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One pharmaceutical company can now brag about a nonhormonal option to treat hot flashes during menopause.
Noven Therapeutics knows that's welcome news to scores of women who've developed a fear of hormone therapy following the increased risk of heart disease and breast cancer seen in the Women's Health Initiative (WHI).
But Brisdelle is just an old medication dressed up in a new feminine name and packaging – it's the antidepressant paroxetine, better known by its brand name, Paxil.
"Some women won't even know it is an antidepressant," says , president of the National Center for Women & Families, a women's health advocacy group, explaining that few may look at the generic name, and of those who do, paroxetine will be much less recognizable than Paxil.
Using antidepressants in menopause is not new. Gynecologists have long been using them off-label to treat hot flashes, particularly in women who can't tolerate hormone therapy – including those with a history of heart disease, blood clots, deep vein thrombosis, and stroke.
In theory, selective serotonin reuptake inhibitors (SSRIs) like paroxetine work for hot flashes because serotonin is thought to play a role in regulating body temperature.
But the question remains as to whether antidepressants are actually effective in this condition. There are no large studies of their off-label use in hot flashes, and efficacy findings in the Brisdelle studies were questionable -- so much so that the FDA's own advisory committee recommended against approving the drug for hot flashes.
FDA Panel Votes Against Brisdelle
In March, that panel voted 10 to 4 against approval because it was concerned that the drug's benefits didn't appear to outweigh its risks. Members said there was little difference in hot flash frequency whether patients were on the drug or on placebo. Some panelists also expressed concerns about the risk of suicidal thinking, for which the antidepressant formulation carries a black box warning.
The overall incidence of these adverse events didn't differ much between the two groups during the trial, but Zuckerman noted that patients with a history of depression or suicidal ideation were excluded from the trials.
"Some doctors might assume that's not a big deal, and if a woman starts feeling depressed or suicidal, she can stop taking the drug," Zuckerman said. "But when a person feels depressed or suicidal, they don't think clearly. They may not fully realize it is caused by the drug, because they start to feel bad about themselves or their lives."
If they do realize the effects, she said, stopping the medication quickly can be dangerous: "There's a rebound effect that can be very harmful. So, it's not a simple matter to try it and stop if it isn't working," she said.
Although it often takes the advice of its advisory committees, the FDA isn't bound by their decisions. So in June, it went ahead and gave Brisdelle the green light anyway, potentially because it saw a dearth of options for hot flash treatment.
Gynecologic Indications for Antidepressants
This certainly isn't the first time an antidepressant drug maker has tried to seek a gynecologic indication for its drug. In the early 2000's, Eli Lilly won an indication for its antidepressant fluoxetine – better known as Prozac – in severe premenstrual syndrome -- now called premenstrual dysphoric disorder (PMDD).
The drug was , and the green and white capsules of Paxil became pink and purple.
When Sarafem was approved, PMDD wasn't listed in the Diagnostic and Statistical Manual of Mental Disorders (DSM), the psychiatrist's bible of diagnoses. It was relegated to a back-of-book index for conditions that need further study. (As of May 2013, the condition is now listed in the main book of the DSM-5).
Many antidepressants at the time were facing patent loss, and the gynecologic indication gave them an additional measure of exclusivity. Several other antidepressants, including sertraline (Zoloft) and paroxetine (Paxil), won approvals for PMDD around that time.
As with Paxil in hot flashes, clinicians had already been using antidepressants off label for their severe PMS cases, according to . But it was attractive that the drugs had been specifically studied for PMS, she said.
Having studies makes use of Brisdelle attractive too, she said.
"It's nice to be able to now give a prescription for a therapy that's been specifically studied and approved, and is in lower doses than typical antidepressants," Thacker told ѻý.
The evidence is also reassuring to patients: "We've had to use antidepressants off-label and it's somewhat disconcerting to women who are not depressed who have bad menopausal symptoms to be told, here, have an antidepressant," she said.
, of Spectrum Health in Grand Rapids, Mich., said she's been using escitalopram (Lexapro) off-label for certain hot flash patients. But she recognizes that "some women are more comfortable with a formal indication, and Brisdelle gives me one more such option."
Zuckerman said that's what the drug maker is counting on to tap into this potentially very lucrative market.
"The company knows that many women will pay full price for the 'new' product instead of buying the old generic product," Zuckerman said.
It remains to be seen whether insurers will pay for the brand-name drug, since the off-label option is significantly cheaper. And the dose, although not an exact match, is comparable: Brisdelle is approved for 7.5 mg, while the lowest dose of Paxil is 10 mg.
Its uptake also depends on patients, who may be more concerned about medication pricing.
"If someone is determined to try it," Zuckerman said, "they should take generic Paxil off label instead, because it is equally ineffective and unsafe and costs less."