Women who are experiencing hot flashes associated with menopause or induced by treatment for breast cancer may now have an effective, nonhormonal treatment, according to researchers at the Mayo Clinic in Rochester, Minn. A pair of recent Mayo studies have confirmed earlier reports that antidepressants are safe and effective in reducing both the frequency and severity of hot flashes by approximately 60 percent.

A follow-up study of more than 100 postmenopausal women, most being treated for breast cancer, showed that venlafaxine (Effexor), a combined serotonin/norepinephrine reuptake inhibitor, reduces hot-flash symptoms over an eight-week period, twice the length of time reported in a previous Mayo study involving nearly 200 women.

The venlafaxine study, which appeared in the February issue of the journal, Oncology Nursing Forum, furthers evidence that the antidepressant is a safe and effective treatment in place of the traditional prescription for estrogen-based hormone replacement therapy.

The study was partially funded by Pfizer Inc., the maker of Effexor.

In women who are being treated for breast cancer, estrogen therapy is contraindicated, because certain types of breast cancers are estrogen dependent. Increasing levels of estrogen is thought to induce these specific types of cancer to grow at accelerated rates and potentially to become more aggressively invasive.

The report on venlafaxine builds on previous studies of the use of paroxetine (Paxil) in treating hot flashes. In those previous studies, as well as the current report, researchers found that the medication seemed to affect patients’ mood as well.

A "notable finding," the authors wrote, relates to responses given by women on a questionnaire relating to side effects experienced during the study. "Several women reported being able to ‘handle stress better’ and ‘think more clearly.’ " Other patients noted that they felt better than ever, or had more energy.

"This finding," the authors added, "makes treatment with venlafaxine a particularly positive intervention, one that perhaps has the potential to target additional symptoms in menopause related to hot flashes."

Previous studies have indicated that about 20 percent to 30 percent of women with cancer suffer from comorbid depression, Donna Stewart, M.D., professor of psychiatry and chair of women’s health at the University of Toronto, told Psychiatric News. "It’s important to note, however," Stewart said, "that not all women who have cancer have affective disorders, and perimenopausal women on the whole have not been shown to have any increased incidence of depression either."

Stewart, who is chair of APA’s Committee on Women, noted that it could be possible that women who have previously had major depression, postpartum depression, or pre-menstrual dysphoric disorder—like symptoms might have a predisposition to developing depressive symptoms during or after menopause; however, research has not shown that so far. She also speculated that the comments made by patients in the venlafaxine study may have simply "picked up on that 20 to 30 percent" of women who are being treated for cancer and have depressive symptoms.

Charles Loprinzi, M.D., a Mayo Clinic oncologist who led the research team, said that at a dose of 75 mg a day, extended-release venlafaxine not only reduced the frequency of hot flashes by 60 percent on average, it also seemed to reduce the severity of the remaining hot flashes that women did experience.

In the team’s second report, which appeared in the March 15 issue of the Journal of Clinical Oncology, they present data on 81 women undergoing treatment for breast cancer and reported "significant and bothersome" hot flashes that had occurred on average at least twice a day. The women were treated with four weeks of fluoxetine (Prozac). Again, results indicated that the SSRI reduced both the severity and frequency of hot flashes overall. However, the response with fluoxetine was not as robust as that seen with venlafaxine.

The fluoxetine study was partially funded by Prozac manufacturer Eli Lilly & Co.

The Mayo Clinic team believes the ability of the antidepressant to alleviate the symptoms of hot flashes is tied to its modulation of serotonin. This would be consistent, they wrote, with the existing evidence that venlafaxine’s actions are mainly related to serotonin and not norepinephrine at lower doses like those used in the current study, and in light of the evidence already gathered with paroxetine, an SSRI.

Loprinzi, a coauthor of both the venlafaxine and fluoxetine reports, remarked in a prepared statement announcing the results of the second study, "The clear message is that now many women with breast cancer do not have to suffer with their hot flashes and that women who want a nonestrogenic choice of treatment now have one."

"Venlafaxine for the Control of Hot Flashes: Results of a Longitudinal Continuation Study" can be accessed on the Web at www.ons.org/xp6/ONS/Library.xml by clicking on Oncology Nursing Forum. An abstract of "Phase III Evaluation of Fluoxetine for Treatment of Hot Flashes" can be accessed at www.jco.org/ by clicking on "Search JCO" and entering the author’s name. ▪

JCO  2002201578