidance, aud hyperarousal) were the maiu output of efficacy. Differences betweeu coutiuuous variables were assessed using one-way or repeated measures of ANOVA tests. Those betweeu categorical variables were assessed using Pearsou Chi-Square test. All statistics were based 011 iuteutiou to treat aud LOCF principles. P values are two-tailed, aud statistical significaiice was 5% level. Results: Of the 103 patients euteriug 12-weeks of treatment period; 38 patients were assigned to fluoxetiue, 35 patients were assigned to moclobemide, aud 30 patients were assigned to tiaueptiue group. The meau ages of groups were as follows; for fluoxetiue 31.517.3, for moclobemide 30.416.9, for tiaueptiue 32.317.3. There was 110 significant differences in the meau ages of groups (F~0.561, df=2, ~~0.572). There were 18(47.4%) women in fluoxetiue group, lS(5 1.4%) in moclobemide group, aud 16(53.3%) in tiaueptiue group. This distribution of sex was uot significantly differeut M2~0.257, df=2, p=O.879). Drop-out rate of the study due to au adverse eveuts or uukuowu reasons was uot siguificautly differeut among fluoxetiue (18.4%), moclobemide (14.3%), aud tiaueptiue (20.0%) groups (X2=0.403, df=2, p=O.817). A verage daily dose of fluoxetiue was 27.419.8 mg, of moclobemide 565.71115.5 mg, aud of tiaueptiue 4 1.315.8. There were 110 siguificaut differences in the total CAPS scores at the baseline assessment among fluoxetiue (83.6115. l), moclobemide (84.9113.4), aud tiaueptiue (82.1118.8) groups (F~0.247, df=2, p=O.781). All three treatments has led to a significant improvement in PTSD severity assessed with CAPS total score (F~421.268, dfT1.00, piO.OOl), although there was 110 significant differences improvement among the treatment groups throughout the study (FTO.296, dfT2.00, ~~0.745). Similarly, total scores of re-experiencing, avoidance, aud hyperarousal clusters that are subscales of CAPS were reduced by all three treatmeuts significantly (respectively F~241.043, df=l ,OO, piO.001; F~301.568, dfT1.00, piO.001; F~435.173, dfT1.00, p
disorders
poteutiated startle in response to a threat stimulus is expressed as a chauge from baseline startle amplitude to startle amplitude in the threat condition The aim of the present study was to examiue the auxiolytic aud sedative effects of LY354740 in humaus using the fear poteutiated startle reflex paradigm. Forty-seven healthy meu aud women participated in the study. All participants were required to have a body mass index betweeu 19 aud 28 kglm2, aud to have 110 clinically significant abnormalities in EKG, lab chemistry, or medical examination Participants were also excluded if they met criteria for auy psychiatric disorder (as determiued using DMS-IV SCID), had a history of drug or alcohol abuse, or had small baseline startle reflexes (meau of less thau 50 iV over uiue startle responses). Participants who met all entry criteria received single doses of placebo (N=16), 20 mg LY354740 (N=15) or 200 mg LY354740 (N=13). Testing consisted of au assessment of baseline startle. Patients were theu giveu study drug. After 3 hours, this was followed by a test of threat of au electric shock aud darkness (fear poteutiated startle test). LY354740 did uot affect baseline startle. Cousisteut with previous results, startle was iucreased by threat of shock aud darkness. The degree of startle poteutiatiou during threat was siguificautly less in LY354740treated participants, thau in placebo-treated participants, resulting in a siguificaut Treatment x Couditiou iuteractiou, F( 1,42)=4.5, pi.04. Additionally, the overall level of anxiety during the test was lower in the LY354047-treated patieuts, compared to the placebo group, F(1,42)=5.702, piO.02 without developmeut of sedation These results are comparable to those observed in the rat model of fear poteutiated startle. In summary, LY354740 treatment was associated with reduced expression of fear poteutiated startle in response to a threat signal without affecting baseline startle response. Additionally, subjective data suggest that LY354740 reduced the overall anxiety level associated with participation in au experiment where uupleasaut shocks were administered. LY35470 appears to be associated with au auxiolytic profile in humans without being sedating.
lp.3.0281 Evaluation profile compared
of
of the cognitive and psychomotor a novel anxiolytic, LY54434-4, to lorazepam in normal volunteers
.I. Boyle’, L. Trick’, S. Soo-ampou’ I. Hindmarch’ ’ University of Surrey, Centre, Guildford, United Kingdom; Neuroscience, Indianapolis, US.A.
, S. Lilley’ , L. Leviue2, HPRU Medical Research 2Eli Lilly & Company,
Objective: LY544344 is the iuactive peptidyl prodrug form of the highly poteut aud selective mGlu2 agonist, LY354740. LY354740 is a novel pharmacological compound, which has previously beeu showu to demonstrate auxiolytic aud autipauic properties in a variety of auimal models (Schoepp et al., 1999). The curreut study was designed to evaluate the effects of repeated doses of LY544344 at a low (7.5 mg) aud supra-high (40 mg) dose compared with lorazepam (J,ZP) aud placebo 011 cognitive, psychomotor aud road driving parameters. Methods: 24 male aud female healthy volunteers (18-35 years) were raudomised, double-blind, to a four-way crossover study, with at least a 3-day washout betweeu treatments. A standard battery of cognitive aud psychomotor tests was administered 2 aud 4 hours post-dose, iucludiug on-the-road car driving. Results: Repeated measures ANOVAs demo&rated that LZP significantly impaired perfonnauce compared to LY544344 7.5 aud 40 mg 011 Choice Reaction Time: Recognition (piO.OOOl),
and
anxiolytics
S365
Motor (p=O.O006 aud 0.0003, respectively) aud Total reaction time (piO.0001); Compensatory Tracking (piO.0001); Rapid Visual Iufonnatiou Processing (piO.0001); Steinberg’ s Short-tenn Memory Scamring Test (p=O.O013 aud p=O.O144, respectively) aud Immediate aud Delayed recall of words (piO.0001). In addition LZP siguificautly impaired on-the-road driving perfonnauce as measured by Brake Reaction Time (piO.0001) compared to LY544344 7.5 aud 40 mg. In contrast, LY544344 7.5 aud 40 mg did uot significantly affect cognitive fuuctiou, psychomotor perfonnauce or driving ability compared to placebo 011 auy of the measures tested. Conclusions: Psychological tests are considered as aualogues of real-life behaviour, since perfonnauce chauges cau reflect the poteutial impainneut of the activities of daily living (Hiudmarch, 1988). This study clearly demonstrates that LZP, a 1,4beuzodiazepiue, impairs cognitive functioning, psychomotor perfonnauce aud car driving ability. More specifically, LZP impairs the cognitive aud motor compoueuts of response to novel stimuli, reduces tracking accuracy, has a detrimental effect 011 the ability to remail1 vigilaut, disrupts working memory aud produces trausieut auterograde amnesia. In contrast, LY544344 at both low aud suprahigh dose displays a distinct behavioural aud cognitive profile to LZP with 110 evidence for impainneut 011 cognition, atteutiou, memory or psychomotor perfonnauce. References [l]
[2]
Hindmarch, I. (1988) A Pharmacological Profile of Fluoxetine and Other Antidepressants on Aspects of Skilled Performance and Car Handling Ability’ , British Journal of Psychiatry,l53: S99-S104. Schoepp, D.D., Mom, J.A., Marek, G.J., Aghajanian, G. and Moghaddam, B. (1999) LY354740: A Systemically Active mGlu2/mGlu3 Receptor Agonist, CNS Drug Reviews, 5: l-12.
lP.3.0291
Efficacy life and disorder
of sertraline functioning (GAD)
in improving in generalized
quality anxiety
of
I. Sjodiu’ , S.P. Kutcher2, A. Raviudrau3, T. Burt4. ‘Psykiatriska Kliniken Universitetsjukhuset, Psychiatry, Linkoping, Sweden; 2Dalhousie University, Psychiatry, Nova Scotia, Canada; 3Royal Ottawa Hospital, Psychiatry & Psychopharmacology, Ottawa, Canada; 4qfzel;Inc., Depression/Anxiety, New York City, US.A. Objective: GAD is a chrouic ilhless associated with significant impainneut in quality of life (QoL) aud fuuctiouiug. Though comorbidity is frequent, community surveys indicate that eveu “pure” GAD results in fuuctioual impainneut that is similar to major depression The goal of this iuvestigatiou was to evaluate effect of short-tenn treatment with sertraliue 011 QoL aud work productivity in GAD. Methods: Adult outpatients were eligible who met DSM-IV criteria for GAD with a minimum HAM-A total score= 18 (anxiety aud teusiou items eachh2). After completion of a single-blind placebo lead-in period patients were randomized to 12 weeks of double-blind treatment with placebo (N=l88; female, 5 1%; meau age, 42 years; baseline HAM-A, 25) or flexible doses (SO&l50 mg) of sertraliiie (N=l82; female, 59%; meaii age, 40 years; baseline HAM-A, 25). Outcomes included the Quality of Life, Eujoymeut, aud Satisfaction scale (Q-LES-Q), the Eudicott Work Productivity impainneut scale (EWP-impainneut), aud a lo-point visual aualogue scale measuring perceived state of health @‘AShealth). Nonnal QoL was defined as a Q-LES-Q score withiu 10% of commuiiity iionns.
S366
P3.
Anxiety
disorders
Results: At baseline, 11.8% of patieuts reported normal Q-LES-Q scores, while 41.2% had markedly abnormal QoL (QLES-Q =2 standard deviatious below the community uorm meau). Treatment with sertraliue resulted in siguificautly greater improvemeut thau placebo 011 the Q-LES-Q (+9.0 11.0 vs. +2.410.9; p i O.OOOl), the EWP-impairment score (-9.211.3 vs. -2.511.4; p i O.OOOl), aud the VAS-health scale (+1.710.2 vs. +0.810.1; p i 0.0001). Improvement in QoL occurred early (siguificaut by first assessment at week 6), aud was cousisteut across all scale items 011 both the Q-LES-Q aud the EWP-impairment scale. Rates of QoL uonnalizatiou 011 sertraliue were progressively higher among study completers (5 l%), responders (66%), aud remitters (HAM-A =7: 71%). Iuterestiugly, a regression analysis found improvement in depressive symptoms (MADRS-change score) to be the ouly clinically meauiugful predictor of improved QoL (partial R2~0.322, piO.001). Conclusion: Sertraliue treatment resulted in siguificaut aud rapid improvement in QoL aud fuuctioual impainneut. Source of Funding: PfizerJuc. References [l]
R.C. Kessler, R.L. Dupont, I? Berglund, H.U. Wittchen, Impairment in pure and comorbid generalized anxiety disorder and major depression at 12 months in two national surveys, Am J Psychiatry 156(1999) pp. 1915-1923.
m P3
030
A polymorphism gene (BHTTLPR) patients
study of serotonin in Korean social
transporter phobia
KS. Oh’, H.K. Yoou2, M.S. Lee3 Y.C. Shiu2. ‘Kanglmk Samsung hospital, Sungkyunkwan &iversity, Psychiatry, Seoul, Republic of Korea; 2Kanglmk Samsung Hospital, Psychiatry, Seoul, Republic of Korea; 3College of Medicine,Korea University, Psychiatry, Seoul, Republic of Korea Serotouergic system have beeu reported to be implicated in the pathogeuesis of anxiety disorders. Polymorphism of serotouiu transporter geue (5-HTTLPR) could be associated with serotouergic fuuctiou variability in social phobia. The authors conducted au comparing study using 5-HTTLPR polymorphism comparing 30 social phobia patients aud 30 age, sex matched uonnal controls in Korea. Fresh bloods were obtained, aud PCR aud RFLP analysis were applied for detecting the polymorphism of 5-HTTLPR gene. We could find three differeut genotypes (l/s, l/l, s/s) of 5-HTTLPR. Niueteeu patients (63.3%) showed l/s type, uiue patients (30.0%) showed s/s type, aud ouly 2 patients (6.7%) showed l/l type. Among 30 uonnal controls, uiue (30.0%) showed l/s type, twenty (66.7%) showed s/s type, aud ouly oue (3.3%) showed l/l type. Our results showed that Korean social phobia patients showed higher proportiou of l/s type wheu compared with uonnal controls. The more systematized studies ueeded to iuvestigate the meauiug of the differeut genotypes in Korean social phobia patients. References [l]
[2]
Greenberg BD, Tolliver TJ, Haung SJ, Li Q, Bengel D, Murphy DL (1999): Genetic variation in the serotonin transporter gene affects serotonin uptake in human blood platelets. Am J Med Genet Neuropsychiatr Genet 88/l 83-87. Ohm K, Suzuki Y, Ochiai M, Tsukamoto T, Tani K (1999): A variable number tandem repeat of the serotonin transporter gene and anxiety disorders. Progress Neuro-Psychophamacol BIOL PSYCHIATRY 23/l: 55-65.
and
anxiolytics
Ip.3.0311 A comparative moclobemide, of PTSD
study of fluoxetine, and tianeptine in the
treatment
E. &der’ ,o. Tura12, T. Aker’ ‘Kocaeli University, Psychological Trauma Centel; Kocaeli, Turkey; 2Kocaeli University, Psychiatry Department, Kocaeli, Turkey Objective: Although autidepressaut drugs have beeu proveu as au effective treatment for PTSD, there are a few comparative studies of autidepressauts that are acting 011 differeut ueurotrausmitters. The maiu aim of this study is to compare the efficacy of differeut class of autidepressaut drugs 011 the PTSD. Methods: After au iufonned couseut the patieuts, who met DSM-IV criteria for PTSD, randomly assigned to flexible doses of fluoxetiue, moclobemide, or tiaueptiue. During this open label study, the patients were uot allowed to take auother psychotropic drug or to participate in a structured psychotherapy. After the first assessment the other assessments were perfonned at the cud of the weeks 2,4, 8, aud 12 using CAPS, CGI-S aud CGI-I. Chauges in the total score of CAPS aud subscale scores of symptom clusters (re-experience, avoidance, aud hyperarousal) were the maiu output of efficacy. Differences betweeu coutiuuous variables were assessed using one-way or repeated measures of ANOVA tests. Those betweeu categorical variables were assessed using Pearsou Chi-Square test. All statistics were based 011 iuteutiou to treat aud LOCF principles. P values are two-tailed, aud statistical significaiice was 5% level. Results: Of the 103 patients euteriug 12-weeks of treatment period; 38 patients were assigned to fluoxetiue, 35 patients were assigned to moclobemide, aud 30 patients were assigned to tiaueptiue group. The meau ages of groups were as follows; for fluoxetiue 31.517.3, for moclobemide 30.416.9, for tiaueptiue 32.317.3. There was 110 significant differences in the meau ages of groups (F~0.561, df=2, ~~0.572). There were 18(47.4%) women in fluoxetiue group, lS(5 1.4%) in moclobemide group, aud 16(53.3%) in tiaueptiue group. This distribution of sex was uot significantly differeut M2~0.257, df=2, p=O.879). Drop-out rate of the study due to au adverse eveuts or uukuowu reasons was uot siguificautly differeut among fluoxetiue (18.4%), moclobemide (14.3%), aud tiaueptiue (20.0%) groups (X2=0.403, df=2, p=O.817). A verage daily dose of fluoxetiue was 27.419.8 mg, of moclobemide 565.71115.5 mg, aud of tiaueptiue 4 1.315.8. There were 110 siguificaut differences in the total CAPS scores at the baseline assessment among fluoxetiue (83.6115. l), moclobemide (84.9113.4), aud tiaueptiue (82.1118.8) groups (F~0.247, df=2, p=O.781). All three treatments has led to a significant improvement in PTSD severity assessed with CAPS total score (F~421.268, dfT1.00, piO.OOl), although there was 110 significant differences improvement among the treatment groups throughout the study (FTO.296, dfT2.00, ~~0.745). Similarly, total scores of re-experiencing, avoidance, aud hyperarousal clusters that are subscales of CAPS were reduced by all three treatmeuts significantly (respectively F~241.043, df=l ,OO, piO.001; F~301.568, dfT1.00, piO.001; F~435.173, dfT1.00, p