Drug Profile

Paroxetine mesylate (BRISDELLE) is the first and only nonhormonal drug approved by the Food and Drug Administration (FDA) for treatment of hot flashes associated with menopause. It is a lower-dose version (7.5 mg) of the antidepressant forms of this drug (PAXIL, PAXIL CR, PEXEVA). Unlike the antidepressant forms of paroxetine, which we list as Limited Use drugs, we have designated paroxetine mesylate as a Do Not Use drug because it has questionable benefits for women with hot flashes but carries well-established risks, including depression.

Paroxetine mesylate was tested in two drug-company-funded studies involving nearly 1,200 postmenopausal women who were experiencing more than seven moderate-to-severe hot flashes per day.[1] Half the women were randomly assigned to receive the drug and the other half to receive a placebo. After 12 weeks of use, the women receiving a placebo had about a 50% reduction in hot flashes (from a median of about 10 per day to slightly more than five per day). Those receiving the drug had about a 60% reduction to approximately four to five hot flashes per day. The study also found only a very small difference between the two groups in the severity of hot flashes. These small effects relative to placebo demonstrated that the drug has little clinically meaningful benefit.

Meanwhile, the same studies provided clear evidence of multiple risks. According to the FDA, adverse reactions that occurred at a notably higher frequency in women receiving paroxetine mesylate included dizziness, nausea, fatigue, and mood swings.[1]

Women who reported having a history of depression, suicidal behavior or thoughts, or other psychiatric disorders were excluded from the studies.[1] Despite these precautions, five women taking paroxetine mesylate discontinued the drug because they developed suicidal thoughts, attempted suicide, or experienced a depressed or elevated mood.[1] Overall, women taking paroxetine mesylate were more than twice as likely to develop depression or suicidal behavior as those taking a placebo.

In March 2013, an FDA advisory committee reviewed the evidence for the effectiveness and safety of low-dose paroxetine mesylate to treat hot flashes. Public Citizen testified before the committee against the drug’s approval for such use, pointing out that the clinical trials failed to show evidence of any clinically significant benefits for paroxetine mesylate in comparison to a placebo.[2] We also highlighted the known risks of the drug.

The advisory committee concluded, by a 10-4 vote, that low-dose paroxetine mesylate did not provide a clinically meaningful improvement in hot flashes.[3] By an identical 10-4 vote, the committee also found that the drug’s benefits did not outweigh its risks and that it thus should not be approved. The FDA, unfortunately, overrode the advice of the committee and approved the drug.

Alternative treatments

For mild hot flashes, use lifestyle-related strategies, such as the following:

• Lower the room temperature and sleep in a cool room.
• Dress in layers that can easily be removed at the start of a hot flash.
• Drink cold water or juice when you feel a hot flash starting.
• Use loose, light sheets and clothing that allow your skin to “breathe.”
• Do not smoke.[4]

If these approaches fail and you develop moderate-to-severe hot flashes that prevent you from working or carrying out other important activities, talk to your doctor about using hormone replacement therapy (HRT) drugs — those containing estrogen, with or without progestin, and designed to replace women’s hormones following menopause. This is an appropriate option for relatively young women (up to age 59 or within 10 years of menopause) who are otherwise healthy.[5] Use only the lowest dose needed to address symptoms. Use a combination estrogen–progestin product if you have an intact uterus and an estrogen-only product if you have had a hysterectomy .

Because HRT increases the risk of breast cancer, blood clots, and adverse cardiovascular events, such as stroke, it should be used for the shortest duration possible to relieve symptoms. Try taking it for three months, then ask your doctor to help you slowly taper down the drug and watch for returning symptoms. Start taking HRT again only if the symptoms return, are severe enough to require treatment, and do not respond to safer nondrug approaches. If your first attempt to quit fails, try again as soon as possible.