The efficacy of the 100-mg dosage was confirmed in a second study that included 484 women who were randomized to either 100 mg or 150 mg desvenlafaxine daily or placebo, and were treated for 26 weeks. Again, the primary efficacy end points were measured after 12 weeks of treatment. The data from this second study were presented in a combined analysis with data from the first study, so that the total group included 843 women: 307 who received 100 mg/day desvenlafaxine, 281 who received 150 mg/day, and 255 who received placebo.
The findings for number and severity of daily hot flashes and number of nighttime awakenings were similar to the results from the first study. The analysis also included a more detailed look at the effect of treatment on sleep. Women who received either the 100- or 150-mg dosage had significant increases in the number of minutes slept and in their self-reported sleep quality, compared with placebo patients, reported Dr. Olivier, senior director for clinical research and development at Wyeth.
This report also included data on mood, based on the Profile of Mood States (POMS) questionnaire. The lower the POMS score, the better a person's mood; a normal score is about 20 points or lower. At baseline, the women in the combined study had an average score of about 27.
After 12 weeks of treatment, the POMS scores had dropped by an average of about 19 points in the women treated with desvenlafaxine, compared with an average fall of about 12 points among women in the placebo group, a statistically significant difference.
The ability of desvenlafaxine treatment to improve the POMS score is likely due to both a direct antidepressant effect of the drug and to a secondary effect mediated by reduced vasomotor symptoms and improved sleep quality, Dr. Olivier said.
The third study involved 508 women who were randomized to daily treatment with 100 mg desvenlafaxine, 2.5 mg tibolone, or placebo and were treated for 12 weeks. Tibolone (Xyvion), a synthetic hormone that is a selective estrogen-receptor modulator, is not approved for use in the United States but is approved for use in Europe and elsewhere. In this study, the 100-mg dosage of desvenlafaxine was not significantly different from placebo for reducing the frequency and severity of hot flashes and nighttime awakenings, and this dosage of desvenlafaxine was significantly worse than tibolone.
“As expected, tibolone was much more effective than the SNRI” for relieving vasomotor symptoms, Dr. Olivier said.
But in an analysis that combined the efficacy data collected in all three studies, the 100-mg/day and 150-mg/day dosages were each significantly better than placebo for reducing vasomotor symptoms. In addition, treatment with these dosages of desvenlafaxine produced the full treatment effect within 7 days of the start of treatment. In contrast, in the placebo group, the full effect of treatment was not seen until 4 weeks had elapsed.
The safety analysis involved a total of 1,131 patients treated with desvenlafaxine, including 495 treated for at least 12 weeks with the 100-mg/day dosage and 336 women treated with 150 mg/day. This analysis included 612 women assigned to treatment with desvenlafaxine for 52 weeks, including 155 women on 100 mg/day and 157 assigned to 150 mg/day.
The results showed that desvenlafaxine was generally safe and well tolerated, with an adverse effect profile similar to those of other SNRIs. The most common adverse events reported with desvenlafaxine were dizziness, headache, and nausea. Discontinuation related to adverse events occurred in 48% of the desvenlafaxine patients, compared with 25% of the placebo patients.
The safety analysis included a detailed assessment of the effect of desvenlafaxine on sexual function in the 689 women assigned to treatment for 52 weeks. Sexual function was scored for arousal, desire, orgasm, and an overall measure; there was no statistically significant change in any of these measures, compared with placebo, Dr. Gass reported. Similar findings were made in a subgroup of 348 women who reported being sexually active before and during the study.
In addition, individual episodes of sexual dysfunction–abnormal orgasm, decreased libido, abnormal sexual function, or anorgasmia–were tallied for each of the treatment groups in this study. There was a suggestion of a dose-dependent relationship in the overall incidence of these events. (See box at left.) However, the rate of events in each treatment group was not significantly different from that in the placebo group, and there was no statistically significant trend in the dose-related incidence of these events. The rate in the women taking 100 mg/day desvenlafaxine was 3.9%, compared with 1.3% in the placebo group, Dr. Gass said.