Raskind 2018.

Study characteristics
Methods	NEW TRIAL ADDED TO UPDATED REVIEW Design: multi‐centre trial, randomised, placebo‐controlled, parallel arm, flexible‐dose, double‐blind Duration of intervention: 16 weeks (double‐blind phase, 24 weeks in total) Placebo run‐in: No information Post‐treatment: Not specified
Participants	Setting: Quote: “13 Department of Veterans Affairs medical centers" Sample size: 304 randomised to prazosin and placebo Mean age: 51.85 years (SD: 13.8) Sex: 297 men and 7 women, military veterans, 115 MDD (38%) Diagnostic measure: DSM‐IV Inclusion criteria: Quote: “Participants were eligible if they met the criteria for PTSD according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM‐IV), and had a total score of at least 50 on the 17‐item Clinician‐Administered PTSD Scale (CAPS; scores range from 0 to 136, with higher scores indicating greater frequency and intensity of symptoms)16; if they had been exposed to one or more traumatic, life‐threatening events in a war zone that preceded the onset of recurrent nightmares; if they reported and could recall combat‐related nightmares; if they had a frequency score of at least 2 and a cumulative score of at least 5 on CAPS item B2 (“recurrent distressing dreams”); cumulative scores range from 0 to 8 [with a range of 0 to 4 for frequency and 0 to 4 for intensity], with higher scores indicating more frequent and more distressing dreams); and if, for at least 4 weeks before randomization, they were receiving a stable dose of nonexcluded medications or had been receiving supportive psychotherapy" Exclusion criteria: Quote: “Exclusion criteria were acute or unstable medical illness; a systolic blood pressure of less than 110 mm Hg while the patient was in the supine position, a decrease in systolic blood pressure of more than 20 mm Hg after 2 minutes of standing, or any decrease in blood pressure accompanied by dizziness; the presence of a psychotic or cognitive disorder; substance dependence within the previous 3 months; current cocaine or stimulant use; active suicidal or homicidal ideation with plan or intent; and psychosocial instability (defined as a short‐term or long‐term situational life crisis). Sleep apnea was not a criterion for exclusion, nor was it screened for except by means of history taking and chart review. However, veterans with a diagnosis of sleep apnea on their medical record who did not adhere to treatment for the condition were excluded. Participants were also excluded if they were receiving prazosin or another α1‐adrenergic antagonist at the time of recruitment or if they had participated in a previous trial of prazosin for PTSD; if they had received prolonged exposure therapy, eye‐movement desensitization and reprogramming, or cognitive processing therapy within 4 weeks before randomization; or if they had taken trazodone within 2 weeks before randomization. Women were excluded if they were pregnant or nursing or if they declined to use an effective birth‐control method" Comorbidity: MD, Anxiety disorders other than PTSD, Alcohol abuse and cannabis abuse Dropout rates: 59/304 (30/152 in the prazosin and 29/151 in the placebo group)
Interventions	Pharmacological intervention: Quote: “Eligible participants were randomly assigned, in 1:1 ratio, to receive prazosin or placebo (in identical 1‐mg, 2‐mg, and 5‐mg capsules) in escalating doses. Flexible‐dose adjustment was used to achieve the maximal alleviation of nightmares with acceptable adverse effects. The maximum allowed dose was 5 mg at midmorning and 15 mg at bedtime for men and 2 mg at midmorning and 10 mg at bedtime for women. The maximum achieved daily dose of prazosin was continued as the maintenance dose"
Outcomes	Primary outcomes: CAPS‐B, PSQI, CGIC Secondary outcomes: CAPS‐B, PSQI, CGIC, PCL‐M, PHQ‐9, QOLI, SF‐12, AUDIT‐C Time points: Quote: "Interview‐based assessments were performed by trained clinician raters at weeks 14, 18, 22, and 26" Data estimation: ITT
Notes	Dates of trial: Not stated Industry‐funded: No. Quote: "There was no industry support of or involvement in the trial" 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: "Eligible participants were randomly assigned, in 1:1 ratio, to receive prazosin or placebo (in identical 1‐mg, 2‐mg, and 5‐mg capsules) in escalating doses. Adaptive randomization was used to achieve balance in the following stratification factors within each site: current antidepressant use (yes vs. no) and a traumatic experience before versus on or after October 7, 2001 (the date of the U.S. invasion of Afghanistan)"
Allocation concealment (selection bias)	Unclear risk	There was insufficient information provided to determine if study medication allocation was concealed. Quote: "Eligible participants were randomly assigned, in 1:1 ratio, to receive prazosin or placebo (in identical 1‐mg, 2‐mg, and 5‐mg capsules) in escalating doses"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Trial office personnel, site personnel, and participants were unaware of the group assignments"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Clinician raters were unaware of assignments as well as participants’ vital signs, adverse events, and dose of the trial drug or placebo"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	A similar proportion of patients withdrew from the prazosin group (30/152, 18%) compared to the placebo group (29/151, 19%). The 2 groups did not differ by sample characteristics at baseline. ITT values were used in the analysis Quote: "A total of 271 participants (90% in the prazosin group and 89% in the placebo group) completed the 10‐week primary outcome assessments, and 284 (94% in the prazosin group and 93% in the placebo group) completed one or more of the 10‐week primary outcome assessments; 59 participants (20% in the prazosin group and 19% in the placebo group) withdrew from the trial before the 26‐week visit. The pattern of missing data did not differ significantly between the groups at either 10 weeks or 26 weeks. The two groups did not differ significantly at baseline with respect to age; race; the experience of war‐zone trauma before versus on or after October 7, 2001; behavioral ratings; coexisting psychiatric disorders; or disability status"
Selective reporting (reporting bias)	Low risk	All outcomes were reported on as per the study protocol
Other bias	Low risk	No other sources of bias were identified