Freeman 2008.

Methods	RCT: parallel
Participants	59 women randomised (25 were pregnant and thus only these women were eligible for this review) Inclusion criteria: perinatal women (pregnant (n = 25) and postpartum (n = 34) with major depressive disorder, 12‐32 weeks GA or postpartum (within 6 months of childbirth); 18‐45 years of age; scored ≥ 9 on EPDS, outpatient status Exclusion criteria: previous intolerance to omega‐3 fatty acids, current use of antidepressants or anticoagulants, psychosis, diagnosis of bipolar disorder, active substance use, or active suicidal ideation. Setting: University of Arizona, USA
Interventions	SUPPLEMENTATION: EPA + DHA versus placebo Group 1: EPA + DHA: 1.9 g/day (1.1 g EPA and 0.8 g DHA, total 4 capsules/day) for 8 weeks: total 12 pregnant women randomised Group 2: placebo: corn oil with a small amount of fish oil for 8 weeks: total 13 pregnant women randomised (9 completed study) Timing of supplementation: pregnant women: from 12‐32 weeks GA All women: were provided with manualised supportive psychotherapy DHA + EPA dose/day: high: 0.8 g DHA + 1.1 g EPA
Outcomes	Women/birth: Hamilton Rating Scale Depression (HAM‐D) biweekly; Edinburgh Postnatal Depression Scale (EPDS) biweekly; Clinical Global Impression; tolerability of omega‐3
Notes	Funding: NIMH K23MH066265; Pronova/EPAX provided study drug and placebo at no cost. Declarations of interest: Dr Marlene Freeman: Research support: NIMH, U.S. FDA, Institute for Mental Health Research (Arizona), Forest, Reliant, Lilly; honorarium from AstraZeneca; Dr Katherine Wisner: Research support: NIMH, Stanley Medical Research Foundation, New York‐Mid Atlantic Consortium for Genetics and Newborn Screening Services (NYMAC), State of Pennsylvania, American Society for Bariatric Surgery, Pfizer, Wyeth (pending) Dr Alan Gelenberg: Consultantships: Eli Lilly, Pfizer, Best Practice, Astra/Zeneca, Wyeth, Cyberonics, Novartis, Forest, GlaxoSmithKline; Stock Options: Vela Pharmaceuticals; Speakers Bureau: Pfizer Pharmaceuticals, GlaxoSmithKline Dr Joseph Hibbeln, Dr. Priti Sinha, Dr Melinda Davis: nothing to disclose
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Described as randomised; no further details reported
Allocation concealment (selection bias)	Unclear risk	Described as randomised; no further details reported
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Placebo‐controlled
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Not reported, but probably done.
Incomplete outcome data (attrition bias) All outcomes	High risk	7/59 women dropped out after the baseline visit; a further woman was diagnosed with hyperthyroidism after randomisation and was then excluded as being ineligible (leaving 51 women who completed at least 2 assessments) – 21 of these women were pregnant meaning 4/25 (16%) pregnant women were lost to follow‐up (all 4 were from the placebo group).
Selective reporting (reporting bias)	High risk	Few outcomes were reported
Other bias	Unclear risk	Some baseline differences – omega‐3 group more likely to be Caucasian; and to enrol earlier in their pregnancy and more likely to take antidepressants