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Nonhormonal Treatment Provides Relief for Hot Flashes

By Heather Hogstrom

The FDA has approved a nonhormonal medication to combat hot flashes in menopausal and postmenopausal women.

Also known as vasomotor symptoms, hot flashes occur when blood vessels close to the skin open suddenly, likely due to hormonal fluctuations, causing a feeling of heat. They are the most common symptom of menopause and can affect women for several years.

While estrogen-based therapies are the treatment of choice for hot flashes, some women have concerns about the safety of hormonal treatments. However, these patients may find relief in a nonhormonal treatment recently approved by the FDA.

Brisdelle, an orally administered selective serotonin reuptake inhibitor (SSRI) for the treatment of moderate to severe vasomotor symptoms associated with menopause, is the first FDA-approved nonhormonal treatment for hot flashes and is expected to become available in pharmacies in November. Brisdelle contains a lower dose (about 7.5 mg) of paroxetine, which is used in drugs such as Paxil to treat psychiatric disorders such as depression.

Two randomized, double-blind studies established the safety and effectiveness of Brisdelle and showed that the drug reduced hot flashes compared with placebo. Women who had seven or more hot flashes per day reported a 57% to 59% reduction in the frequency of hot flashes compared with a 40% to 48% reduction in those taking a placebo.

Although the FDA’s advisory committee on reproductive drugs found Brisdelle’s effectiveness to be inadequate, the FDA decided to approve the drug, viewing it as another useful treatment option for women.

“There are a significant number of women who suffer from hot flashes associated with menopause and who cannot or do not want to use hormonal treatments,” said Hylton V. Joffe, MD, MMSc, director of the division of bone, reproductive, and urologic products in the FDA’s Center for Drug Evaluation and Research, in a press release. “[This] approval provides women with the first FDA-approved, nonhormonal therapeutic option to help ease the hot flashes that are so common in menopause.”

While the FDA approval is new, the treatment is not. “The first studies showing an improvement in menopausal hot flashes with paroxetine came out over a decade ago. We have used this medication as an option for women off-label, but it is nice to have FDA approval,” says Rachel Hess, MD, MS, an associate professor of medicine, epidemiology, and clinical and translational sciences in the Center for Research on Health Care at the University of Pittsburgh. “It provides a good option for women who have hot flashes and are unable to take estrogen or just don't want to take it.”

When prescribing a hormonal treatment or SSRI, physicians should consider which therapy is best suited for each patient, taking into account her age and personal and family medical history. “Estrogens are best for those newly menopausal, within a few years of menopause,” says Shelley Salpeter, MD, a clinical professor of medicine at Stanford University.

While hormone therapy with estrogen is the most effective treatment for hot flashes, it’s not appropriate for some patients. Since paroxetine is not a hormone, it provides an alternative treatment. “The ideal candidate for paroxetine is a woman with hot flashes who cannot, should not, or will not take estrogen,” Hess says. “For example, women with a history of breast cancer should not take estrogen and those with a strong family history of breast cancer may choose not to take estrogen.”

However, the reduction in hot flashes is not as large with paroxetine as it is with estrogen. In fact, researchers aren’t even sure what makes the drug effective in treating menopausal hot flashes.

“We don't know exactly why the SSRIs are effective for managing hot flashes,” Hess says. “In fact, the mechanisms behind hot flashes are an area of active research. The effectiveness of the SSRIs provides further evidence for a central, brain-mediated mechanism, but what that is we don’t know. We think that there is a narrowing of the thermoregulatory zone during menopause, but again, this is a theory.”

Although the mechanism by which Brisdelle treats hot flashes associated with menopause is unknown, the drug’s recommended use is most likely the lowest dose possible for the shortest amount of time, as is recommended for hormonal treatments. “As with any medication used to manage symptoms, it should only be taken while the symptom is bothersome. As women’s hot flashes improve, trying to taper or stop medication is very reasonable,” Hess says.

Keep Patients Informed
When providing patients with information about this nonhormonal therapeutic treatment option, physicians should instruct them about its side effects and drug interactions. Patients should not take Brisdelle if they take monoamine oxidase inhibitors, thioridazine, or pimozide, and they should not take any other medicines that contain paroxetine. It’s also not a safe treatment for hot flashes associated with pregnancy.

Although Brisdelle is not indicated for the treatment of psychiatric conditions, since it contains the same active ingredient as medications for treating depression, it includes a warning that it may increase suicidal thoughts or actions.

The most common adverse reactions reported in clinical trials were headache, fatigue, and nausea and vomiting. Other side effects include an increased risk of developing serotonin syndrome, bone fractures, and abnormal bleeding, and possible reduced effectiveness of tamoxifen if used at the same time. Elderly patients may be at greater risk for low sodium levels in the blood. It also may cause seizures or convulsions, restlessness, cognitive and motor impairment, and acute angle closure in patients with narrow angle glaucoma.

As with hormonal treatments, paroxetine has various associated risks and benefits, so physicians should consider this alternative treatment on a case-by-case basis. Hess believes that paroxetine represents another tool to help women with hot flashes. “It is certainly an option for women who can’t take hormones, although the reduction in hot flashes is not as great,” she says.

Prescription hormone therapy with estrogen still is the most effective treatment for hot flashes because it directly combats women’s changing hormone levels during menopause. “Estrogen production from the ovary decreases with menopause and causes hot flashes; estrogen therapy can reverse those symptoms,” Salpeter explains. “There are many types, doses, and combinations of hormone therapy that would need to be individualized for each patient depending on their risk factors.” For example, patients avoiding estrogen may find relief in progesterone alone.

Offering Alternatives
Although using hormones can increase the risk of breast cancer, heart disease, stroke, and blood clots, for some women the benefits may outweigh the risks. For those who would rather not take hormones or an antidepressant, other treatment options may be on the horizon.

“Other treatment options for hot flashes besides estrogen and paroxetine are an active area of research,” Hess says. “Paced respiration shows promise in the management of hot flashes. In addition, we know that women who smoke or are obese are more prone to hot flashes, so smoking cessation and weight loss, which are good for a lot of reasons, may help manage hot flashes as well.” Other lifestyle changes such as a healthful diet, exercise, and stress management also may help reduce symptoms.

Gabapentin, an antiseizure drug, also may reduce hot flashes, although the FDA has not yet approved this medication. Additionally, patients who experience hot flashes at night may benefit from sleeping medications. Although these medications will not reduce hot flashes, they can prevent sleep disruptions, allowing patients to sleep through the hot flashes.

— Heather Hogstrom is an editorial assistant for Today’s Geriatric Medicine.