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When Antidepressants Don’t Relieve Hot Flashes, Gabapentin Might Help

Consider gabapentin when antidepressants aren’t effective in the nonhormonal treatment of vasomotor symptoms.

To address concerns about risks associated with hormone therapy for treating women with menopausal vasomotor symptoms, the focus has shifted to nonhormonal treatments including antidepressants and the anticonvulsant gabapentin (see Journal Watch Women’s Health May 7 2003). For this 5-week trial, investigators randomized 118 women with hot flashes that were inadequately controlled by an antidepressant to receive both the antidepressant and gabapentin or gabapentin alone (after being weaned off the antidepressant). At study entry, about 75% of participants had a history of breast cancer, about two thirds were taking tamoxifen or an aromatase inhibitor, and most were taking venlafaxine or paroxetine.

Women completed baseline vasomotor symptom diaries for 1 week and then received gabapentin (300 mg) at bedtime for 3 days, twice daily for 3 days, and three times daily for 22 days. Those randomized to concurrent antidepressant therapy continued at their present dose; those randomized to discontinue were weaned off their antidepressants over 7 to 10 days. Regardless of whether or not antidepressants were continued, 91 evaluable participants reported about 50% reduction in the frequency of hot flashes at the 4-week assessment. By the end of week 2, women who discontinued antidepressants tended toward negative mood changes and nervousness. Self-reported quality-of-life parameters were similar in both groups throughout the study.

Comment: In the search for nonhormonal treatments for hot flashes, acupuncture, yoga, Chinese herbs, dong quai, evening primrose oil, ginseng, kava, red clover extract, black cohosh, and soy/phytoestrogens have not proved to be reliably more effective than placebo. Similarly, antidepressants have been shown to be either ineffective or inconsistent. In this study, the need for three-times-daily gabapentin administration is a disadvantage. Overall, however, these findings indicate that off-label use of gabapentin might be useful in breast cancer survivors whose vasomotor symptoms are inadequately controlled by an antidepressant. The authors suggest that delaying the discontinuation of the antidepressant might help determine whether the ensuing undesirable mood changes result from antidepressant withdrawal rather than from gabapentin initiation.

— Andrew M. Kaunitz, MD

Published in Journal Watch Women's Health January 18, 2007

Citation(s):

Loprinzi CL et al. Phase III trial of gabapentin alone or in conjunction with an antidepressant in the management of hot flashes in women who have inadequate control with an antidepressant alone: NCCTG N03C5. J Clin Oncol 2006 Dec 4; [Epub ahead of print]. (http://www.jco.org/cgi/doi/10.1200/JCO.2006.07.5390)

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