Pharmacotherapy for post traumatic stress disorder (PTSD)

 

Characteristics of included studies [ordered by study ID]

Baker 1995 a

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Methods	DESIGN Description: random-assignment, placebo-controlled, parallel arm, flexible dose, double-blind, single-blind placebo run-in BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: Unclear RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 146 DSM-III-R PTSD, average age: 44 years (23-73), 81% male, mean duration of diagnosis: 12.8 years, MDD not present, 60% combat-related SCREENING Primary diagnosis: symptoms at least 6 months, CAPS >= 45, MADRS <= 22 Comorbidity: MADRS
Interventions	Description: brofaromine up to 150 mg/d vs placebo x 12 weeks
Outcomes	Primary outcomes: CAPS Secondary outcomes: IES, DTS, CGI NOTES: CGI (values not reported, CGI-C obtained from Davidson et al, 1997), ITT (LOCF 1 post-baseline assessment) values provided.
Notes	INDUSTRY SUPPORT Industry funded: Not mentioned Medication provided by industry: No Any of the authors work for industry: Yes ADDITIONAL INFORMATION Drop-out rates: total of 35 Quality rating score: 15 Single-blind placebo run-in excluded 28 placebo-responders Obtained additional HAM-D and CAPS-2 summary statistics from Sudie Back
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Brady 2000

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Methods	DESIGN Description: random-assignment, placebo-controlled, parallel arm, flexible dose, double-blind, single blind 2 week placebo run-in BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: Unclear RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 187 DSM-III-R PTSD, 6% combat-related, mean age: 39.9 years (18-69), 27% male, 33% (62/187) with current major depression SCREENING Primary diagnosis: CAPS-1, 6-month duration, CAPS >= 50 at end of placebo run-in Comorbidity: No information
Interventions	Description: sertraline 50-200 mg/d (mean endpoint dose: 133.3 mg/d) versus placebo x 12 weeks
Outcomes	Primary outcomes: CGI-C, CGI-S, CAPS-2, IES. Responders defined as 30% or greater decrease on CAPS-2 and CGI-C of 1 or 2. Secondary outcomes: DTS, HAM-D, Q-LES-Q Data estimation: LOCF (1 post-baseline assessment)
Notes	INDUSTRY SUPPORT Industry funded: Yes Medication provided by industry: No Any of the authors work for industry: Yes ADDITIONAL INFORMATION Drop-out rates: 30/94(32%) on sertraline, 28/93(30%) on placebo. Quality rating score: 31
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Brady 2004

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Methods	DESIGN Description: random-assignment, placebo-controlled, parallel arm, fixed dose, double-blind, 4 day tapering of medication at end of trial, single blind 1 week placebo run-in BLINDING Participants: unclear Assessors: unclear Administrators: unclear ALLOCATION CONCEALMENT Method: unclear RANDOMISATION Method: urn randomisation by gender, depressive disorder, trauma type, and age of index trauma
Participants	SAMPLE Description: 94 DSM-IV PTSD with concurrent alcoholism (LOCF sample), no war veterans, mean age: 36.7 years, 54% male, SCREENING Primary diagnosis: CAPS, SCID, CAPS >= 30% decrease after placebo run-in grounds for exclusion Comorbidity: TLFB
Interventions	Description: sertraline (50 mg/d - 150 mg/d) versus placebo (50 mg/d - 150 mg/d) x 12 weeks
Outcomes	Outcomes: OCDS, CAPS, HAM-D, SID, IES (not clear whether primary or secondary) Data estimation: LOCF (1 post-baseline assessment)
Notes	INDUSTRY SUPPORT Industry funded: unclear Medication provided by industry: Yes Any of the authors work for industry: No ADDITIONAL INFORMATION Drop-out rates: information not provided, 3 patients excluded as responders during placebo run-in Quality rating score: 22
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Braun 1990

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Methods	DESIGN Description: random-assignment, placebo-controlled, crossover, 2 week titrated placebo washout, flexible dose, double-blind, single centre BLINDING Participants: Unclear Assessors: Yes Administrators: Unclear ALLOCATION CONCEALMENT Method: Unclear RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 16 DSM-III PTSD, 25% combat-veterans, mean age: 37.7 years (19-56), 13% (2/16) MDD, described as chronic and treatment-refractory SCREENING Primary diagnosis: Unclear Comorbidity: None
Interventions	Description: alprazolam 1.5mg to 6 mg/d (max avg: 4.65 mg/d) in divided doses vs placebo x 5 weeks each phase of crossover
Outcomes	Outcomes: DSM based PTSD scale, IES, HAM-D, HAM-A, Visual Analogue (not clear which outcomes are secondary or primary). Data estimation: Observed cases for patients who completed 5 weeks of both phases
Notes	INDUSTRY SUPPORT Industry funded: Unclear Medication provided by industry: Unclear Any of the authors work for industry: Unclear ADDITIONAL INFORMATION Drop-out rates: 3/7 (43%) on alprazolam, 3/9 (33%) on placebo. Quality Rating Scale score: 14
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Butterfield 2001

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Methods	DESIGN Description: random-assignment, placebo-controlled, parallel arm, flexible dose, double-blind BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: Unclear RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 15 DSM-IV PTSD, mean age: 43.2 years (26-73), 14 women, 53.3% (8/15) MDD, most common comorbid diagnosis: GAD - 64.3% (9/15), baseline severity on TOP-8: olanzapine (19.3), placebo (21.8) SCREENING Primary diagnosis: SIP Comorbidity: MINI
Interventions	Description: olanzapine 5 mg/d - 20mg/d (max. mean 14.1 mg/d) versys placebo (max. mean: 13.9mg/d) x 10 weeks
Outcomes	Primary outcomes: TOP-8, SPRINT, Secondary outcomes: IES, DTS, CGI-I, SDS, BAS, AIMS Data estimation: ITT (General linear model)
Notes	INDUSTRY SUPPORT Industry funded: Yes Medication provided by industry: No Any of the authors work for industry: No ADDITIONAL INFORMATION Drop-out rates: 3/15 (20%) on olanzapine and 1/5 (20%) on placebo. Quality rating score: 24
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Chung 2004

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Methods	DESIGN Description: random-assignment, placebo-controlled, parallel arm, flexible dose, non-blinded, single centre BLINDING Participants: No Assessors: No Administrators: No ALLOCATION CONCEALMENT Method: None RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 113 DSM-IV Korean war veterans, mean age: 59.8 , mean duration of diagnosis:34.5, 17% (17/100) MDD, baseline severity on CAPS-2: mirtazapine (103.2), sertaline (88.8) SCREENING Primary diagnosis: Unclear Comorbidity: None
Interventions	Description: mirtazapine 15 mg/d - 34.1 mg/d (mean daily dose) versus sertraline 50mg/d - 101.5mg/d (mean daily dose) x 6 weeks
Outcomes	CAPS-2, HAM-D (17 item), CGI-I, CGI-S (no distinction made between primary and secondary outcomes) Data estimation: completer values
Notes	INDUSTRY SUPPORT Industry funded: Yes Medication provided by industry: No Any of the authors work for industry: No ADDITIONAL INFORMATION Drop-out rates: 12.1% (7/58) on mirtazapine, 10.9% (6/55) on sertraline Quality rating score: 27 Patients taking antidepressants were placed on 7 day washout priot to entering trial
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Conner 1999

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Methods	DESIGN Description: random-assignment, placebo-controlled, parallel arm, flexible dose, double-blind, single centre BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: randomisation only known to hospital pharmacy RANDOMISATION Method: computer generated randomisation into groups
Participants	SAMPLE Description: 54 DSM-III PTSD, none combat-related, duration of diagnosis: 6 years (median), median age: 37 years (18-55), 91% female, baseline severity on DGRP: fluoxetine (4.2) placebo (4.6) SCREENING Primary diagnosis: SCID Comorbidity: None
Interventions	Description: fluoxetine (20-60 mg/d; median: 30 mg/d) vs placebo (20-60 mg/d; median: 40 mg/d) x 12 weeks
Outcomes	Primary outcomes: DGRP(change, severity) Secondary outcomes: SIP, DTS, SDS. VS. Data estimation: LOCF (1 post-baseline assessment)
Notes	INDUSTRY SUPPORT Industry funded: No Medication provided by industry: Yes Any of the authors work for industry: No ADDITIONAL INFORMATION Drop-out rates: 6/27(22%) on fluoxetine and 12/27(44%) on placebo. Quality rating score: 28
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Yes	A - Adequate

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Davidson

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Methods	DESIGN Description: Randomised, double-blind, placebo-controlled, parallel flexible dose trial BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: Unclear RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 538 DSM-IV PTSD, 65.4% females, average age: 32 years SCREENING Primary diagnosis: Unclear Comorbidity: Unclear
Interventions	Description: sertraline (25 mg/d -200 mg/d), venlafaxine (37.5 mg/d - 300 mg/d) versus placebo x mean duration of 84 days
Outcomes	CAPS, CGI-S, DTS, GAF (no distinction made between primary and secondary outcomes) Data estimation: Unclear
Notes	INDUSTRY SUPPORT Industry funded: Unclear Medication provided by industry: Unclear Any of the authors work for industry: Unclear ADDITIONAL INFORMATION Drop-out rates: 40.5% (218/538) dropout rate ? Quality rating score: Not calculated
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Davidson 1990

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Methods	DESIGN Description: balanced randomization, placebo-controlled, parallel arms, flexible dose, double-blind, single centre BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: Unclear RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 46 DSM-III PTSD, chronic, combat veterans, presumably all males, inpatients included, 20% (9/46) MDD, most common comorbid diagnosis: GAD (16), baseline severity on IES: amitriptyline (33.1) placebo (36.8) SCREENING Primary diagnosis: SI-PTSD Comorbidity: None
Interventions	Description: amitriptyline (50-300 mg/d) vs placebo x 8 weeks, ongoing supportive psychotherapy
Outcomes	Primary outcomes: CGI-I , SI-PTSD, CGI-S Secondary outcomes: HAM-D, HAM-A, IES, NI, EPI Data estimation: completer values
Notes	INDUSTRY SUPPORT Industry funded: No Medication provided by industry: No Any of the authors work for industry: No ADDITIONAL INFORMATION Drop-out rates: 8/25 (32%) on amitriptyline, 5/21 (24%) on placebo. Quality rating score: 24
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Davidson 2001

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Methods	DESIGN Description: random-assignment, placebo-controlled, parallel arm, flexible dose, double-blind, multicentre, 1 week single-blind placebo run-in BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: Unclear RANDOMISATION Method: computer generated
Participants	SAMPLE Description: 208 DSM-III-R PTSD, 5% war trauma, mean age: 37.1 (18-69), 78% male, duration of diagnosis: 12.3 years, 40% (83/208) MDD, baseline severity on CAPS-2: sertraline (73.9) placebo (73.5) SCREENING Primary diagnosis: CAPS-1, CAPS-2 >= 50, minimum 6 months duration Comorbidity: None
Interventions	Description: sertraline 25 mg/d to between 50-200 mg/d (avg: 146.3 mg/d) vs. placebo x 12 weeks
Outcomes	Primary outcomes: CAPS-2, IES, CGI-S, CGI-I Secondary outcomes: DTS, HAM-D, HAM-A, PSQI Data estimation: LOCF (1 post-baseline assessment)
Notes	INDUSTRY SUPPORT Industry funded: Yes Medication provided by industry: No Any of the authors work for industry: Yes ADDITIONAL INFORMATION Drop-out rates: 30% on sertraline and 27% on placebo (not clear which sample was used as denominator) Quality rating score: 33
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Davidson 2003

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Methods	DESIGN Description: random-assignment, placebo-controlled, parallel arm, fixed dose, double-blind, single centre, 1 week single-blind placeb run-in BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: Unclear RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 29 DSM-IV PTSD, 15% (4/26) war trauma, mean age: 46.5 years, 73% (19/26) MDD, baseline severity on SPRINT: mirtrazapine (21.7), placebo (25) SCREENING Primary diagnosis: SIP =< 20 Comorbidity: MINI
Interventions	Description: mirtrazapine 15 mg/d - 45 mg/d (mean end dose: 38.8 mg/d) versus placebo (mean end dose: 43.3 mg/d) x 8 weeks
Outcomes	Primary outcomes: SPRINT(Clinical Global Improvement & Total Scores) Secondary outcomes: DTS, HADS, SIP, ASEX Data estimation: LOCF (1 post-baseline assessment)
Notes	INDUSTRY SUPPORT Industry funded: Yes Medication provided by industry: No Any of the authors work for industry: Yes ADDITIONAL INFORMATION Drop-out rates: 18% (3/17) on mitrazapine and 33% (3/9) on placebo Quality rating score: 27
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Davis 2001

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Methods	DESIGN Description: random-assignment, placebo-controlled, parallel arm, flexible dose, double-blind, multi-centre BLINDING Participants: Yes Assessors: Yes Administrators: Yes (self-administered) ALLOCATION CONCEALMENT Method: randomisation log kept by pharmacist RANDOMISATION Method: No information
Participants	SAMPLE Description: 42 DSM-IV PTSD, 98% (40/41) combat veterans, mean age: 53.8 years (32-75), 98% (40/41) male, average duration of illness: 29.9 years, 39% (16/41) MDD, baseline severity on CAPS: nefazodone (81) and placebo (83.2) SCREENING Primary diagnosis: SCID Comorbidity: SCID
Interventions	Description: nefazodone 200 mg/d - 600 mg/d (avg final dose: 435mg/d) versus placebo x 12 weeks
Outcomes	Primary outcomes: CAPS Secondary outcomes: HAM-A, HAM-D, PTSD checklist, CADSS, GAFS, CGI Data estimation: LOCF (excluded 1 patient due to compromise of blind)
Notes	INDUSTRY SUPPORT Industry funded: Yes Medication provided by industry: No Any of the authors work for industry: No ADDITIONAL INFORMATION Drop-out rates: 46% (12/26) on nefazodone and 40% (6/15) on placebo Quality rating score: 25
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Yes	A - Adequate

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Eli Lilly

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Methods	DESIGN Description: Randomised, double blind, placebo-controlled, parallel fixed dose trial BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: Unclear RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 411 PTSD SCREENING Primary diagnosis: Unclear Comorbidity: Unclear
Interventions	Description: fluoxetine 20 mg/d (N = 163) and 40 mg/d (N = 160) versus placebo (N = 88) x mean of 84 days
Outcomes	TOP-8,CGI-S (no distinction made between primary and secondary outcomes) Data estimation: ITT
Notes	INDUSTRY SUPPORT Industry funded: Yes Medication provided by industry: Yes Any of the authors work for industry: Yes ADDITIONAL INFORMATION Drop-out rates: 259 (63%) dropouts in total Quality rating score: Not calculated
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Hertzberg 1999

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Methods	DESIGN Description: random-assignment, placebo-controlled, parallel arms, flexible dose, double blind, multi-centre BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: No information RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 15 DSM-IV PTSD, 71% (10/14) war combat, mean age: 43.4 years (29-53), 64% (9/14) male, baseline severity on SI-PTSD: lamotrigine (44.8) and placebo (43) SCREENING Primary diagnosis: SIP Comorbidity: MINI
Interventions	Description: lamotrigine 25 mg/d -500mg/d (avg. max. dose: 380 mg/d) versus placebo x 8 weeks
Outcomes	ITT(LOCF) values provided. Primary outcomes: SIP, DGRP Secondary outcomes: None Data estimation: LOCF (excluded 1 patient)
Notes	INDUSTRY SUPPORT Industry funded: Yes Medication provided by industry: No Any of the authors work for industry: No ADDITIONAL INFORMATION Drop-out rates: 27% (3/11) on lamotrigine and 75% (3/4) on placebo Quality rating score: 23
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Hertzberg 2000

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Methods	DESIGN Description: random-assignment, placebo-controlled, parallel arms, flexible dose, double blind, single centre BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: No information RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 12 DSM-IV PTSD, male Vietnam combat veterans, mean age: 46 years (44-48), 66% (8/12) MDD, baseline severity on DTS: fluoxetine (106) and placebo (111) SCREENING Primary diagnosis: SIP Comorbidity: SCID - DSM-III-R
Interventions	Description: fluoxetine 10 mg/d - 60 mg/d (mean endpoint dose: 48 mg/d) vs placebo x 12 weeks
Outcomes	DTS, SDS, SIP, DGRP (no distinction between primary and secondary outcomes) Data estimation: Presumably LOCF (not clear in text)
Notes	INDUSTRY SUPPORT Industry funded: No Medication provided by industry: Yes Any of the authors work for industry: No ADDITIONAL INFORMATION Drop-out rates: 1/6 (17%) on fluoxetine and 0/6 (0%) on placebo Quality rating score: 21
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Kaplan 1996

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Methods	Description: random-assignment, placebo-controlled, crossover, fixed dose, double-blind, 2 week washout period BLINDING Participants: Yes Assessors: Unclear Administrators: Yes (self administered) ALLOCATION CONCEALMENT Method: Identical capsules used for medication and placebo RANDOMISATION Method: pre-arranged random code
Participants	SAMPLE Description: 17 DSM-III-R PTSD, 23% (3/13) combat-related, mean age for OC: 39.7 year (25-56), 62% male, duration of diagnosis for OC: 0.5-28 years, no comorbid major depression, baseline severity on IES for OC: inositol (35.8) and placebo (34.9) SCREENING Primary diagnosis: No information Comorbidity: No information
Interventions	Description: inositol 12 g/d versus placebo x 4 weeks
Outcomes	IES , SCL-90 (1 centre), HAM-A, HAM-D (other centre) (no distinction between primary and secondary outcomes) Data estimation: Completer values
Notes	INDUSTRY SUPPORT Industry funded: No information Medication provided by industry: No Any of the authors work for industry: No information ADDITIONAL INFORMATION Drop-out rates: 4/17 (24%) Quality rating score: 13
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Katz 1994

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Methods	Description: random-assignment, placebo-controlled, parallel arm, flexible dose, double-blind, multi-centre, 2 week single-blind placebo run-in BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: No information RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 64 DSM-III-R PTSD, 17% (8/45) combat-related, median age: 39 (22-62), 76% male, duration of diagnosis: 2.8 years, baseline severity on CAPS: brofaromine (80.6) and placebo (82.9) SCREENING Primary diagnosis: CAPS > 36, response of >= 20% decrease on CAPS during placebo run-in Comorbidity: HAM-D > 21
Interventions	Description: brofaromine 50 mg/d -150 mg/d versus placebo x 14 weeks
Outcomes	Primary outcomes: CAPS Secondary outcomes: CGI Data estimation: LOCF
Notes	INDUSTRY SUPPORT Industry funded: Yes Medication provided by industry: Unclear Any of the authors work for industry: Yes ADDITIONAL INFORMATION Drop-out rates: 30% (10/33) on brofaromine and 29% (9/31) on placebo Quality rating score: 24 CGI-C values obtained from Davidson et al, 1997
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Kosten 1991

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Methods	DESIGN Description: random-assignment, comparator and placebo-controlled, parallel arm, flexible dose, double-blind, multi-centre BLINDING Participants: Yes Assessors: No Administrators: Unclear ALLOCATION CONCEALMENT Method: No information RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 60 DSM-III-PTSD, all combat veterans, mean age: 39 years, all males, no subjects with comorbid major depression, baseline severity on IES: imipramine (36.5), phenelzine (30.6) and placebo (33) SCREENING Primary diagnosis: SCID Comorbidity: SADS
Interventions	Description: imipramine 50 mg/d - 300 mg/d (avg max. dose: 225 mg/d) versus phenelzine 15 mg/d - 75 mg/d (avg max. dose: 68 mg/d) versus placebo x 8 weeks
Outcomes	Primary outcomes: IES Secondary outcomes: Combat Scale; CAS; HAM-D; HAM-A; RSD Data estimation: LOCF (completers of 3 or more weeks)
Notes	INDUSTRY SUPPORT Industry funded: No Medication provided by industry: Yes Any of the authors work for industry: Yes ADDITIONAL INFORMATION Drop-out rates: 52% (12/23) on impramine, 21% (4/19) on phenelzine and 12/18 (67%) on placebo Quality rating score: 26
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Marshall 2001

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Methods	DESIGN Description: random-assignment, comparator and placebo-controlled, parallel arm, fixed dose, double-blind, 1 week placebo run-in BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: Unclear RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 563 DSM-IV PTSD, mean age: 41.8 years, 57% (315 /551) female, average duration of diagnosis: 15.7 years, approximately 45% (248/551) comorbid MDD, baseline severity on CAPS-2:: paroxetine 20mg/d (75.3), paroxetine 40mg/d (74.3), and placebo ( 74.4) SCREENING Primary diagnosis: MINI, CAPS-1, CAPS-2 >= 50 Comorbidity: No information
Interventions	Description: paroxetine (25 mg/d) or paroxetine (50 mg/d) versus placebo x 12 weeks
Outcomes	Primary outcomes: CAPS-2, CGI-I Secondary outcomes: DTS, TOP-8, SDS, MADRS Data estimation: LOCF (1 post-baseline assessment)
Notes	INDUSTRY SUPPORT Industry funded: Yes Medication provided by industry: No information Any of the authors work for industry: Yes ADDITIONAL INFORMATION Drop-out rates: 35% (66/188) on 20mg/d paroxetine, 40% (74/187) on 40mg/d paroxetine, and 36% (68/188) placebo Quality rating score: 26
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Marshall 2004

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Methods	DESIGN Description: random-assignment, placebo-controlled, parallel arm, flexible dose, double-blind, 1 week single-blind placebo run-in, single centre, with maintenance phase BLINDING Participants: No Assessors: Yes Administrators: Yes ALLOCATION CONCEALMENT Method: No information RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 63 DSM-IV PTSD, no combat-related trauma, mean age: 39.8 years, 67% (35/52) female, 62.5% (30/48) MDD, baseline severity on CAPS: paroxetine (82.8) and placebo (84.2) SCREENING Primary diagnosis: SCID, minimum duration of 3 months PTSD Comorbidity: SCID I
Interventions	Description: paroxetine 10 mg/d - 6 mg/d versus placebo x 10 weeks, followed by 12 week double-blind maintenance phase for responders to paroxetine or placebo
Outcomes	Primary outcomes: CGI, CAPS Secondary outcomes: CAPS-2, IPP, DES, HAM-A, HAM-D, CAP-2 (items 22 & 23) Data estimation: Mixed-effects model regression (1 post-baseline assessment)
Notes	INDUSTRY SUPPORT Industry funded: Yes Medication provided by industry: Unclear Any of the authors work for industry: No ADDITIONAL INFORMATION Drop-out rates: 32% (8/25) on paroxetine and 52% (14/27) on placebo Quality rating score: 21 7 patients removed as responders during placebo run-in Assessments made in either Spanish or English
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Martenyi 2002

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Methods	DESIGN Description: random-assignment, placebo-controlled, parallel arm, fixed dose, double-blind, multi-centre BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: computer drug-labelled emergency codes RANDOMISATION Method: computer generated random sequence
Participants	SAMPLE Description: 301 DSM-IV PTSD, acute, 46% combat-related, mean age: 37.9 years, 81% male, baseline severity on CAPS: fluoxetine ( 80.5) and placebo (81.3) SCREENING Primary diagnosis: SCID-I [modified], CAPS-DX => 50, CGI-S >= 4 Comorbidity: MADRS > 20
Interventions	Description: fluoxetine 20 mg/d - 80 mg/d, (avg dose: 57.8 mg/d) versus placebo x 12 weeks, followed by 24 week relapse prevention period for responders (Martenyi 2002)
Outcomes	Primary outcomes: TOPS-8 Secondary outcomes: CAPS-2, CGI-S, CGI-I, DTS, MADRS, HAM-A, SCL-90-R, DES
Notes	INDUSTRY SUPPORT Industry funded: Yes Medication provided by industry: Not mentioned Any of the authors work for industry: No ADDITIONAL INFORMATION Drop-out rates: not provided Quality rating score: 31 The patient-rated scales, the DTS and SCL-90-R, were translated into other languages
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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McRae 2004

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Methods	DESIGN Description: random-assignment, placebo-controlled, parallel arm, flexible dose, double-blind, multi-centre, 1 week single-blind placebo run-in BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: randomisation sequence kept by research pharmacist RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 37 DSM-IV PTSD, mean age: 40.3 years (18-65), 77% (26/26) female, average duration of diagnosis: 22 years, baseline severity on CAPS: nefazedone (68.85) and placebo (73.77) SCREENING Primary diagnosis: MINI; CAPS-1, minimal 3 month duration, CAPS-2 >= 50 after placebo run-in + CAPS not >30% decrease during run-in Comorbidity: MINI
Interventions	Description: nafazedone 100 mg/d-600 mg/d (avg: 463 mg/d) versus sertraline 50 mg/d-200 mg/d (avg: 153 mg/d) x 12 weeks
Outcomes	Primary outcomes: CAPS-2, CGI-I Secondary outcomes: DTS, MADRS, HAM-A, TOP-8, PSQI, SDS Data estimation: LOCF (1 post-baseline assessment)
Notes	INDUSTRY SUPPORT Industry funded: Yes Medication provided by industry: No Any of the authors work for industry: Yes ADDITIONAL INFORMATION Drop-out rates: 14 dropouts in total Quality rating score: 33 3 patients excluded during run-in
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Yes	A - Adequate

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Pfizer588

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Methods	DESIGN Description: Randomised placebo-controlled, double-blind, parallel, flexible dose trial BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: Unclear RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 193 DSM-III-R PTSD, physical/sexual assault, 74.6% female, average age: 37 years, average duration of illness: 10.5 years, baseline severity on CPS-2: < 50 (except for one participant) SCREENING Primary diagnosis: Unclear Comorbidity: Unclear
Interventions	Description: sertraline (mean completer dose: 156 mg/d) versus placebo x mean of 74 days
Outcomes	CAPS-2, CGI-I, IES, DTS, CGI-S (no distinction made between primary and secondary outcomes) Data estimation: Unclear
Notes	INDUSTRY SUPPORT Industry funded: Medication provided by industry: Any of the authors work for industry: ADDITIONAL INFORMATION Drop-out rates: 50 (25.9%) dropped out in total Quality rating score: Not calculated
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Pfizer589

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Methods	DESIGN Description: Randomised, double-blind, placebo-controlled, parallel flexible dose trial BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: Unclear RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 169 DSM-III-R PTSD, predominantly war-trauma sample (71%), 79.9% female, average age: 45 years, average duration of illness: 18 years SCREENING Primary diagnosis: Unclear Comorbidity: Unclear
Interventions	Description: sertraline (mean completer dose: 156 mg/d) versus placebo x mean duration of 72 days
Outcomes	CAPS-2, CGI-I, CGI-S, IES, DTS (no distinction made between primary and secondary outcomes) Data estimation: Unclear
Notes	INDUSTRY SUPPORT Industry funded: Yes Medication provided by industry: Yes Any of the authors work for industry: Yes ADDITIONAL INFORMATION Drop-out rates: 26 on sertraline, 14 on placebo Quality rating score: Not calculated Prevalence of patients with drug abuse history higher at baseline in medication than placebo group
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

---

Reich 2004

---

Methods	DESIGN Description: random-assignment, placebo-controlled, parallel arm, flexible dose, double-blind, single-centre BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: No information RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 21 DSM-III-R PTSD, mean age: 27.9 years (18-56), 100% female, all suffered childhood physical, sexual, emotion or verbal abuse, 9 participants on concurrent medication, baseline severity on CAPS-2: risperidone (63.5) and placebo (65.6) SCREENING Primary diagnosis: SCID, CAPS-1 Comorbidity: None
Interventions	Description: risperidone mean dose of 0.5 mg q.h.s. (avg dose: 1.4 mg/d) at start to 8 mg/d versus placebo x 8 weeks
Outcomes	Primary outcomes: CAPS-1, CAPS-2 Secondary outcomes: None Data estimation: LOCF and random effects time series modeling methods
Notes	INDUSTRY SUPPORT Industry funded: Yes Medication provided by industry: Unclear Any of the authors work for industry: No ADDITIONAL INFORMATION Drop-out rates: 75% (9/12) on risperidone and 78% (7/9) on placebo Quality rating score: 26
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

---

Reist 1989

---

Methods	DESIGN Description: random-assignment, placebo-controlled, crossover, flexible dose, double-blind, 4 day switched cross-over, multi-centre BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: No information RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 27 DSM-III PTSD, combat veterans, mean age 38.4 years (28-64), all males, 33% (6/18) major depression, most prevalent comorbidity: 50% (9/18) dysthymic disorder, baseline severity on IES: desipramine (55.2) and placebo (56.2) SCREENING Primary diagnosis: Not mentioned Comorbidity: SCID, SCID - DSM-III-R for personality disorders
Interventions	Description: desipramine 50 mg/d -200 mg/d (max avg: 165 mg/d) versus placebo x 8 weeks
Outcomes	HAM-D, HAM-A, BDI, IES (no distinction between primary and secondary outcomes) Data estimation: Completer values
Notes	INDUSTRY SUPPORT Industry funded: No information Medication provided by industry: Unclear Any of the authors work for industry: No ADDITIONAL INFORMATION Drop-out rates: 33% (9/27) Quality rating score: 12 ongoing recreational and group therapies
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

---

Saygin 2002

---

Methods	DESIGN Description: random-assignment, placebo-controlled, parallel arm, flexible-dose, single centre BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: Unclear RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 60 DSM-IV PTSD, earthquake survivors, mean age: 41.5 years, 76% (41/54) male, 9% (5/54) MDD, baseline severity on TOP-8: nefazadone (15.75) and sertraline (19.27) SCREENING Primary diagnosis: SCID-1 Comorbidity: Not mentioned
Interventions	Description: nefazadone 200 mg/d - 400 mg/d (avg: 332.4 mg/d) versus sertraline 50 mg/d-100 mg/d (avg: 68.3 mg/d) x 6 months
Outcomes	PDS, TOP-8, CGI (no distinction between primary and secondary outcomes) Data estimation: Completer values
Notes	INDUSTRY SUPPORT Industry funded: No Medication provided by industry: No Any of the authors work for industry: No ADDITIONAL INFORMATION Drop-out rates: 20% (6/30) on nefazadone and 0% on sertraline Quality rating score: 25 Not clear whether study was blinded
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

---

Shestatzky 1988

---

Methods	DESIGN Description: random-assignment, placebo-controlled, crossover, flexible-dose, double-blind, single centre, 2 week placebo washout BLINDING Participants: Unclear Assessors: Yes Administrators: Unclear ALLOCATION CONCEALMENT Method: Claimed, but method not mentioned RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 13 DSM-III PTSD, mean age: 38.5 years (31-50), average duration of diagnosis: 5.6 years, 2% (2/10) MDD, baseline severity on IES: phenelzine (34) and placebo (36) SCREENING Primary diagnosis: Not mentioned Comorbidity: Not mentioned
Interventions	Description: phenelzine 30 mg/d - 75 mg/d (avg. max dose: 66 mg/d) versus placebo x 5 weeks
Outcomes	CGI-I, CGI-S, CAPS-2. ITT(LOCF) values provided. Primary outcomes: CAPS-2, CGI-I, CGI-S Secondary outcomes: MADRS Data estimation:
Notes	INDUSTRY SUPPORT Industry funded: No Medication provided by industry: No Any of the authors work for industry: No ADDITIONAL INFORMATION Drop-out rates: 54% (7/13) on phenelzine and 0% (0/13) on placebo Quality rating score: 14 much of descriptive data for 4 week completers in both phases; supportive psychotherapy provided to patients
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

---

SKB627

---

Methods	DESIGN Description: Randomised, double-blind, placebo-controlled, parallel flexible dose trial, placebo run-in BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: Unclear RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 322 DSM-IV PTSD, 53.7% female SCREENING Primary diagnosis: Unclear Comorbidity: Unclear
Interventions	Description: paroxetine 20 mg/d - 50 mg/d versus placebo x mean duration of 84 days
Outcomes	CAPS-2, CGI-I (no distinction made between primary and secondary outcomes) Data estimation: ITT
Notes	INDUSTRY SUPPORT Industry funded: Yes Medication provided by industry: Yes Any of the authors work for industry: Yes ADDITIONAL INFORMATION Drop-out rates: Not provided Quality rating score: Not calculated
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

---

Smajkic 2001

---

Methods	DESIGN Description: random-assignment, placebo-controlled, parallel arm, flexible dose, double-blind, single centre BLINDING Participants: No Assessors: No Administrators: No ALLOCATION CONCEALMENT Method: None RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 32 DSM-IV PTSD, bosnian refugees, no combat-related trauma, mean age: 51.34 years (24-63), 56% female, baseline severity on PSS-Sev: sertraline (41.9), venlaxafine (37.8) and paroxetine (37.3) SCREENING Primary diagnosis: PSS Comorbidity: SCID, BDI
Interventions	Description: sertraline 50 mg/d - 100 mg/d versus venlafaxine 75 mg/d - 150 mg/d versus paroxetine (max dose 20mg/d) x 6 weeks
Outcomes	Primary outcomes: PSS Secondary outcomes: GAF, BDI Data estimation: Completer values
Notes	INDUSTRY SUPPORT Industry funded: No Medication provided by industry: No Any of the authors work for industry: No ADDITIONAL INFORMATION Drop-out rates: 0% sertraline, 62% (8/13) venlafaxine and 0% paroxetine Quality rating score: 17 Scales translated into Bosnian. Participants received concurrent case management and supportive therapy
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	D - Not used

---

Tucker 2001

---

Methods	Description: random-assignment, placebo-controlled, parallel arm, flexible-dose, double-blind, multi-centre, 1 week placebo run-in BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: Unclear RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 323 DSM-IV PTSD, 7% (21/307) combat-related, mean age: 40.8 years, 66% female, average duration of diagnosis: 14.9 years, 35% (108/307) with comorbid major depression, baseline severity on CAPS-2: paroxetine (73.2) and placebo (74.3) SCREENING Primary diagnosis: CAPS-1; MINI, CAPS-2 < 50 after placebo run-in Comorbidity: Not mentioned
Interventions	Description: paroxetine 20 mg/d -50 mg/d (mean dose: 27.6 mg/d) versus placebo x 12 weeks
Outcomes	Primary outcomes: CAPS-2 (score < 20 = 'remission'), CGI-I Secondary outcomes: DTS, TOP-8, SDS, MADRS Data estimation: LOCF (1 post-baseline assessment)
Notes	INDUSTRY SUPPORT Industry funded: Yes Medication provided by industry: Unclear Any of the authors work for industry: Yes ADDITIONAL INFORMATION Drop-out rates: 46% (70/151) on paroxetine and 42% (66/156) on placebo Quality rating score: 27
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

---

Tucker 2003

---

Methods	DESIGN Description: random-assignment, placebo-controlled, parallel arm, flexible-dose, double-blind, single centre, 1-2 week taper at end BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: Unclear RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 59 DSM-IV PTSD, mean age: 38.5 years, 72% (42/58) female, 3% (2/58) combat related, 78% (45/58) major depression, baseline severity on CAPS: citalopramine (91), sertraline (83.9) and placebo (94.2) SCREENING Primary diagnosis: SCID-IV, CAPS-I >=50 Comorbidity: Unclear
Interventions	Description: citalopram 20 mg/d - 50 mg/d (final avg: 36.2 mg/d)) versus sertraline 50 mg/d - 200 mg/d (final avg: 134.1mg/d)) versus placebo x 10 weeks
Outcomes	Primary outcomes: CAPS Secondary outcomes: IES (revised), BDI (revised) Data estimation: LOCF (2 post-baseline assessment)
Notes	INDUSTRY SUPPORT Industry funded: Yes Medication provided by industry: Unclear Any of the authors work for industry: Yes ADDITIONAL INFORMATION Drop-out rates: +-20% (5/58) on citalopramine, +- 26% (6/23) on sertraline and +- 30% (3/10) on placebo Quality rating score: 26
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

---

van der Kolk 1994

---

Methods	DESIGN Description: random-assignment, placebo-controlled, parallel arm, flexible-dose, double-blind, multi-centre BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: No information RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 64 DSM-II-R PTSD, 44% (28/64) combat-related trauma, mean age: 40.4 years (22-55), 66% (42/64) male, 54.8% (34/64) MDD SCREENING Primary diagnosis: CAPS >= 45 Comorbidity: Not mentioned
Interventions	Description: fluoxetine 20 mg/d - 60 mg/d (avg. dose: 40 mg/d) versus placebo x 5 weeks
Outcomes	CAPS, BDHI, HAM-D, DES, DESI, acoustic startle response, rorschach inkblot test (no distinction between primary and secondary outcomes) Data estimation: Completer values
Notes	INDUSTRY SUPPORT Industry funded: Yes Medication provided by industry: Unclear Any of the authors work for industry: No ADDITIONAL INFORMATION Drop-out rates: 36% (12/33) on fluoxetine and 13% (4/31) on placebo Quality rating score: 22 Supportive psychotherapy was permitted
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

---

van der Kolk 2004

---

Methods	DESIGN Description: random-assignment, placebo-controlled, parallel arm, flexible-dose, double-blind, multi-centre, 6 month follow-up BLINDING Participants: Unclear Assessors: Yes Administrators: Unclear ALLOCATION CONCEALMENT Method: No information RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 59 DSM-IV PTSD, mean age: 34.9 years (18-65), 86% (51/59) female, average duration of diagnosis: 13.3 years, baseline severity on CAPS: fluoxetine (73.7) and placebo (70.3) SCREENING Primary diagnosis: Trauma incident >= 1 year ago, GAF < 40 Comorbidity: Not mentioned
Interventions	Description: fluoxetine 10 mg/d - 60 mg/d versus Eye Movement Desensitization and Reprocessing (EMDR) versus placebo x 5 weeks
Outcomes	Primary outcomes: CAPS Secondary outcomes: BDI Data estimation: LOCF
Notes	INDUSTRY SUPPORT Industry funded: No Medication provided by industry: Unclear Any of the authors work for industry: No ADDITIONAL INFORMATION Drop-out rates: 13% (4/30) on fluoxetine and 10% (3/29) on placebo Quality rating score: 28
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

---

Zohar 2002

---

Methods	DESIGN Description: random-assignment, placebo-controlled, parallel arm, flexible dose, double-blind, mutli-centre, 1 week single blind placebo run-in BLINDING Participants: Unclear Assessors: Unclear Administrators: Unclear ALLOCATION CONCEALMENT Method: No information RANDOMISATION Method: Unclear
Participants	SAMPLE Description: 51 PTSD, 76% (32/42) combat-related trauma, mean age: 40 years, 88% (37/42) male, baseline severity on CAPS-2: sertraline (91.2) and placebo (93.3) SCREENING Primary diagnosis: minimum 6 month PTSD, CAPS-1, CGI-S >=4, CAPS-2 >=50 required after placebo run-in Comorbidity: Unclear
Interventions	Description: sertraline 50 mg/d - 200 mg/d (120 mg/d) versus placebo (avg:147 mg/d) x 10 weeks
Outcomes	Primary outcomes: CAPS-2, CGI-I, CGI-S Secondary outcomes: MADRS Data estimation: LOCF (1 post-baseline assessment)
Notes	INDUSTRY SUPPORT Industry funded: Yes Medication provided by industry: Unclear Any of the authors work for industry: Yes ADDITIONAL INFORMATION Drop-out rates: 26% (6/23) on fluoxetine and 26% (5/19) on placebo Quality rating score: 30
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

---

 Acronyms for scales: AIMS: Abnormal Involuntary Movement Scale; ASEX: Arizona Sexual Experience Scale; ASI: Addiction Severity Index; BAS: Barnes Akathisia Scale; BDHI: Buss-Durkee Hostility Inventory; BDI: Beck Depression Inventory; CADSS: Clinician Administered Dissociative States Scale; CAPS-2: Clinician Administered PTSD Scale - part 2; CAS: Covi Anxiety Scale; CES: Combat Exposure Scale; CES-D: Center for Epidemiologic Studies Depression Scale (self-rated); CGI-I: Clinical Impression - Improvement Scale; CS: Columbia Scale; DESI: Disorders of Extreme Stress Inventory; DES: Dissociative Experiences Scale; DGRP: Duke Global Rating for PTSD; DTS: Davidson Trauma Scale; EPI: Eyesenck Personality Inventory; HADS: Hospital Anxiety and Depression Scale; HAM-A: Hamilton Anxeity Scale; IPP: Inventory of Personal Problems; MADRS: Montgomery-Asberg Depression Rating Scale; MISS: Mississippi Scale for Combat-Related PTSD; NI: Newcastle Index; OCDS: Obsessive Compulsive Drinking Scale; PDS: Posttraumatic Stress Disorder Scale PSQI: Pittsburgh Sleep Quality Index; PSS: PTSD Symptoms Scale; RSD: Raskin Scale for Depression; SADS: Schedule for Affective Disorders and Schizophrenia; SAS: Simpson-Angus Scale; SCID: Structured Clinical Interview for DSM; SCID-P: Structured Clinical Interview for DSM, Psychotic screen; SCL-90-R: Hopkins 90-item Symptom Checklist-Revised; SDS: Sheehan Disability Scale; SI-PTSD: DSM based PTSD scale; SIP: Structured Interview for PTSD; SPRINT: Short PTSD Rating Interview scale; TLFB: Time-Line Follow-Back; VS: Vulnerability to the effects of stress scale; VAS: Visual Analog Scale; UKUSERS: UKU Side Effect Rating Scale; SPRINT: Short PTSD Rating Interview; TOP-8: Treatment Outcome PTSD Scale

 

Characteristics of excluded studies [ordered by study ID]

---

Study	Reason for exclusion
Aerni 2004	All 3 patients received concurrent medication. In addition, one of the patients was treated with concurrent psychotherapy
Bartzokis 2005	Augmentation trial of adjunctive risperidone for chronic, combat-related PTSD. To be included in an upcoming review of pharmacotherapy augmentation strategies in treatment-resistant anxiety disorders.
Bremner 1997	Pharmacotherapy impact assessment trial
Coupland 1997	Pharmacotherapy impact assessment trial
Eftekhari 2004	Comparison of treatment of chronic PTSD with prolonged exposure or sertraline. No placebo or other medication used as control.
Frank 1988	An extension of this database was subsequently published (Kosten et al, 1991).
Frommberger 1998	Open label comparison of paroxetine and CBT. No placebo or alternative medication control
Gelpin 1996	Trial of prophlactic treatment of recent trauma survivors with benzodiazepines. To be included in an upcoming review of pharmacotherapy augmentation strategies in treatment-resistant anxiety disorders
Hamner 1997	Buspirone potentiation of antidepressants for combat-veteran PTSD sufferers. May be included in an upcoming review of pharmacotherapy augmentation strategies in treatment-resistant anxiety disorders.
Hamner 1999	Pharmacotherapy impact assessment trial
Hamner 2003	Risperidone augmentation of medication for war-veteran PTSD sample with psychotic symptoms. May be included in an upcoming review of pharmacotherapy augmentation strategies in treatment-resistant anxiety disorders
Heresco-Levy 2002	Augmentation trial of d-cycloserine for PTSD. May be included in an upcoming review of pharmacotherapy augmentation strategies in treatment-resistant anxiety disorders.
Jacobs-Rebhun 2000	Trial of treatment for sleep disorders associated with PTSD
Kanter 2001	Pharmacotherapy impact assessment trial
Kellner 2000	Pharmacotherapy impact assessment trial. Not a treatment study
Kline 1994	Open uncontrolled trial of sertraline for treatment-resistant combat veteran PTSD patients
Monnelly 2003	Augmentation of risperidone for irritable aggression symptoms in combat-veteran PTSD sufferers. May be included in an upcoming review of pharmacotherapy augmentation strategies in treatment-resistant anxiety disorders.
Morgan 1995	Pharmacotherapy impact assessment trial
Nagy 1996	The poster presentation provided neither response rates, nor means/standard deviations before and after medication/placebo.
Otto 2003	Augmentation trial and comparison group receives medication and cognitive-behaviour therapy
Pitman 1990	Pharmacotherapy impact assessment trial
Pitman 2002	Participants were allowed to continue with concommitant psychiatric treatments
Pivac 2004	Open, non-randomised trial of olanzapine versus fluphenazine for psychotic combat-related PTSD
Randall 1995	Pharmacotherapy impact assessment trial
Raskind 2003	Trial classified as an augmentation trial for treatment resistant PTSD. To be included in an upcoming review of pharmacotherapy augmentation strategies in treatment-resistant anxiety disorders
Reist 1995	Pharmacotherapy impact assessment trial
Reist 2001	Pharmacotherapy impact assessment trial
Schelling 2004	Trial of hydrocortisone for post-operative complications in cardiac surgery. As trials is concerned with the development of PTSD following surgery, and diagnosis with PTSD does not fall within its inclusion criteria, this is better considered a prophylaxis trial, and will be included in an upcoming protocol
Southwick 1997	Pharmacotherapy impact assessment trial
Stein 2002	Augmentation trial of adjunctive olanzapine for SSRI resistant combated-related PTSD. To be included in an upcoming review of pharmacotherapy augmentation strategies in treatment-resistant anxiety disorders
Vaiva 2003	Pharmacotherapy impact assessment trial
van der Kolk 1989	Pharmacotherapy impact assessment trial
Zatzick 2004	Pharmacotherapy component of collaborative care intervention non-randomised as only offered to patients with persistent PTSD symptoms

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Comparison 1. Medication versus Placebo: Primary global and PTSD symptom outcomes

---

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

---

 1 CAPS: Total score

17

2507

Mean Difference (IV, Random, 95% CI)

-5.76 [-8.16, -3.36]

---

1.1 SSRIs

12

1909

Mean Difference (IV, Random, 95% CI)

-5.59 [-8.60, -2.58]

---

1.2 MAOIs

2

178

Mean Difference (IV, Random, 95% CI)

-5.06 [-15.93, 5.81]

---

1.4 Other medication

3

420

Mean Difference (IV, Random, 95% CI)

-5.51 [-11.53, 0.52]

---

 2 CAPS: Individual SSRI agents

12

1907

Mean Difference (IV, Random, 95% CI)

-5.95 [-8.90, -1.00]

---

2.1 Citalopram versus placebo

1

33

Mean Difference (IV, Random, 95% CI)

-13.41 [-33.00, 8.18]

---

2.2 Fluoxetine versus placebo

1

59

Mean Difference (IV, Random, 95% CI)

-0.90 [-12.31, 10.51]

---

2.3 Paroxetine versus placebo

4

940

Mean Difference (IV, Random, 95% CI)

-10.49 [-13.87, -7.11]

---

2.4 Sertraline versus placebo

6

875

Mean Difference (IV, Random, 95% CI)

-3.78 [-6.90, -0.65]

---

 3 Clinical Global Impressions scale improvement item (CGI-I)

13

1272

Risk Ratio (M-H, Random, 95% CI)

1.49 [1.28, 1.73]

---

3.1 SSRIs

7

999

Risk Ratio (M-H, Random, 95% CI)

1.59 [1.39, 1.82]

---

3.2 MAOIs

2

178

Risk Ratio (M-H, Random, 95% CI)

1.16 [0.79, 1.72]

---

3.3 TCAs

1

40

Risk Ratio (M-H, Random, 95% CI)

3.00 [0.98, 9.14]

---

3.4 Other medication

3

55

Risk Ratio (M-H, Random, 95% CI)

1.53 [0.73, 3.20]

---

 4 CGI-I: Individual SSRI agents

7

999

Risk Ratio (M-H, Random, 95% CI)

1.59 [1.39, 1.82]

---

4.1 fluoxetine versus placebo

2

65

Risk Ratio (M-H, Random, 95% CI)

1.35 [0.96, 1.89]

---

4.2 paroxetine versus placebo

3

719

Risk Ratio (M-H, Random, 95% CI)

1.62 [1.38, 1.90]

---

4.3 sertraline versus placebo

2

215

Risk Ratio (M-H, Random, 95% CI)

1.71 [1.22, 2.40]

---

 

Comparison 2. Medication versus Placebo: Secondary measures of PTSD

---

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

---

 1 Symptom severity: Other measures

6

147

Std. Mean Difference (IV, Random, 95% CI)

-0.44 [-0.87, -0.01]

---

1.1 SSRIs

2

59

Std. Mean Difference (IV, Random, 95% CI)

-0.31 [-1.66, 1.05]

---

1.2 MAOIs

0

0

Std. Mean Difference (IV, Random, 95% CI)

Not estimable

---

1.3 TCAs

1

33

Std. Mean Difference (IV, Random, 95% CI)

-0.63 [-1.33, 0.07]

---

1.4 Other medications

3

55

Std. Mean Difference (IV, Random, 95% CI)

-0.30 [-0.92, 0.32]

---

 2 Self-rated scales: Total score

9

880

Std. Mean Difference (IV, Random, 95% CI)

-0.32 [-0.50, -0.14]

---

2.1 SSRIs

5

769

Std. Mean Difference (IV, Random, 95% CI)

-0.21 [-0.36, -0.07]

---

2.2 MAOIs

1

37

Std. Mean Difference (IV, Random, 95% CI)

-1.06 [-1.75, -0.36]

---

2.3 TCAs

1

33

Std. Mean Difference (IV, Random, 95% CI)

-0.90 [-1.62, -0.18]

---

2.4 Other medication

2

41

Std. Mean Difference (IV, Random, 95% CI)

-0.43 [-1.20, 0.33]

---

 3 CAPS subscale: Re-experiencing/intrusion

9

1304

Mean Difference (IV, Random, 95% CI)

-2.06 [-3.02, -1.10]

---

3.1 SSRIs

7

1242

Mean Difference (IV, Random, 95% CI)

-1.97 [-3.11, -0.83]

---

3.2 MAOIs

0

0

Mean Difference (IV, Random, 95% CI)

Not estimable

---

3.3 TCAs

0

0

Mean Difference (IV, Random, 95% CI)

Not estimable

---

3.4 Other medication

2

62

Mean Difference (IV, Random, 95% CI)

-2.38 [-6.52, 1.76]

---

 4 CAPS subscale: Avoidance/numbing

9

1304

Mean Difference (IV, Random, 95% CI)

-4.06 [-5.41, -2.70]

---

4.1 SSRIs

7

1242

Mean Difference (IV, Random, 95% CI)

-4.19 [-5.58, -2.80]

---

4.2 MAOIs

0

0

Mean Difference (IV, Random, 95% CI)

Not estimable

---

4.3 TCAs

0

0

Mean Difference (IV, Random, 95% CI)

Not estimable

---

4.4 Other medication

2

62

Mean Difference (IV, Random, 95% CI)

-1.56 [-7.56, 4.44]

---

 5 CAPS subscale: Hyperarousal

9

1304

Mean Difference (IV, Random, 95% CI)

-3.10 [-4.10, -2.10]

---

5.1 SSRIs

7

1242

Mean Difference (IV, Random, 95% CI)

-3.07 [-4.09, -2.04]

---

5.2 MAOIs

0

0

Mean Difference (IV, Random, 95% CI)

Not estimable

---

5.3 TCAs

0

0

Mean Difference (IV, Random, 95% CI)

Not estimable

---

5.4 Other medication

2

62

Mean Difference (IV, Random, 95% CI)

-3.77 [-8.37, 0.84]

---

 6 Self-rated subscale: Re-experiencing/Intrusion

4

268

Std. Mean Difference (IV, Random, 95% CI)

-0.43 [-0.98, 0.13]

---

6.1 SSRIs

1

183

Std. Mean Difference (IV, Random, 95% CI)

-0.18 [-0.47, 0.11]

---

6.2 MAOIs

1

37

Std. Mean Difference (IV, Random, 95% CI)

-1.07 [-1.77, -0.38]

---

6.3 TCAs

1

33

Std. Mean Difference (IV, Random, 95% CI)

-0.75 [-1.46, -0.04]

---

6.4 Other medication

1

15

Std. Mean Difference (IV, Random, 95% CI)

0.51 [-0.58, 1.61]

---

 7 Self-rated subscale: Avoidance/numbing

4

268

Std. Mean Difference (IV, Random, 95% CI)

-0.49 [-0.90, -0.08]

---

7.1 SSRIs

1

183

Std. Mean Difference (IV, Random, 95% CI)

-0.19 [-0.48, 0.10]

---

7.2 MAOIs

1

37

Std. Mean Difference (IV, Random, 95% CI)

-0.81 [-1.49, -0.14]

---

7.3 TCAs

1

33

Std. Mean Difference (IV, Random, 95% CI)

-0.90 [-1.62, -0.18]

---

7.4 Other medication

1

15

Std. Mean Difference (IV, Random, 95% CI)

-0.30 [-1.38, 0.78]

---

 8 Self-rated subscale: Hyperarousal

1

15

Std. Mean Difference (IV, Random, 95% CI)

-0.06 [-1.13, 1.01]

---

8.4 Other medication

1

15

Std. Mean Difference (IV, Random, 95% CI)

-0.06 [-1.13, 1.01]

---

 

Comparison 3. Medication versus Placebo: Comorbid symptoms

---

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

---

 1 Depression Scale (typically Hamilton Depression)

7

459

Std. Mean Difference (IV, Random, 95% CI)

-0.34 [-0.57, -0.10]

---

1.1 SSRIs

4

364

Std. Mean Difference (IV, Random, 95% CI)

-0.19 [-0.39, 0.02]

---

1.2 MAOIs

1

37

Std. Mean Difference (IV, Random, 95% CI)

-0.40 [-1.06, 0.25]

---

1.3 TCAs

1

33

Std. Mean Difference (IV, Random, 95% CI)

-1.16 [-1.90, -0.41]

---

1.4 Other medication

1

25

Std. Mean Difference (IV, Random, 95% CI)

-0.89 [-1.78, -0.01]

---

 2 Depression Scale - Change scores

3

887

Std. Mean Difference (IV, Random, 95% CI)

-0.33 [-0.60, -0.07]

---

2.1 SSRIs

3

887

Std. Mean Difference (IV, Random, 95% CI)

-0.33 [-0.60, -0.07]

---

2.2 MAOIs

0

0

Std. Mean Difference (IV, Random, 95% CI)

Not estimable

---

2.3 TCAs

0

0

Std. Mean Difference (IV, Random, 95% CI)

Not estimable

---

2.4 Other medication

0

0

Std. Mean Difference (IV, Random, 95% CI)

Not estimable

---

 3 Anxiety - Hamilton Anxiety Scale

3

287

Mean Difference (IV, Random, 95% CI)

-2.17 [-7.22, 2.88]

---

3.1 SSRIs

2

254

Mean Difference (IV, Random, 95% CI)

0.58 [-1.97, 3.14]

---

3.3 TCAs

1

33

Mean Difference (IV, Random, 95% CI)

-7.60 [-12.74, -2.46]

---

3.4 Other medication

0

0

Mean Difference (IV, Random, 95% CI)

Not estimable

---

 4 Anxiety - Other scales

2

62

Std. Mean Difference (IV, Random, 95% CI)

-0.75 [-1.28, -0.22]

---

4.2 MAOIs

1

37

Std. Mean Difference (IV, Random, 95% CI)

-0.67 [-1.34, -0.01]

---

4.4 Other medication

1

25

Std. Mean Difference (IV, Random, 95% CI)

-0.88 [-1.77, -0.00]

---

 

Comparison 4. Medication versus Placebo: Quality of Life Scales

---

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

---

 1 Sheehan Disability Scale

5

752

Mean Difference (IV, Random, 95% CI)

-2.54 [-3.68, -1.41]

---

1.1 SSRIs

4

737

Mean Difference (IV, Random, 95% CI)

-2.56 [-3.70, -1.41]

---

1.4 Other medications

1

15

Mean Difference (IV, Random, 95% CI)

-1.5 [-10.53, 7.53]

---

 

Comparison 5. Medication versus Placebo: Drop-out Rate

---

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

---

 1 Drop-out rate due to treatment emergent adverse effects

21

2116

Risk Ratio (M-H, Random, 95% CI)

1.44 [1.04, 2.00]

---

1.1 SSRIs

10

1649

Risk Ratio (M-H, Random, 95% CI)

1.42 [0.99, 2.05]

---

1.2 MAOIs

3

196

Risk Ratio (M-H, Random, 95% CI)

1.02 [0.29, 3.57]

---

1.3 TCAs

2

100

Risk Ratio (M-H, Random, 95% CI)

5.45 [0.68, 43.88]

---

1.4 Other medication

6

171

Risk Ratio (M-H, Random, 95% CI)

1.69 [0.53, 5.43]

---

 2 Drop-out rate due to treatment emergent adverse effect: SSRI medications

10

1649

Risk Ratio (M-H, Random, 95% CI)

1.42 [0.99, 2.05]

---

2.1 Fluoxetine

3

367

Risk Ratio (M-H, Random, 95% CI)

0.86 [0.25, 2.96]

---

2.2 Paroxetine

3

751

Risk Ratio (M-H, Random, 95% CI)

1.48 [0.94, 2.31]

---

2.3 Sertraline

4

531

Risk Ratio (M-H, Random, 95% CI)

1.54 [0.73, 3.26]

---

 

Comparison 6. Medication versus Placebo: Extension data

---

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

---

 2 Relapse data: Number of participants to relapse

2

215

Risk Ratio (M-H, Random, 95% CI)

0.29 [0.12, 0.70]

---

2.1 SSRIs

2

215

Risk Ratio (M-H, Random, 95% CI)

0.29 [0.12, 0.70]

---

 3 Continuation trials: Symptom severity on the CAPS

1

16

Mean Difference (IV, Random, 95% CI)

9.62 [-3.53, 22.77]

---

3.1 SSRIs

1

16

Mean Difference (IV, Random, 95% CI)

9.62 [-3.53, 22.77]

---

 

Comparison 7. Subgroup analyses - Methodological criteria

---

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

---

 1 Single versus multi-centre trials

14

1895

Mean Difference (IV, Random, 95% CI)

-5.62 [-8.95, -2.29]

---

1.1 Single centre trials

6

302

Mean Difference (IV, Random, 95% CI)

-2.20 [-7.95, 3.55]

---

1.2 Multi-centre trials

8

1593

Mean Difference (IV, Random, 95% CI)

-6.49 [-10.75, -2.22]

---

 2 Single versus multi-centre trials

13

Risk Ratio (M-H, Random, 95% CI)

Subtotals only

---

2.1 Single centre trials

6

188

Risk Ratio (M-H, Random, 95% CI)

1.77 [1.20, 2.60]

---

2.2 Multi-centre trials

7

1084

Risk Ratio (M-H, Random, 95% CI)

1.44 [1.20, 1.72]

---

 3 Industry versus non-industry funded trials

13

1899

Mean Difference (IV, Random, 95% CI)

-6.49 [-9.64, -3.34]

---

3.1 Industry funded trials

12

1840

Mean Difference (IV, Random, 95% CI)

-6.83 [-10.09, -3.57]

---

3.2 Non-industry funded trials

1

59

Mean Difference (IV, Random, 95% CI)

-0.90 [-12.31, 10.51]

---

 4 Industry versus non-industry funded trials

12

Risk Ratio (M-H, Random, 95% CI)

Subtotals only

---

4.1 Industry funded trials

9

1053

Risk Ratio (M-H, Random, 95% CI)

1.61 [1.41, 1.84]

---

4.2 Non-industry funded trials

3

105

Risk Ratio (M-H, Random, 95% CI)

1.53 [0.81, 2.87]

---

 

Comparison 8. Subgroup analyses - Clinical criteria

---

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

---

 1 Inclusion of major depression vs. non-inclusion: CAPS

11

1455

Std. Mean Difference (IV, Random, 95% CI)

-0.31 [-0.45, -0.16]

---

1.1 Trials including patients with major depressive disorder

9

1304

Std. Mean Difference (IV, Random, 95% CI)

-0.35 [-0.46, -0.23]

---

1.2 Trials excluding patients with major depressive disorder

2

151

Std. Mean Difference (IV, Random, 95% CI)

-0.48 [-1.52, 0.56]

---

 2 Inclusion of major depression vs. non-inclusion: Clinical Global Impressions scale improvement item (CGI-I)

7

Risk Ratio (M-H, Random, 95% CI)

Subtotals only

---

2.1 Trials including patients with major depressive disorder

7

812

Risk Ratio (M-H, Random, 95% CI)

1.62 [1.39, 1.89]

---

2.2 Trials excluding patients with major depressive disorder

0

0

Risk Ratio (M-H, Random, 95% CI)

Not estimable

---

 3 Inclusion of war veterans versus non-inclusion: CAPS

12

1801

Mean Difference (IV, Random, 95% CI)

-6.18 [-9.69, -2.66]

---

3.1 Trials including war veterans

4

385

Mean Difference (IV, Random, 95% CI)

-1.73 [-7.54, 4.07]

---

3.2 Trials without war veterans

8

1416

Mean Difference (IV, Random, 95% CI)

-7.54 [-11.37, -3.71]

---

 4 Inclusion of war veterans versus non-inclusion: CGI-I

13

Risk Ratio (M-H, Random, 95% CI)

Subtotals only

---

4.1 Trials including war veterans

8

317

Risk Ratio (M-H, Random, 95% CI)

1.40 [0.99, 2.00]

---

4.2 Trials without war veterans

5

955

Risk Ratio (M-H, Random, 95% CI)

1.59 [1.39, 1.81]

---

 

Comparison 9. Sensitivity analyses

---

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

---

 1 Clinical Global Impressions scale improvement item (CGI-I) : non-response

13

1272

Risk Ratio (M-H, Random, 95% CI)

0.66 [0.60, 0.74]

---

1.1 SSRIs

7

999

Risk Ratio (M-H, Random, 95% CI)

0.65 [0.58, 0.74]

---

1.2 MAOIs

2

178

Risk Ratio (M-H, Random, 95% CI)

0.80 [0.44, 1.44]

---

1.3 TCAs

1

40

Risk Ratio (M-H, Random, 95% CI)

0.6 [0.38, 0.96]

---

1.4 Other medication

3

55

Risk Ratio (M-H, Random, 95% CI)

0.59 [0.35, 0.98]

---

 2 "Worst case" loss to follow up analysis

12

1275

Risk Ratio (M-H, Random, 95% CI)

1.37 [1.12, 1.69]

---

2.1 SSRIs

7

1027

Risk Ratio (M-H, Random, 95% CI)

1.52 [1.33, 1.74]

---

2.2 MAOIs

2

175

Risk Ratio (M-H, Random, 95% CI)

0.28 [0.01, 5.42]

---

2.3 TCAs

1

43

Risk Ratio (M-H, Random, 95% CI)

2.64 [0.86, 8.12]

---

2.4 Other medication

2

30

Risk Ratio (M-H, Random, 95% CI)

1.12 [0.51, 2.47]

---

 3 "Best case" loss to follow up analysis

12

1262

Risk Ratio (M-H, Random, 95% CI)

1.52 [1.22, 1.90]

---

3.1 SSRIs

7

1018

Risk Ratio (M-H, Random, 95% CI)

1.64 [1.44, 1.87]

---

3.2 MAOIs

2

172

Risk Ratio (M-H, Random, 95% CI)

0.48 [0.06, 3.86]

---

3.3 TCAs

1

43

Risk Ratio (M-H, Random, 95% CI)

3.5 [1.13, 10.81]

---

3.4 Other medication

2

29

Risk Ratio (M-H, Random, 95% CI)

1.14 [0.52, 2.51]

---

 

Comparison 10. Head-to-head comparisons

---

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

---

 1 Clinician administered scales: Symptom severity

3

432

Std. Mean Difference (IV, Random, 95% CI)

-0.04 [-0.23, 0.14]

---

1.1 Nefazodone versus sertraline

2

80

Std. Mean Difference (IV, Random, 95% CI)

-0.19 [-0.63, 0.25]

---

1.2 Venlafaxine versus sertraline

1

352

Std. Mean Difference (IV, Random, 95% CI)

-0.01 [-0.22, 0.20]

---

 2 Comorbid symptoms: Depression (MADRS)

1

26

Mean Difference (IV, Random, 95% CI)

-0.84 [-7.88, 6.20]

---

 3 Comorbid symptoms: Anxiety (Hamilton Anxiety Scale)

1

26

Mean Difference (IV, Random, 95% CI)

-3.23 [-10.90, 4.44]

---