Martenyi 2002b.

Study characteristics
Methods	Design: multi‐centre trial, randomised, placebo‐controlled, parallel arm, flexible‐dose, double‐blind; relapse prevention component of Martenyi 2002a Duration of intervention: 24 weeks Placebo run‐in: 1‐ to 2‐week diagnostic evaluation period during which no study drug was given at acute phase (i.e. 12 weeks) Post‐treatment: Not specified
Participants	Setting: Quote: "18 study centres in Belgium, Bosnia, Croatia, Yugoslavia, Israel and South Africa" Sample size: 131 randomised to fluoxetine and placebo Mean age: 38.2 years Sex: 106 men and 25 women, 47% trauma combat‐related Diagnostic measure: DSM‐IV, SCID–I, CAPS–DX Inclusion criteria: Quote: “Participants were men and women aged 18–65 years who met DSM–IV criteria for PTSD according to the SCID–I and the CAPS–DX. To enrol, patients had to have a total score ≥ 50 on the CAPS–DX and a score ≥ 4 on the CGI–S scale at baseline (visit 2). Individuals with MADRS scores > 20 at baseline were ineligible for the study" Exclusion criteria: Quote: “Exclusion criteria included serious comorbid illness, concomitant psychotherapy, serious suicidal risk or risk to others, and diagnosis of an Axis I psychiatric disorder (defined by DSM–IV criteria) 5 years before the primary traumatic episode. Patients with lifetime diagnoses of bipolar disorder, obsessive–compulsive disorder (OCD) or schizophrenia were excluded. Those with a diagnosis of any Axis I psychiatric disorder or comorbidity following the primary traumatic episode, except generalised anxiety disorder, depression, panic disorder or social phobia, were also excluded. Patients with a history of alcohol or substance misuse following the primary traumatic episode were allowed to enrol if the misuse had resolved at least 6 months before study entry" Comorbidity: MADRS > 20 Dropout rates: 33/131 (12/69 in the fluoxetine and 21/62 in the placebo group)
Interventions	Pharmacological intervention: Quote: “Fluoxetine‐treated patients initially received 20mg/day. This dose could be increased by 20‐mg increments at each of three titration points based on predefined response criteria (CGI–S ≥ 3) to a maximum dosage of 80mg/day. Acute response to fluoxetine v. placebo has been described elsewhere. After 12 weeks of acute treatment with fluoxetine or placebo, participants who responded to treatment by a 50% decrease in the eight‐item TOP–8 score from baseline, a CGI–S score ≤ 2, and failing DSM–IV diagnostic criteria for PTSD continued in a 24‐week relapse prevention phase. Those patients who had received fluoxetine were randomised either tocontinue without variation from final dosage in the acute phase or to placebo treatment. In order to maintain blinding, patients switching to placebo did not undergo a tapering regimen"
Outcomes	Primary 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 Time points: No information Data estimation: Baseline, endpoint, LOCF
Notes	Dates of trial: Quote: "The study was conducted from June 1998 to August 2000" Industry‐funded: Yes. Quote: "This work was sponsored by Eli Lilly & Co." Medication provided by industry: No information Any of the authors work for industry: No
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	It was reported that the participants were randomised, but no mention is made of the method of randomisation Quote: "After a 1‐ to 2‐week evaluation period, participants were randomised to 12 weeks’ double‐blind acute treatment with fluoxetine or placebo"
Allocation concealment (selection bias)	Unclear risk	There was insufficient information provided to determine if study medication allocation was concealed
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	The study was described as "double‐blind", although no information was provided on which parties were blinded and how blinding was achieved Quote: "This was a double‐blind, randomised, placebo‐controlled study"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	The study was described as "double‐blind", although no information was provided on blinding of outcome assessors
Incomplete outcome data (attrition bias) All outcomes	High risk	More participants withdrew from the placebo group (21/62, 34%) compared to the fluoxetine group (12/69, 17%). Reasons for withdrawal include: adverse events, clinical relapse, patient decision, lack of efficacy, noncompliance, lost to follow‐up. The 2 groups did not differ by sample characteristics at baseline. Baseline, endpoint and LOCF values were used for the estimation of data. Quote: "Demographic as well as disease characteristics following 12 weeks of acute fluoxetine treatment were similar in both groups"
Selective reporting (reporting bias)	Unclear risk	The study protocol was not available for this study
Other bias	Unclear risk	Funding for study provided by industry Quote: "This work was sponsored by Eli Lilly & Co."