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Food and Drug Administration-Required Black-Box Warning
Antidepressants, including selective serotonin reuptake inhibitors (SSRIs), have been shown to increase the risk of suicidal thoughts and behavior in pediatric and young adult patients when used to treat major depressive disorder and other psychiatric disorders. Because BRISDELLE is an SSRI, patients should be monitored closely for worsening and for emergence of suicidal thoughts and...
Food and Drug Administration-Required Black-Box Warning
Antidepressants, including selective serotonin reuptake inhibitors (SSRIs), have been shown to increase the risk of suicidal thoughts and behavior in pediatric and young adult patients when used to treat major depressive disorder and other psychiatric disorders. Because BRISDELLE is an SSRI, patients should be monitored closely for worsening and for emergence of suicidal thoughts and behaviors. Families and caregivers also should be advised of the need for close observation and communication with the prescriber.
Additional Important Safety Warnings
- Paroxetine may increase the risk of depression in postmenopausal women.
- As with other SSRIs, paroxetine can cause serotonin syndrome, a potentially fatal condition.
- Paroxetine may reduce the effectiveness of the breast cancer drug tamoxifen (SOLTAMOX).
- Paroxetine may increase the risk of bleeding when the drug is used concomitantly with nonsteroidal anti-inflammatory drugs (for example, ibuprofen [ADVIL, IBU-TAB, MOTRIN]), aspirin or other drugs that affect blood clotting.
- Angle-closure glaucoma (sudden increase of pressure in the eye because eye fluids cannot drain properly) can occur in certain susceptible patients who are treated with drugs like paroxetine.
- Paroxetine can cause dangerously low blood sodium levels.
- Paroxetine may increase the risk of seizures.
- Paroxetine can trigger manic episodes in susceptible patients.
These warnings have been paraphrased from the FDA-approved product labeling.
Paroxetine (BRISDELLE) is the first and only nonhormonal drug approved by the Food and Drug Administration (FDA) for treatment of hot flashes associated with menopause.[1] It is a lower-dose version (7.5 milligrams [mg]) of the antidepressant forms of this drug, which are sold under the brand names PAXIL and PEXEVA at doses of 10 mg to 40 mg. Unlike the antidepressant forms of paroxetine, which we designate as Limited Use, we have designated BRISDELLE as a Do Not Use drug because it has questionable benefits for women with hot flashes but carries well-established risks, including depression.
Questionable benefits
Paroxetine was tested in two drugcompany-funded, placebo-controlled, randomized studies involving nearly 1,200 postmenopausal women who were experiencing more than seven moderate-to-severe hot flashes per day.[2] Half of 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 studies also found only a very small difference between the two groups in the severity of hot flashes. These small effects compared with placebo demonstrated that the drug has little clinically meaningful benefit.
Significant risks
Meanwhile, the same randomized studies provided clear evidence of multiple risks. According to the FDA, adverse reactions that occurred at a notably higher frequency in women receiving paroxetine included dizziness, nausea, fatigue and mood swings.[3]
Importantly, women who reported having a history of depression, suicidal behavior or thoughts, or other psychiatric disorders were excluded from the studies.[4] Despite these precautions, five women taking paroxetine discontinued the drug because they developed suicidal thoughts, attempted suicide or experienced a depressed or elevated mood, whereas no women receiving a placebo discontinued the drug for these reasons.[5] Overall, women taking paroxetine were more than twice as likely as those taking a placebo to develop depression or suicidal or self-injury behavior. The FDA required that the product labeling for Brisdelle include a black-box warning about the drug’s risks of suicidal behavior (see Text Box, above).
In March 2013, an FDA advisory committee reviewed the evidence for the effectiveness and safety of low-dose paroxetine to treat hot flashes. Public Citizen testified before the committee and opposed the drug’s approval for such use, pointing out that the clinical trials failed to show evidence of any clinically significant benefits for paroxetine in comparison with a placebo.[6] We also highlighted the known serious risks of the drug (see Text Box).
The advisory committee concluded, by a 10-4 vote, that low-dose paroxetine did not provide a clinically meaningful improvement in hot flashes.[7] 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 dangerously overrode the advice of the committee and approved the drug.
What You Can Do
For mild hot flashes, you should use lifestyle-related strategies first, such as the following, which are recommended by the National Institute on Aging:[8]
- 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.
- Avoid alcohol, spicy foods and caffeine as these can make hot flashes worse.
- Use loose, light sheets and clothing that allow your skin to “breathe.”
- Do not smoke.
- Try mind-body practices like yoga or other self-calming techniques.
If these approaches fail, and you develop hot flashes severe enough to prevent you from working or carrying out other important activities, talk to your doctor about using hormone therapy drugs — those containing estrogen, with or without a progestin, 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.[9] 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 hormone therapy increases the risk of breast cancer (see the article for details), 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 hormone therapy 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.
References
[1] Sebela Pharmaceuticals. Label: paroxetine (BRISDELLE). April 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/204516s005lbl.pdf. Accessed December 5, 2019.
[2] Food and Drug Administration. Background document for meeting of Advisory Committee for Reproductive Health Drugs, March 4, 2013, NDA 204-516, paroxetine mesylate capsules 7.5 mg. https://wayback.archive-it.org/7993/20170405210758/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM341590.pdf. Accessed December 5, 2019.
[3] Ibid.
[4] Ibid.
[5] Ibid.
[6] Carome MA, Almashat S, Wolfe SM. Testimony before the FDA’s Advisory Committee on Reproductive Health Drugs on new drug application (NDA) 204-516, paroxetine mesylate capsules for treatment of vasomotor symptoms associated with menopause. March 4, 2013. http://www.citizen.org/documents/2100.pdf. Accessed December 5, 2019.
[7] Food and Drug Administration. Summary minutes of the meeting of the Advisory Committee for Reproductive Health Drugs. March 4, 2013. https://wayback.archive-it.org/7993/20170404150004/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM350729.pdf. Accessed December 5, 2019.
[8] National Institute on Aging. Hot Flashes: What Can I Do? June 26, 2017. https://www.nia.nih.gov/health/hot-flashes-what-can-i-do. Accessed December 5, 2019.
[9] Stuenkel CA, Manson JE, Pal L. A decade after the Women’s Health Initiative – the experts do agree. Menopause. 2012; 19(8):846-847.
