The mothers, Omega-3 and mental health study

Ellen Mozurkewich, Julie Chilimigras, Chelsea Klemens, Kristie Keeton, Lucy Allbaugh, Susan Hamilton, Deborah Berman, Delia Vazquez, Sheila Marcus, Zora Djuric, Anjel Vahratian, Ellen Mozurkewich, Julie Chilimigras, Chelsea Klemens, Kristie Keeton, Lucy Allbaugh, Susan Hamilton, Deborah Berman, Delia Vazquez, Sheila Marcus, Zora Djuric, Anjel Vahratian

Abstract

Background: Major depressive disorder (MDD) during pregnancy and postpartum depression are associated with significant maternal and neonatal morbidity. While antidepressants are readily used in pregnancy, studies have raised concerns regarding neurobehavioral outcomes in exposed infants. Omega-3 fatty acid supplementation, most frequently from fish oil, has emerged as a possible treatment or prevention strategy for MDD in non-pregnant individuals, and may have beneficial effects in pregnant women. Although published observational studies in the psychiatric literature suggest that maternal docosahexaenoic acid (DHA) deficiency may lead to the development of MDD in pregnancy and postpartum, there are more intervention trials suggesting clinical benefit for supplementation with eicosapentaenoic acid (EPA) in MDD.

Methods/design: The Mothers, Omega-3 and Mental Health study is a double blind, placebo-controlled, randomized controlled trial to assess whether omega-3 fatty acid supplementation may prevent antenatal and postpartum depressive symptoms among pregnant women at risk for depression. We plan to recruit 126 pregnant women at less than 20 weeks gestation from prenatal clinics at two health systems in Ann Arbor, Michigan and the surrounding communities. We will follow them prospectively over the course of their pregnancies and up to 6 weeks postpartum. Enrolled participants will be randomized to one of three groups: a) EPA-rich fish oil supplement (1060 mg EPA plus 274 mg DHA) b) DHA-rich fish oil supplement (900 mg DHA plus 180 mg EPA; or c) a placebo. The primary outcome for this study is the Beck Depression Inventory (BDI) score at 6 weeks postpartum. We will need to randomize 126 women to have 80% power to detect a 50% reduction in participants' mean BDI scores with EPA or DHA supplementation compared with placebo. We will also gather information on secondary outcome measures which will include: omega-3 fatty acid concentrations in maternal plasma and cord blood, pro-inflammatory cytokine levels (IL-1β, IL-6, and TNF-α) in maternal and cord blood, need for and dosage of antidepressant medications, and obstetrical outcomes. Analyses will be by intent to treat.

Discussion: This study compares the relative effectiveness of DHA and EPA at preventing depressive symptoms among pregnant women at risk.

Clinical trial registration number: NCT00711971.

References

    1. Kessler R, Berglund P, Demler O, Jin R, Koretz D, Merikangas K. et al.The epidemiology of major depressive disorder: Results from the National Comorbidity Survey Replication (NCS-R) JAMA. 2003;289:3095–3105. doi: 10.1001/jama.289.23.3095.
    1. Epidemiology, pathogenesis, and neurobiology of depression.
    1. Stewart W, Ricci J, Chee E, Hahn S, Morganstein D. Cost of lost productive work time among US workers with depression. JAMA. 2003;289:3135–3144. doi: 10.1001/jama.289.23.3135.
    1. Murray C, Lopez A. Alternative projections of mortality and disability by cause 1990-2020: Global burden of disease study. Lancet. 1997;349:1498–1504. doi: 10.1016/S0140-6736(96)07492-2.
    1. Lopez A, Mathers C, Ezzati M, Jamison D, Murray CJL. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet. 2006;367:1747–1757. doi: 10.1016/S0140-6736(06)68770-9.
    1. Yonkers K, Ramin S, Rush J, Navarrete C, Carmody T, March D, Heartwell S, Leveno K. Onset and persistence of postpartum depression in an inner-city maternal health clinic system. Am J Psychiatry. 2001;158:1856–1863. doi: 10.1176/appi.ajp.158.11.1856.
    1. Hibbeln J. Seafood consumption, the DHA content of mothers' milk and prevalence rates of postpartum depression: A cross-national, ecological analysis. J Affect Disord. 2002;69:15–29. doi: 10.1016/S0165-0327(01)00374-3.
    1. Evans J, Heron J, Francomb H, Oke S, Golding J. Cohort study of depressed mood during pregnancy and after childbirth. BMJ. 2001;323:257–260. doi: 10.1136/bmj.323.7307.257.
    1. Bennett H, Einarson A, Taddio A, Koren G, Einarson T. Prevalence of depression during pregnancy: Systematic review. Obstet Gynecol. 2004;103:698–709. doi: 10.1097/01.AOG.0000116689.75396.5f.
    1. Flynn H, Blow F, Marcus S. Rates and predictors of depression treatment among pregnant women in hospital-affiliated obstetrics practices. Gen Hosp Pyschiatry. 2006;28:289–295. doi: 10.1016/j.genhosppsych.2006.04.002.
    1. Marangell L, Martinez J, Zboyan H, Chong H, Puryear L. Omega-3 fatty acids for the prevention of postpartum depression: Negative data from a preliminary, open-label pilot study. Depress Anxiety. 2004;19:20–23. doi: 10.1002/da.10148.
    1. Cripe S, Frederick I, Qiu C, Williams M. Risk of preterm delivery and hypertensive disorders of pregnancy in relation to maternal co-morbid mood and migraine disorders during pregnancy. Paediatric and perinatal epidemiology. 2011;25:116–123. doi: 10.1111/j.1365-3016.2010.01182.x.
    1. Grace S, Evindar A, Stewart D. The effect of postpartum depression on child cognitive development and behavior: A review and critical analysis of the literature. Arch Womens Ment Health. 2003;6:263–274. doi: 10.1007/s00737-003-0024-6.
    1. Alwan S, Reefhuis J, Rasmussen S, Friedman J. Patterns of antidepressant medication use among pregnant women in a United States population. Journal of clinical pharmacology. 2011;51:264–270. doi: 10.1177/0091270010373928.
    1. Kornum JB, Nielsen RB, Pedersen L, Mortensen PB, Norgaard M. Use of selective serotonin-reuptake inhibitors during early pregnancy and risk of congenital malformations: updated analysis. Clinical Epidemiology. 2010;2:29–36.
    1. Hendrick V, Stowe Z, Altshuler L, Hwang S, Lee E, Haynes D. Placental passage of antidepressant medications. Am J Psychiatry. 2003;160:993–996. doi: 10.1176/appi.ajp.160.5.993.
    1. Zeskind P, Stephens L. Maternal selective serotonin reuptake inhibitor use during pregnancy and newborn neurobehavior. Pediatrics. 2004;113:368–375. doi: 10.1542/peds.113.2.368.
    1. Oberlander T, Eckstein Grunau R, Fitzgerald C, Ellwood A, Misri S, Rurak D. et al.Prolonged prenatal psychotropic medication exposure alters neonatal acute pain response. Pediatr Res. 2002;51:443–453. doi: 10.1203/00006450-200204000-00008.
    1. Casper R, Fleisher B, Lee-Ancajas J, Gilles A, Gaylor E, DeBattista A. et al.Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy. J Pediatr. 2003;142:402–408. doi: 10.1067/mpd.2003.139.
    1. Lattimore K, Donn S, Kaciroti N, Kemper A, Neal C, Vazquez D. Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and effects on the fetus and newborn: A meta-analysis. J Perinatol. 2005;25:595–604. doi: 10.1038/sj.jp.7211352.
    1. Sanz E, De-las-Cuevas C, Kiuru A, Bate A, Edwards R. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: A database analysis. Lancet. 2005;365:482–487.
    1. Ruchkin V, Martin A. SSRIs and the developing brain. Lancet. 2005;365:451–453.
    1. Freeman MP, Hibbeln JR, Wisner KL, Davis JM, Mischoulon D, Peet M, Keck PE Jr, Marangell LB, Richardson AJ, Lake J, Stoll AL. Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry. Journal of Clinical Psychiatry. 2006;67:1954–1967. doi: 10.4088/JCP.v67n1217.
    1. Appleton KM, Hayward RC, Gunnell D, Peters TJ, Rogers PJ, Kessler D, Ness AR. Effects of n-3 long-chain polyunsaturated fatty acids on depressed mood: systematic review of published trials. Am J Clin Nutr. 2006;84:1308–1316.
    1. Lin PY, Su KP. A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. The journal of clinical psychiatry. 2007;68:1056–1061. doi: 10.4088/JCP.v68n0712.
    1. Appleton K, Rogers P, Ness A. Updated systematic review and meta-analysis of the effects of n-3 long-chain polyunsaturated fatty acids on depressed mood. The American journal of clinical nutrition. 2010;91:757–770. doi: 10.3945/ajcn.2009.28313.
    1. Jans LAW, Giltay E, Van der Does AJW. The efficacy of n-3 fatty acids DHA and EPA (fish oil) for perinatal depression. British journal of nutrition. 2010;104:1577–1585. doi: 10.1017/S0007114510004125.
    1. Makrides M, Gibson R, McPhee A, Yelland L, Quinlivan J, Ryan P. Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: a randomized controlled trial. JAMA (Chicago, Ill) 2010;304:1675–1683.
    1. Ross BM, Seguin J, Sieswerda LE. Omega-3 fatty acids as treatments for mental illness: which disorder and which fatty acid?. [Review] [116 refs] Lipids in Health & Disease. 2007;6
    1. Martins J. EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials. Journal of the American College of Nutrition. 2009;28:525–542.
    1. Navarro P, Ascaso C, Garcia-Esteve L, Aguado J, Torres A, Martin-Santos R. Postnatal psychiatric morbidity: a validation study of the GHQ-12 and the EPDS as screening tools. General Hospital Psychiatry. 2007;29:1–7. doi: 10.1016/j.genhosppsych.2006.10.004.
    1. Matthey S. Calculating clinically significant change in postnatal depression studies using the Edinburgh Postnatal Depression Scale. Journal of Affective Disorders. 2004;78:269–272. doi: 10.1016/S0165-0327(02)00313-0.
    1. Eberhard-Gran M, Eskild A, Tambs K, Opjordsmoen S, Samuelsen SO. Review of validation studies of the Edinburgh Postnatal Depression Scale. Acta Psychiatrica Scandinavica. 2001;104:243–249. doi: 10.1034/j.1600-0447.2001.00187.x.
    1. Jardri R, Pelta J, Maron M, Thomas P, Delion P, Codaccioni X, Goudemand M. Predictive validation study of the Edinburgh Postnatal Depression Scale in the first week after delivery and risk analysis for postnatal depression. Journal of affective disorders. 2006;93:169–176. doi: 10.1016/j.jad.2006.03.009.
    1. Beck A, Ward C, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry. 1961;4:561–571.
    1. Beck CT, Gable RK. Comparative Analysis of the Performance of the Postpartum Depression Screening Scale With Two Other Depression Instruments. [Article] Nursing Research. 2001;50(4):242–250. doi: 10.1097/00006199-200107000-00008.
    1. Holcomb W Jr, Stone L, Lustman P, Gavard J, Mostello D. Screening for depression in pregnancy: Characteristics of the Beck Depression Inventory. Obstet Gynecol. 1996;88:1021–1025. doi: 10.1016/S0029-7844(96)00329-8.
    1. Steer R, Scholl T, Beck A. Revised Beck Depression Inventory scores of inner-city adolescents: Pre- and postpartum. Psychol Rep. 1990;66:315–320. doi: 10.2466/PR0.66.1.315-320.
    1. Steer R, Scholl T, Hediger M, Fischer R. Self-reported depression and negative pregnancy outcomes. J Clin Epidemiol. 1992;45:1093–1099. doi: 10.1016/0895-4356(92)90149-H.
    1. Beck A, Steer R, Garbin M. Psychometric properties of the Beck Depression Inventory: Twenty-five years of evaluation. Clin Psychol Rev. 1988;8:77–100. doi: 10.1016/0272-7358(88)90050-5.
    1. Freeman M, Hibbeln J, Wisner K, Watchman M, Gelenberg A. An open trial of Omega-3 fatty acids for depression in pregnancy. Acta Neuropsychiatrica. 2006;18:21–24. doi: 10.1111/j.0924-2708.2006.00113.x.
    1. Freeman M, Hibbeln J, Wisner K, Brumbach B, Watchman M, Gelenberg A. Randomized dose-ranging pilot trial of omega-3 fatty acids for postpartum depression. Acta Psychiatr Scand. 2005. pp. 1–5.
    1. Peet M, Horrobin DF. A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs. Arch Gen Psychiatry. 2002;59:913–919. doi: 10.1001/archpsyc.59.10.913.
    1. Berto P, D'Ilario D, Ruffo P, Di Virgilio R, Rizzo F. Depression: Cost-of-illness studies in the international literature, a review. J Ment Health Policy Econ. 2000;3:3–10. doi: 10.1002/1099-176X(200003)3:1<3::AID-MHP68>;2-H.

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