ANNOTATION (Christina Wichman)

The Finding: The median total VMS duration was 7.4 years. For women who could identify a final menstrual period (FMP), the median duration of VMS was 4.5 years. Women who were premenopausal or early perimenopausal when they first reported frequent VMS had the longest total VMS duration. Other factors contributing to longer duration of VMS included African American background, younger age, lower educational level, greater perceived stress and symptom sensitivity, and higher depressive and anxiety symptoms.

Strength and Weaknesses: SWAN study is the largest and longest (up to 13 years) longitudinal study to date to report on total VMS duration and post-FMP persistence. It also had the capability of studying racial/ethnic influences on VMS duration. VMS duration may be been underestimated as VMS were only measured annually and the time frame for inquiry was 2 weeks preceding visit; onset or occurrence may have been missed as VMS fluctuate over time. Despite the long study period, some women continued to report frequent VMS, so continued follow-up may be necessary.

Relevance: Up to 80% of women experience VMS during menopausal transition. Because a significant proportion of women experience VMS for greater than 5 years, many women may not want to tolerate symptoms without intervention; these women will require interventions that are safe and well-tolerated over long-term use.

ANNOTATION (Erin Smith)

The Finding: Paroxetine and sertraline should be considered as first-line treatment for breastfeeding women who require antidepressants. Short-term neonatal adverse effects were reported in 0.9% (2/228) of paroxetine cases—one case of irritability and one case of lethargy, poor weight gain, and hypotonia that persisted for 4-6 weeks of life. 0.4% (1/279) of sertraline cases experienced an adverse effect—this infant developed neonatal sleep myoclonus that spontaneously resolved at 6 months. The RID* (relative infant dose, expressed as the rate of the weight-adjusted maternal dose) was 0.54%-2.2% and 0.34%-3% for sertraline and paroxetine respectively. A detectable serum concentration was reported in 10/279 and 31/228 infants for sertraline and paroxetine respectively. No adverse effects on neurodevelopment were reported.

Strength and Weaknesses: This is the first systematic review of SRIs and breastfeeding and includes a large number of studies (104) covering a wide range of medications (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, duloxetine and venlafaxine/desvenlafaxine). Most of the available evidence is from case reports or studies with small sample sizes (in this review, numbers ranged from 1-87, mostly < 20). Most studies focus on pharmacokinetic indices rather than clinical relevance, and those that do focus on the latter tend to examine short-term outcomes in infants. There is a paucity of data on long-term neurocognitive outcomes. Prenatal drug exposure, maternal habits (smoking) and infant metabolism are potential confounding factors.

Relevance: 75% of postpartum women in the US initiate breastfeeding.¹ The prevalence of postpartum depression is upwards of 10-15%, and it has been estimated that at least 50% of affected mothers will be prescribed an antidepressant.^2,3 Therefore, a large number of women who require antidepressant treatment in the postpartum period also want to breastfeed. The most commonly prescribed agents are SRIs (SSRIs and SNRIs). In the face of limited available information regarding the safety of these agents in neonates, women rely on the expertise of their providers, who must give evidence-based recommendations on how best to proceed. Many physicians are unfamiliar or uncomfortable with the perinatal literature and may result in discontinuation of psychiatric medications during pregnancy, delay in initiating vital treatments until breastfeeding is complete, or unnecessary recommendation of bottle-feeding. Given that pregnancy and the postpartum period are high risk for the emergence of psychiatric disorders, stopping or deferring treatment is an ill-advised strategy. This systematic review has determined that if the severity of a woman’s symptoms merit antidepressant treatment, evidence suggests sertraline or paroxetine as the preferred choices because of their superior safety profiles in exposed infants.