Intervention Review

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Pharmacotherapy for post traumatic stress disorder (PTSD)

  1. Dan J Stein1,*,
  2. Jonathan C Ipser1,
  3. Soraya Seedat2,
  4. Carli Sager1,
  5. Taryn Amos1

Editorial Group: Cochrane Common Mental Disorders Group

Published Online: 25 JAN 2006

Assessed as up-to-date: 14 OCT 2005

DOI: 10.1002/14651858.CD002795.pub2


How to Cite

Stein DJ, Ipser JC, Seedat S, Sager C, Amos T. Pharmacotherapy for post traumatic stress disorder (PTSD). Cochrane Database of Systematic Reviews 2006, Issue 1. Art. No.: CD002795. DOI: 10.1002/14651858.CD002795.pub2.

Author Information

  1. 1

    University of Cape Town, Department of Psychiatry and Mental Health, Cape Town, South Africa

  2. 2

    University of Stellenbosch, MRC Research Unit for Anxiety and Stress Disorders, Tygerberg, Western Cape, South Africa

*Dan J Stein, Department of Psychiatry and Mental Health, University of Cape Town, Education Centre, Valkenberg Hospital, Private Bage X1, Observatory, Cape Town, 7925, South Africa. dan.stein@uct.ac.za.

Publication History

  1. Publication Status: Edited (no change to conclusions), comment added to review
  2. Published Online: 25 JAN 2006

SEARCH

 
Characteristics of included studies [ordered by study ID]
Baker 1995 a

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: brofaromine up to 150 mg/d vs placebo x 12 weeks


OutcomesPrimary 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.


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Brady 2000

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: sertraline 50-200 mg/d (mean endpoint dose: 133.3 mg/d) versus placebo x 12 weeks


OutcomesPrimary 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)


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Brady 2004

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: sertraline (50 mg/d - 150 mg/d) versus placebo (50 mg/d - 150 mg/d) x 12 weeks


OutcomesOutcomes: OCDS, CAPS, HAM-D, SID, IES (not clear whether primary or secondary)

Data estimation: LOCF (1 post-baseline assessment)


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Braun 1990

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: 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


OutcomesOutcomes: 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


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Butterfield 2001

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: olanzapine 5 mg/d - 20mg/d (max. mean 14.1 mg/d) versys placebo (max. mean: 13.9mg/d) x 10 weeks


OutcomesPrimary outcomes: TOP-8, SPRINT,
Secondary outcomes: IES, DTS, CGI-I, SDS, BAS, AIMS

Data estimation: ITT (General linear model)


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Chung 2004

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: mirtazapine 15 mg/d - 34.1 mg/d (mean daily dose) versus sertraline 50mg/d - 101.5mg/d (mean daily dose) x 6 weeks


OutcomesCAPS-2, HAM-D (17 item), CGI-I, CGI-S (no distinction made between primary and secondary outcomes)

Data estimation: completer values


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Conner 1999

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: fluoxetine (20-60 mg/d; median: 30 mg/d) vs placebo (20-60 mg/d; median: 40 mg/d) x 12 weeks


OutcomesPrimary outcomes: DGRP(change, severity)
Secondary outcomes: SIP, DTS, SDS. VS.

Data estimation: LOCF (1 post-baseline assessment)


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Low riskA - Adequate

Davidson 1990

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: amitriptyline (50-300 mg/d) vs placebo x 8 weeks, ongoing supportive psychotherapy


OutcomesPrimary outcomes: CGI-I , SI-PTSD, CGI-S
Secondary outcomes: HAM-D, HAM-A, IES, NI, EPI

Data estimation: completer values


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Davidson 2001a

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: sertraline 25 mg/d to between 50-200 mg/d (avg: 146.3 mg/d) vs. placebo x 12 weeks


OutcomesPrimary outcomes: CAPS-2, IES, CGI-S, CGI-I
Secondary outcomes: DTS, HAM-D, HAM-A, PSQI

Data estimation: LOCF (1 post-baseline assessment)


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Davidson 2001b

MethodsDESIGN
Description: random-assignment, placebo-controlled, relapse prevention study for participants undergoing acute and continuation treatment in Brady 2000 and Davidson 2001a

BLINDING
Participants: Unclear
Assessors: Unclear
Administrators: Unclear

ALLOCATION CONCEALMENT
Method: Unclear

RANDOMISATION
Method: unclear


ParticipantsSAMPLE

96 DSM-III-R PTSD, mean age=43.4 years, SD=10.3, 30% male

SCREENING

Responders (CGI ≤ 2, ≥30% improvement on total severity score for CAPS) in last two sessions of 28 week continuation treatment with sertraline


InterventionsSertraline 50-200 mg/d (avg 137 mg/day) vs. placebo (avg 145 mg/day) x 28 weeks


OutcomesPrimary outcomes: Rates and times to event for 1) relapse, 2) relapse or discontinuation because of clinical deterioration (self-
rated), and 3) acute exacerbation of PTSD.
Secondary outcomes: CAPS, HAM-D, QLES

Data estimation: Not applicable for primary outcomes (Kaplan Meier survival analysis)


NotesINDUSTRY SUPPORT
Industry funded: Yes (as reported in acute and continuation phase studies)
Medication provided by industry: No (as reported in acute and continuation phase studies)
Any of the authors work for industry: Yes

Davidson 2003

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: 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


OutcomesPrimary outcomes: SPRINT(Clinical Global Improvement & Total Scores)
Secondary outcomes: DTS, HADS, SIP, ASEX

Data estimation: LOCF (1 post-baseline assessment)


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Davidson 2004

MethodsDESIGN
Description: Randomised, double-blind, placebo-controlled, parallel flexible dose trial

BLINDING
Participants: Unclear
Assessors: Unclear
Administrators: Unclear

ALLOCATION CONCEALMENT
Method: Unclear

RANDOMISATION
Method: Unclear


ParticipantsSAMPLE
Description: 538 DSM-IV PTSD, 65.4% females, average age: 32 years

SCREENING
Primary diagnosis: Unclear
Comorbidity: Unclear


InterventionsDescription: sertraline (25 mg/d -200 mg/d), venlafaxine (37.5 mg/d - 300 mg/d) versus placebo x mean duration of 84 days


OutcomesCAPS, CGI-S, DTS, GAF (no distinction made between primary and secondary outcomes)

Data estimation: Unclear


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Davis 2001

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: nefazodone 200 mg/d - 600 mg/d (avg final dose: 435mg/d) versus placebo x 12 weeks


OutcomesPrimary outcomes: CAPS
Secondary outcomes: HAM-A, HAM-D, PTSD checklist, CADSS, GAFS, CGI

Data estimation: LOCF (excluded 1 patient due to compromise of blind)


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Low riskA - Adequate

Eli Lilly 2006

MethodsDESIGN
Description: Randomised, double blind, placebo-controlled, parallel fixed dose trial

BLINDING
Participants: Unclear
Assessors: Unclear
Administrators: Unclear

ALLOCATION CONCEALMENT
Method: Unclear

RANDOMISATION
Method: Unclear


ParticipantsSAMPLE
Description: 411 PTSD

SCREENING
Primary diagnosis: Unclear
Comorbidity: Unclear


InterventionsDescription: fluoxetine 20 mg/d (N = 163) and 40 mg/d (N = 160) versus placebo (N = 88) x mean of 84 days


OutcomesTOP-8,CGI-S (no distinction made between primary and secondary outcomes)

Data estimation: ITT


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Hertzberg 1999

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: lamotrigine 25 mg/d -500mg/d (avg. max. dose: 380 mg/d) versus placebo x 8 weeks


OutcomesITT(LOCF) values provided.
Primary outcomes: SIP, DGRP
Secondary outcomes: None

Data estimation: LOCF (excluded 1 patient)


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Hertzberg 2000

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: fluoxetine 10 mg/d - 60 mg/d (mean endpoint dose: 48 mg/d) vs placebo x 12 weeks


OutcomesDTS, SDS, SIP, DGRP (no distinction between primary and secondary outcomes)

Data estimation: Presumably LOCF (not clear in text)


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Kaplan 1996

MethodsDescription: 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


ParticipantsSAMPLE
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


InterventionsDescription: inositol 12 g/d versus placebo x 4 weeks


OutcomesIES , SCL-90 (1 centre), HAM-A, HAM-D (other centre)
(no distinction between primary and secondary outcomes)

Data estimation: Completer values


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Katz 1994

MethodsDescription: 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


ParticipantsSAMPLE
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


InterventionsDescription: brofaromine 50 mg/d -150 mg/d versus placebo x 14 weeks


OutcomesPrimary outcomes: CAPS
Secondary outcomes: CGI

Data estimation: LOCF


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Kosten 1991

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: 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


OutcomesPrimary outcomes: IES
Secondary outcomes: Combat Scale; CAS; HAM-D; HAM-A; RSD

Data estimation: LOCF (completers of 3 or more weeks)


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Marshall 2001

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: paroxetine (25 mg/d) or paroxetine (50 mg/d) versus placebo x 12 weeks


OutcomesPrimary outcomes: CAPS-2, CGI-I
Secondary outcomes: DTS, TOP-8, SDS, MADRS

Data estimation: LOCF (1 post-baseline assessment)


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Marshall 2004

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: 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


OutcomesPrimary 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)


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Martenyi 2002a

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: fluoxetine 20 mg/d - 80 mg/d, (avg dose: 57.8 mg/d) versus placebo x 12 weeks


OutcomesPrimary outcomes: TOPS-8
Secondary outcomes: CAPS-2, CGI-S, CGI-I, DTS, MADRS, HAM-A, SCL-90-R, DES


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Martenyi 2002b

MethodsDESIGN
Description: random-assignment, placebo-controlled, relapse prevention component of Martenyi 2002b

BLINDING
Participants: Unclear
Assessors: Unclear
Administrators: Unclear

ALLOCATION CONCEALMENT
Method: unclear

RANDOMISATION
Method: unclear


Participants131 DSM-IV PTSD, 81% male, avg age = 38.2 years, 47% trauma combat related. Patients required to present with 50% decrease after 12 weeks of acute treatment with fluoxetine on the TOP-8 score, a CGI–S score <= 2, and failed diagnostic criteria for PTSD


InterventionsFluoxetine max avg dose at endpoint: 53 mg/d vs placebo x 24 weeks. Responders to 12 weeks of acute treatment with placebo maintained on placebo. No discontinuation taper of fluoxetine from the acute to relapse prevention phase


OutcomesPrimary outcomes: Time to relapse on TOPS-8 (>= 40% increase for 12 week acute baseline) and CGI-S (>= 2 on CGI-S from 12 week acute baseline)
Secondary outcomes: CAPS-2, CGI-I, DTS, MADRS, HAM-A, SCL-90-R


NotesINDUSTRY SUPPORT
Industry funded: Yes
Medication provided by industry: Not mentioned
Any of the authors work for industry: No

McRae 2004

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: 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


OutcomesPrimary outcomes: CAPS-2, CGI-I
Secondary outcomes: DTS, MADRS, HAM-A, TOP-8, PSQI, SDS

Data estimation: LOCF (1 post-baseline assessment)


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Low riskA - Adequate

Pfizer588

MethodsDESIGN
Description: Randomised placebo-controlled, double-blind, parallel, flexible dose trial

BLINDING
Participants: Unclear
Assessors: Unclear
Administrators: Unclear

ALLOCATION CONCEALMENT
Method: Unclear

RANDOMISATION
Method: Unclear


ParticipantsSAMPLE
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


InterventionsDescription: sertraline (mean completer dose: 156 mg/d) versus placebo x mean of 74 days


OutcomesCAPS-2, CGI-I, IES, DTS, CGI-S (no distinction made between primary and secondary outcomes)

Data estimation: Unclear


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Pfizer589

MethodsDESIGN
Description: Randomised, double-blind, placebo-controlled, parallel flexible dose trial

BLINDING
Participants: Unclear
Assessors: Unclear
Administrators: Unclear

ALLOCATION CONCEALMENT
Method: Unclear

RANDOMISATION
Method: Unclear


ParticipantsSAMPLE
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


InterventionsDescription: sertraline (mean completer dose: 156 mg/d) versus placebo x mean duration of 72 days


OutcomesCAPS-2, CGI-I, CGI-S, IES, DTS (no distinction made between primary and secondary outcomes)

Data estimation: Unclear


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Reich 2004

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: 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


OutcomesPrimary outcomes: CAPS-1, CAPS-2
Secondary outcomes: None

Data estimation: LOCF and random effects time series modeling methods


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Reist 1989

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: desipramine 50 mg/d -200 mg/d (max avg: 165 mg/d) versus placebo x 8 weeks


OutcomesHAM-D, HAM-A, BDI, IES
(no distinction between primary and secondary outcomes)

Data estimation: Completer values


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Saygin 2002

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: 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


OutcomesPDS, TOP-8, CGI (no distinction between primary and secondary outcomes)

Data estimation: Completer values


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Shestatzky 1988

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: phenelzine 30 mg/d - 75 mg/d (avg. max dose: 66 mg/d) versus placebo x 5 weeks


OutcomesCGI-I, CGI-S, CAPS-2. ITT(LOCF) values provided.
Primary outcomes: CAPS-2, CGI-I, CGI-S
Secondary outcomes: MADRS

Data estimation:


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

SKB627

MethodsDESIGN
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


ParticipantsSAMPLE
Description: 322 DSM-IV PTSD, 53.7% female

SCREENING
Primary diagnosis: Unclear
Comorbidity: Unclear


InterventionsDescription: paroxetine 20 mg/d - 50 mg/d versus placebo x mean duration of 84 days


OutcomesCAPS-2, CGI-I (no distinction made between primary and secondary outcomes)

Data estimation: ITT


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Smajkic 2001

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: sertraline 50 mg/d - 100 mg/d versus venlafaxine 75 mg/d - 150 mg/d versus paroxetine (max dose 20mg/d) x 6 weeks


OutcomesPrimary outcomes: PSS
Secondary outcomes: GAF, BDI

Data estimation: Completer values


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskD - Not used

Tucker 2001

MethodsDescription: 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


ParticipantsSAMPLE
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


InterventionsDescription: paroxetine 20 mg/d -50 mg/d (mean dose: 27.6 mg/d) versus placebo x 12 weeks


OutcomesPrimary outcomes: CAPS-2 (score < 20 = 'remission'), CGI-I
Secondary outcomes: DTS, TOP-8, SDS, MADRS

Data estimation: LOCF (1 post-baseline assessment)


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Tucker 2003

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: 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


OutcomesPrimary outcomes: CAPS
Secondary outcomes: IES (revised), BDI (revised)

Data estimation: LOCF (2 post-baseline assessment)


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

van der Kolk 1994

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: fluoxetine 20 mg/d - 60 mg/d (avg. dose: 40 mg/d) versus placebo x 5 weeks


OutcomesCAPS, BDHI, HAM-D, DES, DESI, acoustic startle response, rorschach inkblot test (no distinction between primary and secondary outcomes)

Data estimation: Completer values


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

van der Kolk 2004

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: fluoxetine 10 mg/d - 60 mg/d versus Eye Movement Desensitization and Reprocessing (EMDR) versus placebo x 5 weeks


OutcomesPrimary outcomes: CAPS
Secondary outcomes: BDI

Data estimation: LOCF


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

Zohar 2002

MethodsDESIGN
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


ParticipantsSAMPLE
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


InterventionsDescription: sertraline 50 mg/d - 200 mg/d (120 mg/d) versus placebo (avg:147 mg/d) x 10 weeks


OutcomesPrimary outcomes: CAPS-2, CGI-I, CGI-S
Secondary outcomes: MADRS

Data estimation: LOCF (1 post-baseline assessment)


NotesINDUSTRY 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

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Unclear riskB - Unclear

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Aerni 2004All 3 patients received concurrent medication. In addition, one of the patients was treated with concurrent psychotherapy

Bartzokis 2005Augmentation 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 1997Pharmacotherapy impact assessment trial

Coupland 1997Pharmacotherapy impact assessment trial

Eftekhari 2004Comparison of treatment of chronic PTSD with prolonged exposure or sertraline. No placebo or other medication used as control.

Frank 1988An extension of this database was subsequently published (Kosten et al, 1991).

Frommberger 1998Open label comparison of paroxetine and CBT. No placebo or alternative medication control

Gelpin 1996Trial 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 1997Buspirone 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 1999Pharmacotherapy impact assessment trial

Hamner 2003Risperidone 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 2002Augmentation trial of d-cycloserine for PTSD. May be included in an upcoming review of pharmacotherapy augmentation strategies in treatment-resistant anxiety disorders.

Jacobs-Rebhun 2000Trial of treatment for sleep disorders associated with PTSD

Kanter 2001Pharmacotherapy impact assessment trial

Kellner 2000Pharmacotherapy impact assessment trial. Not a treatment study

Kline 1994Open uncontrolled trial of sertraline for treatment-resistant combat veteran PTSD patients

Monnelly 2003Augmentation 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 1995Pharmacotherapy impact assessment trial

Nagy 1996The poster presentation provided neither response rates, nor means/standard deviations before and after medication/placebo.

Otto 2003Augmentation trial and comparison group receives medication and cognitive-behaviour therapy

Pitman 1990Pharmacotherapy impact assessment trial

Pitman 2002Participants were allowed to continue with concommitant psychiatric treatments

Pivac 2004Open, non-randomised trial of olanzapine versus fluphenazine for psychotic combat-related PTSD

Randall 1995Pharmacotherapy impact assessment trial

Raskind 2003Trial 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 1995Pharmacotherapy impact assessment trial

Reist 2001Pharmacotherapy impact assessment trial

Schelling 2004Trial 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 1997Pharmacotherapy impact assessment trial

Stein 2002Augmentation 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 2003Pharmacotherapy impact assessment trial

van der Kolk 1989Pharmacotherapy impact assessment trial

Zatzick 2004Pharmacotherapy component of collaborative care intervention non-randomised as only offered to patients with persistent PTSD symptoms

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

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 CAPS: Total score172507Mean Difference (IV, Random, 95% CI)-5.76 [-8.16, -3.36]

    1.1 SSRIs
121909Mean Difference (IV, Random, 95% CI)-5.59 [-8.60, -2.58]

    1.2 MAOIs
2178Mean Difference (IV, Random, 95% CI)-5.06 [-15.93, 5.81]

    1.4 Other medication
3420Mean Difference (IV, Random, 95% CI)-5.51 [-11.53, 0.52]

 2 CAPS: Individual SSRI agents121909Mean Difference (IV, Random, 95% CI)-5.59 [-8.60, -2.58]

    2.1 Citalopram versus placebo
135Mean Difference (IV, Random, 95% CI)4.78 [-15.95, 25.51]

    2.2 Fluoxetine versus placebo
159Mean Difference (IV, Random, 95% CI)-0.90 [-12.31, 10.51]

    2.3 Paroxetine versus placebo
4940Mean Difference (IV, Random, 95% CI)-10.49 [-13.87, -7.11]

    2.4 Sertraline versus placebo
6875Mean Difference (IV, Random, 95% CI)-3.78 [-6.90, -0.65]

 3 Clinical Global Impressions scale improvement item (CGI-I)131272Risk Ratio (M-H, Random, 95% CI)1.49 [1.28, 1.73]

    3.1 SSRIs
7999Risk Ratio (M-H, Random, 95% CI)1.59 [1.39, 1.82]

    3.2 MAOIs
2178Risk Ratio (M-H, Random, 95% CI)1.16 [0.79, 1.72]

    3.3 TCAs
140Risk Ratio (M-H, Random, 95% CI)3.0 [0.98, 9.14]

    3.4 Other medication
355Risk Ratio (M-H, Random, 95% CI)1.53 [0.73, 3.20]

 4 CGI-I: Individual SSRI agents7999Risk Ratio (M-H, Random, 95% CI)1.59 [1.39, 1.82]

    4.1 fluoxetine versus placebo
265Risk Ratio (M-H, Random, 95% CI)1.35 [0.96, 1.89]

    4.2 paroxetine versus placebo
3719Risk Ratio (M-H, Random, 95% CI)1.62 [1.38, 1.90]

    4.3 sertraline versus placebo
2215Risk Ratio (M-H, Random, 95% CI)1.71 [1.22, 2.40]

 
Comparison 2. Medication versus Placebo: Secondary measures of PTSD

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Symptom severity: Other measures6147Std. Mean Difference (IV, Random, 95% CI)-0.44 [-0.87, -0.01]

    1.1 SSRIs
259Std. Mean Difference (IV, Random, 95% CI)-0.31 [-1.66, 1.05]

   1.2 MAOIs
00Std. Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    1.3 TCAs
133Std. Mean Difference (IV, Random, 95% CI)-0.63 [-1.33, 0.07]

    1.4 Other medications
355Std. Mean Difference (IV, Random, 95% CI)-0.30 [-0.92, 0.32]

 2 Self-rated scales: Total score9882Std. Mean Difference (IV, Random, 95% CI)-0.31 [-0.51, -0.11]

    2.1 SSRIs
5771Std. Mean Difference (IV, Random, 95% CI)-0.20 [-0.34, -0.06]

    2.2 MAOIs
137Std. Mean Difference (IV, Random, 95% CI)-1.06 [-1.75, -0.36]

    2.3 TCAs
133Std. Mean Difference (IV, Random, 95% CI)-0.90 [-1.62, -0.18]

    2.4 Other medication
241Std. Mean Difference (IV, Random, 95% CI)-0.43 [-1.20, 0.33]

 3 CAPS subscale: Re-experiencing/intrusion91304Mean Difference (IV, Random, 95% CI)-2.06 [-3.02, -1.10]

    3.1 SSRIs
71242Mean Difference (IV, Random, 95% CI)-1.97 [-3.11, -0.83]

   3.2 MAOIs
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

   3.3 TCAs
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    3.4 Other medication
262Mean Difference (IV, Random, 95% CI)-2.38 [-6.52, 1.76]

 4 CAPS subscale: Avoidance/numbing91304Mean Difference (IV, Random, 95% CI)-4.06 [-5.41, -2.70]

    4.1 SSRIs
71242Mean Difference (IV, Random, 95% CI)-4.19 [-5.58, -2.80]

   4.2 MAOIs
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

   4.3 TCAs
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    4.4 Other medication
262Mean Difference (IV, Random, 95% CI)-1.56 [-7.56, 4.44]

 5 CAPS subscale: Hyperarousal91304Mean Difference (IV, Random, 95% CI)-3.10 [-4.10, -2.10]

    5.1 SSRIs
71242Mean Difference (IV, Random, 95% CI)-3.07 [-4.09, -2.04]

   5.2 MAOIs
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

   5.3 TCAs
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    5.4 Other medication
262Mean Difference (IV, Random, 95% CI)-3.77 [-8.37, 0.84]

 6 Self-rated subscale: Re-experiencing/Intrusion4268Std. Mean Difference (IV, Random, 95% CI)-0.43 [-0.98, 0.13]

    6.1 SSRIs
1183Std. Mean Difference (IV, Random, 95% CI)-0.18 [-0.47, 0.11]

    6.2 MAOIs
137Std. Mean Difference (IV, Random, 95% CI)-1.07 [-1.77, -0.38]

    6.3 TCAs
133Std. Mean Difference (IV, Random, 95% CI)-0.75 [-1.46, -0.04]

    6.4 Other medication
115Std. Mean Difference (IV, Random, 95% CI)0.51 [-0.58, 1.61]

 7 Self-rated subscale: Avoidance/numbing4268Std. Mean Difference (IV, Random, 95% CI)-0.49 [-0.90, -0.08]

    7.1 SSRIs
1183Std. Mean Difference (IV, Random, 95% CI)-0.19 [-0.48, 0.10]

    7.2 MAOIs
137Std. Mean Difference (IV, Random, 95% CI)-0.81 [-1.49, -0.14]

    7.3 TCAs
133Std. Mean Difference (IV, Random, 95% CI)-0.90 [-1.62, -0.18]

    7.4 Other medication
115Std. Mean Difference (IV, Random, 95% CI)-0.30 [-1.38, 0.78]

 8 Self-rated subscale: Hyperarousal115Std. Mean Difference (IV, Random, 95% CI)-0.06 [-1.13, 1.01]

    8.4 Other medication
115Std. Mean Difference (IV, Random, 95% CI)-0.06 [-1.13, 1.01]

 
Comparison 3. Medication versus Placebo: Comorbid symptoms

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Depression Scale (typically Hamilton Depression)7459Std. Mean Difference (IV, Random, 95% CI)-0.34 [-0.57, -0.10]

    1.1 SSRIs
4364Std. Mean Difference (IV, Random, 95% CI)-0.19 [-0.39, 0.02]

    1.2 MAOIs
137Std. Mean Difference (IV, Random, 95% CI)-0.40 [-1.06, 0.25]

    1.3 TCAs
133Std. Mean Difference (IV, Random, 95% CI)-1.16 [-1.90, -0.41]

    1.4 Other medication
125Std. Mean Difference (IV, Random, 95% CI)-0.89 [-1.78, -0.01]

 2 Depression Scale - Change scores3887Std. Mean Difference (IV, Random, 95% CI)-0.33 [-0.60, -0.07]

    2.1 SSRIs
3887Std. Mean Difference (IV, Random, 95% CI)-0.33 [-0.60, -0.07]

   2.2 MAOIs
00Std. Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

   2.3 TCAs
00Std. Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

   2.4 Other medication
00Std. Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 3 Anxiety - Hamilton Anxiety Scale3287Mean Difference (IV, Random, 95% CI)-2.17 [-7.22, 2.88]

    3.1 SSRIs
2254Mean Difference (IV, Random, 95% CI)0.58 [-1.97, 3.14]

    3.3 TCAs
133Mean Difference (IV, Random, 95% CI)-7.60 [-12.74, -2.46]

   3.4 Other medication
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 4 Anxiety - Other scales262Std. Mean Difference (IV, Random, 95% CI)-0.75 [-1.28, -0.22]

    4.2 MAOIs
137Std. Mean Difference (IV, Random, 95% CI)-0.67 [-1.34, -0.01]

    4.4 Other medication
125Std. Mean Difference (IV, Random, 95% CI)-0.88 [-1.77, -0.00]

 
Comparison 4. Medication versus Placebo: Quality of Life Scales

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Sheehan Disability Scale5752Mean Difference (IV, Random, 95% CI)-2.54 [-3.68, -1.41]

    1.1 SSRIs
4737Mean Difference (IV, Random, 95% CI)-2.56 [-3.70, -1.41]

    1.4 Other medications
115Mean Difference (IV, Random, 95% CI)-1.5 [-10.53, 7.53]

 
Comparison 5. Medication versus Placebo: Drop-out Rate

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Drop-out rate due to treatment emergent adverse effects212116Risk Ratio (M-H, Random, 95% CI)1.44 [1.04, 2.00]

    1.1 SSRIs
101649Risk Ratio (M-H, Random, 95% CI)1.42 [0.99, 2.05]

    1.2 MAOIs
3196Risk Ratio (M-H, Random, 95% CI)1.02 [0.29, 3.57]

    1.3 TCAs
2100Risk Ratio (M-H, Random, 95% CI)5.45 [0.68, 43.88]

    1.4 Other medication
6171Risk Ratio (M-H, Random, 95% CI)1.69 [0.53, 5.43]

 2 Drop-out rate due to treatment emergent adverse effect: SSRI medications101649Risk Ratio (M-H, Random, 95% CI)1.42 [0.99, 2.05]

    2.1 Fluoxetine
3367Risk Ratio (M-H, Random, 95% CI)0.86 [0.25, 2.96]

    2.2 Paroxetine
3751Risk Ratio (M-H, Random, 95% CI)1.48 [0.94, 2.31]

    2.3 Sertraline
4531Risk Ratio (M-H, Random, 95% CI)1.54 [0.73, 3.26]

 
Comparison 6. Medication versus Placebo: Extension data

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 2 Relapse data: Number of participants to relapse2215Risk Ratio (M-H, Random, 95% CI)0.29 [0.12, 0.70]

    2.1 SSRIs
2215Risk Ratio (M-H, Random, 95% CI)0.29 [0.12, 0.70]

 3 Continuation trials: Symptom severity on the CAPS116Mean Difference (IV, Random, 95% CI)9.62 [-3.53, 22.77]

    3.1 SSRIs
116Mean Difference (IV, Random, 95% CI)9.62 [-3.53, 22.77]

 
Comparison 7. Subgroup analyses - Methodological criteria

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Single versus multi-centre trials141895Mean Difference (IV, Random, 95% CI)-5.62 [-8.95, -2.29]

    1.1 Single centre trials
6302Mean Difference (IV, Random, 95% CI)-2.20 [-7.95, 3.55]

    1.2 Multi-centre trials
81593Mean Difference (IV, Random, 95% CI)-6.49 [-10.75, -2.22]

 2 Single versus multi-centre trials13Risk Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Single centre trials
6188Risk Ratio (M-H, Random, 95% CI)1.77 [1.20, 2.60]

    2.2 Multi-centre trials
71084Risk Ratio (M-H, Random, 95% CI)1.44 [1.20, 1.72]

 3 Industry versus non-industry funded trials131899Mean Difference (IV, Random, 95% CI)-6.49 [-9.64, -3.34]

    3.1 Industry funded trials
121840Mean Difference (IV, Random, 95% CI)-6.83 [-10.09, -3.57]

    3.2 Non-industry funded trials
159Mean Difference (IV, Random, 95% CI)-0.90 [-12.31, 10.51]

 4 Industry versus non-industry funded trials12Risk Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 Industry funded trials
91053Risk Ratio (M-H, Random, 95% CI)1.61 [1.41, 1.84]

    4.2 Non-industry funded trials
3105Risk Ratio (M-H, Random, 95% CI)1.53 [0.81, 2.87]

 
Comparison 8. Subgroup analyses - Clinical criteria

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Inclusion of major depression vs. non-inclusion: CAPS111455Std. Mean Difference (IV, Random, 95% CI)-0.31 [-0.45, -0.16]

    1.1 Trials including patients with major depressive disorder
91304Std. Mean Difference (IV, Random, 95% CI)-0.35 [-0.46, -0.23]

    1.2 Trials excluding patients with major depressive disorder
2151Std. 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)7Risk Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Trials including patients with major depressive disorder
7812Risk Ratio (M-H, Random, 95% CI)1.62 [1.39, 1.89]

   2.2 Trials excluding patients with major depressive disorder
00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 3 Inclusion of war veterans versus non-inclusion: CAPS121801Mean Difference (IV, Random, 95% CI)-6.18 [-9.69, -2.66]

    3.1 Trials including war veterans
4385Mean Difference (IV, Random, 95% CI)-1.73 [-7.54, 4.07]

    3.2 Trials without war veterans
81416Mean Difference (IV, Random, 95% CI)-7.54 [-11.37, -3.71]

 4 Inclusion of war veterans versus non-inclusion: CGI-I13Risk Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 Trials including war veterans
8317Risk Ratio (M-H, Random, 95% CI)1.40 [0.99, 2.00]

    4.2 Trials without war veterans
5955Risk Ratio (M-H, Random, 95% CI)1.59 [1.39, 1.81]

 
Comparison 9. Sensitivity analyses

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Clinical Global Impressions scale improvement item (CGI-I) : non-response131272Risk Ratio (M-H, Random, 95% CI)0.66 [0.60, 0.74]

    1.1 SSRIs
7999Risk Ratio (M-H, Random, 95% CI)0.65 [0.58, 0.74]

    1.2 MAOIs
2178Risk Ratio (M-H, Random, 95% CI)0.80 [0.44, 1.44]

    1.3 TCAs
140Risk Ratio (M-H, Random, 95% CI)0.6 [0.38, 0.96]

    1.4 Other medication
355Risk Ratio (M-H, Random, 95% CI)0.59 [0.35, 0.98]

 2 "Worst case" loss to follow up analysis121275Risk Ratio (M-H, Random, 95% CI)1.37 [1.12, 1.69]

    2.1 SSRIs
71027Risk Ratio (M-H, Random, 95% CI)1.52 [1.33, 1.74]

    2.2 MAOIs
2175Risk Ratio (M-H, Random, 95% CI)0.28 [0.01, 5.42]

    2.3 TCAs
143Risk Ratio (M-H, Random, 95% CI)2.64 [0.86, 8.12]

    2.4 Other medication
230Risk Ratio (M-H, Random, 95% CI)1.12 [0.51, 2.47]

 3 "Best case" loss to follow up analysis121262Risk Ratio (M-H, Random, 95% CI)1.52 [1.22, 1.90]

    3.1 SSRIs
71018Risk Ratio (M-H, Random, 95% CI)1.64 [1.44, 1.87]

    3.2 MAOIs
2172Risk Ratio (M-H, Random, 95% CI)0.48 [0.06, 3.86]

    3.3 TCAs
143Risk Ratio (M-H, Random, 95% CI)3.5 [1.13, 10.81]

    3.4 Other medication
229Risk Ratio (M-H, Random, 95% CI)1.14 [0.52, 2.51]

 
Comparison 10. Head-to-head comparisons

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Clinician administered scales: Symptom severity3432Std. Mean Difference (IV, Random, 95% CI)-0.04 [-0.23, 0.14]

    1.1 Nefazodone versus sertraline
280Std. Mean Difference (IV, Random, 95% CI)-0.19 [-0.63, 0.25]

    1.2 Venlafaxine versus sertraline
1352Std. Mean Difference (IV, Random, 95% CI)-0.01 [-0.22, 0.20]

 2 Comorbid symptoms: Depression (MADRS)126Mean Difference (IV, Random, 95% CI)-0.84 [-7.88, 6.20]

 3 Comorbid symptoms: Anxiety (Hamilton Anxiety Scale)126Mean Difference (IV, Random, 95% CI)-3.23 [-10.90, 4.44]