While mental health disorders are prevalent among pregnant women, limited research, with limited strength of evidence (SOE) has examined the effectiveness, benefits, and harms of pharmacotherapy for perinatal mental health disorders, according to a meta-analysis published in Psychiatric Research and Clinical Practice.

The researchers searched PubMed, the Cochrane Library, PsycINFO, and EMBASE for English-language articles from database inception through June 5, 2020. They also searched ClinicalTrials.gov, the Cochrane Register of Controlled Trials, the World Health Organization International Clinical Trials Registry Platform, and reference lists to find studies detailing the benefits and harms of US Food and Drug Administration-approved drugs and off-label drugs used for mental health disorders. The included studies compared women receiving psychotropic drugs with those who were not.

They assessed SOE of 164 studies as high, moderate, low, or insufficient based on guidance from the Grading of Recommendations Assessment, Development and Evaluation working group, and Evidence-based Practice Center Program.

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A total of 3 randomized controlled trials (RCT) with moderate SOE indicated that postpartum brexanolone for depression in third trimester or postpartum is associated with improved depressive symptoms 60 hours after infusion (least square [LS] mean difference in the Hamilton Rating Scale for Depression [HAM‐D], −4.1, standard error [SE] 0.9, P <.001) and at 30 days after treatment (LS mean difference, SE −2.6, 1.1, P =.02).

Brexanolone may carry a higher risk of sedation and loss of consciousness compared with placebo. Pooled relative risk (RR) for somnolence with brexanolone compared with placebo was 2.00 (95% CI, 0.78 to 5.16) and the absolute risk difference (ARD) was 0.05 (95% CI, −0.01 to 0.12).

Several studies with low SOE indicated benefits or risks of pharmacotherapy in these patients. A total of 2 RCT indicated compared with a placebo, sertraline for postpartum depression may improve response.

There were 2 cohort studies indicated that discontinuing mood stabilizers used for bipolar disorders during pregnancy may be tied to increased recurrence compared with continuing the drugs. In addition, 2 studies indicated preeclampsia is higher in women who have taken non-selective serotonin reuptake inhibitors (SSRI) drugs, particularly serotonin‐norepinephrine reuptake inhibitors (SNRI) and tricyclic antidepressant (TCA). There was 1 cohort study indicated that continuing quetiapine or olanzapine during the first half of pregnancy may be tied to an increased risk of gestational diabetes mellitus compared with their discontinuation prior to pregnancy. Ectopic pregnancy may increase with benzodiazepine exposure 90 days prior to conception, according to 1 study. SNRI exposure in the first trimester may be tied to higher rate of spontaneous abortion, another study suggested. Finally, 1 study indicated that the use of lithium during the first trimester may carry a higher association to overall congenital and cardiac anomalies than use of lamotrigine.

The researchers found that many studies had insufficient or low SOE due to a lack of control for confounding, small sample, inconsistency in definitions, and their nature as observational evidence.

Limitations of the study include the risk of confounding with limited data on the severity of psychiatric illness and the exclusion of studies with overlapping arms and studies that reported outcomes for pharmacotherapy exposures for clinical conditions other than mental health disorders.


Viswanathan M, Middleton JC, Stuebe AM, et al. Maternal, fetal, and child outcomes of mental health treatments in women: a meta‐analysis of pharmacotherapy. Psych Res Clin Pract. Published online May 5, 2021. doi:10.1176/appi.prcp.20210001