by Charles Bankhead
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 midrange 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 to 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.
Charles Bankhead is a MedPage Today staff writer.
Originally published in MedPage Today. Visit MedPageToday.com for more oncology news.