Braun 1990.

Study characteristics
Methods	Design: single‐centre, randomised, placebo‐controlled, cross‐over, flexible dose, double‐blind Duration of intervention: 5 weeks Placebo run‐in: 2 week titrated placebo washout; 4‐day tapering of medication at end of trial Post‐treatment: Not specified
Participants	Setting: Jerusalem Health Center Ezrath Nashim Hospital Outpatient Clinic Sample size: 16 randomised to alprazolam and placebo Mean age: 37.7 years (19 ‐ 56), 25% combat‐veterans, 13% (2/16) MDD Sex: not specified Diagnostic measure: DSM‐III Inclusion criteria: Quote: “Patients referred to the Jerusalem Health Centre – Ezrath Nashim Hospital Outpatient Clinic who fulfilled DSM‐III criteria for PTSD were eligible for the study, provided that they were physically healthy, had not suffered significant head injury, and were able and willing to give written informed consent. All participants were free of psychotropic medication for at least 2 weeks before commencing treatment. During that period, the diagnosis was confirmed by semi‐structured interview, and baseline psychiatric ratings” Exclusion criteria: Not specified Comorbidity: None Dropouts: 6/16 (3/7 in the alprazolam and 3/9 in the placebo group)
Interventions	Pharmacological intervention: Quote: “The patients were randomly assigned to treatment with alprazolam or placebo. The initial alprazolam dose of 1.5 mg/day in divided doses was increased to the maximum tolerated dose (up to 6 mg/day) within 2 weeks. The maximum dose was maintained for a further 3 weeks. The alprazolam dose was then tapered and discontinued over the next 2 weeks with substitution of placebo. Those patients which received placebo in the first leg of the trial then commenced alprazolam treatment, while those who has received alprazolam commenced placebo. The second leg of the trial lasted 5 weeks. The complete trials thus extended 12 weeks, 5 weeks for each experimental leg separated by a 2‐week interim phase"
Outcomes	Outcomes: DSM‐based PTSD scale, IES, HAM‐D, HAM‐A, Visual Analogue (not clear which outcomes are secondary or primary) Time points: Baseline and at 5 weeks Data estimation: Observed cases for participants who completed 5 weeks of both phases
Notes	Dates of trial: Not stated. Industry‐funded: Unclear Medication provided by industry: Unclear Any of the authors work for industry? Unclear
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: "The authors report a random‐assignment, double‐blind, cross crossover trial comparing alprazolam and placebo in posttraumatic stress disorder (PTSD)"
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: "The authors report a random‐assignment, double‐blind, cross crossover trial comparing alprazolam and placebo in posttraumatic stress disorder (PTSD)"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Clinical response was monitored by means of rating scales administered at baseline and then weekly throughout the trial by a rater who was blind to treatment assignment (P.B.)"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	A similar proportion of participants withdrew from the alprazolam group (3; 43%) compared to the placebo group (3; 33%). Sample characteristics were provided in a table for 10 participants at baseline only. Reasons for withdrawals were not provided. Observed cases for patients who completed 5 weeks of both phases were provided Quote: "Six subjects dropped out during this phase: 3 alprazolam‐treated patients withdrew after 1, 4, and 5 weeks, respectively, and 3 placebo‐treated patients withdrew after 1, 3, and 4 weeks. None of the dropout complained of adverse effect"
Selective reporting (reporting bias)	Unclear risk	The study protocol was not available for this study
Other bias	Low risk	No other sources of bias were identified