Dowd 2020.

Study characteristics
Methods	NEW TRIAL ADDED TO UPDATED REVIEW Design: single‐centre trial, randomised, placebo‐controlled, parallel arm, fixed dose, double‐blind Duration of intervention: 12 weeks Placebo run‐in: Not specified Post‐treatment: Not specified
Participants	Setting: Not stated Sample size: 25 randomised to eszopiclone and placebo Mean age: 43 years (SD, 12.2) Sex: 15 men and 10 women, 1 combat‐related trauma (4%) Diagnostic measure: DSM‐IV confirmed with CAPS Inclusion criteria: Quote: “Subjects included male and female outpatients, aged 18‐65 years of age with a primary DSM‐IV diagnosis of PTSD and confirmed with CAPS score of > 45. Associated sleep disturbance was operationalized as (1) positive score on diagnostic criterion item D1: “difficulty falling or staying asleep”; (2) sleep latency > 30 min; and (3) total sleep time < 6.5 h at least three times per week over the previous month" Exclusion criteria: Quote: “A lifetime history of psychotic disorders was exclusionary, as was a history of alcohol/substance abuse in the last 3 months. Concurrent use of antidepressants or benzodiazepines (on a stable dose for at least 6 wk) was allowed. Patients receiving current psychotherapy initiated within 3 months of randomization or ongoing psychotherapy of any duration directed specifically toward treatment of PTSD and/or sleep disturbance (e.g., CBT) were excluded, but general supportive individual, couple/family therapy > 3 months duration was permitted. Patients who had current legal actions related to trauma or an ongoing relationship with their assailant were also excluded" Dropout rates: 9/25 (6/13 in the eszopiclone and 3/12 in the placebo group)
Interventions	Pharmacological intervention: Quote: “The study was a 12‐wk, double blind, randomized controlled trial with 3 mg of ESZ or PBO at bedtime with a one‐month follow‐up visit"
Outcomes	Primary outcomes: change in CAPS, PSQI Secondary outcomes: SPRINT, Self‐report sleep diary, Actigraphy to assess for change in sleep, including total sleep time, initial insomnia and number of awakenings, MADRS, CGI‐S, LIFE‐RIFT Time points: Quote: "CAPS was assessed six times throughout the study; PSQI, SPRINT and Self‐report sleep diary was administered weekly; Actigraphy data was collected daily for the week between baseline and week 1 as well as between week 11 and week 12" Data estimation: ITT and completers
Notes	Dates of trial: Quote: "Recruitment began in September of 2012 and completed in 2015" Industry‐funded: No. Quote: "Supported by the National Institute of Mental Health, No. 5R34MH91338‐03 and No. K23 MH103394 (to Zalta AK)" 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 patients were randomised however no mention is made of the method of randomisation Quote: "The study was a 12‐wk, double blind, randomized controlled trial with 3 mg of ESZ or PBO at bedtime with a one‐month follow‐up visit"
Allocation concealment (selection bias)	Low risk	Quote: "Investigators were blind to the randomization sequence, which was designed by the Medical Center’s research pharmacy"
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Information on the blinding of personal was provided; nothing on whether participants were blinded, however Quote: "Investigators were blind to the randomization sequence, which was designed by the Medical Center’s research pharmacy"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	The study was described as "double‐blind", though no information was provided on blinding of outcome assessors Quote: "The study was a 12‐wk, double blind, randomized controlled trial with 3 mg of ESZ or PBO at bedtime with a one‐month follow‐up visit"
Incomplete outcome data (attrition bias) All outcomes	High risk	More participants withdrew from the eszopiclone group (6/13; 46%) compared to the placebo (2/12; 25%) group. No information was provided on sample characteristics at endpoint. ITT and LOCF population Quote: "Of the 25 randomized subjects (13 ESZ, 12 PBO) 9 did not complete the study (ESZ = 6, PBO = 3). Four experienced worsening symptoms (2 ESZ, 2 PBO), 1 had memory disturbance (ESZ) and 4 were lost to follow up (3 ESZ, 1 PBO) ... The primary analysis used last observation carried forward approach in a modified intent to treat population that excluded subject who did not receive at least 1 dose of study drug"
Selective reporting (reporting bias)	Unclear risk	The study protocol was available for this study. Memory recall bias and inflammatory markers were not assessed in the final paper
Other bias	Low risk	No other sources of bias reported