May 10, 2007 (San Diego) — Women who cannot or will not take hormone replacement therapy to manage menopausal symptoms may soon have another option.
Several randomized, placebo-controlled, double-blind studies presented here at the 55th annual clinical meeting of the American College of Obstetricians and Gynecologists showed that desvenlaxafine (DVS; Pristiq), a metabolite of the antidepressant venlaxafine (Effexor), relieved vasomotor symptoms of menopause such as hot flashes and night sweats and improved mood and sleep in menopausal women. Like venlaxafine, DVS is a selective serotonin-norepinephrine reuptake inhibitor. The studies were funded by Wyeth, the company that makes both drugs.
Cooling Down Hot FlashesIn one study, 689 women were randomized to receive DVS in a dose of 50, 100, 150, or 200 mg per day, or a placebo, for 52 weeks, for the treatment of vasomotor symptoms. To be included in the study, the women had to be experiencing at least 7 moderate to severe hot flashes per day or 50 per week. Their average age was 53.5 years, and they had an average of 11 hot flashes per day.
At the 3 highest doses, a median 50% reduction in the number of hot flashes was seen in 5 to 7 days compared with 24 days for those receiving placebo. After 4 weeks of treatment, the 100-mg dose elicited a significant decrease in the number of daily hot flashes compared with placebo. At 12 weeks, hot flashes decreased 55% from baseline among women in the 50-mg group, 64% for the 100-mg group, and 60% among women taking 150 and 200 mg, compared with a 50% reduction for women in the placebo group.
The difference in the average number of hot flashes was statistically significant in the 100- and 150-mg groups, compared with placebo, and the reductions observed at 12 weeks persisted throughout the remaining 40 weeks of the study. Women taking 100, 150, and 200 mg per day also reported a significant decrease in the number of nighttime awakenings due to hot flashes compared with placebo. Women in the 50-, 100-, and 200-mg groups also reported a significant decrease in mood disturbances.
The most common adverse effects were nausea, dizziness, insomnia, and somnolence.
A separate analysis of the same study population showed no negative effect of DVS on libido, orgasm, or other components of sexual function.
“This is a major breakthrough for women: the first nonhormonal therapy for menopausal symptoms,” Margery Gass, MD, lead author of both studies, told Medscape. She noted that the nausea lasts an average of 3 days and can be minimized by starting patients on the lowest dose and gradually titrating upward. Dr. Gass, who is director of the Menopause and Osteoporosis Center at University Hospital in Cincinnati, Ohio, added that she hopes the US Food and Drug Administration will approve DVS by July.
Effects on Sleep and MoodA separate paper included a pooled analysis of 843 women randomized to 100 or 150 mg of DVS per day or placebo and examined the effect of DVS on sleep and mood. Each participant completed a profile of mood states (POMS) questionnaire at baseline and 12 weeks. The POMS questionnaire measures 6 dimensions of mood: tension-anxiety, depression-dejection, anger-hostility, vigor-activity, fatigue-inertia, and confusion-bewilderment, with higher scores indicating greater mood disturbance. At baseline, the subjects had an average score of 27.8. The women also kept sleep diaries, recording nighttime awakenings, time to fall asleep, and minutes slept, and rated their sleep quality on a scale of 1 to 5, with 5 being very good.
At 12 weeks, both of the DVS groups reported a significant decrease in nighttime awakenings and an increase of approximately 40 minutes slept per night compared with about 30 minutes more in the placebo group (P < .05). Total POMS scores decreased by a mean of 19.33 points among women in the 100-mg group and 18.64 points among women in the 150-mg group, both significantly more than the 11.87-point decrease observed in the placebo group. No significant differences were seen between doses in any of the parameters studied.
The brightening in mood was most likely a result of the sleep improvements, although it may also reflect a direct effect of DVS on the brain, said lead author David Archer, MD, professor of obstetrics and gynecology at Eastern Virginia Medical School in Norfolk. Like Dr. Gass, he cautioned that hormones are still the most effective treatment for menopausal symptoms, but said that “this is a significant alternative.”
Good candidates for DVS are breast cancer survivors on aromatase inhibitor therapy, who cannot take hormones, said Lila Nachtigall, MD, professor of obstetrics and gynecology at New York University. “Something like this would be perfect for that group,” said Dr. Nachtigall, who was not involved in any of these studies and has no financial interest in the product.
Beyond that, “it’s so good to have more than one drug, because there are women who just won’t take hormones,” Dr. Nachtigall told Medscape. “If DVS helps the hot flashes in that group, that’s a good thing.”
Obstet Gynecol. 2007;109(4[suppl]):75S, 76S, 78S.
Source:
http://www.medscape.com/viewarticle/556290?src=mp
