Testimony of Dr. Mary Carol Jennings on Paroxetine (Brisdelle)

Testimony by Mary Carol Jennings, MD

March 4, 2013

My name is Dr. Mary Carol Jennings and I speak today on behalf of the National Research Center for Women & Families.

Our nonprofit research center’s medical and public health experts analyze and review research to provide objective information to patients, providers, and policy makers.  We do not accept funding from pharmaceutical companies so I have no conflicts of interest.

I trained in obstetrics and gynecology at Boston University Medical Center.   So, like all of you, I understand the need for safer alternatives to hormone drugs for hot flashes. The question is: is paroxetine a safe and effective alternative, or will it harm more patients than it helps?

Paxil is widely used and available for depression and several other indications.  The key questions today are whether there is clear scientific evidence that this version of paroxetine works for hot flashes, and if so, do the benefits outweigh the risks.

As the FDA has clearly stated in their memo to you, the company reported a significant reduction of the frequency of hot flashes at week 4 but only in one study at week 12.  And, one of the studies did NOT show a significant reduction in severity of hot flashes through week 12.

What are the risks?  FDA notes that the greatest risk is depression and suicide.  Although women with a history of depression or suicidal thoughts were excluded from this study, the data clearly show that the women taking paroxetine were more likely to have suicidal thoughts and behaviors than the women taking placebo. This was true even on the small dose of 7.5 mg .

The CDC tells us that women between the ages of 45-54 have the highest rates of suicide in the country.  That is the same age group most likely to take a drug for hot flashes.

There are other debilitating risks that are already on the label, including vaginal bleeding, mood swings, and nausea.  And if a patient starts and then stops taking the drug, they tend to suffer muscle complaints, fatigue, restless feelings in the legs, and disrupted sleep.

In summary, the risks of paroxetine include many of the same symptoms as menopause, and if a woman stops taking it, she may suffer even more.   Might the drug improve hot flashes while making other symptoms much worse?

The FDA must decide if the benefits of this drug for hot flashes outweigh the risks.    FDA has concluded that the benefits outweigh the risks for depression and OCD, which can be debilitating and even fatal conditions.

However, the approval decision is different for hot flashes, because hot flashes are not fatal.  Although they can be debilitating, they do go away by themselves with time, which depression and OCD often do not.

I also want to speak on behalf of breast cancer patients who might consider this drug for the hot flashes caused by tamoxifen  FDA scientists expressed concern that paroxetine’s (inhibitory) effect on the liver enzyme (CYP2D6) that processes tamoxifen may reduce the effectiveness of this cancer drug.

The benefits of paroxetine for severe depression may outweigh the risks – even for breast cancer patients taking tamoxifin.  But, the data today do not prove that the benefits for hot flashes outweigh the risks for breast cancer patients or for any other patients.

If the benefits are questionable, there is no reason to approve paroxetine for this new indication.  The drug is already available off label for women who want it, and in generic form, at a similar low dose, making it an easy – and less expensive — option than the same drug with a new name specifically approved for hot flashes.

The FDA is under undue pressure from Congress and others to approve new drugs.  You are here today as scientific voices to look at the data.  Would you recommend or prescribe this drug for a sister, wife, or mother for hot flashes, based on the data provided today?   For the women on the panel, would you take it yourself?  Or would you want more proof that the benefits for hot flashes outweigh the risks?

The March 4th Advisory Committee voted 10-4 against approval of paroxetine. In spite of this recommendation, FDA approved paroxetine (marketed as Brisdelle) for treatment of hot flashes on June 28, 2013.