March 10, 2008 — Gabapentin at 900 mg/day was effective in treating hot flashes, according to the results of a randomized, double-blind, controlled trial published in the March issue of Menopause.

"Gabapentin, a γ-aminobutyric acid, has been shown to reduce hot flashes in breast cancer patients, in women with chemically and/or surgically induced menopause, and in a small sample of women in natural menopause," write Debra A. Butt, MSc, MD, CCFP, from the University of Toronto in Toronto, Ontario, Canada, and colleagues. "Despite the promising evidence, gabapentin has not been adequately studied in postmenopausal women who enter menopause naturally."

The goal of this study was to compare the effectiveness and tolerability of gabapentin vs placebo for the treatment of hot flashes in women who enter menopause naturally.

Between March 2004 and April 2006, this study took place in the community and primary care settings across the Greater Toronto Area. Eligibility criteria were natural menopause, ages 45 to 65 years, with at least 14 hot flashes per week.

Of 200 eligible women, 197 were randomized to receive gabapentin 300-mg oral capsules or placebo 3 times daily for 4 weeks, and 193 (98%) completed the study. The main endpoint was the mean percentage change from baseline to week 4 in daily hot flash score, which was calculated from the participants' diaries. Secondary endpoints included changes in weekly mean hot flash scores and frequencies, quality of life, and adverse events. Analysis was by intent-to-treat.

From baseline to week 4, hot flash scores decreased by 51% (95% confidence interval [CI],
43% - 58%) in the gabapentin group and by 26% (95% CI, 18% - 35%) in the placebo group
(P < .001). In the gabapentin group, the Menopause-Specific Quality-of-Life vasomotor score decreased by 1.7 (95% CI, 1.3 - 2.1; P < .001).

Compared with the placebo group, the gabapentin group had a higher proportion of women who reported dizziness (18%), unsteadiness (14%), and drowsiness (12%) at week 1, but these symptoms decreased by week 2 and returned to baseline by week 4.

"Gabapentin at 900 mg/day is an effective and well-tolerated treatment for hot flashes," the study authors write.

Limitations of the study include lack of data beyond treatment week 4; dosage data available only for 900 mg/day, although a higher dose might have had a greater benefit in the reduction of hot flashes; and study population highly educated, predominantly white, and not ethnically diverse, limiting generalizability to other populations.

"Gabapentin seems to be an effective treatment for hot flashes with few side effects in women who are moderately affected by such symptoms in the general population," the study authors conclude. "Longer term studies of at least 3 months are needed to determine whether gabapentin continues to have a beneficial effect over a longer period."

The Physicians' Services Incorporated Foundation and the University of Toronto, Faculty of Medicine Dean's Fund funded this study. Pfizer, Inc, donated the gabapentin capsules. The study authors have disclosed no relevant financial relationships.

Menopause. 2008;15:310-318.

Clinical Context

Study Highlights

• The objective of this study was to compare the effectiveness and tolerability of gabapentin vs placebo for the treatment of hot flashes in women who enter menopause naturally.
• Between March 2004 and April 2006, this study was conducted in the community and in primary care settings across the Greater Toronto Area.
• Eligible women were in natural menopause, aged 45 to 65 years, with at least 14 hot flashes per week.
• Of 200 eligible women, 197 were randomized to receive gabapentin 300-mg oral capsules or placebo 3 times daily for 4 weeks, and 193 (98%) completed the study.
• The main endpoint was the mean percentage change from baseline to week 4 in daily hot flash score, which was calculated from the participants' diaries.
• Secondary endpoints included changes in weekly mean hot flash scores and frequencies, quality of life, and adverse events.
• Analysis was by intent-to-treat.
• From baseline to week 4, hot flash scores decreased by 51% (95% CI, 43% - 58%) with the gabapentin group and by 26% (95% CI, 18% - 35%) with the placebo group (P < .001).
• The frequency of hot flashes was an average of 8.5 per day at baseline, which decreased by week 4 to 4.5 per day with gabapentin vs 6.5 per day with placebo.
• Analysis of the change in hot flash scores from baseline during each week of the study showed a rapid onset of action of gabapentin that was statistically significant in the first week and was maintained for 4 weeks.
• In the gabapentin group, the Menopause-Specific Quality-of-Life vasomotor score decreased by 1.7 (95% CI, 1.3 - 2.1; P < .001).
• Women in the gabapentin group experienced an improved quality of life after 4 weeks of treatment and said they would recommend this treatment to others.
• Withdrawal rate from the study was 10%, primarily because of dizziness (18% in the gabapentin group at week 1).
• Most withdrawals (10/14) occurred in the first week.
• Compared with the placebo group, the gabapentin group also had a higher proportion of women who reported unsteadiness (14%) and drowsiness (12%) at week 1.
• All adverse effects decreased by week 2 and returned to baseline by week 4.
• Based on these findings, the investigators concluded that gabapentin at 900 mg/day was an effective and well-tolerated treatment of hot flashes in women who entered menopause naturally.
• They also suggest that women who can tolerate the initiation of gabapentin would note a reduction in adverse effects after the first week. A lower initial dose and slower rate of titration may improve tolerability.
• Limitations of the study include lack of data beyond week 4; dosage data available only for 900 mg/day, although a higher dose might have had a greater benefit; and study population highly educated and predominantly white, limiting generalizability to other ethnic groups.

Pearls for Practice

• Gabapentin at 900 mg/day was an effective treatment of hot flashes in women who entered menopause naturally. Gabapentin at 900 mg/day was associated with a 51% reduction in hot flash scores from baseline to week 4. The average frequency of hot flashes decreased from 8.5 per day at baseline to 4.5 per day with gabapentin by week 4. Gabapentin had rapid onset of action that was evident in the first week and was maintained for 4 weeks.
• Gabapentin at 900 mg/day was a well-tolerated treatment of hot flashes in women who entered menopause naturally. Withdrawal rate from the study was 10%, primarily because of dizziness (18% in the gabapentin group at week 1). Compared with the placebo group, the gabapentin group also had a higher proportion of women who reported unsteadiness and drowsiness at week 1. All adverse effects decreased by week 2 and returned to baseline by week 4.

CME Test