Menopausal women battling hot flashes may have a new weapon to add to their arsenal: paroxetine.

Researchers at Johns Hopkins and 17 other institutions found that a slow-release form of the antidepression, antianxiety medication, sold under the brand name Paxil, reduced hot flashes in a group of menopausal women by up to 65 percent, or 3.3 flashes per day. Their work is published in the June 4 issue of The Journal of the American Medical Association.

Hot flashes traditionally have been treated with estrogen and progestin hormone supplements, which can reduce their frequency by 80 percent to 90 percent. But results of the Women's Health Initiative study--blaming the hormones for increased risk of heart attack, stroke, blood clots and breast cancer--have sent women and their physicians searching for alternatives.

Paroxetine is "the best nonhormonal drug we know about right now," said lead author Vered Stearns, an assistant professor of oncology at Johns Hopkins' Sidney Kimmel Comprehensive Cancer Center. "If a woman wants to try nonhormonal therapy, she will know within days whether it's going to work."

Stearns was at the University of Michigan when the study was completed. In earlier studies, Stearns investigated the quick-release form of paroxetine primarily in breast cancer survivors and showed a similar reduction in hot flashes.

The physiology behind hot flashes isn't fully known, Stearns said, though scientists think they occur as falling estrogen levels throw off the central nervous system's temperature control mechanism. The possibility of using paroxetine for hot flashes emerged from the observation that women with a history of breast cancer taking certain antidepressants had fewer hot flashes. The medications that worked inhibited the brain's reuptake of serotonin, a natural chemical that modulates mood, emotion, sleep and appetite.

Between October 2001 and March 2002, Stearns and colleagues studied 165 menopausal women experiencing at least two to three hot flashes a day. Eighty percent had experienced hot flashes for at least a year, and 93 percent had no history of breast cancer. Participants filled out a questionnaire about the severity of symptoms, then were randomly assigned to take paroxetine at 12.5 or 25 milligrams, or a placebo, every day for six weeks.

The subjects answered additional questions about their symptoms three weeks and six weeks later, and had vital signs measured. The women also kept daily hot flash diaries, recording the frequency and severity of their hot flashes during the study period.

Among the 138 women who completed the study, the 25 mg paroxetine pills reduced hot flashes by 64.6 percent or 3.2 flashes per day, and the 12.5 mg pills reduced symptoms by 62.2 percent or 3.3 flashes per day; the placebo reduced them by only 37.8 percent or 1.8 flashes per day. The 25 mg pills showed significant improvements for many of the women within one week of treatment. The most frequently reported side effects were mild to moderate headache, nausea and insomnia.

Sixty percent of women taking paroxetine had a 50 percent or greater reduction in hot flashes, from 6.5 hot flashes per day to 3.2 hot flashes per day. In addition, up to 30 percent of women using it had no flashes by the sixth week of the study.

Stearns cautioned that the drug remains experimental. The optimal dose and whether it will work for minority women are still unknown.

GlaxoSmithKline Pharmaceuticals supported the study.