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SSRI Slashes Hot-Flash Rate

2010-05-27T09:29:03-04:00
Charles Bankhead

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SSRI Slashes Hot-Flash Rate

The study reviewed here suggests that the antidepressant medicine Celexa (chemical name: citalopram) can lower the number and severity of hot flashes in post-menopausal women.

In this study, 254 post-menopausal women -- none of whom had been diagnosed with breast cancer -- who were having at least 14 hot flashes per week for a month or longer were split into four groups:

  • the first group got 10 milligrams of Celexa each day
  • the second group got 20 milligrams of Celexa each day
  • the third group got 30 milligrams of Celexa each day
  • the fourth group got a placebo (sugar pill) each day

All of the women recorded the frequency and severity of their hot flashes before treatment and 6 weeks after the study started.

The women who were taking Celexa had a greater decrease in the frequency and the severity of hot flashes after 6 weeks of treatment compared to women taking the placebo.

All the women were having about eight or nine hot flashes each day before the study started. The number of hot flashes decreased between 43% and 55% in women who took Celexa for 6 weeks. Women who were taking the highest dose of Celexa (30 milligrams) had the largest decrease in hot flashes. The number of hot flashes also decreased in women taking the placebo, but by only 20%.

Before the study started, the women rated the severity of the hot flashes using a hot flash score. The average hot flash score was:

  • about 14 to 17 among the women who would get a dose of Celexa
  • 12 among the women who would get the placebo

After taking Celexa for 6 weeks, hot flash scores decreased an average of 49% to 55%. The decrease in hot flash scores was greater for women who were taking the highest dose of Celexa. Hot flash scores dropped by an average of 23% in women who took the placebo for 6 weeks.

Although this study looked at women who weren't diagnosed with breast cancer, many post-menopausal women who have been diagnosed with breast cancer have hot flashes, particularly as a hormonal therapy side effect. For some of these women, the hot flashes may be affecting their quality of life so much that they and their doctors are considering medicine to treat the hot flashes.

Research has shown that other antidepressant medicines can help ease hot flashes, including:

  • SSRI (serotonin-specific reuptake inhibitor) antidepressants
    • Prozac (chemical name: fluoxetine)
    • Paxil (chemical name: paroxitene)
  • SNRI (serotonin-norepinephrine reuptake inhibitor) antidepressants
    • Effexor (chemical name: venlafaxine)

Still, taking one of these medicines while you're taking tamoxifen can interfere with the benefits of tamoxifen. Tamoxifen often causes bothersome hot flashes as a treatment side effect.

Tamoxifen is used to:

  • reduce breast cancer risk in women who haven't been diagnosed but are at higher-than-average risk for disease
  • lower the risk of breast cancer coming back (recurrence) in women diagnosed with early-stage, hormone-receptor-positive breast cancer
  • treat advanced-stage, hormone-receptor-positive breast cancer

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 the antidepressants listed above, interfere with how CYP2D6 works and reduce tamoxifen's effectiveness against breast cancer.

Celexa is an SSRI antidepressant, but unlike other SSRIs such as Prozac and Paxil, Celexa does NOT interfere with CYP2D6 and may be a better choice to treat hot flashes in women taking tamoxifen. Celexa also seems to have two other advantages over other possible antidepressant treatments for hot flashes:

  • Celexa only has to be taken once a day (by mouth).
  • Celexa is available as a generic medicine, which could mean lower cost.

If you're a post-menopausal woman having troublesome hot flashes because of breast cancer treatment, you might want to ask your doctor about hot flash treatment options and if a medicine such as Celexa makes sense for you. There are other non-prescription techniques you can try to help avoid and ease hot flashes. Visit the Breastcancer.org Hot Flashes page in the Treatment Side Effects section to learn more about hot flashes and how to manage them.

More Research News on Menopause (9 Articles)

(MedPage Today) -- Hot-flash frequency and severity declined by 50% in postmenopausal women treated for six weeks with the antidepressant citalopram, according to data from a placebo-controlled, randomized clinical trial.

The trial, conducted among 254 women with frequent hot flashes (at least 14 hot flashes a week for a month or longer) found that the lowest of three citalopram doses was as effective as the highest for dousing hot flashes, but the mid-range dose appeared to have broader activity against symptoms, according to an article published online in the Journal of Clinical Oncology.

Citalopram's effects on hot flashes is not unique; a number of antidepressants in the selective serotonin reuptake inhibitor (SSRI) class have been shown to reduce hot flashes. However, citalopram may offer advantages over other SSRIs.

"Citalopram, unlike paroxetine, can be given with tamoxifen," Debra L. Barton, RN, PhD, of the Mayo Clinic in Rochester, Minn., and colleagues wrote. As little as 10 mg/d of citalopram is needed for a 46% reduction in daily frequency of hot flashes.

"This, coupled with the minimal adverse effect profile at this dose, makes this particularly useful for women who have difficulty taking pharmacologic agents and appears to be more tolerable than either gabapentin or pregabalin," the authors noted.

Citalopram is also only taken once per day and is available generically. "Therefore, it has the dosing advantage of venlafaxine, extended release, without the cost," they added.

Up to 75% of women may experience hot flashes, a vasomotor symptom associated with menopause and breast cancer treatments (either tamoxifen or aromatase inhibitors), which can negatively impact quality of life. The physiology is not definitively understood and hot flashes can vary considerably in frequency, severity, and persistence. In some women, hot flashes resolve within two years but for others symptoms can persist for years, especially in long-term treatment for breast cancer.

Several drugs in the SSRI class have reduced hot flashes by 50% or more in placebo-controlled clinical trials, including paroxetine, fluoxetine, and venlafaxine (Effexor). However, uncertainty surrounding the etiology of hot flashes and how SSRIs act to ameliorate them suggest that the effects cannot be assumed to be a class effect.

For example, clinical trials of the SSRI sertraline have shown more modest reductions in hot flashes. In addition, some doubt persists about serotonergic agents' effect on hot flashes, since not all clinical trials have yielded positive results, the authors noted.

Moreover, certain SSRIs, such as paroxetine and fluoxetine, are potent inhibitors of CYP2D6 and cannot be used to manage tamoxifen-associated hot flashes.

Mixed results have also come from other clinical trials of citalopram to treat hot flashes. In addition, the appropriate dose of the drug for hot-flash prevention has not been determined.

The uncertainty surround use of SSRIs to treat hot flashes, combined with the mixed results with citalopram, provided a rationale to evaluate the antidepressant in a placebo-controlled randomized clinical trial.

The Mayo Clinic investigators enrolled 254 postmenopausal women who were not receiving hormone therapy or cancer treatment and reported at least 14 hot flashes per week for a month or longer. The women were randomized to placebo or to one of three daily doses of citalopram: 10, 20, or 30 mg.

The primary endpoint was the change from baseline to six weeks in hot flash score, as determined by a self-report diary maintained by each patient. Patients recorded and rated the severity of each hot flash on a scale of 1 (mild) to 4 (very severe). Daily scores were added and averaged on a weekly basis.

Investigators also wanted to determine the best dose of citalopram for hot-flash prevention and to evaluate the toxicity of citalopram.

The baseline daily hot flash score averaged 12 in the placebo group and 14 to 17 in the three citalopram groups. After six weeks of treatment, hot flash scores had declined by 23% in the placebo group and by 49%, 50%, and 55% in the women assigned to 10, 20, and 30-mg doses of citalopram, respectively (P≤0.002 versus placebo). Differences between citalopram groups were not significant.

Baseline daily hot-flash frequency averaged 8.0-9.0 across the four groups. At the end of the study, weekly frequency had declined by 20% with placebo and by 43% to 50% in the three citalopram groups.

Secondary endpoints of the trial included the change in scores on scales to assess mood and the degree to which hot flashes interfered with daily activities. The 20-mg dose of citalopram significantly reduced scores on individual components of the scales compared with placebo (P=0.02 to P=0.01). The 10- and 30-mg doses of citalopram had less effect on the scores compared with placebo.

The authors note that one limitation of the study was its limited time period of seven weeks, therefore long-term control of hot flashes or the occurrence of adverse effects with citalopram could not be determined.

The authors reported no disclosures.

Primary source: Journal of Clinical Oncology Source reference: Barton DL et al. "Phase III, placebo-controlled trial of three doses of citalopram for the treatment of hot flashes: NCCTG Trial N05C9" J Clin Oncol 2010; DOI: 10.1200/JCO.2009.26.6379.

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