A Revision on the Effectiveness of Omega-3 Polyunsaturated Fatty Acids as Monotherapy in the Treatment of Major Depressive Disorder

Table 1

Principal RCTs on the effectiveness of omega-3 fatty acids as monotherapy in the treatment of MDD.

Study	Year	Study duration	Omega-3formulation vs. placebo	Formulation	Subjects, n(I/C)	Population	Diagnosis	Rating	Results
Marangell et al.	2003	6 weeks	2 g DHA	DHA	35 (18/17)	Adult outpatients	MDD	MADRS, HDRS	−
Freeman et al.	2008	8 weeks	1.1 g EPA + 0.8 g DHA	Omega-3	59 (31/28)	Women	MDD	HDRS, CGI, EPDS	−
Su et al.	2008	8 weeks	2.2 g EPA + 1.2 g DHA	Omega-3	36 (18/18)	Women	MDD	HDRS, EPDS, BDI	+
Rees et al.	2008	6 weeks	6 g fish oil soft gelatin (27.3% DHA, 6.9% EPA)	Omega-3	26 (13/13)	Women	MDD	HDRS, MADRS, EPDS	−
Jazayeri et al.	2008	8 weeks	1 g EPA/fluoxetine	EPA/fluoxetine	60 (20/20/20)	Adult outpatients	MDD	HDRS	+
Mischoulon et al.	2015	8 weeks	EPA/DHA (EPA enriched: 1.06 g EPA + 274 mg DHA; DHA enriched: 900 mg DHA + 180 mg EPA)	EPA/DHA	196 (66/65/65)	Adult outpatients	MDD	HDRS, QIDS-SR-16, CGI-S	−
Gabbay et al.	2018	10 weeks	2.4 g EPA + 1.2 g DHA	Omega-3	51 (24/27)	Adolescents	MDD	CDRS-R, CGI	−
Chang et al.	2020	12 weeks	2 g EPA + 1 g DHA	Omega-3	59 (30/29)	Patients with cardiovascular comorbidity	MDD	HDRS, BDI	−

BDI, Beck Depression Inventory; CDRS-R, Children’s Depression Rating Scale-Revised; CGI, clinical global impression; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; EPDS, Edinburgh postnatal depression scale; HDRS, Hamilton depression rating scale; I/C, intervention/control; MADRS, Montgomery–Asberg depression rating scale; MDD, major depressive disorder; PUFAs, polyunsaturated fatty acids; QIDS-SR-16, 16-Item Quick Inventory of Depressive Symptomatology-Self Report; RCTs, randomized clinical trials; +, significant results; −, nonsignificant results.