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Clonidine, gabapentin, and some SSRIs effective for hot flashes.

* Clinical Question

Which nonhormonal therapies are effective in the management of menopausal hot flashes?

* Bottom Line

Evidence supports the nonhormonal treatment of menopausal hot flashes with paroxetine (Paxil), clonidine (Catapres), gabapentin (Neurontin), and soy isoflavone extract. The overall effect size of all nonhormonal treatments is less than that of estrogen. Treatment should be individualized according to symptom severity and risk profiles. (LOE=1a-)

Study Design

Meta-analysis (randomized controlled trials)


Various (meta-analysis)


Recent concerns about adverse effects of hormonal therapy has increased interest in alternative treatments of menopausal hot flashes. These investigators thoroughly searched Medline, The Cochrane Registry, other large databases, reference lists of recent systematic reviews and relevant articles, and they consulted experts. To be included, studies must be English-language randomized double-blind placebo-controlled trials evaluating the treatment of menopausal hot flashes with nonhormonal interventions. Two reviewers independently rated the quality of trials; disagreements were resolved by consensus agreement with a third reviewer. Formal assessment found no evidence of publication bias.

A total of 43 trials met inclusion criteria, including 10 trials of antidepressants, 10 of clonidine, 6 of other prescribed medications, and 17 of isoflavone extracts. Among various antidepressants, high-quality studies supported only the efficacy of paroxetine (Paxil). Of the 10 trials comparing clonidine with placebo, only 3 met criteria for fair quality. Four of the 10 trials reported a reduced hot-flash frequency with clonidine compared with placebo and 6 found no difference, with the overall meta-analysis reporting a small benefit.

The efficacy of clonidine is strongest in women taking tamoxifen for breast cancer. Two fair-quality trials of gabapentin (Neurontin) reported significantly reduced hot-flash frequency compared with placebo. Only 1 of 6 trials of red clover isoflavones reported reduced hot-flash frequency compared with placebo. Soy isoflavones were compared with placebo in 11 trials, mostly of poor quality. Although the results were heterogeneous, overall results showed that soy isoflavone extract was significantly better than placebo.


Among various antidepressants, only paroxetine was shown in high-quality studies to reduce hot flashes

Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies for menopausal hot flashes. Systematic review and meta-analysis. JAMA 2006; 295:2057-2071.

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Article Details
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Author:Nelson, H.D.; Vesco, K.K.; Haney, E.
Publication:Journal of Family Practice
Geographic Code:1USA
Date:Aug 1, 2006
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