Hamner 2008.

Study characteristics
Methods	NEW TRIAL ADDED TO UPDATED REVIEW Design: single‐centre trial, randomised, placebo‐controlled, parallel arm, flexible‐dose, double‐blind Duration of intervention: 10 weeks Placebo run‐in: 1‐week single‐blind placebo lead‐in Post‐treatment: Not specified
Participants	Setting: Quote: “Ralph H. Johnson VA Medical Center in Charleston, SC" Sample size: 29 randomised to divalproex and placebo Mean age: 52.35 years (SD, 6.8) Sex: 28 men and 1 women, MDD = 20 (69%) Diagnostic measure: DSM‐IV, SCID and CAPS‐1 Inclusion criteria: Quote: “Patients were eligible for the study if they were between age 18 and 65, were competent to give informed consent, and had a score ≥ 50 on the CAPS‐1" Exclusion criteria: Quote: “Exclusion criteria included: history of hypersensitivity to divalproex; unstable medical conditions or medical contraindications to the safe administration of divalproex alcohol or substance use disorders within 1 month of study entry; diagnoses of schizophrenia, schizoaffective disorder, or bipolar disorder; or change in psychotropic medication within 4 weeks of randomization" Comorbidity: Comorbid Axis I: MD, Other anxiety disorder, History of substance use disorder Dropout rates: 13/28 (6/15 in the divalproex and 7/13 in the placebo group)
Interventions	Pharmacological intervention: Quote: “Divalproex was initiated at 750 mg/d in divided doses and increased by 250 mg every 3 to 4 days, if tolerated, until positive clinical response was achieved or desired trough levels were reached"
Outcomes	Primary outcomes: CAPS‐2 Secondary outcomes: IES, CGI‐I, HAM‐D, LSAS, PSQI, PSQI‐A Time points: Quote: "Clinical evaluation and tolerability assessment were performed weekly for the first 2 weeks, then biweekly until the end of the study" Data estimation: ITT
Notes	Dates of trial: Not stated Industry‐funded: Yes. Quote: "The study was funded by Abbott Laboratories" 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 participants were randomised, but no mention is made of the method of randomisation Quote: "Patients were randomized to receive placebo or divalproex"
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: "A 10‐week randomized, double‐blind, placebo‐control trial was conducted with patients from the Ralph H. Johnson VA Medical Centre in Charleston, SC"
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 divalproex group (6/15, 40%) compared to the placebo group (7/13; 54%). ITT sample was used throughout the analysis Quote: "The study enrolled 29 patients; 13 were randomized to placebo and 16 to divalproex. One patient in the latter group did not have at least one post randomization visit for efficacy assessments, thus the analysis sample consisted of 15 in the divalproex and 13 in the placebo groups. The baseline characteristics of the subject participants were similar in both groups. The proportion of patients that completed the study was slightly higher in the divalproex group (n = 9 [56.3%]) vs placebo (n = 6 [46.2%]), although the difference was not statistically significant. Early protocol terminations occurred for 7 patients taking divalproex (2 for lack of efficacy; 1 for increased blood pressure; 1 for unsteady gait; 1 for nausea, diarrhoea, and weakness; 1 for noncompliance with protocol; and 1 was lost to follow‐up) and for 7 patients taking placebo (3 for lack of efficacy; 1 for lethargy; 1 due to an unstable medication condition; 1 for lack of time; and 1 was lost to follow‐up). Study completers and study dropouts did not statistically differ on any background characteristic, suggesting an absence of bias among completers compared to those with attrition"
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: "The study was funded by Abbott Laboratories". "All were male except for one female"