An ideal treatment for major depressive disorder (MDD) in women would be efficacious, safe, and offer broad health benefits.  MDD is prevalent in women of childbearing years, and recent research underscores the risk of recurrence of mood episodes during pregnancy.  Concerns many women and their health care providers have about antidepressant exposure during pregnancy and breastfeeding increase the public health significance regarding safe non-medication treatment options.

Omega-3 fatty acids have been a topic of interest in mood disorders, with promising evidence from epidemiological, preclinical, and clinical studies that support a role in mood disorders (Freeman et al., 2006).  Omega-3 fatty acids have established health benefits, with specific benefits for fetal and infant development (Kris-Etherton et al., 2003; McGregor et al., 2001).   Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are two key omega-3 fatty acids and are the main omega-3 fatty acids studied in mood disorders.  Meta-analyses of randomized controlled trials have consistently demonstrated a significant benefit of omega-3 fatty acids in major depressive disorder and bipolar depression with heterogeneity in study designs and results, and to date they have been most thoroughly studied as an augmentation strategy (Freeman et al., 2006).

Maternal omega-3 fatty acid intake has established benefits for obstetrical and infant outcomes (McGregor et al., 2001;Dunstan et al., 2006; Hibbeln et al., 2007). In animals, maternal brain DHA levels are depleted when omega-3 fatty acid intake is deficient during pregnancy (Levant et al., 2006).  In the U.S., pregnant and postpartum women consume less omega-3 fatty acids than is recommended, with demand noted to be higher during pregnancy and lactation.  Dietary intake during pregnancy was demonstrated to decrease further subsequent to U.S. Food and Drug Administration mercury advisories regarding fish intake during pregnancy (Benisek et al., 2000; Oken et al, 2003).  Fortunately, omega-3 fatty acid capsules appear free of significant levels of mercury or other contaminants (Foran et al., 2003).

Three randomized placebo-controlled trials have been conducted for perinatal MDD.  In two of three, investigators did not detect a significant difference between omega-3 fatty acids and placebo (Rees et al., 2008; Freeman et al., 2008).  Su et al., (2008) found a significant benefit of omega-3 fatty acids compared with placebo in prenatal MDD.  All three studies were small, and Su et al. utilized the highest dose.  All were also relatively short trials, lasting up to 8 weeks.  In the two studies that did not demonstrate differences between omega-3 fatty acids and placebo, both omega-3 fatty acid and placebo groups improved significantly from baseline, suggesting that other factors were associated with improvement and may have obscured the ability to detect an effect of omega-3 fatty acids, especially if they are mild to moderately effective (Rees et al., 2008; Freeman et al., 2008).  Dose may be especially important to consider, as the Su et al.  study used the highest dose.  Omega-3 fatty acid capsules appear well tolerated by pregnant and postpartum women (Freeman et al., 2008).

As recommended by the American Heart Association, adults should eat fish at least twice per week, and those with coronary artery disease should consume at least one gram per day of EPA and DHA daily.  Considering the comorbidity between medical and psychiatric conditions, and a possible adjunctive benefit of omega-3 fatty acids for individuals with mood disorders, clinicians and patients should consider the addition of omega-3 fatty acids to the treatment plans of women with mood disorders.

Marlene P. Freeman, MD

Dunstan JA, Simmer K., Dixon G, Prescott SL. Cognitive assessment at 21/2 years following fish oil supplementation in pregnancy: a randomized controlled trial. Arch Dis Child Fetal Neonatal Ed. Pediatr Res. 2006; 62(6):689-94.

Freeman MP, Hibbeln JR, Wisner KL, Davis JM, Mischoulon D, Peet M, Keck Jr PE, Marangell LB, Richardson AJ, Lake J, Stoll AL. Omega-3 Fatty Acids: Evidence Basis for Treatment and Future Research in Psychiatry [American Psychiatric Association Subcommittee Report]. J Clin Psychiatry. 2006. 67:1954-1967.

Freeman MP, Davis M, Sinha P, Wisner KL, Hibbeln JR, Gelenberg AJ.  Omega-3 fatty acids and supportive psychotherapy for perinatal depression: a randomized placebo-controlled study. J Affect Disord. 2008;110(1-2):142-8.

Kris-Etherton PM, Harris WS, Appel, LJ, AHA Nutrition Committee, American Heart Association. Omega-3 fatty acids and cardiovascular disease: new recommendations from the American Heart Association. Arterioscler Thromb Vasc BioI. 2003. 23(2): 151-2.

Levant B, Radel JD, Carlson SE. Reduced Brain DHA Content After a Single Reproductive Cycle in Female Rats Fed a Diet Deficient in N-3 Polyunsaturated Fatty Acids. Biol Psychiatry; 2006. 60(9):987-90.

McGregor JA, Allen KG, Harris MA, Reece M, Wheeler M, French JI. Morrison J., The omega-3 story: nutritional prevention of preterm birth and other adverse pregnancy outcomes. Obstet Gynecol Surv. 2001. 56(5 SuppI1):S1-13.

Rees AM, Austin MP, Parker GB. Omega-3 fatty acids as a treatment for perinatal depression: randomized double-blind placebo-controlled trial. Aust N Z J Psychiatry. 2008. 42(3): 199-205.

Su KP, Huang SY, Chiu TH, Huang KC, Huang CL, Chang HC, Pariante CM. Omega-3 fatty acids for major depressive disorder during pregnancy: results from a randomized double-blind, placebo-controlled trial. J Clin Psychiatry, 2008; 69(4):644-51.