For women taking antidepressants, how do we decide whether or not they should maintain their medication during pregnancy? Based on our previous research and clinical experiences, we know that many women who discontinue antidepressant therapy will relapse during pregnancy.  Our decision is typically guided by the severity of the woman’s illness.  If she has had recurrent or severe depression, we are more likely to recommend continuing treatment during pregnancy.  On the other hand, if a woman has had only one or two episodes of depression and typically has milder symptoms, we would recommend using non-pharmacologic strategies to reduce the risk of recurrent illness during pregnancy.  

While this approach is clinically sound, our ability to reliably predict whether a woman will relapse during pregnancy remains imperfect.  Much research has focused on the reproductive safety of medications; however, we have much less data documenting the clinical course of depressive illness during pregnancy and identifying risk factors for relapse in women with histories of depression.    In a recent systematic review and meta-analysis Bayrampour and colleagues focused on the impact of antidepressant discontinuation on risk for relapse of depression during pregnancy.

The researchers identified eight original studies which (1) included pregnant women who discontinued antidepressants before pregnancy (within the three months prior to conception) or during pregnancy, (2) assessed relapse of depression during pregnancy, and (3) were published in English. Six of these studies fulfilled the quality criteria.  Two studies were excluded because they had a high likelihood of performance and detection biases.  The final analysis included four studies with a total sample of 518 women: 302 women who maintained treatment and 206 women who discontinued antidepressant. 

The frequency of antidepressant discontinuation varied from 22% to 78%.  The frequency of relapse varied widely, ranging from 15% to 68%, with four studies reporting a relapse rate above 60%. All studies reported that the highest relapse rates occurred during the first trimester. 

Greater risk of relapse was observed in younger (< 32 years of age) women.  Risk of relapse was not affected by ethnicity, educational level, or baseline antidepressant treatment. One study documented higher rates of relapse in unmarried women.

Factors related to the chronicity and severity of illness were the most commonly reported predictors of relapse. Women with a duration of depressive illness of more than 5 years had nearly a threefold increased risk of relapse.  Women with a history of severe depression also relapsed more quickly than women with mild depression (80% vs 38%).  Other predictors of relapse included the number of previous episodes and a history of suicide attempts.

In the meta-analysis, pooled data from the four studies did not demonstrate a  higher risk of relapse for women who discontinued antidepressants compared to women who continued antidepressants (RR = 1.74; 95% CI, 0.97 to 3.10). However, in a subanalysis based on the severity or recurrence of depressive illness, the risk of relapse was significantly higher for women with severe/recurrent depression (RR = 2.30; 95% CI, 1.58 to 3.35) but not for women with mild or moderate severity (RR = 1.59; 95% CI, 0.83 to 3.04).

Although this study focuses on the impact of medication discontinuation, probably the most important and clinically relevant finding is that women with histories of depressive illness are at high risk for relapse during pregnancy.  In the pooled analysis, 171 of the 518 women relapsed (33.0%).  If you restrict the analysis to women with severe depression, the risk rises to 55.6%, and if you look at women with severe depression who discontinue medication, the risk of recurrent illness during pregnancy is 67.6%.  

This report is consistent with previous studies demonstrating high rates of relapse in women with histories of severe or recurrent depression who discontinue antidepressants during pregnancy.  However, this study observes that women with histories of mild to moderate depression appear to have the same risk of relapse whether or not they continue antidepressant medication.  The findings of this meta-analysis lend support to what we do clinically; we recommend continuation of maintenance treatment in women with more recurrent or severe depression, and we suggest that women with milder forms of depression may be able to discontinue treatment during pregnancy.  

In making recommendations regarding the use of medications during pregnancy, we ask many questions about a woman’s clinical history.  One of the most important questions we can ask is: Have you ever tried to discontinue your antidepressant in the past? What happened?  If a woman has relapsed after medication discontinuation in the past (assuming an adequate duration of treatment), she is likely to relapse again if she attempts to discontinue medication during pregnancy.  Until we have better predictors of relapse, this is one of the most useful questions we can use to predict relapse.  

Ruta Nonacs, MD PhD

Bayrampour H, Kapoor A, Bunka M, Ryan D.  The Risk of Relapse of Depression During Pregnancy After Discontinuation of Antidepressants: A Systematic Review and Meta-Analysis.  J Clin Psychiatry. 2020 Jun 9;81(4):19r13134. Free Article