NCT01000493.

Study characteristics
Methods	NEW TRIAL ADDED TO UPDATED REVIEW Design: multi‐centre trial, randomised, placebo‐controlled, parallel arm, fixed‐dose, double‐blind Duration of intervention: 12 weeks Placebo run‐in: No information Post‐treatment: follow‐up visit 14, 28 and 42 days after the last dose of study medication
Participants	Setting: United States Sample size: 129 randomised to orvepitant and placebo Mean age: 36.7 years (11.59) Sex: 30 men and 99 women, non‐combat‐related Diagnostic measure: No information Inclusion criteria: Quote: “Aged 18‐64 years, inclusive; A primary diagnosis of noncombat‐related Post traumatic Stress Disorder (PTSD); Subjects with symptom severity considered to be at least moderate to severe" Exclusion criteria: Quote: “Subjects whose symptoms are better accounted for by a diagnosis other than Post traumatic Stress Disorder (PTSD), subjects diagnosed with dementia; subjects diagnosed with a current/recent eating disorder such as anorexia nervosa or bulimia; subjects with a diagnosed history of schizophrenia, schizoaffective disorder, or Bipolar Disorder; Subjects who have a history of failing to respond to adequate treatment for PTSD with an antidepressant/anti‐anxiety drug, i..e, failure to improve following administration of at least two other antidepressants/anti‐anxiety drugs, each given for at least 4 weeks" Comorbidity: No information Dropout rates: 94/129 (55/69 in the orvepitant and 39/60 in the placebo group)
Interventions	Pharmacological intervention: Experimental: Orvepitant 60 mg/day; Placebo comparator: Placebo
Outcomes	Primary outcomes:CAPS‐17 Secondary outcomes: CAPS‐17, CAPS‐A, CAPS‐B, CAPS‐C, CAPS‐D, CGI‐I, CGI‐S, SPRINT, DTS, PSQI, PSQI‐A, CAPS‐B2, HAM‐D, CPFQ, MSFQ Total Score in men and women, C‐SSRS Time points: CAPS: Baseline (Day 1 pre‐dose) and Week 1, 4, 8, 12; CGI‐I, CGI‐S, HAM‐D, CPFQ, MSFQ and C‐SSRS: Baseline, Week 1, 2, 4, 6, 8, 10 and 12; DTS, PSQI and PSQI‐A: Baseline (Day 1 pre‐dose) and up to Week 12 Data estimation: ITT, completer analysis
Notes	Dates of trial: November 2009 to June 2010 Industry‐funded: Yes. GlaxoSmithKline 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 patients were randomised however no mention is made of the method of randomisation Quote: "This is a 12‐week, randomized, multicenter, double‐blind, placebo controlled, fixed‐dose parallel group study to assess the efficacy and safety of orvepitant (60 mg/day) versus placebo in subjects with a diagnosis of noncombat‐related Posttraumatic Stress Disorder (PTSD), whose symptoms are considered moderate or severe"
Allocation concealment (selection bias)	Unclear risk	There was insufficient information provided to determine if study medication allocation was concealed. Quote: "Those subjects randomised to receive placebo will receive study medication identical in appearance to that received by subjects assigned to receive orvepitant"
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 is a 12‐week, randomized, multicenter, double‐blind, placebo controlled, fixed‐dose parallel group study to assess the efficacy and safety of orvepitant (60 mg/day) versus placebo in subjects with a diagnosis of noncombat‐related Posttraumatic Stress Disorder (PTSD), whose symptoms are considered moderate or severe"
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	A high dropout rate was reported for the orvepitant group (55/69, 78%) and the placebo group (39/60, 65%). No information was provided on whether the 2 groups differed by sample characteristics at baseline and endpoint. Data estimation for ITT and LOCF values. Reasons for withdrawal include: adverse event, lack of efficacy; protocol violation; study closed/terminated; lost to follow‐up; physician decision; withdrawal by subject
Selective reporting (reporting bias)	Low risk	All outcomes were assessed as specified by the protocol.
Other bias	Unclear risk	Funding for study provided by industry, i.e. GlaxoSmithKline