Marshall 2001.

Study characteristics
Methods	Design: multi‐centre trial, randomised, placebo‐controlled, parallel arm, fixed‐dose, double‐blind Duration of intervention: 12 weeks Placebo run‐in: 1‐week placebo run‐in Post‐treatment: Not specified
Participants	Setting: Outpatients. Sample size: 551 randomised to paroxetine and placebo Mean age: 41.8 years Sex: 236 men and 315 women, approximately 45% (248/551) comorbid MDD Diagnostic measure: DSM‐IV Inclusion criteria: Quote: “Study subjects were male and female outpatients 18 years or older who met DSM‐IV criteria for chronic PTSD as determined by the diagnostic version of the Clinician‐Administered PTSD Scale, part 1, and the Mini International Neuropsychiatric Interview. The Clinician‐Administered PTSD Scale is a validated clinical interview designed to assess the frequency and severity of each of the 17 DSM‐IV‐defined PTSD symptoms as well as criterion F (social and occupational impairment). The Clinician‐ Administered PTSD Scale, part 1, is used to assess a patient’s current and lifetime DSM‐IV diagnosis of PTSD, while the Clinician‐Administered PTSD Scale, part 2, is used to evaluate symptom severity and change. Concurrent affective and anxiety disorders were allowed in study patients, provided that PTSD was considered the principal diagnosis (i.e., the main focus of attention or need for treatment) and the onset of PTSD preceded that of concurrent disorders. Furthermore, patients could not have had another axis I disorder as a principal diagnosis within 6 months of screening. A Clinician‐Administered PTSD Scale, part 2, total score of 50 points or higher was required for study entry. For female patients of childbearing potential, participation was contingent on a negative serum pregnancy test and a medically accepted method of contraception" Exclusion criteria: Quote: “Other exclusion criteria were 1) receiving disability payments or involvement in litigation related to PTSD or any other psychiatric illness, 2) alcohol or substance abuse or dependence within 6 months of screening, 3) taking psychotropic medications within 2 weeks of the first dose of study medication (or 4 weeks for fluoxetine), 4) having psychotherapy or ECT within 12 weeks of screening, 5) being a homicidal or suicidal risk, 6) intolerance to paroxetine or any other SSRI, or 7) having a serious medical condition" Comorbidity: MDD Drop‐out rates: 208/563 (140/375 in the paroxetine and 68/188 in the placebo group)
Interventions	Pharmacological intervention: Quote: “Eligible patients entered a 1‐week placebo run‐in period to evaluate compliance with study procedures, followed by random assignment to one of the three treatments. All paroxetine‐treated patients started therapy at 20 mg/day; patients assigned to the 40‐mg/day group then received 30 mg/day during week 2 and 40 mg/day from the beginning of week 3. Chloral hydrate was permitted at doses up to 1000 mg per night for sleep disturbance only during the placebo run‐in period and week 1"
Outcomes	Primary outcomes: CAPS‐2, CGI‐I Secondary outcomes: DTS, TOP‐8, CAPS‐2, SDS, MADRS Time points: Quote: "Assessments were conducted at weeks 1, 2, 4, 6, 8, and 12. Safety assessments conducted at screening and endpoint or at study discontinuation included a complete physical examination, a laboratory evaluation (including clinical chemistry and hematology tests and a urinalysis), and an ECG. At each scheduled visit, the patient’s sitting heart rate and blood pressure were also documented" Data estimation: LOCF (1 post‐baseline assessment)
Notes	Dates of trial: Not stated Industry‐funded: Yes. Quote: "Supported by GlaxoSmithKline and NIMH grant MH‐01412 (to Dr. Marshall)" Medication provided by industry: No information 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 patients were randomised however no mention is made of the method of randomisation Quote: "Outpatients with chronic PTSD according to DSM‐IV criteria and a score of 50 or more on the Clinician‐Administered PTSD Scale, part 2, were randomly assigned to take placebo (N=186), 20 mg/day of paroxetine (N=183), or 40 mg/day of paroxetine (N=182) for 12 weeks"
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: "This study was a 12‐week, double‐blind comparison of 20 mg/ day and 40 mg/day of paroxetine and of placebo in adults with chronic 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	A similar proportion of participants withdrew from the paroxetine groups (20mg: 61/188, 32%; 40mg: 69/187, 37%) compared to the placebo group (66/188; 36%). The two groups did not differ by sample characteristics at baseline. Reasons for withdrawal were not provided Quote: "Statistical analyses were based on the data set with the last observation carried forward for the patients who were randomly assigned to groups and who had at least one treatment assessment (intent‐to‐treat group). A total of 840 patients entered the screening/placebo run‐in phase of the study. Of these, 277 patients were not randomly assigned to treatment groups at baseline for the reasons shown in Figure 1. Of the 563 patients randomly assigned to receive treatment, 12 patients (two receiving placebo and five in each paroxetine dose group) were lost to follow‐up before the first postbaseline assessment. The remaining 551 patients had at least one treatment assessment and comprised the intent‐to‐treat group for all analyses (186 receiving placebo, 183 receiving 20 mg/day of paroxetine, and 182 receiving 40 mg/day of paroxetine). Figure 1 summarizes patient disposition throughout the study. Patient demographic characteristics did not differ across the three randomly assigned groups"
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: "Supported by GlaxoSmithKline and NIMH grant MH‐01412 (to Dr. Marshall)"