The Antidepressant Venlafaxine Can Reduce Hot Flashes in Breast Cancer Survivors

ROCHESTER, Minn—Low doses of the antidepressant venlafaxine (Effexor) can reduce hot flashes in breast cancer survivors by 61%, compared to a 27% reduction with placebo, Charles L. Loprinzi, MD, told a plenary session of the ASCO meeting. “This is a sizable reduction in hot flashes for women who can’t take estrogen replacement,” he added.

Hot flashes, some severe enough to be debilitating, are a major problem in many postmenopausal women, including cancer survivors in whom antineoplastic therapy has induced early menopause. Although hot flashes can be alleviated by estrogen or progesterone preparations, they are frequently withheld from these women due to concerns about whether hormones might adversely affect the natural history of breast cancer.

The results, from a North Central Cancer Treatment Group (NCCTG) trial, may also have broader applications. “Because it so clearly works and is reasonably tolerated, use of venlafaxine may be an option for women without breast cancer who don’t want to use estrogen and/or progesterone medications to alleviate hot flashes,” Dr. Loprinzi observed.

“The appearance of this paper in a plenary session represents a growing maturity in the field of oncology in considering the whole patient,” commented Daniel F. Hayes, MD, of Georgetown University, Washington, DC, discussant for the session. Dr. Hayes said that 60% of postmenopausal women report hot flashes, and that 10% to 20% describe them as “nearly intolerable.”

Daily Diary Kept

The NCCTG study was a four-arm, double-blind, placebo-controlled randomized clinical trial to evaluate venlafaxine. Women with bothersome hot flashes (defined as 14 or more episodes per day) were randomized to 4 weeks of treatment with placebo or with venlafaxine at doses of 37.5 mg/day, 75 mg/day, or 150 mg/day. Hot flashes were recorded in a daily hot flash diary used by more than 800 patients in a series of clinical trials.

The table on page 18 illustrates the percentage of baseline hot flash scores (calculated by multiplying the number of hot flashes by their mean severity) during the fourth treatment week as compared to the baseline week.

Dr. Loprinzi reported that the 37.5-mg/day dose reduced hot flashes by 40%, and the 75-mg/day dose reduced hot flashes by 60%. The 150-mg/day dose was not significantly more effective than 75 mg/day at reducing hot flashes and was associated with more toxicity problems such as mouth dryness, decreased appetite, nausea, and constipation.

“There were no significant constipation problems on the 75-mg/day arm,” Dr. Loprinzi said. Less than 7% of patients stopped venlafaxine due to toxicity.

Improvements in Libido

Dr. Loprinzi said the researchers also found “improvements in libido in all four study arms, but more marked improvement with venlafaxine than with placebo. The moral is, if you want an improvement in your libido, enter an NCCTG hot flash study,” he joked.

He concluded that “these data definitively support the prestudy hypothesis that venlafaxine can substantially reduce hot flashes. This represents a new treatment modality for women with hot flashes.”

Dr. Hayes said that the mechanisms that cause hot flashes are not clear. Estrogen can reduce hot flashes by 50% to 100%, but there is concern giving estrogen to many cancer survivors. Other treatments such as vitamin E and dietary soy have shown only marginal efficacy.

“It seems reasonable to offer a trial of a selective serotonin reuptake inhibitor (SSRI) to women or men (such as those being treated for prostate cancer) who have hot flashes and cannot or do not choose to take hormonal therapy,” Dr. Hayes said.