For women with histories of major depression, choosing whether to maintain or to discontinue treatment with an antidepressant during pregnancy is often challenging.  This is a process which requires careful and thoughtful consideration, weighing the risk of adverse outcomes associated with exposure to a particular antidepressant against the risk of recurrent illness in the setting of medication discontinuation.

In a recent study, Bérard and colleagues assessed risk for depressive symptoms in women who either maintained or discontinued antidepressant treatment during pregnancy.  Women participating in the study were eligible if they contacted MothertoBaby for information regarding the reproductive safety of medications taken during pregnancy and if they were less than 14 weeks of gestation. The Edinburgh Postnatal Depression Scale (EPDS) was used to measure depressive symptoms during the first and second half of pregnancy. Depressive symptoms were identified using an EPDS score of ? 13. 

A total of 367 pregnant women were included. Among the participants, 38 were using antidepressant at the time of conception but discontinued it before the end of the second trimester, and 180 used antidepressants throughout the pregnancy.  Among the women who maintained treatment, 46 modified antidepressant dosage before the end of the second trimester, and the remaining 134 made no changes in dose across pregnancy. A reference group of 149 non-users were women who were not taking antidepressants who had contacted MothertoBaby regarding the use of a non-teratogenic medication.  

At the time of recruitment (during the first half of pregnancy), only one of the women reported depressive symptoms (0.7%).  Women with histories of depression who had either continued or discontinued antidepressant use were more likely to report depressive symptoms: discontinued 26.3%, continued 13.4%, continued with dose increase 7.1%, continued with dose decrease 18.8%.

At the assessment during the second half of pregnancy, the only women who showed improvement in depressive symptoms were those that had adjusted the dose of antidepressant:  no use 3.4%, discontinued 21.1%, continued 13.2%, continued with dose increase 0%, continued with dose decrease 3.3%.

After adjusting for possible confounding factors, the researchers noted that women who discontinued antidepressant were 5.95 times as likely to report depressive symptoms as non-users (95%CI: 1.54-23.02).  Women who continued antidepressant without dosage modification were also likely to report depressive symptoms (aOR 4.59, 95%CI: 1.44-14.64). In contrast, women who adjusted dosage of antidepressant during pregnancy were about as likely to report depression during pregnancy as non-users (adjusted odds ratio 0.58, 95%CI: 0.06-5.52). 

The findings parallel other prospective studies which have shown high rates of depressive symptoms among women who discontinue antidepressants during pregnancy.  Depressive symptoms were less common in this group than in the previous study from Cohen and colleagues; the authors speculate this difference may be due to the fact that the women in the current study had less severe illness.  

The authors argue for individualized treatment in this setting, noting that the women who adjusted the dosage of their antidepressant fared better than the women who maintained the same dosage across pregnancy.  It makes sense that women who increased the dosage did better, as there is evidence that antidepressant levels tend to drop during pregnancy. More puzzling is the finding that women who decreased the dose of medication also tended to do better than women who maintained the same dosage.  One could argue that dose adjustment — whether an increase or decrease — is a reflection of more individualized or attentive care. Ongoing treatment with an antidepressant is important for reducing risk of illness, but this study suggests that the additional monitoring which takes place in the setting of adjusting the treatment may also play a beneficial role.  

 

Ruta Nonacs, MD PhD

 

Impact of antidepressant use, discontinuation, and dosage modification on maternal depression during pregnancy.

Bérard A, Sheehy O, Zhao JP, Chambers C, Roth M, Bozzo P, Johnson D, Kao K, Lavigne S, Wolfe L, Quinn D, Dieter K; MotherToBaby Collaborative Research Committee.  Eur Neuropsychopharmacol. 2019 Jun 24.