Lespérance 2011.

Study characteristics
Methods	Randomised controlled parallel‐arm trial, 8 weeks
Participants	Participants: 432 outpatients with mean age = 46.0 (SD = 12.4) years, 68.5% women, were recruited via adverts, physician referrals and caseloads of study investigators from 8 academic and psychiatric clinics in Canada. The study ran from Oct 2005 to Jan 2009. Comorbidities: Yes in some participants: anxiety disorders (52.8%), possible physical comorbidities Adjunctive therapy: Yes for some participants: 40.3% antidepressants at baseline, 14.8% undergoing psychotherapy, 27.1% regularly used at least 1 other psychotropic medication Inclusion criteria: aged 18 years and over, met diagnostic criteria for MDE (MINI 5), score ≥ 27 IDS‐SR, clinically significant depressive symptoms for ≥ 4 weeks, if taking antidepressants ‐ to have been at maximum dosage for > 4 weeks, or if not on antidepressants to have been intolerant for ≥ 2 previous antidepressants or refused to take them despite medical advice Exclusion criteria: known allergy or intolerance to fish/sunflower oil, taken > 14 g of n‐3PUFA supplements during past 4 weeks, diagnosis of alcohol/drug abuse/dependency during past 12 months or bipolar disorder (MINI), significant suicidal risk based on clinical judgement, history of MI, pancreatic insufficiency or coagulation diseases, regularly taking drugs or herbs with antiplatelet or anticoagulant properties, non‐menopausal pregnant women or those not taking contraception
Interventions	Intervention: EPA/DHA combination (EPA = 1050 mg/d, DHA = 150 mg/d), 3 x capsules daily, plus ongoing therapy Comparator: Sunflower oil + 2% fish oil (to help blind), 3 x capsules daily, plus ongoing therapy Treatment received for 8 weeks
Outcomes	Primary: IDS‐SR, MADRS at baseline, 1, 2, 4 and 8 weeks, Adverse events Secondary: Trial non‐completion
Notes	Funded by Isodis Natura and Foundation Du Centre Hospitalier de l'Universite de Montreal and the CRCHUM Supplements provided by Isodis Natura Conflicts of Interest: CoIs declared by 3 authors Compliance: Reported in results, but method of assessment not reported Depressed mood (continuous): Analysis conducted on MADRS scores at 8 weeks, unadjusted ITT data provided by authors. Adverse events: Adverse events only gained from completers, only includes events reported by ≥ 5% population. Serious adverse events reported by event not by individual. Serious adverse events reported: Intervention group = 7 (3 physical, 4 psychological), Comparator group = 4 (4 physical). Number of participants with non‐serious adverse events: Intervention group = 322 events in 161 participants (215 GI, 107 other), Comparator group = 294 events in 148 participants (181 GI, 113 other). Data in the analysis are for non‐serious adverse events Trial non‐completion: Intervention = 30 (reasons not reported), Comparator = 27 (reasons not reported)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated, "randomly permuted blocks of 2 and 4, _ stratified by study site and baseline antidepressant use/non‐use." (P.1056 and correspondence from author)
Allocation concealment (selection bias)	Low risk	"Group assignment _ using sequentially‐numbered containers", generated by co‐ordinating centre. "Only technician preparing containers had access to randomisation codes" (P.1056)
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Study research personnel and participants were blinded. 2% fish oil was added to placebo to control for fishy aftertaste. James' blinding index used to check blinding of treatment allocation (P. 1056)
Blinding of outcome assessment (detection bias) All outcomes	Low risk	IDS‐SR and MADRS both low ‐ study psychiatrists, personnel were blinded
Blinding of outcome assessment (Adverse Events)	Low risk	AEs ‐ participant‐assessed
Incomplete outcome data (attrition bias) All outcomes	High risk	ITT analysis and although similar dropouts in each group, > 10% dropout
Incomplete outcome data (Adverse Events)	High risk	AEs ‐ only reported AEs reported by > 5% of participants, > 10% dropout
Selective reporting (reporting bias)	Low risk	All outcomes reported (correspondence with author)
Other bias	Low risk	Study appeared to be free from other sources of bias.