Coryell (1g/d) 2005.

Study characteristics
Methods	Double‐blind, randomised parallel‐arm trial for 6 weeks, following 4‐week open‐label trial of escitalopram (10 mg/d) to prospectively identify SSRI non‐responders (< 50% improvement) for augmentation
Participants	Participants: 11 participants with a mean age of 28.8 (SD 9.3, range 18 ‐ 48) years, 9 women and 2 men (split across Coryell (1g/d) 2005 and Coryell (2g/d) 2005). Participants recruited via clinician referrals and advertisements, in Iowa City, USA, dates ‐ not reported. Comorbidities: Possible physical and/or psychiatric comorbidities Adjunctive therapy: Yes for all participants ‐ escitalopram Inclusion: Aged 18 ‐ 55 years; current diagnosis of MDD; meets DSM‐IV criteria Antidepressant for no more than 3 days within the past month or antidepressant for at least the past month with no change in type or dose Exclusion: More than 2 adequate antidepressant trials in the current episode; meets DSM‐IV criteria for substance dependence in the past year; substance abuse within the past month; meets DSM‐IV criteria for an eating disorder in the past year; allergy to fish; bleeding disorder/taking warfarin; omega‐3 supplements for 3 or more days in the past 4‐month period; known to be pregnant; taking medications known to produce affective symptoms; history of non‐response to escitalopram/Lexapro
Interventions	Intervention: EPA/DHA combination (740 mg EPA/d + 400 mg DHA/d), 2 capsules, plus 2 placebo capsules Comparator: 4 placebo capsules (oil, 6% ALA ‐ email from trialist) All participants receive 4 capsules with either 0 or 2 capsules containing EPA/DHA. Treatment was received for 6 weeks
Outcomes	Primary: MADRS scores, measurements at 6 weeks. Adverse events Secondary: HDRS, Response based on 50% improvement based on MADRS and HDRS
Notes	Supplements provided by Ocean Nutrition Canada Ltd. Conflicts of interest: None Compliance: Capsule counts at each study visit Depressed mood (continuous): Analysis conducted on MADRS scores at 6 weeks, using unpublished ITT data (missing data for HDRS). Placebo group split across 2 intervention groups (1 g/d = 2 participants, 2 g/d = 2 participants). Adverse events: Data on serious and non‐serious adverse events were collected. No serious AEs were reported, but no data on non‐serious adverse events were available. Values in the analysis are for serious adverse events Trial non‐completion: No withdrawals
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated, simple randomisation (email correspondence from trialist)
Allocation concealment (selection bias)	Unclear risk	Researcher was blind to allocation, research nurse was not blind to allocation. Both had contact with participants and unclear who allocated participants (email correspondence from trialist)
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Researcher was blinded, research nurse was not blinded, and both had contact with participants. Participants were stated as 'blinded', but no details of blinding of taste. Possible attempts to check blinding, but no data available (email correspondence from trialist)
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome assessments made by researcher, and researcher was blinded (email correspondence from trialist)
Blinding of outcome assessment (Adverse Events)	Unclear risk	Outcome assessments made by participants, and unclear if they were blinded (email correspondence from trialist)
Incomplete outcome data (attrition bias) All outcomes	Low risk	Complete MADRS outcome data, and ITT analysis (email correspondence from trialist)
Incomplete outcome data (Adverse Events)	Unclear risk	No serious AEs were reported, but data on non‐serious adverse events are not available (email correspondence from trialist)
Selective reporting (reporting bias)	High risk	Data not published (email correspondence from trialist)
Other bias	Low risk	Study appeared to be free from other sources of bias