Certain Antidepressants Taken for Hot Flashes Linked to Higher Risk of Breaking a Bone

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Many women use a low dose of an antidepressant medicine to ease the frequency and severity of hot flashes and night sweats. These medicines work by rebalancing or intercepting chemicals in the brain that transmit the hot flash alarm: epinephrine and serotonin. Studies have shown that antidepressants lead to a 50-60% reduction in hot flashes among women who use them.

In 2013, the U.S. Food and Drug Administration (FDA) approved a low-dose formula of the SSRI antidepressant Paxil (chemical name: paroxetine), under the brand name Brisdelle, to treat hot flashes.

There are two types of antidepressant medicines:

  • SSRIs: selective serotonin reuptake inhibitors
  • SNRIs: serotonin and norepinephrine reuptake inhibitors

A study suggests that SSRI antidepressants may be linked to a higher risk of breaking a bone in women taking the medicines to ease hot flashes.

The research was published online on June 25, 2015 by the journal Injury Prevention. Read “SSRI use and risk of fractures among perimenopausal women without mental disorders.”

Some common SSRIs used to treat hot flashes and night sweats are:

  • Celexa (chemical name: citalopram)
  • Lexapro (chemical name: escitalopram)
  • Prozac (chemical name: fluoxetine)
  • Brisdelle and Paxil

SSRIs are used to treat a number of conditions other than depression, including irritable bowel syndrome and premature ejaculation, as well as hot flashes. SSRIs are now the third most commonly prescribed class of medicines in the United States.

In this study, the researchers looked at the records of 137,031 women ages 40 to 64 who started taking an SSRI antidepressant between 1998 and 2010. The women had not been diagnosed with depression or other mental health disorder. It’s not clear if any of the women had been diagnosed with breast cancer.

The information came from the PharMetrics Claims Database. This database contains information on 61 million people who are enrolled in 98 managed health care plans in the United States.

The SSRIs the women in the study took included Celexa, Lexapro, Prozac, Brisdelle, and Paxil.

The researchers compared the women taking the SSRIs to 236,294 women of similar ages taking H2 antagonists or proton pump inhibitor medicines during the same time period.

Both H2 antagonists and proton pump inhibitors reduce the production of stomach acid and are used to treat gastroesophageal reflux disease (GERD), also called acid reflux, and ulcers. Common H2 antagonists are Tagamet (chemical name: cimetidine), Pepcid (chemical name: famotidine), and Zantac (chemical name: ranitidine). Common proton pump inhibitors are Prilosec (chemical name: omeprazole), Prevacid (chemical name: lansoprazole), and Nexium (chemical name: esomeprazole).

The H2 antagonists and proton pump inhibitors the women in the study took included Tagamet, Nexiuim, Prevacid, and Zantac.

After the first year of treatment, the women taking an SSRI were 76% more likely to break a bone than women on an H2 antagonist or proton pump inhibitor. This higher risk lasted for at least 5 years after the women started taking an SSRI. Compared to women taking an H2 antagonist or proton pump inhibitor, women taking an SSRI were:

  • 73% more likely to break a bone 2 years after starting treatment
  • 67% more likely to break a bone 5 years after starting treatment

"To our knowledge, the current study is the first to examine whether SSRI use is related to fracture risks in a population of middle-aged women without known psychiatric disorders, a demographic for which, given the recent FDA approval of paroxetine [Brisdelle] for the treatment of VMS (vasomotor menopausal symptoms), SSRI use may increase," the researchers wrote.

It’s not clear why the women taking an SSRI had a higher risk of breaking a bone.

But the researchers suggested that SSRI antidepressants may make it more likely that bones will start to become weaker rather than stronger. Other studies have found that people taking an SSRI for a mental health disorder are also more likely to break a bone than people not taking an SSRI.

The researchers also suggested that more studies be done to see if taking an SSRI for a shorter period of time would help decrease the risk of breaking a bone.

While this study is concerning, there are several things to keep in mind:

  • Though the increase in risk of breaking a bone seems very large, the actual number of women taking an SSRI who broke a bone was relatively small (about 2%).
  • Many of the women were taking other medicines besides SSRIs that could have affected their bone density and risk of breaking a bone. The researchers did not account for these other medicines.
  • The researchers also didn’t take into account the different doses of SSRIs the women were taking.
  • It’s also not clear if the women in the study who had osteoporosis were being treated for it.

If you’re having troublesome hot flashes because of menopause or breast cancer treatment, talk to your doctor about all your options to ease them and ask whether an SSRI antidepressant makes sense for you.

Some antidepressants may cause problems for women taking tamoxifen. An enzyme called CYP2D6 helps tamoxifen work in the body. Some research has shown that women with an abnormal gene that blocks their bodies’ ability to produce CYP2D6 don’t get the same benefits from tamoxifen as women who produce CYP2D6. Other research has shown that some medicines -- including Paxil and Prozac -- can interfere with how CYP2D6 works and might reduce tamoxifen’s effectiveness against breast cancer. Still, the subject is controversial and not all experts agree that a lack of CYP2D6 or taking an antidepressant reduces tamoxifen’s effectiveness.

There are also non-medicinal treatments that have helped many women ease hot flashes, including:

  • yoga
  • massage
  • meditation
  • avoiding caffeine, alcohol, and cigarettes
  • eating a low-fat diet
  • acupuncture

Visit the Breastcancer.org Menopause Symptoms: Hot Flashes section to learn more about hot flashes and how to manage them.



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