NATIONAL HARBOR, MD. – Extended-release gabapentin at daily doses of either 1,200 mg or 1,800 mg significantly reduced the number and severity of hot flashes and significantly improved sleep problems, compared with a placebo, in postmenopausal women.
Currently, hormone therapy is the only approved treatment for hot flashes in North America and Europe, according to Dr. Mira Baron of Rapid Medical Research Inc., Cleveland, and colleagues.
In previous studies, gabapentin has shown effectiveness in reducing the frequency and severity of hot flashes, but its short half-life may limit its usefulness, the researchers said. However, an extended-release, once-daily dose of gabapentin was approved by the U.S. Food and Drug Administration in February 2011 to treat postherpetic neuralgia, she said at the annual meeting of the North American Menopause Society.
In Breeze 2, a phase III, double-blind, placebo-controlled trial conducted at 45 sites in the United States, Dr. Baron and colleagues compared the effectiveness of 1,200 mg of extended-release gabapentin once daily vs. 1,800 mg twice daily (600 mg in the morning and 1,200 mg at night) on the frequency and severity of hot flashes.
A total of 559 women completed 12 weeks of treatment and were included in the intent-to-treat population; 190 were randomized to once-daily treatment, 186 were randomized to twice-daily treatment, and 183 were randomized to a placebo. Participants used an electronic diary to record the frequency and severity of their hot flashes during the study.
The average age of the patients was 53 years, and the mean age at menopause was 44 years. The eligible participants reported at least seven moderate to severe hot flashes per day during a 1-week baseline period before they started the study.
Overall, the median daily number of hot flashes dropped significantly after 12 weeks of treatment in both treatment groups, compared with the placebo group. The number of daily hot flashes dropped to three in the placebo group and to two in the two treatment groups.
In addition, the severity of the hot flashes decreased significantly from baseline in both treatment groups, compared with the placebo group. The mean change in vasomotor severity score, compared with baseline, was –0.9 in the once-daily group, –0.8 in the twice-daily group, and –0.6 in the placebo group. The reduction in the severity of vasomotor symptoms was significant for both treatment doses, compared with the placebo. "However, the 1,800-mg dosage yielded more significant changes than the 1,200-mg dosage," the researchers noted.
In a second study, Dr. Risa Kagan of the Alta Bates Summit Medical Center in Berkeley, Calif., and colleagues studied the effectiveness of extended-release gabapentin on improving the sleep problems commonly reported by postmenopausal women.
The researchers compared the effects of extended-release gabapentin vs. a placebo on sleep problems in postmenopausal women using data from the Breeze 1 study, which was a phase III, double-blind, placebo-controlled trial conducted at 48 sites in the United States. A total of 531 women made up the intent-to-treat population, and they were randomized to gabapentin 1,200 mg once daily, to 1,800 mg twice daily (600 mg in the morning and 1,200 mg at night), or to a placebo.
Overall, global scores on the PSQI (Pittsburgh Sleep Quality Index) improved significantly with both gabapentin doses, compared with the placebo, at three separate time points.
After 4 weeks, the mean difference in the global PSQI scores was –1.74 in the once-daily group and –1.68 in the twice-daily group. After 12 weeks, the mean differences in the global PSQI scores for the two treatment groups, compared with placebo, were –1.16 and –0.80, respectively. After 24 weeks, the mean differences in the global PSQI scores for the two treatment groups, compared with placebo, were –0.77 and –0.93, respectively.
"The largest differences between the active arms and the placebo arm were observed at week 4," the researchers said. "The decrease in the magnitude of improvement over time likely resulted from the fact that the PSQI instrument requests reporting for the previous 4 weeks." However, the global scores did improve throughout the study, they noted.
No significant difference in daytime dysfunction scores was observed between either of the treatment groups and the placebo group.
Although the drug is not currently approved for this indication, the findings suggest that extended-release gabapentin might have potential as a treatment option for hot flashes and sleep disturbances in postmenopausal women who are reluctant to use hormonal therapies, the researchers said.
The studies were supported by Depomed. Dr. Baron had no personal financial conflicts to disclose. One of the study coauthors on her study is an employee of Depomed. Dr. Kagan disclosed serving as a consultant or advisory board member for multiple companies, including Amgen, Bionovo, Depomed, Merck, Pfizer, and Shionogi. She disclosed receiving research support from Bionovo, BioSante Pharmaceuticals, Boehringer-Ingelheim, Depomed, and Pfizer, and serving on the speakers bureau for Amgen, Novogyne, and Novo Nordisk.