Pharmacotherapy of Postpartum Depression: Current Approaches and Novel Drug Development.

Postpartum depression is one of the most common complications of childbirth. Untreated postpartum depression can have substantial adverse effects on the well-being of the mother and child, negatively impacting child cognitive, behavioral, and emotional development with lasting consequences. There are a number of therapeutic interventions for postpartum depression including pharmacotherapy, psychotherapy, neuromodulation, and hormonal therapy among others, most of which have been adapted from the treatment of major depressive disorder outside of the peripartum period. Current evidence of antidepressant treatment for postpartum depression is limited by the small number of randomized clinical trials, underpowered samples, and the lack of long-term follow-up. The peripartum period is characterized by rapid and significant physiological change in plasma levels of endocrine hormones, peptides, and neuroactive steroids. Evidence supporting the role of neuroactive steroids and γ-aminobutyric acid (GABA) in the pathophysiology of postpartum depression led to the investigation of synthetic neuroactive steroids and their analogs as potential treatment for postpartum depression. Brexanolone, a soluble proprietary intravenous preparation of synthetic allopregnanolone, has been developed. A recent series of open-label and placebo-controlled randomized clinical trials of brexanolone in postpartum depression demonstrated a rapid reduction in depressive symptoms, and has led to the submission for regulatory approval to the US Food and Drug Administration (decision due in March 2019). SAGE-217, an allopregnanolone analog, with oral bioavailability, was recently tested in a randomized, double-blind, placebo-controlled phase III study in severe postpartum depression, with reportedly positive results. Finally, a 3ß-methylated synthetic analog of allopregnanolone, ganaxolone, is being tested in both intravenous and oral forms, in randomized, double-blind, placebo-controlled phase II studies in severe postpartum depression.

Pharmacotherapy for Perinatal Depression.

Perinatal depression is associated with serious risks for the mother, baby, and family. When considering treating perinatal depression with a drug indicated for the treatment of depression, the major concerns are whether the drug increases the risks of teratogenicity, pregnancy complications, poor neonatal adaptation, or neurodevelopmental disorders. Although different studies have produced different results, the majority have not shown increases in risk for selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, tricyclic antidepressants, or the noradrenergic/dopaminergic drug bupropion. In this review we will discuss the reproductive safety data for these medications as well as monoamine oxidase inhibitors and benzodiazepines.

Suicidal Ideation During the Postpartum Period.

OBJECTIVE: To examine the association between suicidal ideation (SI), 3 weeks, 3 months, and 6 months postpartum with demographic, psychosocial, clinical factors, and depressive/anxiety symptoms (measured 24-48 hours after delivery), among a cohort of postpartum women. METHODS: This study included 1,073 mothers who gave birth in a large tertiary New York City hospital (2009-2010). Later, self-report SI was assessed using the suicide measure from the Edinburgh Postnatal Depression Scale and from the Patient Health Questionnaire. RESULTS: Two percent of participants presented with SI during the first 6 months postpartum. In bivariate analyses, race/ethnicity, nativity, insurance, and language were significantly correlated with SI 3 weeks, 3 months, and 6 months postpartum. Screening positive for depression (p = 0.0245) and anxiety (0.0454), assessed 1-2 days postpartum, was significantly correlated with later SI in bivariate analyses, as were antepartum complications (p = 0.001), depressive history (0.001), and self-efficacy (0.045). In adjusted models, antepartum complications (OR = 4.681, 95% CI = 1.99-10.99) and depressive history (OR-3.780, 95% CI = 1.514-9.441) were significantly associated with later postpartum SI. Heightened self-efficacy reduced the odds of later SI (p = 0.050). CONCLUSION: Findings suggest that SI among a relatively healthy group of new mothers occurs with some frequency. Mothers with a history of depression and antepartum complications may be at increased risk.

Bipolar Disorder in Pregnancy and Postpartum: Principles of Management.

Pregnancy and postpartum represent times of increased vulnerability for women with bipolar disorder, yet this condition remains under-diagnosed and under-treated. As 50 % of pregnancies are unplanned, the risks associated with the illness and the potential risks associated with treatment should be considered when a woman of reproductive age first presents for evaluation. This article reviews the epidemiology of perinatal bipolar disorder, screening recommendations, and treatment with pharmacotherapy and electroconvulsive therapy (ECT). An overview of the data in pregnancy and lactation is presented for lithium, lamotrigine, valproic acid, newer antipsychotics, and ECT. General principles of management include close monitoring in pregnancy and postpartum, careful adjustment of the treatment regimen to attenuate the risk of relapse, and avoidance of valproic acid when possible. Thoughtful consideration of these issues will minimize the risks to the mother and baby.