Advisory Panel Votes No, But FDA Approves Antidepressant for Hot Flashes Anyway

OK, here we go again. Antidepressants are being touted as a treatment for menopausal hot flashes. This is nothing new because antidepressants have been prescribed for treatment of hot flashes for quite some time. A 2003 study reported in JAMA (Journal of the American Medical Association) showed a slight improvement in hot flashes for women using paroxetine (the active ingredient in antidepressants and the new hot flash treatment – Brisdelle) versus placebo. Other studies, show similar results and antidepressants for hot flashes have been prescribed off-label for about a decade. What’s new is that an antidepressant has now been ‘officially approved and recommended’ by the FDA.

So much about this FDA approval just didn’t set right with me. Perhaps, I am just tired of so many procedures, surgeries and drugs being recommended and approved for women, when in reality, most are not remotely helpful and can actually be quite harmful in the long run. So, I did some research and I uncovered a number of things that are very interesting, concerning and even somewhat alarming about Brisdelle and paroxetine.

What is Brisdelle?

Brisdelle is a selective serotonin reuptake inhibitor (SSRI) that contains the active ingredient paroxetine. Paroxetine is the SSRI used in common antidepressants such as Paxil, Aropax,Pexeva, Seroxat, Sereupin.

Side Effects of Paroxetine

The most common side effects associated with Brisdelle and other SSRIs include headache, fatigue and nausea or vomiting. As a paroxetine-based SSRI, Brisdelle may have side effects such as reduced sex drive and an elevated risk of osteoporotic fractures – both already risk factors for many menopausal women. Although the dosage of paroxetine in Brisdelle, approved for hot flashes, is lower than that typically prescribed for depression, the medication will still carry a black-box warning regarding paroxetine’s link to suicide (a known side-effect of paroxetine-based antidepressants is an increased risk of suicide). The black-box warning is the most serious warning that can be placed on the label of any prescription drug. Additional warnings will include an increased risk of bleeding and a risk of developing the rare, but increasingly more common adverse event ‘Serotonin Syndrome’. Serotonin Syndrome is a condition where there’s too much serotonin – leading to excessive nerve cell activity and causing a deadly collection of symptoms including confusion, changes in blood pressure, irregular heartbeat, seizures and unconsciousness.

Brisdelle Background

Noven Pharmaceuticals makes Brisdelle and funded the studies on the use of Brisdelle to treat hot flashes. Dr. James A. Simon, Clinical Professor of Obstetrics and Gynecology at the George Washington University School of Medicine in Washington DC, led the study. Dr. Simon openly reports having a financial relationship with Noven. The fact that Noven supported the study and provided the drug for the study, along with the fact that the lead doctor overseeing the study has financial ties with Noven, is troubling in my opinion, but standard fair in pharmaceutical research.

The FDA Approval of Brisdelle

The media is correctly reporting that the FDA approved Brisdelle. What seems to be missing from the headlines and discussion is the fact that the FDA’s advisory panel on reproductive health drugs voted against approval by a very large margin.  Indeed, the advisory panel voted 10 to 4 against Noven’s request for Paroxetine Mesylate, formulated as low-dose Mesylate salt of Paroxetine (7.5 mg/day), saying the drug’s minimal benefit didn’t outweigh its risks.

Panel members who voted against the drug pointed to the fact that women who experienced an average of 10 hot flashes per day experienced as few as 4 after 12 weeks of being on Brisdelle while women on the placebo went from having 10 a day to around 5. “I voted against recommending approval when I looked at the magnitude of the treatment effect relative to the magnitude of the placebo effect where there is no risk involved,” said Daniel L. Gillen, PhD, from the University of California, Irvine.

The FDA did not say why it ignored the advisory panel’s recommendation and approved the drug. Technically, it doesn’t have to follow the recommendation of its panel, but it is highly unusual that it didn’t in this case, since the vote was overwhelmingly negative. Where is the outrage? Where is the investigative reporting to determine why the FDA overrode its own advisory panel?

Why Approve Brisdelle?

What are we to make of this new drug that has been approved by the FDA for the treatment of menopausal hot flashes?  In my opinion, I don’t believe the FDA really needed to bother approving it because doctors routinely prescribe antidepressants off-label for women – for everything from heavy periods to insomnia and sometimes for no reason at all. Perhaps that is why they approved Brisdelle in the first place, it’s already being prescribed widely to women in this age group. A recent report suggests that 25% of women aged 44-59 are using antidepressants and overall there has been a 400% increase in antidepressant use from 2005-2008. Since women are already using antidepressants and there are currently no effective treatments for menopausal hot flashes, why not capitalize on this?  According to the New York Times:

Women “are begging for alternatives,” Dr. Andrew London, an obstetrician and gynecologist in the Baltimore area, told the committee, which met in Silver Spring, Md. If there were no approved drugs, he added, “They will get help on their own without us.”  

Brisdelle looks like just one more way to entice women to spend money on antidepressants and it could very well be dangerous.

The Dangers of Prescription Medications

According to Melody Petersen, author of “Our Daily Meds”, approximately 100,000 Americans die every year from their prescription drugs that they took just as the doctor directed. “This isn’t when a doctor or a pharmacist made a mistake or the patient accidentally took too much. This is when everything went right” she said.

My Take on Brisdelle and other Antidepressants for Hot Flashes

I am personally very leery of using paroxetine (no matter how small the dosage) to combat hot flashes. Simply stated, paroxetine is one of the most potent and selective of the SSRI-type drugs and the dangerous side-effects associated with it are well documented. With all of the evidence against Brisdelle or paroxetine and very little for it, I certainly don’t trust that it is a safe and effective treatment for menopausal hot flashes. Even if it has some small potential to help, I am not sure it would be worth the risks. I am very suspect of the FDA’s approval on this one. I don’t think I’ll be taking paroxetine anytime soon for any reason – least of all for relief of hot flashes.