Objectives:

To evaluate the benefits and harms of pharmacological therapy for depression in women during pregnancy or the postpartum period.

Data sources:

Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature (CINAHL^®), MEDLINE^®, Scopus^®, ClinicalTrials.gov, and Scientific Information Packets from pharmaceutical manufacturers. Databases were searched from their inception to July 2013.

Review methods:

We included studies comparing pharmacological treatments for depression during or after pregnancy with each other, with nonpharmacological treatments, or with usual care or no treatment. Outcomes included both maternal and infant or child benefits and harms. Dual review was used for study inclusion, data abstraction, and quality assessment. We assessed study quality using methods of the Drug Effectiveness Review Project. We graded the strength of the body of evidence according to the methods of the Effective Health Care Program. Direct evidence comprised studies that compared interventions of interest in the population of interest (i.e., depressed women) and measured the outcomes of interest. Studies comparing groups of depressed women with control groups with no evidence of depression were considered indirect.

Results:

We included 15 observational studies that provided direct evidence on benefits and harms of antidepressants for depression during pregnancy. We included six randomized controlled trials and two observational studies of antidepressant treatment for depression in postpartum women. Studies of depressed pregnant women primarily compared antidepressant treatment with no treatment, and studies of postpartum women also compared antidepressants alone with combination antidepressant-nonpharmacological treatments. This evidence was insufficient to draw conclusions on the comparative benefits or harms of antidepressants for the outcomes of maternal depression symptoms, functional capacity, breastfeeding, mother-infant dyad interactions, and infant and child development for either pregnant or postpartum women with depression. Low-strength evidence suggests that neonates of women with depression taking selective serotonin reuptake inhibitors (SSRIs) during pregnancy had higher risk of respiratory distress than neonates of untreated women but that risk of preterm birth or neonatal convulsions does not differ between these groups. Direct evidence on the risk of major malformations and neonatal development with exposure to antidepressants in utero was insufficient to draw conclusions. For postpartum women with depression, evidence was insufficient to evaluate the full range of benefits and harms of treatment. Low-strength evidence was unable to show a benefit of adding brief psychotherapy or cognitive behavioral therapy to SSRIs.

To address gaps in the direct evidence, we included an additional 109 observational studies of pregnant women receiving antidepressants for mixed or unreported reasons compared with pregnant women not taking antidepressants whose depression status was unknown. Signals from this indirect evidence suggest that future research should focus on the comparative risk of congenital anomalies and neonatal motor developmental delays. Although the absolute increased risk of autism spectrum disorder or attention-deficit hyperactivity disorder in the child associated with antidepressant use for depression in pregnancy may be very small, this issue also merits attention in future research. Future research should compare available treatments in groups of women with depression and have adequate sample sizes. Investigations should also take into account potential confounding, including age, race, parity, other exposures (e.g., alcohol, smoking, and other potential teratogens), and the impact of dose, severity of depression, timing of diagnosis, or prior depressive episodes.

Conclusions:

Evidence about the comparative benefits and harms of pharmacological treatment of depression in pregnant and postpartum women was largely inadequate to allow well-informed decisions about treatment. For pregnant women, this was mainly because comparison groups were not exclusively depressed women. For postpartum women, the lack of evidence arose chiefly from a scarcity of studies. These are major limitations, as depression is known to be associated with serious adverse outcomes. Given the prevalence of depression and its impact on the lives of pregnant women, new mothers, and children, new research to fill this informational gap is essential.