Davidson 2003.

Study characteristics
Methods	Design: single‐centre, randomised, placebo‐controlled, parallel arm, flexible dose, double‐blind Duration of intervention: 8 weeks Placebo run‐in: 1 week single‐blind placebo run‐in Post‐treatment: Not specified
Participants	Setting: North Carolina. Quote: “Subjects were recruited by advertisements or from within the clinical practice of the investigators" Sample size: 29 randomised to mirtazapine and placebo Mean age: 46.5 years Sex: 7 men and 13 women (for 20 participants), 15% (4/26) war trauma, 73% (19/26) MDD Diagnostic measure: DSM‐IV Inclusion criteria: Quote: “Subjects were required to be 18 years of age or older, to carry a primary diagnosis of chronic PTSD by DSM‐IV criteria, with a minimum score of 20 on the Structured Interview for PTSD (SIP), to show fluency in English, and to provide written informed consent. Included in the informed consent process was an explanation that participants were free to withdraw from the trial without penalty and that the study medicine (and other treatments) were available outside of the protocol if desired. Consent was obtained from the study coordinator and treating physician" Exclusion criteria: Quote: "Subjects were excluded on the basis of the following: 1) lifetime schizophrenia, bipolar disorder, or cognitive dysfunction owing to medical condition; 2) history of alcohol or other substance use disorder within 3 months; 3) mental retardation; 4) significant risk of violence or suicide; 5) unstable medical condition; 6) clinically significant laboratory or EKG abnormality or positive urine screen for illicit drugs; 7) nonresponse to mirtazapine 30 mg/day for 8 weeks; 8) concomitant therapy with other psychotropic medications or herbs; 9) need for concurrent psychotherapy; and 10) pregnancy or lactation. Comorbidity was assessed by means of the Mini–International Neuropsychiatric Interview (MINI)" Comorbidity: MINI, MD, agoraphobia, generalised anxiety, panic disorder, social anxiety Dropouts: 6/26 (3/17 in the mirtazapine and 3/9 in the placebo group)
Interventions	Pharmacological intervention: Quote: “Subjects were randomized to mirtazapine or placebo, at an initial dose of 15 mg daily, which was increased at weekly intervals, if tolerated, to 45 mg per day of mirtazapine or matching dose of placebo"
Outcomes	Primary outcomes: SPRINT(Clinical Global Improvement & Total Scores) Secondary outcomes: DTS, HADS, SIP, ASEX Time points: Quote: “At baseline, subjects were randomly assigned to treatment, and returned at weeks 1, 2, 3, 4, 6, and 8" Data estimation: ITT, LOCF (1 post‐baseline assessment)
Notes	Dates of trial: Not stated Industry‐funded: Yes. Quote: "Acknowledgment of financial support for this study from Organon to Dr. Davidson, as well as honoraria to him for consultation" Medication provided by industry: No Any of the authors work for industry? Yes
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: "Twenty‐nine patients were randomized to receive drug up to 45 mg/day or placebo double‐blind on a 2:1 ratio for 8 weeks, with data being available for analysis in 26"
Allocation concealment (selection bias)	Unclear risk	There was insufficient information provided to determine if study medication allocation was concealed. Quote: "Subjects were randomized to mirtazapine or placebo, at an initial dose of 15 mg daily, which was increased at weekly intervals, if tolerated, to 45 mg per day of mirtazapine or matching dose of placebo"
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: "Twenty‐nine patients were randomized to receive drug up to 45 mg/day or placebo double‐blind on a 2:1 ratio for 8 weeks, with data being available for analysis in 26"
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 placebo group (3/9; 33%) compared to the mirtazapine (3/17; 18%) group, however the two groups did not differ with regards to sample characteristics at baseline. Reasons for treatment withdrawal were provided. Data estimation was based on intent to treat last observation carried forward efficacy analyses Quote: "Twenty‐nine subjects were randomized, three failing to return. Twenty (69%) completed the 8‐week period. Early dropouts occurred for three subjects on mirtazapine and three on placebo. Reasons for dropout in the mirtazapine group were: sedation, panic attacks, increased anxiety and irritability (n = 1 each). Placebo dropouts occurred because of lack of efficacy (n = 2) and pain (n = 1). There were no differences between drug and placebo groups in mean (SD) age (48.4 13.6 vs. 42.9 11.7), gender (n = 13 women [81%] and n = 7 men [78%]), marital status (n = 7 [40%] and n = 4 [44%] married) or ethnicity (n = 9 [47%], n = 8 [89%]). Intent to treat last observation carried forward efficacy analyses were conducted by means of analysis of covariance (ANCOVA), with baseline as covariate and treatment as a grouping variable"
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: "Acknowledgment of financial support for this study from Organon to Dr. Davidson, as well as honoraria to him for consultation"