Women’s Mental Health

Annotated Abstracts of Journal Articles
2014, 2nd Quarter

Women’s Mental Health

Annotations by Christina Wichman, DO, FAPM
June 2014

  1. Low-Dose Estradiol and the Serotonin-Norepinephrine Reuptake Inhibitor Venlafaxine for Vasomotor Symptoms: A Randomized Clinical Trial

Additional publication note:

On June 15-16, 2014, the New York Times carried a two-part story on maternal mental illness. It highlighted the experiences of two women who became psychiatrically ill during the postpartum period. The articles focused on the range of disorders which can emerge during the postpartum period—not only depression, but bipolar disorder, anxiety, OCD, and psychosis. It provided a broad overview from a lay person’s standpoint of maternal mental health issues and puts a very real face to these potentially devastating disorders.

Low-Dose Estradiol and the Serotonin-Norepinephrine Reuptake Inhibitor Venlafaxine for Vasomotor Symptoms: A Randomized Clinical Trial

Joffe H, Guthrie KA, LaCroix AZ, et al
JAMA Intern Med 2014 May 26 [Epub ahead of print]

ANNOTATION (Christina Wichman)

The Finding: Vasomotor symptom (VMS) frequency was reduced significantly more with estradiol (52.9%) and with venlafaxine (47.6%) than with placebo (28.6%). Low-dose estradiol reduced the frequency of symptoms by 0.6 more per day than venlafaxine (P=.09).

Strength and Weaknesses: This was a multisite, randomized, placebo-controlled 8-week trial; additional benefit from venlafaxine may have been noted had the trial been further extended. Women were recruited via mass mailings via purchased mailing lists and health plan enrolment files, which may have provided for a sample with increased frequency and severity of VMS as compared to the general population. Additionally, there were several exclusion criteria, further concerning for generalizability to the general population of peri-menopausal and menopausal women. Perhaps most importantly, the sample size was not large enough to provide adequate power for a direct non-inferiority comparison between estradiol and venlafaxine, only comparison of each to placebo.

Relevance: VMS are incredibly prevalent among women during midlife, affecting up to 80% of women; while estrogen therapy (ET) remains the gold standard of treatment of VMS, current recommendations are that ET should be used at the lowest possible dosage for the shortest possible duration due to identified risks in the post-menopausal population. This study demonstrates low-dose oral estradiol and venlafaxine are effective treatments for VMS; estradiol remains superior in terms of reduced symptom frequency and patient satisfaction; however, venlafaxine should also be considered as an alternative, especially in patients with comorbid symptoms that may benefit from a SNRI.

ABSTRACT (JAMA Internal Medicine)

Importance: Estrogen therapy is the gold standard treatment for hot flashes and night sweats, but some women are unable or unwilling to use it because of associated risks. The serotonin-norepinephrine reuptake inhibitor venlafaxine hydrochloride is used widely as a nonhormonal treatment. While the clinical impression is that serotonin-norepinephrine reuptake inhibitors are less effective than estrogen, these medications have not been simultaneously evaluated in one clinical trial to date.

Objective: To determine the efficacy and tolerability of low-dose oral 17β-estradiol and low-dose venlafaxine extended release in alleviating vasomotor symptoms (VMS).

Design, Setting, and Participants: In total, 339 perimenopausal and postmenopausal women with at least 2 bothersome VMS per day (mean, 8.1 per day) were recruited from the community to MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health) clinical network sites between December 5, 2011, and October 15, 2012.

Interventions: Participants were randomized to double-blind treatment with low-dose oral 17β-estradiol (0.5 mg/d) (n=97), low-dose venlafaxine hydrochloride extended release (75 mg/d) (n=96), or placebo (n=146) for 8 weeks.

Main Outcomes and Measures: The primary outcome was the mean daily frequency of VMS after 8 weeks of treatment. Secondary outcomes were VMS severity, bother, and interference with daily life. Intent-to-treat analyses compared the change in VMS frequency between each active intervention and placebo and between the 2 active treatments.

Results: Compared with baseline, the mean VMS frequency at week 8 decreased to 3.9 (95% CI, 2.9-4.9) VMS per day (52.9% reduction) in the estradiol group, to 4.4 (95% CI, 3.5-5.3) VMS per day (47.6% reduction) in the venlafaxine group, and to 5.5 (95% CI, 4.7-6.3) VMS per day (28.6% reduction) in the placebo group. Estradiol reduced the frequency of symptoms by 2.3 more per day than placebo (P<.001), and venlafaxine reduced the frequency of symptoms by 1.8 more per day than placebo (P=.005). The results were consistent for VMS severity, bother, and interference. Low-dose estradiol reduced the frequency of symptoms by 0.6 more per day than venlafaxine (P=.09). Treatment satisfaction was highest (70.3%) for estradiol (P<.001 vs placebo), lowest (38.4%) for placebo, and intermediate (51.1%) for venlafaxine (P=.06 vs placebo). Both interventions were well tolerated.

Conclusions and Relevance: Low-dose oral estradiol and venlafaxine are effective treatments for VMS in women during midlife. While the efficacy of low-dose estradiol may be slightly superior to that of venlafaxine, the difference is small and of uncertain clinical relevance.

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