Approximately 18% of women suffer from perinatal depression.1 Untreated prenatal depression is associated with obstetrical and neonatal complications2-7 and is a strong risk factor for postpartum depression.8 Postpartum depression has been associated with negative effects on child development. In spite of the risks of untreated perinatal depression, women often discontinue antidepressant treatment during attempts to conceive or during pregnancy. Safety profiles of antidepressant use during pregnancy are increasingly being studied, although women often seek alternatives during pregnancy. More than a quarter of women report the use of a complementary and alternative medicine (CAM) therapy during pregnancy.9 Despite the prevalence of CAM use, the number of adequately powered, well-designed controlled clinical trials of CAM treatments for prenatal depression is limited. This article will review several CAM treatments for prenatal unipolar depression: omega-3 fatty acids, folate, St John’s Wort, bright light therapy, massage therapy, and exercise.
Omega-3 Fatty Acids
Omega-3 fatty acids are among the most commonly used CAM treatments in the United States.10 Omega-3 fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential fatty acids with well-established health benefits and particular benefits for obstetrical outcomes and infant development.11,12 Consensus guidelines recommend pregnant women consume at least 200 mg of DHA daily13 to optimize pregnancy outcomes and fetal health.
Meta-analyses of randomized controlled trials (RCTs) demonstrate a significant antidepressant benefit of omega-3 fatty acids in mood disorders overall, especially when used as augmentation to antidepressants. However, some RCTs assessing the effectiveness of omega-3 fatty acid supplementation have not demonstrated a benefit in acute treatment or prevention of perinatal depression.14-16 The Omega-3 Fatty Acids Subcommittee, assembled by the American Psychiatric Association, recommends patients with depression take 1 gram EPA + DHA daily. Current evidence may support the use of a 1- to 9-g supplement of EPA + DHA daily for patients with mood disorders, although use of more than 3 g daily should be monitored by a physician because of possible anticoagulant effects at higher doses.17 Based on positive findings from RCTs and meta-analyses in non-perinatal depression, pregnant patients with depression may consume 1 g of EPA + DHA daily as augmentation of other conventional depression treatments, but there is little evidence of efficacy as monotherapy.
Folate, available as folic acid, folinic acid, and 5-methyltetrahydrofolate or L-methylfolate, is important in the synthesis of nucleic acids and amino acid metabolism. Many studies report an association of low folate levels and an increased risk of depression18-20 and low blood folate has been associated with a poorer response to treatment with antidepressants in major depression.21 Epidemiological data, however, do not demonstrate that higher folate intake during pregnancy lessens the risk of the development of postpartum depression.22 Folate and L-methylfolate have been best studied as augmentation strategies to concomitant antidepressant treatment in non-perinatal depression.23,24
To reduce the risk of neural tube birth defects, women of reproductive age are recommended to consume 0.4 to 1 mg of folic acid daily. There have been no studies published on the efficacy of folate monotherapy or augmentation therapy for depression during pregnancy. Considering the potential decrease in birth defects and RCT data that mainly support a positive effect of antidepressant augmentation with folate (ie, folic acid 0.4 to 5 mg/d or folinic acid 15 to 30 mg/d), folate can be an important adjunctive strategy for prenatal depression that carries little risk and may be especially effective in those women with low serum folate levels.
1. Gavin NI, Gaynes BN, Lohr KN, et al. Perinatal depression: a systematic review of prevalence and incidence. Obstet Gynecol. 2005;106(5, pt 1):1071-1083.
2. Bodnar LM, Wisner KL, Moses-Kolko E, et al. Prepregnancy body mass index, gestational weight gain, and the likelihood of major depressive disorder during pregnancy. J Clin Psychiatry. 2009;70:1290-1296.
3. Britton JR. Infant temperament and maternal anxiety and depressed mood in the early postpartum period. Women Health. 2011;51:55-71.
4. Chung TK, Lau TK, Yip AS, et al. Antepartum depressive symptomatology is associated with adverse obstetric and neonatal outcomes. Psychosom Med. 2001;63:830-834.
5. Cripe SM, Frederick IO, Qiu C, Williams MA. Risk of preterm delivery and hypertensive disorders of pregnancy in relation to maternal co-morbid mood and migraine disorders during pregnancy. Paediatr Perinat Epidemiol. 2011;25:116-123.
6. Grote NK, Bridge JA, Gavin AR, et al. A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction. Arch Gen Psychiatry. 2010;67:1012-1024.
7. Jablensky AV, Morgan V, Zubrick SR, et al. Pregnancy, delivery, and neonatal complications in a population cohort of women with schizophrenia and major affective disorders. Am J Psychiatry. 2005;162(1):79-91.
8. Gotlib IH, Whiffen VE, Wallace PM, Mount JH. Prospective investigation of postpartum depression: factors involved in onset and recovery. J Abnorm Psychol. 1991;100:122-132.
9. Bishop JL, Northstone K, Green JR, Thompson EA. The use of complementary and alternative medicine in pregnancy: data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Complement Ther Med. 2011;19:303-310.
10. Barnes PM, Bloom B, Nahin RL. Complementary and alternative medicine use among adults and children: United States, 2007. Natl Health Stat Rep. 2009(12):1-23.
11. Hibbeln JR, Davis JM, Steer C, et al. Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): an observational cohort study. Lancet. 2007;369:578-585.
12. McGregor JA, Allen KG, Harris MA, et al. The omega-3 story: nutritional prevention of preterm birth and other adverse pregnancy outcomes. Obstet Gynecol Surv. 2001;56(5 suppl 1):S1-S13.
13. Koletzko B, Lien E, Agostoni C, et al. The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: review of current knowledge and consensus recommendations. J Perinat Med. 2008;36:5-14.
14. 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;42:199-205.
15. Freeman MP, Davis M, Sinha P, et al. Omega-3 fatty acids and supportive psychotherapy for perinatal depression: a randomized placebo-controlled study. J Affect Disord. 2008;110:142-148.
16. Doornbos B, van Goor SA, Dijck-Brouwer DA, et al. Supplementation of a low dose of DHA or DHA+AA does not prevent peripartum depressive symptoms in a small population based sample. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33:49-52.
17. Freeman MP, Hibbeln JR, Wisner KL, et al. Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry. J Clin Psychiatry. 2006;67:1954-1967.
18. Kendrick T, Dunn N, Robinson S, et al. A longitudinal study of blood folate levels and depressive symptoms among young women in the Southampton Women’s Survey. J Epidemiol Community Health. 2008;62:966-972.
19. Watanabe H, Ishida S, Konno Y, et al. Impact of dietary folate intake on depressive symptoms in young women of reproductive age. J Midwifery Womens Health. 2012;57:43-48.
20. Nguyen PH, Grajeda R, Melgar P, et al. Micronutrient supplementation may reduce symptoms of depression in Guatemalan women. Arch Latinoam Nutr. 2009;59:278-286.
21. Papakostas GI, Petersen T, Mischoulon D, et al. Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 1: predictors of clinical response in fluoxetine-resistant depression. J Clin Psychiatry. 2004;65:1090-1095.
22. Miyake Y, Sasaki S, Tanaka K, et al. Dietary folate and vitamins B12, B6, and B2 intake and the risk of postpartum depression in Japan: the Osaka Maternal and Child Health Study. J Affect Disord. 2006;96:133-138.
23. Coppen A, Bailey J. Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial. J Affect Disord. 2000;60:121-130.
24. Papakostas GI, Shelton RC, Zajecka JM, et al. L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials. Am J Psychiatry. 2012;169:1267-1274.
25. Rayburn WF, Christensen HD, Gonzalez CL. Effect of antenatal exposure to Saint John's wort (Hypericum) on neurobehavior of developing mice. Am J Obstet Gynecol. 2000;183:1225-1231.
26. Dugoua JJ, Mills E, Perri D, Koren G. Safety and efficacy of St. John's wort (hypericum) during pregnancy and lactation. Can J Clin Pharmacol. 2006;13:e268-e276.
27. Gregoretti B, Stebel M, Candussio L, et al. Toxicity of Hypericum perforatum (St John’s wort) administered during pregnancy and lactation in rats. Toxicol Appl Pharmacol. 2004;200:201-205.
28. Moretti ME, Maxson A, Hanna F, Koren G. Evaluating the safety of St John’s Wort in human pregnancy. Reprod Toxicol. 2009;28:96-99.
29. Klier CM, Schmid-Siegel B, Schafer MR, et al. St John’s wort (Hypericum perforatum) and breastfeeding: plasma and breast milk concentrations of hyperforin for 5 mothers and 2 infants. J Clin Psychiatry. 2006;67:305-309.
30. Lee A, Minhas R, Matsuda N, et al. The safety of St John’s wort (Hypericum perforatum) during breastfeeding. J Clin Psychiatry. 2003;64:966-968.
31. Eastman CI, Young MA, Fogg LF, et al. Bright light treatment of winter depression: a placebo-controlled trial. Arch Gen Psychiatry. 1998;55:883-889.
32. Golden RN, Gaynes BN, Ekstrom RD, et al. The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence. Am J Psychiatry. 2005;162:656-662.
33. Sit D, Wisner KL, Hanusa BH, et al. Light therapy for bipolar disorder: a case series in women. Bipolar Disord. 2007;9:918-927.
34. Oren DA, Wisner KL, Spinelli M, et al. An open trial of morning light therapy for treatment of antepartum depression. Am J Psychiatry. 2002;159:666-669.
35. Epperson CN, Terman M, Terman JS, et al. Randomized clinical trial of bright light therapy for antepartum depression: preliminary findings. J Clin Psychiatry. 2004;65:421-425.
36. Wirz-Justice A, Bader A, Frisch U, et al. A randomized, double-blind, placebo-controlled study of light therapy for antepartum depression. J Clin Psychiatry. 2011;72:986-993.
37. Hou WH, Chiang PT, Hsu TY, et al. Treatment effects of massage therapy in depressed people: a meta-analysis. J Clin Psychiatry. 2010;71:894-901.
38. Field T, Diego MA, Hernandez-Reif M, et al. Massage therapy effects on depressed pregnant women. J Psychosom Obstet Gynaecol. 2004;25:115-122.
39. Field T, Figueiredo B, Hernandez-Reif M, et al. Massage therapy reduces pain in pregnant women, alleviates prenatal depression in both parents and improves their relationships. J Bodyw Mov Ther. 2008;12:146-150.
40. Field T, Diego M, Hernandez-Reif M, et al. Pregnancy massage reduces prematurity, low birthweight and postpartum depression. Infant Behav Dev. 2009;32:454-460.
41. Field T, Diego M, Hernandez-Reif M, et al. Yoga and massage therapy reduce prenatal depression and prematurity. J Bodyw Mov Ther. 2012;16:204-209.
42. Krogh J, Nordentoft M, Sterne JA, Lawlor DA. The effect of exercise in clinically depressed adults: systematic review and meta-analysis of randomized controlled trials. J Clin Psychiatry. 2010;72:529-538.
43. Mota-Pereira J, Silverio J, Carvalho S, et al. Moderate exercise improves depression parameters in treatment-resistant patients with major depressive disorder. J Psychiatr Res. 2011;45:1005-1011.
44. Strawbridge WJ, Deleger S, Roberts RE, Kaplan GA. Physical activity reduces the risk of subsequent depression for older adults. Am J Epidemiol. 2002;156:328-334.
45. Chalder M, Wiles NJ, Campbell J, et al. A pragmatic randomised controlled trial to evaluate the cost-effectiveness of a physical activity intervention as a treatment for depression: the treating depression with physical activity (TREAD) trial. Health Technol Assess. 2012;16:1-164, iii-iv.
46. Artal R, O’Toole M. Guidelines of the American College of Obstetricians and Gynecologists for exercise during pregnancy and the postpartum period. Br J Sports Med. 2003;37:6-12.
47. Bell BB, Dooley MP. Exercise in Pregnancy (RCOG Statement 4). Royal College of Obstetricians and Gynaecologists; 2006.
48. Robledo-Colonia AF, Sandoval-Restrepo N, Mosquera-Valderrama YF, et al. Aerobic exercise training during pregnancy reduces depressive symptoms in nulliparous women: a randomised trial. J Physiother. 2012;58:9-15.
49. Da Costa D, Rippen N, Dritsa M, Ring A. Self-reported leisure-time physical activity during pregnancy and relationship to psychological well-being. J Psychosom Obstet Gynaecol. 2003;24:111-119.