Van der Kolk 1994.

Study characteristics
Methods	Design: multi‐centre, randomised, placebo‐controlled, parallel, flexible‐dose, double‐blind Duration of intervention: 5 weeks Placebo run‐in: 2 weeks Post‐treatment: Not specified
Participants	Setting: Quote: “Two sites: the Massachusetts General Hospital Trauma Clinic and the Boston Veterans Administration Outpatient Clinic" Sample size: 64 randomised to fluoxetine and placebo Mean age: 40.4 years (22 ‐ 55) Sex: 42 men and 22 women, 44% (28/64) combat‐related trauma, 54.8% (34/64) MDD Diagnostic measure: DSM‐II‐R Inclusion criteria: Quote: “Subjects were outpatients who met DSM‐III‐R primary Axis I diagnosis of PTSD, including a score of 45 or above on the CAPS" Exclusion criteria: Quote: "Subjects were excluded if they reported diagnoses of schizophrenia, bipolar I disorder, organic mental disorder, or drug or alcohol addiction within 6 months of the initial interview or met criteria for any of these disorders in the psychiatric evaluation. Patients were requested to abstain from illicit drug and alcohol use and to report any medications taken during the study. Also, patients with clinically significant cardiovascular, renal, hepatic, endocrine, or neurologic disease and pregnant or nursing mothers were excluded. Supportive psychotherapy was permitted" Comorbidity: MDD Dropout rates: 16/64 (12/33 in the fluoxetine and 4/31 in the placebo group)
Interventions	Pharmacological intervention: Quote: “Subjects were instructed to take one capsule (20 mg of fluoxetine or placebo) the first day, none the second day, and one daily for the remainder of the first week unless troublesome side effects emerged. During each weekly visit, the dosage was adjusted by, at most, one additional capsule every other day. Dosage was increased until a significant clinical effect was obtained (reduction in symptoms), with a maximum possible dose of three capsules (60 mg) per day"
Outcomes	Outcomes: CAPS, BDHI, HAM‐D, DES, DESI, acoustic startle response, Rorschach Inkblot Test (no distinction between primary and secondary outcomes) Time points: Quote: "At Visit 1 (baseline) and again at Visit 6 (endpoint)". Data estimation: Completer values
Notes	Dates of trial: Not stated Industry‐funded: Yes. Quote: "Funded, in part, by a grant from Eli Lilly and Company, Indianapolis" 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 patients were randomised however no mention is made of the method of randomisation Quote: "64 subjects with PTSD entered a 5‐week randomized double‐blind trial comparing fluoxetine and placebo"
Allocation concealment (selection bias)	Unclear risk	There was insufficient information provided to determine if study medication allocation was concealed. Quote: "Medication was randomized and administered in double‐blind fashion"
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: "64 subjects with PTSD entered a 5‐week randomized double‐blind trial comparing fluoxetine and placebo"
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 fluoxetine (12/33, 36%) compared to the placebo group (4/31, 13%). Reasons for withdrawal were not provided. Data estimation points were based on completer values. The 2 groups did not differ by sample characteristics at baseline Quote: "Sixty ‐four subjects entered the study, of whom 47 completed the study. There was no significant difference between groups on marital status, nor on education. There were no correlations between severity at intake and dropout. Age and current diagnostic criteria for major depression was not statistically significant"
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: "Funded, in part, by a grant from Eli Lilly and Company, Indianapolis"