Antidepressants as a Treatment for Hot Flashes in Women

Denise R. Kockler; Michelle W. McCarthy


Am J Health Syst Pharm. 2004;61(3) 

In This Article


Although the results of these studies demonstrate that venlafaxine, fluoxetine, and paroxetine reduce hot flashes, significant limitations exist. The total number of unique patients considered evaluable in the venlafaxine, fluoxetine, and paroxetine studies was 219, 66, and 179, respectively. The studies were conducted over short periods with no efficacy information beyond 13 weeks of treatment. The primary study endpoints were based on subjective data; however, use of hot flash diaries has been validated in the medical literature.[25] In addition, results for some of the secondary endpoints were not described in the published articles, and none of the authors reported the rate of compliance.

Because of the serious adverse events associated with long-term hormone therapy and general contraindications for use in certain patients, other nonhormonal agents are needed for the management of hot flashes. Results of clinical trials report that venlafaxine, fluoxetine, and paroxetine reduce the frequency (mean reduction, 50-67%) and severity of hot flashes, although the reductions are not as great as those observed with estrogen therapy. These antidepressants were generally well tolerated, with the primary adverse events being dry mouth, constipation, decreased appetite, and nausea. Dosages lower than those commonly used to treat depression were evaluated in clinical trials. For example, venlafaxine therapy was initiated at 37.5 mg daily and adjusted to 75 mg daily, as necessary. The lack of additional benefit does not warrant the significant increase in adverse events observed with daily venlafaxine doses greater than 75 mg. Agent selection should be based on tolerability and the slight differences in adverse-effect profiles. Venlafaxine has been studied in more patients than fluoxetine and paroxetine, and efficacy and safety data are available for 13 weeks of venlafaxine treatment compared with 5 and 6 weeks for fluoxetine and paroxetine, respectively.


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