Davidson 1990.

Study characteristics
Methods	Design: single‐centre, randomised, placebo‐controlled, parallel, flexible dose, double‐blind Duration of intervention: 8 weeks Placebo run‐in: not specified Post‐treatment: Not specified
Participants	Setting: Quote: “Patients were referred to the study either from the inpatient service or from the Mental Hygiene Clinic at the Durham (NC) Veterans Administration Medical Center" Sample size: 46 randomised to amitriptyline and placebo Mean age: Not specified Sex: Not specified, combat veterans, 20% (9/46) MDD Diagnostic measure: DSM‐III Criteria for PTSD (SI‐PTSD) Inclusion criteria: Quote: “To be eligible in the study, patients were required to meet DSM‐III criteria for PTSD, as well as to be free of schizophrenia, bipolar disorder, a history of serious violence within the past 5 years, and any medical condition that would contraindicate the use of amitriptyline" Exclusion criteria: See inclusion criteria Comorbidity: MD, history of PD, GAD and alcohol use Dropouts: 13/46 (8/25 in the amitriptyline and 5/21 in the placebo group)
Interventions	Pharmacological intervention: Quote: “Patients were treated with amitriptyline hydrochloride or placebo at doses that varied between 50‐80 mg/d. The initial starting dose of 50 mg was increased to 75 mg and then to 100 mg within the first week. The dose was then increased to 150 mg then 200 mg before the end of 2 weeks. It could then be increased further if necessary and tolerated"
Outcomes	Primary outcomes: CGI‐I, SI‐PTSD, CGI‐S Secondary outcomes: HAM‐D, HAM‐A, IES, NI, EPI Time points: Quote: “The duration of treatment was 8 weeks, with the assessments bring made at baseline and weeks 1 (side effects only), 2, 4, 6 and 8" Data estimation: completer values
Notes	Dates of trial: Not stated Industry‐funded: No Medication provided by industry: No 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: "The clinical trial employed a balanced randomisation to amitriptyline or placebo"
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: "Medication was administered double‐blind, and no other psychotropic agents were permitted during the trial with the exception of chloral hydrate as necessary"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "The key ratings was performed by a rater uninvolved in prescribing and monitoring medication dose, but who was performing PTSD ratings"
Incomplete outcome data (attrition bias) All outcomes	Low risk	A similar proportion of participants withdrew from the amitriptyline group (8/25, 32%) compared to the placebo group (5/21; 24%). Reasons for treatment withdrawal were provided. No information was provided on sample characteristics at endpoint. Data estimation was based on completer values. Quote: "Forty (87%) of 46 patients completed the minimum 4 weeks of treatment that was required for inclusion in the efficacy analysis. Thirty‐five patients (76%) completed 6 weeks of treatment and 33 (71%) completed 8 weeks of treatment. Three patients receiving amitriptyline dropped out of the study earlier than 4 weeks: 2 from intolerable side effects and 1 from alcohol intoxication. Three patients receiving placebo also dropped out prior to week 4: 1 due to myocardial infarction, 1 who failed to return at week 2, and 1 from worsening nightmares. In the patients who dropped out at week 4 and 6, their last observations were carried forward to week 8"
Selective reporting (reporting bias)	Unclear risk	The study protocol was not available for this study
Other bias	Low risk	No other sources of bias were identified. The trial was supported by a veterans grant, but no other disclosures were made about medication or industry