Antidepressants Emerge as Coolant for Hot Flashes

By TARA PARKER-POPE
Doctors are writing a new prescription for menopause: the antidepressant.
It’s not that all menopausal women are depressed. Instead, the antidepressant has emerged as the drug of choice among women searching for new ways to cool the hot flash.
There is no way to track how often antidepressants are prescribed to treat hot flashes, the unpredictable, sticky wave of heat that for many women is the defining symptom of menopause. None are specifically approved for hot flashes, and doctors who prescribe them are doing so “off label.”
Menopause researchers say antidepressant use is becoming increasingly common as both women and doctors seek alternatives to menopause hormones. The use of hormone drugs has fallen precipitously since 2002, when a government study linked hormone use in older women to stroke and breast cancer.
It isn’t clear why antidepressants seem to cool hot flashes, at least in some women. The link was made by chance in studies of women with breast cancer. Some cancer drugs set off hot flashes, and researchers noticed that women who were also taking the antidepressants known as a selective serotonin reuptake inhibitors had fewer flashes.
Studies looking at the use of these and other serotonin-altering drugs to treat hot flashes in healthy menopausal women have been disappointing. Two, Wyeth’s Effexor and GlaxoSmithKline’s Paxil, have shown a meaningful benefit in high-quality controlled studies, according to a review published last year in The Journal of the American Medical Association.
For women, that translates into some relief, but not as much as they would receive from estrogen drugs. In one Effexor trial, the antidepressant users reported about 60 percent fewer hot flashes. By comparison, studies of hormones show estrogen reduces the frequency of hot flashes 80 percent.
Although Effexor did help, it worked best at a high dose, meaning that women also complained of numerous side effects, including constipation, dry mouth and nausea.
“Some women are fine with them and say it helps and it makes a difference,” said Cynthia Pearson, executive director of the National Women’s Health Network, an advocacy group. “Other women, after two to three weeks, they say, ‘Forget it, I don’t feel like myself.’”
Studies are finding a wide variation in responses to the drugs. A study of the antidepressant Zoloft — sponsored by its maker, Pfizer, and published this month in the journal Menopause — reported that one-third of the subjects actually had more hot flashes while taking the drug, a third stayed about the same or experienced just a slight benefit, and a third reported far fewer hot flashes. The finding is similar to trends shown in other studies of antidepressants for hot flashes, including Prozac and Paxil.
The challenge, then, is in figuring out which women have the most to gain from taking the drugs. Unfortunately, the number of women studied has been so small that no big conclusions can be drawn. In the Zoloft trial, 27 women were in the high-benefit group.
But one interesting trend emerged. Women who were recently menopausal, meaning that they had just stopped having their periods, received the most benefits from antidepressant treatment. Women on either side of the menopausal transition, those who had been menopausal for a year or those who were just starting to experience the effects of hormonal fluctuations, fared worse on the drug.
The biggest concern about antidepressant use for menopause is that the drugs may worsen some symptoms already common during menopause — things like anxiety, sleep problems and loss of libido. And while the drugs have been used safely for years in people with depression, there’s no long-term data on their use in healthy women with healthy brains.
“We think of them as being safer than estrogen, but we’ve got trials of 20,000 women for eight or nine years with estrogen, and we don’t have anything like that,” Deborah Grady, director of the Women’s Clinical Research Center at the University of California, San Francisco, said about the antidepressants.
Wyeth is seeking approval from the Food and Drug Administration for another serotonin-altering drug, Pristiq, specifically for the treatment of hot flashes. But the agency said in the summer that it needed more data before considering the request.
For women who choose to try an antidepressant to relieve hot flashes, doctors advise a psychiatric workup and regular follow-up in the first weeks after starting the drug. In some patients, antidepressants can touch off severe manic symptoms if they have histories of bipolar disorder or manic personality traits, doctors say.
“They are helpful for some women, but right now it’s impossible to predict for whom they will work,” said Dr. Shari Lusskin, director of reproductive psychiatry at the New York University Medical Center. “It offers an option for women who don’t want to take hormones. But we don’t know what long-term use of these drugs does to people who are not depressed.”