Katz 1994.

Study characteristics
Methods	Design: multi‐centre, randomised, placebo‐controlled, parallel arm, flexible‐dose, double‐blind Duration of intervention: 14 weeks Placebo run‐in: 2 week single‐blind placebo run‐in Post‐treatment: Not specified
Participants	Setting: Quote: "Outpatients in three countries" Sample size: 64 randomised to brofaromine and placebo Mean age: 39 years (25 ‐ 56) Sex: 49 men 15 women, 7% (8/45) combat‐related Diagnostic measure: DSM‐III‐R (confirmed by CAPS) Inclusion criteria: Quote: “This trial was restricted to male and female outpatients 18‐65 years old fulfilling DSM‐III‐R definitions; full satisfaction of CAPS criteria, therefore, provided a further objective check on diagnostic acceptability. Patients were obliged to fully satisfy B, C and D criteria and have a minimum total score of 36 for entry. In principle, a CAPS score as low as 18 can technically satisfy a PTSD diagnosis; a score of two times this level was employed to further assure the validity of the diagnosis and adequate severity" Exclusion criteria: Quote: “Patients were excluded from trial entry if they had a comorbid primary depression, based upon psychiatric interview and a Hamilton Depression Rating Scale (HAM‐D) score of > 21, with > 2 on item 1 (depressed mood). Patients were also excluded if they had a placebo response (≥ 20% decrease on the CAPS during their placebo run‐in). Patients were required to meet standard criteria of medical eligibility. Patients known to abuse alcohol or drugs were excluded from trial entry. With the exception of chloral hydrate and short acting benzodiazepines hypnotics for sleep, other medications with central nervous system (CNS) effects could be not employed in this trial" Comorbidity: HAM‐D > 21 Dropout rates: 19/64 (10/33 in the brofaromine and 9/31 in the placebo group)
Interventions	Pharmacological intervention: Quote: “A one‐ to four‐week drug‐free phase preceded a two‐week single‐blind placebo phase. Following a fixed titration, a flexible dosage schedule was utilized. Dosing started at 50 mg/day or 1 identical placebo tablet/day and was titrated up to a maximum of 150mg/day or 3 tablets. Final dosage was determined by the investigator, and represented the treating physicians judgment of a therapeutic best dose. Patients were studied for up to 14 weeks in the double‐blind phase. Twice daily dosing was routinely employed, with drugs taken with accompanying food. The modal dose was 2 tablets"
Outcomes	Primary outcome: CAPS Secondary outcome: CGI Time points: Quote: "Weekly CAPS ratings" Data estimation: LOCF
Notes	Dates of trial: Not stated Industry‐funded: Yes. Quote: "This study was supported in part by Ciba‐Geigy Corporation" Medication provided by industry: Unclear Any of the authors work for industry: Yes CGI‐C values obtained from Davidson et al, 1997
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	It was reported that the prticipants were randomised, but no mention is made of the method of randomisation Quote: "This was a multicentre, randomized, double‐blind, parallel trial conducted in outpatients in three countries"
Allocation concealment (selection bias)	Unclear risk	There was insufficient information provided to determine if study medication allocation was concealed. Quote: "Dosing started at 50 mg/day or 1 identical placebo tablet/day and was titrated up to a maximum of 150mg/day or 3 tablets"
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: "Patients were studied for up to 14 weeks in the double‐blind phase"
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	Low risk	A similar proportion of participants withdrew from the brofaromine group (10/33, 30%) compared to the placebo group (9/31; 29%). LOCF values were used Quote: "Patients appeared well‐mated on standard demographics criteria, and entered with similar severities of illness based upon the CAPS. Safety and tolerability were assessed via an examination of serious events, hospitalizations, and discontinuations due to medical events. One patient receiving brofaromine elected to discontinue due insomnia and agitation"
Selective reporting (reporting bias)	Unclear risk	The study protocol was not available for this study
Other bias	Unclear risk	Quote: "This study was supported in part by Ciba‐Geigy Corporation; It is evident that while a majority of patients were male, a substantial proportion were female"