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The management of mood disorders in pregnancy: alternatives to antidepressants

  • Erica M. Richards (a1) and Jennifer L. Payne (a2)

The management of mood disorders during pregnancy is complex due to risks associated with medication use and risks associated with untreated depression. Antidepressant use during pregnancy is an exposure for the unborn child, and it currently remains unclear what long-term repercussions there might be from this exposure, though available data are reassuring. On the other hand, there are risks for both the mother and child of untreated depression during pregnancy. There is a real need for research into nonpharmacological strategies for the prevention of relapse of mood disorders in pregnant women who are off medications. We have reviewed a number of potential candidate interventions including psychotherapies, exercise, light box therapy (LBT), repetitive transcranial magnetic stimulation (rTMS), electroconvulsive therapy (ECT), holistic strategies, and nutritional and herbal supplements. Currently there is a lack of evidence supporting the use of such strategies in the prevention of depressive relapse during pregnancy, though most of these strategies have at least some support for their use in the treatment of a major depressive episode. Carefully conducted research using one or more of these strategies in women who want to discontinue antidepressants for pregnancy is sorely needed.

Corresponding author
*Address for correspondence: Jennifer L. Payne, MD, Associate Professor of Psychiatry, Johns Hopkins School of Medicine, Department of Psychiatry, 550 N. Broadway, Suite 305, Baltimore, MD 21205, USA. (Email
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1.Payne JL, Meltzer-Brody A. Antidepressant use during pregnancy: current controversies and treatment strategies. Clin Obstet Gynecol. 2009; 52(3): 469482.
2.O'Hara MW, Swain AM. Rates and risk of postpartum depression—a meta-analysis. Int Rev Psychiatry. 1996; 8(1): 3754.
3.Gaynes BN, Gavin N, Meltzer-Brody S, etal. Perinatal depression: prevalence, screening accuracy, and screening outcomes. Evid Rep Technol Assess (Summ). 2005; (119): 18.
4.Dietz PM, Williams SB, Callaghan WM, etal. Clinically identified maternal depression before, during, and after pregnancies ending in live births. Am J Psychiatry. 2007; 164(10): 15151520.
5.Yonkers KA, Ramin SM, Rush AJ, etal. Onset and persistence of postpartum depression in an inner-city maternal health clinic system. Am J Psychiatry. 2001; 158(11): 18561863.
6.Payne JL, Roy PS, Murphy-Eberenz K, etal. Reproductive cycle-associated mood symptoms in women with major depression and bipolar I disorder. J Affect Disord. 2007; 99: 221229.
7.Mills JL. Depressing observations on the use of selective serotonin-reuptake inhibitors during pregnancy. New Engl J Med. 2006; 354(6): 636638.
8.Cooper WO, Willy ME, Pont SJ, Ray WA. Increasing use of antidepressants in pregnancy. Am J Obstet Gynecol. 2007; 196(6): 544545.
9.Andrade SE, Raebel MA, Brown J, etal. Use of antidepressant medications during pregnancy: a multisite study. Am J Obstet Gynecol. 2008; 198(2): 194.e1194.e5.
10.Mitchell AA, Gilboa SM, Werler MM, etal. Medication use during pregnancy, with particular focus on prescription drugs: 1976–2008. Am J Obstet Gynecol. 2011; 205(1): 51.e151.e8.
11.Yonkers KA, Wisner KL, Steward DE, etal. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Obstet Gynecol. 2009; 114(3): 703713.
12.Hemels M, Einarson A, Koren G, Lanctot K, Einarson T. Antidepressant use during pregnancy and the rates of spontaneous abortions: a meta-analysis. Ann Pharmacother. 2005; 39: 803809.
13.Källén BAJ, Otterblad Olausson P. Maternal use of selective serotonin re-uptake inhibitors in early pregnancy and infant congenital malformations. Birth Defects Res A Clin Mol Teratol. 2007; 79: 301308.
14.Källén B, Otterblad Olausson P. Antidepressant drugs during pregnancy and infant congenital heart defect. Reprod Toxicol. 2006; 21: 221222.
15.Cole JA, Modell JG, Haight BR, etal. Buproprion in pregnancy and the prevalence of congenital malformations. Pharmacoepidemiol Drug Saf. 2007; 16: 474484.
16.Louik C, Lin A, Werler M, Hernandez-Diaz S, Mitchell A. First-trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. New Engl J Med. 2007; 356: 26752683.
17.Alwan S, Reefhuis J, Rasmussen SA, Olney RS, Friedman JM. National Birth Defects Prevention Study. Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects. New Engl J Med. 2007; 356: 26842692.
18.Chambers CD, Hernandez-Diaz S, Van Marter LJ, etal. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. New Engl J Med. 2006; 354(6): 579587.
19.Källén B, Olausson PO. Maternal use of selective serotonin re-uptake inhibitors and persistent pulmonary hypertension of the newborn. Pharmacoepidemiol Drug Saf. 2008 Aug; 17(8): 801806.
20.Kieler H, Artama M, Engeland A, etal. Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries. BMJ. 2012; 344: d8012.
21.Andrade SE, McPhillips H, Loren D, etal. Antidepressant medication use and risk of persistent pulmonary hypertension of the newborn. Pharmacoepidemiol Drug Saf. 2009; 18(3): 246252.
22.Wichman CL, Moore KM, Lang TR, etal. Congenital heart disease associated with selective serotonin reuptake inhibitor use during pregnancy. Mayo Clin Proc. 2009; 84(1): 2327.
23.Wilson KL, Zelig CM, Harvey JP, etal. Persistent pulmonary hypertension of the newborn is associated with mode of delivery and not with maternal use of selective serotonin reuptake inhibitors. Am J Perinatol. 2011; 28(1): 1924.
24.Oberlander TF, Misri S, Fitzgerald CE, etal. Pharmacological factors associated with transient neonatal symptoms following prenatal psychotropic medication exposure. J Clin Psychiatry. 2004; 65(2): 230237.
25.Levinson-Castiel R, Merlob P, Linder N, Sirota L, Klinger G. Neonatal abstinence syndrome after in utero exposure to selective serotonin reuptake inhibitors in term infants. Arch Pediat Adolesc Med. 2006; 160: 173176.
26.Chambers CD, Johnson KA, Dick LM, Felix RJ, Jones KL. Birth outcomes in pregnant women taking fluoxetine. New Engl J Med. 1996; 335: 10101015.
27.Ter Horst PG, Jansman FG, van Lingen RA, etal. Pharmacological aspects of neonatal antidepressant withdrawal. Obstet Gynecol Surv. 2008; 63(4): 267279.
28.Koch S, Jäger-Roman E, Lösche G, etal. Antiepileptic drug treatment in pregnancy: drug side effects in the neonate and neurological outcome. Acta Paediatr. 1996; 85(6): 739746.
29.Cohen LS, Altshuler LL, Harlow BL, etal. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA. 2006; 295(5): 499507.
30.Cohen LS, Nonacs RM, Bailey JW, etal. Relapse of depression during pregnancy following antidepressant discontinuation: a preliminary prospective study. Arch Womens Ment Health. 2004; 7(4): 217221.
31.Murray L, Sinclair D, Cooper P, etal. The socioemotional development of 5-year-old children of postnatally depressed mothers. J Child Psychol Psychiatry. 1999; 40(8): 12591271.
32.Marmorstein NR, Malone SM, Lacono WG. Psychiatric disorders among offspring of depressed mothers: associations with paternal psychopathology. Am J Psychiatry. 2004; 161(9): 15881594.
33.Li D, Liu L, Odouli R. Presence of depressive symptoms during early pregnancy and the risk of preterm delivery: a prospective cohort study. Hum Reprod. 2009; 24(1): 146153.
34.Zuckerman B, Amaro H, Bauchner H, Cabral H. Depressive symptoms during pregnancy: relationship to poor health behaviors. Am J Obstet Gynecol. 1989; 160(5 pt 1): 11071111.
35.Orr ST, Blazer DG, James SA, Reiter JP. Depressive symptoms and indicators of maternal health status during pregnancy. J Womens Health (Larchmt). 2007; 16(4): 535542.
36.Ashman SB, Dawson G, Panagiotides H, Yamada E, Wilkinson CW. Stress hormone levels of children of depressed mothers. Devel Psychopathol. 2002; 14(2): 333349.
37.Diego MA, Field T, Hernandez-Reif M, etal. Prepartum, postpartum, and chronic depression effects on newborns. Psychiatry. 2004; 67(1): 6380.
38.Essex MJ, Klein MH, Cho E, Kalin NH. Maternal stress beginning in infancy may sensitize children to later stress exposure: effects on cortisol and behavior. Biol Psychiatry. 2002; 52(8): 776784.
39.Halligan SL, Herbert J, Goodyer IM, Murray L. Exposure to postnatal depression predicts elevated cortisol in adolescent offspring. Biol Psychiatry. 2004; 55(4): 376381.
40.Brennan PA, Pargas R, Walker EF, etal. Maternal depression and infant cortisol: influences of timing, comorbidity and treatment. J Child Psychol Psychiatry. 2008; 49(10): 10991107.
41.O'Connor TG, Ben-Shlomo Y, Heron J, etal. Prenatal anxiety predicts individual differences in cortisol in pre-adolescent child. Biol Psychiatry. 2005; 58(3): 211217.
42.Lindahl V, Pearson JL, Colpe L. Prevalence of suicidality during pregnancy and the postpartum. Arch Womens Ment Health. 2005; 8(2): 7787.
43.Akman I, Kuscu K, Ozdemir N, etal. Mothers’ postpartum psychological adjustment and infantile colic. Arch Dis Child. 2006; 91(5): 417419.
44.Flynn HA, Davis M, Marcus SM, Cunningham R, Blow FC. Rates of maternal depression in pediatric emergency department and relationship to child service utilization. Gen Hosp Psychiatry. 2004; 26(4): 316322.
45.McLearn KT, Minkovitz CS, Strobino DM, Marks E, Hou W. The timing of maternal depressive symptoms and mothers’ parenting practices with young children: implications for pediatric practice. Pediatrics. 2006; 118(1): e174e182.
46.Grace SL, Evindar A, Stewart DE. 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(4): 263274.
47.Kim DR, Sockol L, Barber JP, etal. A survey of patient acceptability of repetitive transcranial magnetic stimulation (TMS) during pregnancy. J Affect Disord. 2011; 129(1–3): 385390.
48.Dennis CE. Treatment of postpartum depression, part 2: a critical review of nonbiological interventions. J Clin Psychiatry. 2004; 65: 12521265.
49.Dennis CL, Ross LE, Grigoriadis S. Psychosocial and psychological interventions for treating antenatal depression. Cochrane Database Syst Rev. 2007; 18(3): CD006309.
50.Dimidjian S, Goodman S. Nonpharmacologic intervention and prevention strategies for depression during pregnancy and the postpartum. Clin Obstet Gynecol. 2009; 52: 498515.
51.O'Hara MW, Stuart S, Gorman LL, etal. Efficacy of interpersonal psychotherapy for postpartum depression. Arch Gen Psychiatry. 2000; 57: 10391045.
52.Brandon AR, Ceccotti N, Hynan LS, etal. Proof of concept: partner-assisted interpersonal psychotherapy for perinatal depression. Arch Womens Ment Health. 2012; 15(6): 469480.
53.Zlotnick C, Miller IW, Pearlstein T, etal. A preventive intervention for pregnant women on public assistance at risk for postpartum depression. Am J Psychiatry. 2006; 163: 14431445.
54.Teasdale JD, Segal Z, Williams JMG, etal. Prevention of relapse/recurrence in major depression by mindfulness-based cognitive therapy. J Consult Clin Psychol. 2000; 68: 615623.
55.Ma SH, Teasdale JD. Mindfulness-based cognitive therapy for depression: replication and exploration of differential relapse prevention effects. J Consult Clin Psychol. 2004; 72: 3140.
56.U.S. Department of Health and Human Services. 2008 Physical Activity Guidelines for Americans. Washington, DC: Department of Health and Human Services; 2008.
57.Blumenthal JA, Babyak MA, Moore KA, etal. Effects of exercise training on older patients with major depression. Arch Intern Med. 1999; 159(19): 23492356.
58.Babyak M, Blumenthal JA, Herman S, etal. Exercise treatment for major depression: maintenance of therapeutic benefit at 10 months. Psychosom Med. 2000; 62(5): 633638.
59.Blumenthal JA, Babyak MA, Doraiswamy PM, etal. Exercise and pharmacotherapy in the treatment of major depressive disorder. Psychosom Med. 2007; 69(7): 587596.
60.Robledo-Colonia AF, Sandoval-Restrepo N, Mosquera-Valderrama YF, Escobar-Hurtado C, Ramírez-Vélez R. Aerobic exercise training during pregnancy reduces depressive symptoms in nulliparous women: a randomised trial. J Physiother. 2012; 58(1): 915.
61.Lam RW, Levitt AJ. Canadian Consensus Guidelines for the Treatment of Seasonal Affective Disorder. Vancouver: Clinical and Academic Publishing; 1999.
62.American Psychiatric Association. Practice Guidelines for the Treatment of Psychiatric Disorders, Compendium 2000. Washington, DC: American Psychiatric Association; 2000.
63.Lewy AJ, Wehr TA, Goodwin FK, Newsome DA, Markey SP. Light suppresses melatonin secretion in humans. Science. 1980; 210: 12671269.
64.Wirz-Justice A, Terman M, Oren DA, etal. Brightening depression. Science. 2004; 303: 467469.
65.Levitt AJ, Joffe RT, Moul DE, etal. Side effects of light therapy in seasonal affective disorder. Am J Psychiatry. 1993; 150: 650652.
66.Terman M, Terman JS. Bright light therapy: side effects and benefits across the symptom spectrum. J Clin Psychiatry. 1999; 60: 799808.
67.Gallin PF, Terman M, Reme CE, etal. Ophthalmologic examination of patients with seasonal affective disorder, before and after bright light therapy. Am J Ophthalmol. 1995; 119: 202210.
68.Kripke DF, Mullaney DJ, Klauber MR, Risch SC, Gillin JC. Controlled trial of bright light for nonseasonal major depressive disorders. Biol Psychiatry. 1992; 31: 119134.
69.Kripke DF. Light treatment for nonseasonal depression: speed, efficacy, and combined treatment. J Affect Disord. 1998; 49: 109117.
70.Yamada N, Martin-Iverson MT, Daimon K, Tsujimoto T, Takahashi S. Clinical and chronobiological effects of light therapy on nonseasonal affective disorders. Biol Psychiatry. 1995; 37: 866873.
71.Golden RN, Gaynes BN, Ekstrom RD, etal. The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence. Am J Psychiatry. 2005; 162: 656662.
72.Even C, Schroder CM, Friedman S, Rouillon F. Efficacy of light therapy in nonseasonal depression: a systematic review. J Affect Disord. 2008; 108: 1123.
73.Oren DA, Wisner KL, Spinelli M, etal. An open trial of morning light therapy for treatment of antepartum depression. Am J Psychiatry. 2002; 159: 666669.
74.Epperson CN, Terman M, Terman JS, etal. Randomized clinical trial of bright light therapy for antepartum depression: preliminary findings. J Clin Psychiatry. 2004; 65: 421425.
75.Wirz-Justice A, Bader A, Frisch U, etal. A randomized, double-blind, placebo-controlled study of light therapy for antepartum depression. J Clin Psychiatry. 2011; 72(7): 986993.
76.Gershon AA, Dannon PN, Grunhaus L. Transcranial magnetic stimulation in the treatment of depression. Am J Psychiatry. 2003; 160(5): 835845.
77.Nahas Z, Bohning DE, Molloy MA, etal. Safety and feasibility of repetitive transcranial magnetic stimulation in the treatment of anxious depression in pregnancy: a case report. J Clin Psychiatry. 1999; 60(1): 5052.
78.Klirova M, Novak T, Kopecek M, Mohr P, Strunzova V. Repetitive transcranial magnetic stimulation (rTMS) in major depressive episode during pregnancy. Neuro Endocrinol Lett. 2008; 29(1): 6970.
79.Zhang D, Hu Z. rTMS may be a good choice for pregnant women with depression. Arch Womens Ment Health. 2009; 12(3): 189190.
80.Zhang X, Liu K, Sun J, Zheng Z. Safety and feasibility of repetitive transcranial magnetic stimulation (rTMS) as a treatment for major depression during pregnancy. Arch Womens Ment Health. 2010; 13(4): 369370.
81.Kim DR, Epperson N, Paré E, etal. An open label pilot study of transcranial magnetic stimulation for pregnant women with major depressive disorder. J Womens Health (Larchmt). 2011; 20(2): 255261.
82.Janicak PG, O'Reardon JP, Sampson SM, etal. Transcranial magnetic stimulation in the treatment of major depressive disorder: a comprehensive summary of safety experience from acute exposure, extended exposure, and during reintroduction treatment. J Clin Psychiatry. 2008; 69(2): 222232.
83.Kennedy SH, Milev R, Giacobbe P, etal. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. IV. neurostimulation therapies. J Affect Disord. 2009; 117(suppl 1): S44S53.
84.UK ECT Review Group. Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet. 2003; 361: 799808.
85.Heijnen WT, Birkenhager TK, Wierdsma AI, etal. Antidepressant pharmacotherapy failure and response to subsequent electroconvulsive therapy: a meta-analysis. J Clin Psychopharmacol. 2010; 30: 616619.
86.Rabheru K, Persad E. A review of continuation and maintenance electroconvulsive therapy. Can J Psychiatry. 1997; 42: 476484.
87.Rabheru K. Maintenance electroconvulsive therapy after acute response. J ECT. 2012; 28: 3947.
88.O'Reardon JP, Cristancho MA, von Andreae CV, etal. Acute and maintenance electroconvulsive therapy for treatment of severe major depression during the second and third trimesters of pregnancy with infant follow-up to 18 months: case report and review of the literature. J ECT. 2011; 27: e23e26.
89.Dennis CL, Allen K. Interventions (other than pharmacological, psychosocial or psychological) for treating antenatal depression. Cochrane Database Syst Rev. 2008; 8(4): CD006795.
90.Sado M, Ota E, Stickley A, Mori R. Hypnosis during pregnancy, childbirth and the postnatal period for preventing postnatal depression. Cochrane Database Syst Rev. 2012; 6(4): CD009062.
91.Manber R, Schnyer RN, Lyell D, etal. Acupuncture for depression during pregnancy: a randomized controlled trial. Obstet Gynecol. 2010; 115(3): 511520.
92.Chung KF, Yeung WF, Zhang ZJ, etal. Randomized non-invasive sham-controlled pilot trial of electroacupuncture for postpartum depression. J Affect Disord. 2012; 142(1–3): 115121.
93.Freeman MP. Complementary and alternative medicine for perinatal depression. J Affect Disord. 2009; 112(1–3): 110.
94.Parker G, Gibson NA, Brotchie H, etal. Omega-3 fatty acids and mood disorders. Am J Psychiatry. 2006; 163(6): 969978.
95.Lin PY, Mischoulon D, Freeman MP, etal. Are omega-3 fatty acids antidepressants or just mood-improving agents? The effect depends upon diagnosis, supplement preparation, and severity of depression. Mol Psychiatry. 2012; 17(12): 11611163.
96.Su KP, Huang SY, Chiu TH, etal. 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): 644651.
97.Hösli I, Zanetti-Daellenbach R, Holzgreve W, Lapaire O. Role of omega 3-fatty acids and multivitamins in gestation. J Perinat Med. 2007; 35(suppl 1): S19S24.
98.Cerutti R, Sichel MP, Perin M, Grussu P, Zulian O. Psychological distress during puerperium: a novel therapeutic approach using S-adenosylmethionine. Current Therapeutic Research. 1993; 53(6): 707716.
99.Lansdowne AT, Provost SC. Vitamin D3 enhances mood in healthy subjects during winter. Psychopharmacology. 1998; 135: 319323.
100.Jorde R, Sneve M, Figenschau Y, Svartberg J, Waterloo K. Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial. J Intern Med. 2008; 264: 599609.
101.Kjærgaard M, Waterloo K, Wang CE, etal. Effect of vitamin D supplement on depression scores in people with low levels of serum 25-hydroxyvitamin D: nested case–control study and randomised clinical trial. Br J Psychiatry. 2012; 201: 360368.
102.Sanders KM, Stuart AL, Williamson EJ, etal. Annual high-dose vitamin D3 and mental well-being: randomised controlled trial. Br J Psychiatry. 2011; 198: 357364.
103.Cassidy-Bushrow AE, Peters RM, Johnson DA, Li J, Rao DS. Vitamin D nutritional status and antenatal depressive symptoms in African American women. J Womens Health (Larchmt). 2012; 21(11): 11891195.
104.Coppen A, Baily J. Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial. J Affect Disord. 2000; 60(2): 121130.
105.Lewis SJ, Araya R, Leary S, Smith GD, Ness A. Folic acid supplementation during pregnancy may protect against depression 21 months after pregnancy, an effect modified by MTHFR C677T genotype. Eur J Clin Nutr. 2012; 66(1): 97103.
106.Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial. JAMA. 2002; 287: 18071814.
107.Lecrubier Y, Clerc G, Didi R, Kieser M. Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial. Am J Psychiatry. 2002; 159(8): 13611366.
108.Howland RH. Update on St. John's Wort. J Psychosoc Nurs Ment Health Serv. 2010; 48(11): 2024.
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