Over the last decade, the number of reproductive-age women treated for depression has increased significantly. Given the incomplete information available regarding the reproductive safety of many antidepressant medications, many women choose to discontinue pharmacologic treatment during pregnancy. However, several studies estimate that about 10 to 15% of women suffer from depression during pregnancy (O’Hara et al, 1990; Evans et al, 2001). A recent study from the Center for Women’s Mental Health indicates that the risk for depression is particularly high among women with histories of major depression (Cohen et al, 2006).

In this study, a total of 201 pregnant women were recruited from three sites: the Perinatal and Reproductive Psychiatry Clinical Research Program at Massachusetts General Hospital, the UCLA Pregnancy & Postpartum Mood Disorders Program and the Emory Women’s Mental Health Program. All of the participants had a history of major depression prior to conception. They were considered eligible if they were currently or recently (<12 weeks prior to last menstrual period) treated with an antidepressant and were euthymic for at least 3 months prior to conception. All women were recruited prior to 16 weeks’ gestation and were followed prospectively using longitudinal psychiatric assessments on a monthly basis across pregnancy.

The mean age of the participants was 34.1 years. Approximately 90% were married and more than half reported completing a college education. The mean age at first onset of depression was 18.8 years (SD = 6.8), with approximately half the sample reporting first onset of mood disorder prior to 18 years of age. The women in the sample were noted to have highly recurrent depression, with 44% reporting 5 or more prior episodes. Comorbid psychiatric illness was noted in 93 women (53% of the sample). The most common comorbid diagnoses were anxiety disorders (35%) and eating disorders (17%).

Of the 201 participants, 13 miscarried, 5 electively terminated their pregnancy, 12 were lost to follow-up prior to completion of pregnancy, and 8 chose to withdraw from the study. The main outcome measure was relapse of major depression as defined using the Structured Clinical Interview for DSM-IV Diagnosis (SCID) criteria. Among the 201 women in the sample, 86 (43%) experienced a relapse of major depression during pregnancy. Of the 82 women who maintained antidepressant treatment throughout pregnancy, 21 (26%) relapsed compared with 44 (68%) of the 65 women who discontinued medication. Women who discontinued medication were 5 times as likely to relapse as compared to women who maintained their antidepressant treatment across pregnancy (hazard ratio, 5.0; 95% confidence interval, 2.8-9.1; P<.001).

This study also examined whether certain demographic and clinical variables predicted risk for relapse during pregnancy. No statistically significant association was noted between depressive relapse and race, education level, or baseline antidepressant treatment. However, there was a trend for married women to be somewhat protected against relapse of depression compared with single women (HR, 0.4; 95% CI, 0.1-1.3; P = .13). Women who were older than 32 years were noted to have a 60% reduction in risk for relapse compared with younger women (<32 years; HR, 0.4; 95% CI, 0.2-0.8; P = .01). Risk of illness was greater in women with a longer duration of depressive illness of (> 5 years; HR, 2.7; 95% CI, 1.5-4.7; P = .009) and in those with a history of more recurrent depressive illness (>4 episodes; HR, 3.6; 95% CI, 1.9-7.0; P<.001).

These findings have important clinical implications. While several certain studies have raised concern regarding the use of antidepressants during pregnancy (see Summer 2005 and Winter 2005 Newsletters), this study suggests that women who discontinue treatment are at extremely high risk for recurrent illness. Pregnancy does not appear to be protective with respect to risk of relapse of major depression. Women with histories of depression should be informed of their risk of depressive relapse during pregnancy following antidepressant discontinuation. Given this information, some women with more recurrent or severe depressive illness may choose to maintain antidepressant therapy during attempts to conceive and during pregnancy in order to limit their risk of illness.


Ruta Nonacs, MD PhD


Cohen LS, Altshuler LL, Harlow BL, Nonacs R, et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA. 2006;295(5):499-507.


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.


O’Hara MW, Zekoski EM, Philipps LH, Wright EJ. Controlled prospective study of postpartum mood disorders: Comparison of childbearing and nonchildbearing women. Journal of Abnormal Psychology. 1990; 99:3-15.


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