Can Venlafaxine Treat Menopausal Hot Flashes?

Jodi H. Walker, PharmD


May 13, 2011


Has venlafaxine been studied for management of hot flashes associated with menopause?

Response from Jodi H. Walker, PharmD
Adjunct Experiential Faculty and Associate Professor, Albany College of Pharmacy, Albany, New York; Clinical Pharmacy Coordinator, VA Medical Center, Bath, New York

Menopause is associated with a variety of symptoms in women including sleep disturbances, mood changes, vaginal dryness, and cognitive disturbances. Vasomotor symptoms, commonly known as hot flashes, are also prevalent. A hot flash is a spontaneous sensation of heat lasting from 2-4 minutes. The sensation usually starts around the face and upper chest and gradually spreads throughout the rest of the body. Hot flashes are usually associated with perspiration, followed by chills and shivering. They are common among perimenopausal and postmenopausal women, occurring in 35%-50% and 30%-80%, respectively.[1]

Traditionally, hot flashes have been treated using estrogen therapy, which can provide 95% efficacy for these vasomotor symptoms. However, the benefit of estrogen use may not outweigh the risk in certain populations of women including breast cancer survivors or those at increased risk of stroke.[2]

Evans and colleagues[3] studied venlafaxine, a selective serotonin-norepinephrine reuptake inhibitor, for the management of postmenopausal hot flashes. Patients were randomized to receive extended-release venlafaxine 37.5 mg once daily for 1 week, then 75 mg daily for 11 weeks or placebo following the same dosing regimen. Hot flash score decreased by 51% in the venlafaxine group and 15% in the placebo group. Little difference in severity was reported. Dry mouth, sleeplessness, and decreased appetite were observed more in the treatment group; nausea, constipation, headache, and decreased libido were similar between the groups.

Because of the perceived risk of hormone therapy in breast cancer patients, alternate forms of therapy for menopausal symptoms have been investigated in this patient population. Carpenter and colleagues[4] found that physiologic hot flashes decreased by 22% compared with baseline in patients receiving extended-release venlafaxine 37.5 mg daily and by 14% in patients receiving 75 mg daily.

The mechanism by which venlafaxine alleviates hot flash severity and frequency is unknown; it may be more psychological than physiologic. The antidepressive effects of venlafaxine may help women cope with hot flashes better, as opposed to decreasing their frequency or intensity.[3] However, Carpenter and colleagues[4] noted the time to greatest effect was seen after 1 week. Because the antidepressant effect can take several weeks, this may suggest a different mechanism of action.

Regardless of the mechanism, venlafaxine appears to be a viable alternative to patients who are unwilling or unable to receive hormone therapy. Doses of extended-release venlafaxine 37.5 mg daily and 75 mg daily have both been shown to be effective in reducing frequency and severity of postmenopausal hot flashes with minimal or tolerable side effects.

Desvenlafaxine has also been investigated for the treatment of hot flashes, though not as extensively as venlafaxine. Speroff and colleagues conducted a randomized, double-blind trial comparing the efficacy and safety of desvenlafaxine with placebo for the treatment of menopausal vasomotor symptoms.[5] A total of 707 postmenopausal women were randomized to receive desvenlafaxine 50 mg, 100 mg, 150 mg, or 200 mg or placebo daily for 52 weeks. Patients taking desvenlafaxine 100 mg had the greatest reduction of hot flash frequency and severity. By week 12, patients in the 100 mg group had a 64% reduction in the average number of daily hot flashes and a 31% reduction in severity. The authors concluded that desvenlafaxine 100 mg may be an effective treatment for vasomotor symptoms associated with menopause.

Carroll and Kelley conducted a meta-analysis evaluating selective serotonin reuptake inhibitors and selective serotonin-norepinephrine reuptake inhibitors for the treatment of hot flashes in women with and without a history of breast cancer.[6] Studies involving venlafaxine, desvenlafaxine, paroxetine, sertraline, and other antidepressants were included in analysis. The authors concluded that venlafaxine and paroxetine appear to be the most studied and most effective antidepressants used to reduce the frequency and severity of hot flashes. Other antidepressants may be considered as second or third line agents for those who cannot tolerate or have failed therapy with venlafaxine or paroxetine.

The author wishes to acknowledge Alexander Novotny, PharmD candidate, for his contributions in researching and compiling this response.


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