This work may not be copied, distributed, displayed, published, reproduced, transmitted, modified, posted, sold, licensed, or used for commercial purposes. By downloading this file, you are agreeing to the publisher’s Terms & Conditions.


Achieving the Balance: Treating Depressed Pregnant Women With Antidepressants

Sophie Grigoriadis, MD, PhD, FRCPC; Lana Mamisashvili, MSW; and Lori E. Ross, PhD

Published: April 15, 2013

Achieving the Balance: Treating Depressed Pregnant Women With Antidepressants

Major depressive disorder is a common, recurring, serious, and potentially life-threatening condition. The period prevalence for major depression during pregnancy appears to be 12.7% and for any depressive disorder, 18.4%.1 Women who have had 1 depressive episode are at risk for recurrence, and those having more than 3 episodes are candidates for long-term antidepressant treatment.2 Numerous studies have reported many potential consequences of depression on both the mother and infant. Timely treatment is essential, and research suggests that it can enhance outcomes for both mother and child.3 Unfortunately, depression is undertreated.4,5 Moreover, conflicting reports on the potential adverse effects of antidepressant medications exist in the literature. Psychosocial interventions are effective but are often time consuming, not always easily accessible, and possibly insufficient for women with severe illness.6,7 As clinicians, we have to inform our patients of the evidence for treatment and weigh the risks and benefits of each option. In the perinatal period, the process of making treatment decisions is exceedingly complex, as the needs of the mother and infant must both be given consideration and weighed against potential adverse effects for both.

In an effort to understand the effects of depression and antidepressant medications during pregnancy to best inform our patients, our team synthesized the literature. We developed a quality assessment tool, the Systematic Appraisal of Quality in Observational Research8 to evaluate each article and performed meta-analyses when possible. Three systematic reviews and meta-analyses resulting from this work appear in JCP’s Online Exclusives this month and include the following outcomes: congenital malformations9 (including cardiac), poor neonatal adaptation,10 and the impact of maternal depression on various outcomes (including premature delivery, gestational age, birth weight, low birth weight, neonatal intensive care unit admissions, Apgar scores, preeclampsia, and breastfeeding initiation).11 The strength of our work rests on our attention to study quality, the use of adjusted data when possible, the evaluation of potential moderator variables, and the consideration of many outcomes.

The findings of our meta-analyses suggest that antidepressants do not seem to be associated with an increased risk for congenital malformations in general.9 The risk for major malformations was also not significant in our primary analysis. Although we identified a statistically significant association between cardiovascular malformations and exposure to any antidepressant during pregnancy, the small magnitude of this effect brings into question its clinical significance. In contrast, we identified a statistically and clinically significant increase in risk for poor neonatal adaptation syndrome associated with antenatal antidepressant exposure, as well as associations with the specific signs of respiratory distress and tremors.10 These findings suggest a potential role for neonatologists in monitoring and caring for infants exposed to antidepressants in utero. Finally, our analyses reveal that antenatal maternal depression is associated with increased risk for premature delivery and lower rates of breastfeeding initiation, although in both cases, the odds ratios are relatively small.11 Our work also highlights a striking need for additional research of adequate quality, with attention to appropriate measures of exposure, outcome, and relevant potential confounders.

This program of research is timely, considering that the prescription rate for antidepressant medication has increased dramatically12,13 and that these medications appear to be more commonly used by women regardless of depression severity.14 As such, more and more women will face decisions about the use of antidepressant medications during pregnancy. Our hope is that by providing a stronger evidence base, this work will help to facilitate the complex and often difficult decision-making process that women must engage in with their clinicians and, ultimately, result in optimal outcomes for both mother and baby.

Author affiliations: Women’s Mood and Anxiety Clinic: Reproductive Transitions, Department of Psychiatry, Sunnybrook Health Sciences Centre (Drs Grigoriadis and Ms Mamisashvili); Sunnybrook Research Institute, Women’s College Hospital, University Health Network (Dr Grigoriadis); Women’s College Research Institute (Drs Grigoriadis and Ross); Department of Psychiatry, University of Toronto (Drs Grigoriadis and Ross); and Social and Epidemiological Research Department, Centre for Addiction and Mental Health (Dr Ross); Toronto, Ontario, Canada.

Potential conflicts of interest: In the last 5 years, Dr Grigoriadis has received honoraria as a consultant and a member of an advisory committee or for lectures from Wyeth, GlaxoSmithKline, Pfizer, Servier, Eli Lilly Canada and Lundbeck; and has received research grant support from the Canadian Institutes of Health Research (CIHR), Ontario Ministry of Health, Ontario Mental Health Foundation, and CR Younger Foundation. Dr Ross and Ms Mamisashvili report no financial or other conflicts of interest.

Funding/support: Funding for the research discussed in this commentary was provided by a Research Syntheses grant from the Canadian Institutes of Health Research (CIHR), KRS-83127, and the Ontario Ministry of Health and Long-Term Care through the Drug Innovation Fund, grant #2008-005. Dr Grigoriadis holds a New Investigator Award in Women’s Health Research from the CIHR in partnership with the Ontario Women’s Health Council, award NOW-88207. Dr Ross holds a New Investigator Award from CIHR and the Ontario Women’s Health Council, award NOW-84656. In addition, support to the Center for Addiction and Mental Health for salary of scientists and infrastructure was provided by the Ontario Ministry of Health and Long-Term Care.

Disclaimer: The views expressed here do not necessarily reflect those of the Ministry of Health and Long-Term Care.


1. Gaynes B, Gavin N, Meltzer-Brody S, et al. Perinatal Depression: Prevalence, Screening Accuracy and Screening Outcomes. Evidence Report/Technology Assessment No. 119. AHRQ Publication No 5-E006-2. Rockville, MD: Agency for Healthcare Research and Quality; 2005.

2. American Psychiatric Association. In: Gelenberg, AJ, Freeman, MP, Markowitz, JC, et al, eds. Practice Guidelines for the Treatment of Patients with Major Depressive Disorder, 3rd ed. Arlington, VA: American Psychiatric Association: 2010.

3. Weissman MM, Pilowsky DJ, Wickramaratne PJ, et al; STAR*D-Child Team. Remissions in maternal depression and child psychopathology: a STAR*D-child report. JAMA. 2006;295(12):1389-1398. PubMed doi:10.1001/jama.295.12.1389

4. Dietz PM, Williams SB, Callaghan WM, et al. Clinically identified maternal depression before, during, and after pregnancies ending in live births. Am J Psychiatry. 2007;164(10):1515-1520. PubMed doi:10.1176/appi.ajp.2007.06111893

5. Bennett IM, Marcus SC, Palmer SC, et al. Pregnancy-related discontinuation of antidepressants and depression care visits among Medicaid recipients. Psychiatr Serv. 2010;61(4):386-391. PubMed doi:10.1176/

6. Dennis CL, Hodnett ED. Psychosocial and psychological interventions for treating postpartum depression. Cochrane Database Syst Rev. 2007; (4)CD006116. 10.1002/14651858.CD006116.pub2 PubMed

7. Yonkers KA, Wisner KL, Stewart DE, et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Gen Hosp Psychiatry. 2009;31(5):403-413. PubMed doi:10.1016/j.genhosppsych.2009.04.003

8. Ross LE, Grigoriadis S, Mamisashvili L, et al. Quality assessment of observational studies in psychiatry: an example from perinatal psychiatric research. Int J Methods Psychiatr Res. 2011;20(4):224-234. PubMed doi:10.1002/mpr.356

9. Grigoriadis S, VonderPorten EH, Mamisashvili L, et al. Antidepressant exposure during pregnancy and congenital malformations: is there an association? a systematic review and meta-analysis of the best evidence. J Clin Psychiatry. 2013;74(4):e293-e308

10. Grigoriadis S, VonderPorten EH, Mamisashvili L, et al. The effect of prenatal antidepressant exposure on neonatal adaptation: a systematic review and meta-analysis. J Clin Psychiatry. 2013;74(4):e309-e320

11. Grigoriadis S, VonderPorten EH, Mamisashvili L, et al. The impact of maternal depression during pregnancy on perinatal outcomes: a systematic review and meta-analysis. J Clin Psychiatry. 2013;74(4):e321-e341

12. Patten SB, Beck C. Major depression and mental health care utilization in Canada: 1994 to 2000. Can J Psychiatry. 2004;49(5):303-309. PubMed

13. National Center for Health Statistics. Table 95. Health, United States, 2010: With Special Feature on Death and Dying. Hyattsville, MD. US Department of Health and Human Services; 2011:319-321

14. Pratt LA, Brody DJ, Gu Q. Antidepressant Use in Persons Aged 12 and Over: United States, 2005-2008. NCHS Data Brief, No 76. Hyattsville, MD: National Center for Health Statistics; 2011.

Submitted: February 5, 2013; accepted February 5, 2013.

Corresponding author: Sophie Grigoriadis, MD, PhD, FRCPC, Women’s Mood and Anxiety Clinic: Reproductive Transitions, Department of Psychiatry, FG 29, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, ON M4N 3M5 (

Editor’s Note: We encourage authors to submit papers for consideration as a part of our Focus on Women’s Mental Health section. Please contact Marlene P. Freeman, MD, at

Related Articles

Volume: 74

Quick Links: