|March 2013 · Vol. 25, No. 3
EXAMINING THE EVIDENCE
Does desvenlafaxine alleviateYes, according to this 12-week randomized, double-blind, placebo-controlled trial of 365 women, desvenlafaxine (100 mg daily) reduced the number of moderate and severe hot flashes by 7.3 (62%) per day versus 4.5 (38%) per day for placebo. The severity score for women taking desvenlafaxine declined by 0.59 (25%) per day versus 0.28 (12%) per day for women taking placebo. The minimal clinically important difference—a reduction of 5.35 moderate and severe hot flashes per day—was achieved by 64% of women taking desvenlafaxine, compared with 41% of women taking placebo (P <.001).
moderate to severe hot flashes
in a clinically meaningful way?
Holly L. Thacker, MD
Director of the Center for Specialized Women’s Health, Cleveland Clinic, Cleveland, Ohio. Dr. Thacker is also Associate Professor, Department of Obstetrics and Gynecology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, and the author of the Cleveland Clinic Guide to Menopause (Kaplan; 2009). She is Executive Director of Speaking of Women’s Health (www.speakingofwomenshealth.com; on Twitter at @SPKwomenshealth).
Untreated vasomotor symptoms (VMS) in menopausal women remain a personal, social, and economic problem. Women with untreated symptoms have a reduced ability to work and drop out of the workforce at an alarming rate.1 We know that menopausal hormone therapy (HT), the only treatment approved by the Food and Drug Administration (FDA), is the most effective therapy for VMS. However, many women cannot take HT (eg, those who have estrogen-sensitive cancer or thromboembolic disease). And since the Women’s Health Initiative, many women simply refuse HT. That leaves millions of women searching for relief, with many of them turning to unregulated and unstudied therapies.2
This study by Pinkerton and colleagues is a robust comparison of oral desvenlafaxine (100 mg daily, with a 1-week run-in of 50-mg daily) and placebo. It showed a statistically and clinically significant reduction of moderate to severe VMS in postmenopausal women and was safe, well-tolerated, and effective. To date, however, the FDA has not approved the use of desvenlafaxine, or any other nonhormonal agent, for menopausal VMS. Desvenlafaxine is FDA approved for the treatment of major depressive disorder (MDD).
Desvenlafaxine is the active isomer of venlafaxine, and the doses of venlafaxine used for the treatment of MDD or anxiety disorder (150 mg or higher) are generally higher than the off-label doses of venlafaxine used for VMS (37.5–75.0 mg), which have been studied in breast cancer survivors with VMS.3 I use both desvenlafaxine (Pristiq; 50–100 mg) and venlafaxine (Effexor; 37.5–75.0 mg) in my practice. Venlafaxine is generic and, therefore, cheaper. However, if my patient has VMS, depression, and/or anxiety, then I favor desvenlafaxine over venlafaxine.
Many neuropsychiatric drugs are used off label to treat VMS in women without depression; however, side effects and stigma associated with taking a mood medicine for a non–mood-related disorder, as well as concerns about weight gain and sexual side effects, discourage many women from using them. The lack of labeling advice is another deterrent. The clinician needs to assess the risks and benefits of HT versus nonhormonal therapies in women with VMS. Choosing an appropriate treatment requires taking into consideration the preferences of the patient, any medical comorbidities, and evidence on the safety and efficacy of nonhormonal agents, primarily selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).4
WHAT THIS EVIDENCE MEANS FOR PRACTICE
Menopausal HT should be offered to most women with bothersome VMS, provided they have no contraindications, because HT also benefits the bone and treats urogenital atrophy. If nonhormonal agents are required or desired, off-label desvenlafaxine (100 mg daily after a 1-week run-in of 50 mg daily, to reduce side effects), can be prescribed, especially in women who have concurrent MDD or anxiety or both.
HOLLY L. THACKER, MD
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1. Geukes M, van Aalst MP, Nauta MC, et al. The impact of menopausal symptoms on work ability. Menopause. 2012;19(3):278–282.
2. Williams RE, Kalilani L, DiBenedetti DB, et al. Healthcare seeking and therapy for menopausal symptoms in the US. Maturitas. 2007;58(4):348–358.
3. Carpenter JS, Storniolo AM, Johns S, et al. Randomized, double-blind, placebo-controlled crossover trials of venlafaxine for hot flashes after breast cancer. Oncologist. 2007;12(1):124–135.
4. Thacker HL. Assessing risks and benefits of nonhormonal treatments for VMS in perimenopausal and postmenopausal women. J Womens Health. 2011;20(7):1007–1016.
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