Women’s Mental Health

Annotated Abstracts of Journal Articles
2015, 1st Quarter

Women’s Mental Health

Annotations by Christina Wichman, DO, FAPM and Erin Smith, MD
March 2015

  1. Duration of menopausal vasomotor symptoms over the menopause transition
  2. Serotonin reuptake inhibitors and breastfeeding: a systematic review

PUBLICATION #1 — Women’s Mental Health
Duration of menopausal vasomotor symptoms over the menopause transition

Orsolini L, Bellantuono C
Hum Psychopharmacol 2015; 30(1):4-20

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.


Importance: The expected duration of menopausal vasomotor symptoms (VMS) is important to women making decisions about possible treatments.

Objectives: To determine total duration of frequent VMS (≥6 days in the previous 2 weeks) (hereafter total VMS duration) during the menopausal transition, to quantify how long frequent VMS persist after the final menstrual period (FMP) (hereafter post-FMP persistence), and to identify risk factors for longer total VMS duration and longer post-FMP persistence.

Design, Setting, and Participants: The Study of Women’s Health Across the Nation (SWAN) is a multiracial/multiethnic observational study of the menopausal transition among 3302 women enrolled at 7 US sites. From February 1996 through April 2013, women completed a median of 13 visits. Analyses included 1449 women with frequent VMS.

Main Outcomes and Measures: Total VMS duration (in years) (hot flashes or night sweats) and post-FMP persistence (in years) into postmenopause.

Results: The median total VMS duration was 7.4 years. Among 881 women who experienced an observable FMP, the median post-FMP persistence was 4.5 years. Women who were premenopausal or early perimenopausal when they first reported frequent VMS had the longest total VMS duration (median, >11.8 years) and post-FMP persistence (median, 9.4 years). Women who were postmenopausal at the onset of VMS had the shortest total VMS duration (median, 3.4 years). Compared with women of other racial/ethnic groups, African American women reported the longest total VMS duration (median, 10.1 years). Additional factors related to longer duration of VMS (total VMS duration or post-FMP persistence) were younger age, lower educational level, greater perceived stress and symptom sensitivity, and higher depressive symptoms and anxiety at first report of VMS.

Conclusions and Relevance: Frequent VMS lasted more than 7 years during the menopausal transition for more than half of the women and persisted for 4.5 years after the FMP. Individual characteristics (eg, being premenopausal and having greater negative affective factors when first experiencing VMS) were related to longer-lasting VMS. Health care professionals should counsel women to expect that frequent VMS could last more than 7 years, and they may last longer for African American women.

Back to top of page

PUBLICATION #2 — Women’s Mental Health
Serotonin reuptake inhibitors and breastfeeding: a systematic review

Avis NE, Crawford SL, Greendale G, Bromberger JT, Everson-Rose SA, Gold EB, et al
JAMA Intern Med 2015; 175(4):531-9


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.


Objective: The postnatal period represents a critical phase for mothers because of physiological hormonal changes, the increase of emotional reactions and a greater susceptibility for the onset/recrudescence of psychiatric disorders. Despite the evidence of an increasing utilization of antidepressant drugs during breastfeeding, there is still few reliable information on the neonatal safety of the selective serotonin reuptake inhibitors (SSRIs) and selective noradrenergic reuptake inhibitors (SNRIs) [serotonin reuptake inhibitors (SRIs)] in nursing mothers. The aim of this study is to provide a systematic review on the neonatal safety profile of these drugs during breastfeeding, also assessing the limits of available tools.

Methods: MEDLINE and PubMed databases were searched without any language restrictions by using the following set of keywords: ((SSRIs OR selective serotonin inhibitor reuptake OR SNRIs OR selective serotonin noradrenaline inhibitor reuptake) AND (breastfeeding OR lactation OR breast milk)). A separate search was also performed for each SSRIs (paroxetine, fluvoxamine, fluoxetine, sertraline, citalopram and escitalopram) and SNRIs (venlafaxine and duloxetine).

Results: Sertraline and paroxetine show a better neonatal safety profile during breastfeeding as compared with other SRIs. Less data are available for fluvoxamine, escitalopram and duloxetine. Few studies followed up infants breastfeed for assessing the neurodevelopmental outcomes.

Conclusions: Literature review clearly indicates paroxetine and sertraline as the drugs that should be preferred as first line choice in nursing women who need an antidepressant treatment.



LactMed: an NIH/NLM TOXNET database of drugs and other chemicals to which breastfeeding mothers may be exposed. Search/browse at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT

Annotator’s Footnote

* RID = Relative Infant Dose. The RID is calculated by dividing the infant’s dose via milk (mg/kg/day) by the mothers dose in mg/kg/day. The RID indicates how much medication the infant is exposed to on a weight-normalized basis. The recommended safety limit is 10% of the weight-adjusted maternal dose.


1 CDC National Immunization Surveys: 2012 and 2013 data, 2011 births. www.cdc.gov/breastfeeding/data/NIS_data

2 O’Hara MW, Swain AM: Rates and risk of postpartum depression: a meta-analysis.
Int Rev Psychiatry 1996; 8:37-54

3 Georgiopoulos AM, Bryan TL, Wollan P, Yawn BP: Routine screening for postpartum depression.
J Fam Pract 2001; 50(2):117–122

Back to top of page