McRae 2004.

Study characteristics
Methods	Design: multi‐centre trial, randomised, placebo‐controlled, parallel arm, flexible dose, double‐blind Duration of intervention: 12 weeks Placebo run‐in: 1 week single‐blind placebo run‐in Post‐treatment: Not specified
Participants	Setting: Quote: “The research was conducted at outpatient psychiatric clinics in two academic medical centers (Medical University of South Carolina and Dartmouth Medical School)" Sample size: 37 randomised to nefazodone and sertraline Mean age: 40.3 years (18 ‐ 65) Sex: 6 men and 20 women (for 26 participants) Diagnostic measure: DSM‐IV Inclusion criteria: Quote: “Subjects were male and female outpatients 18–65 years of age who met DSM‐IV criteria for a principle diagnosis of PTSD as determined by Part 1 of the CAPS‐1. To meet inclusion criteria, subjects had to have a minimum 3‐month duration of PTSD symptoms and a total severity score of at least 50 on the CAPS‐2 at the end of a 1‐week placebo wash‐out period" Exclusion criteria: Quote: “Additional exclusion criteria were: 1) any clinically significant medical condition or laboratory abnormality that could be expected to progress, recur, or change such that it might bias the assessment of the clinical and mental status of the subject; 2) history of seizure disorder or organic brain disease; 3) pregnancy or breast‐feeding; 4) current diagnosis of a psychotic disorder, bulimia or anorexia, bipolar disorder, or obsessive compulsive disorder; 5) current substance abuse or dependence (defined as not having a documented recovery of at least 3 months duration); 6) current diagnosis of major depression, panic disorder, or agoraphobia if these conditions were not deemed secondary to PTSD; 7) current use of any psychotropic medication or other medication that would interfere with assessment of effectiveness or compromise safety of study participants, including medications that are substrates of the cytochrome P450 system; 8) hypersensitivity to nefazodone or sertraline; 9) history of nonresponse to nefazodone or sertraline; and 10) treatment refractory patients (defined as patients who had three trials of psychotropic treatment of adequate dose and duration for treatment of PTSD). In addition, subjects could not be receiving PTSD‐specific psychotherapy" Comorbidity: MINI Dropout rates: 14 dropouts in total (insufficient information to determine dropout rates for the 2 groups separately)
Interventions	Pharmacological intervention: Quote: “Treatment was initiated at 25 mg twice daily for sertraline and 50 mg twice daily for nefazodone, and titrated up based on response and tolerability to a target dose of 100 mg twice daily for sertraline and 300 mg twice daily for nefazodone"
Outcomes	Primary outcomes: CAPS‐2, CGI‐I Secondary outcomes: DTS, MADRS, HAM‐A, TOP‐8, PSQI, SDS Time points: Quote: "The CAPS‐2 was carried out at the end of the placebo wash‐out period and at Weeks 4, 8, and 12. The CAPS‐2 carried out at the end of the placebo wash‐out was used as the baseline CAPS rating. The CGI‐I was rated weekly. The DTS was completed weekly. The TOP‐8 was completed at the end of the placebo wash‐out period and Weeks 2, 4, 6, 8, 10, and 12. The MADRS, HAM‐A, PSQI, and SDS were completed at the end of the placebo wash‐out period and Weeks 4, 8, and 12" Data estimation: LOCF (1 post‐baseline assessment)
Notes	Dates of trial: Not stated Industry‐funded: Yes. Quote: "Contract grant sponsor: Bristol‐Myers Squibb" Medication provided by industry: No Any of the authors work for industry: Yes 3 patients excluded during run‐in
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: "Thirty‐seven male and female outpatients meeting DSM‐IV criteria for PTSD were randomly assigned to receive nefazodone (maximum dose 600 mg /day; average dose 463 mg/day) or sertraline (maximum dose 200/day; average dose 153 mg/day). Treatment randomization information was kept by a research pharmacist"
Allocation concealment (selection bias)	Low risk	Quote: "All medication was packaged in identical opaque gelatin capsules with cornstarch filler. Treatment randomization information was kept by a research pharmacist"
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: "This 12‐week, randomized, double‐blind study compares the effectiveness, safety, and tolerability of nefazodone and sertraline for the treatment of PTSD"
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	There is insufficient information to determine dropout rates for the 2 groups separately. Overall 54% of the participants dropped out of the study. Did not use ITT or LOCF Quote: "For the analyzed sample there were no significant differences between groups in any of the baseline demographic and clinical characteristics. Twenty‐three subjects completed the 12‐week trial. Four subjects withdrew early because of adverse effects (two subjects from each treatment group). Five subjects did not return for scheduled visits and could not be contacted, three subjects withdrew for personal reasons, one subject was discontinued from the study after being diagnosed with sleep apnea, and one subject was discontinued by the investigator for displaying volatile behavior. There were no between group differences in rate of or reason for early termination"
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: "Contract grant sponsor: Bristol‐Myers Squibb" Quote: "The major limitations of this study are the small sample size, high attrition rate, and lack of a placebo control group"