Martenyi 2002a.

Study characteristics
Methods	Design: multi‐centre trial, randomised, placebo‐controlled, parallel arm, flexible‐dose, double‐blind, 24 weeks relapse prevention phase (i.e. Martenyi 2002b) Duration of intervention: 12 weeks Placebo run‐in: 1‐ to 2‐week diagnostic evaluation period during which no study drug was given Post‐treatment: Not specified
Participants	Setting: Quote: "18 study centers in Belgium, Bosnia, Croatia, Israel, South Africa and Yugoslavia" Sample size: 301 randomised to fluoxetine and placebo Mean age: 37.9 years (SD: 13.9) Sex: 244 men and 57 women, 6% combat‐related Diagnostic measure: DSM‐IV, CAPS Inclusion criteria: Quote: “Participants in the trial were men and women aged 18 to 65 years who met DSM‐IV criteria for PTSD according to the Structured Clinical Interview for DSM‐IV Axis I Disorders, Investigator Version and the CAPS, Current Diagnostic Version (CAPS‐DX), To enrol, patients must have had a total score ≥ 50 on the CAPS‐DX and a score ≥ 4 on the Clinical Global‐Impression‐Severity of Illness scale (CGI‐S) at baseline (Visit 2). Patient with a Montgomery‐Asberg Depression Rating Scale (MADRS) score > 20 at baseline were ineligible for the study" Exclusion criteria: Quote: “Exclusion criteria included a serious comorbid illness, serious suicidal risk or hetero‐ aggressivity, or a diagnosis of an Axis I psychiatric disorder as defined by DSM‐IV criteria within the 5 years prior to the primary traumatic episode. Patients diagnosed with bipolar disorder, OCD, or schizophrenia at any time were excluded. Patients with a diagnosis of any Axis I psychiatric disorder or comorbidity following the primary traumatic episode, with the exception of generalized anxiety disorder, depression, panic disorder, or social phobia, were excluded. Patients with substance abuse following the traumatic episode were allowed to enrol, provided the abuse had resolved at least 6 months prior to study entry" Comorbidity: MADRS > 20 Dropout rates: 139/301 (95/226 in the fluoxetine and 4/75 in the placebo group)
Interventions	Pharmacological intervention: Quote: “Fluoxetine‐treated patients initially received a dosage of 20 mg/day. This dose could have been increased in 20‐mg increments at each of the 3 titration points based on predefined response criteria to a maximum dosage of 80 mg/day. Patients were seen at 3‐week intervals throughout the 12‐week acute treatment period" Description: fluoxetine 20 mg/d ‐ 80 mg/d, (avg dose: 57.8 mg/d) versus placebo x 12 weeks
Outcomes	Primary outcomes: TOPS‐8 Secondary outcomes: CAPS‐2, CGI‐S, CGI‐I, DTS, MADRS, HAM‐A, SCL‐90‐R, DES Time points: No information Data estimation: Baseline, Endpoint, LOCF (repeated measures)
Notes	Dates of trial: Not stated Industry‐funded: Yes. Quote: "This work was sponsored by Eli Lilly and Company" Medication provided by industry: No information Any of the authors work for industry: Yes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A computer generated randomization sequence was used to determine each patients treatment group assignment. Emergency codes, generated by a computer drug‐labelling system, were available to the investigator. These codes, which revealed the patients treatment group, were opened during the study only if the choice of follow‐up treatment depended on the patients treatment assignment"
Allocation concealment (selection bias)	Low risk	Quote: "A computer generated randomization sequence was used to determine each patients treatment group assignment. Emergency codes, generated by a computer drug‐labelling system, were available to the investigator. These codes, which revealed the patients treatment group, were opened during the study only if the choice of follow‐up treatment depended on the patients treatment assignment"
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	The study was described as "double‐blind", though no information was provided on which parties were blinded and how blinding was achieved Quote: "This was a double‐blind randomized, placebo‐controlled study conducted in Europe, Israel, and South Africa, primarily in war‐torn countries"
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	Unclear risk	More participants withdrew from the fluoxetine group (95/226, 42%) compared to the placebo group (4/75, 5%). Reasons for withdrawal were not provided, only for dropout due to adverse events, although not specific by group. The two groups did not differ by sample characteristics at baseline. LOCF values were used for the estimation of data Quote: "Demographic data and baseline clinical characteristics were similar for both groups, with the exception of a statistically significant difference in CGI‐S score"
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 and Company" Reliability and validity of instruments used