Research
General gynecology
Desvenlafaxine for the treatment of vasomotor symptoms associated with menopause: a double-blind, randomized, placebo-controlled trial of efficacy and safety

Presented at the 55th Annual Clinical Meeting of the American College of Obstetricians and Gynecologists, San Diego, CA, May 5-9, 2007; the 63rd Annual Clinical Meeting of the Society of Obstetricians and Gynecologists of Canada, Ottawa, ON, Canada, June 21-26, 2007; the 5th Latin American Congress on Climacteric and Menopause, Quito, Ecuador, Oct. 15-19, 2007; the 10th Annual Conference of the National Association of Nurse Practitioners in Women's Health, Philadelphia, PA, Oct. 10-13, 2007; the Annual Meeting of the American College of Clinical Pharmacy, Denver, CO, Oct. 14-17, 2007; and the Fifth Amsterdam Menopause Symposium, Amsterdam, the Netherlands, June 19-21, 2007.
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Objective

The objective of the study was to assess the efficacy and safety of desvenlafaxine (administered as desvenlafaxine succinate) for the treatment of vasomotor symptoms.

Study Design

This was a 26 week, double-blind, placebo-controlled trial of 567 postmenopausal women (mean age, 53.7 years; time since natural menopause, 4.8 years) experiencing 50 or more hot flushes (HFs) per week, randomly assigned to desvenlafaxine (100 or 150 mg) or placebo. Change from baseline in average daily number of moderate to severe HFs and average daily HF severity were compared with placebo at weeks 4, 12, and 26.

Results

A significantly greater decrease from baseline in number of HFs occurred at weeks 4 and 12 with 100 and 150 mg desvenlafaxine compared with placebo (week 12 reductions: 60%, 66%, and 47%, respectively; all P ≤ .002). Only the 150 mg dose showed significant improvement from baseline at 26 weeks compared with placebo (week 26 reductions: 61%, 69%, and 51%, respectively), although the study was not powered to demonstrate efficacy beyond the initial 12 weeks of therapy. The average daily severity decreased significantly more at weeks 4 and 12 with desvenlafaxine compared with placebo (all P ≤ .002). Significantly more desvenlafaxine-treated subjects than placebo-treated subjects discontinued because of adverse events during week 1 only.

Conclusion

Desvenlafaxine is an effective treatment for menopausal HFs.

Section snippets

Materials and Methods

For this registration trial, methods, including inclusion criteria and primary outcome measures, were based on US Food and Drug Administration guidelines and European Medicines Agency guidance for VMS trials.18, 27

Results

From August 2004 through December 2004, 987 women were screened and 567 subjects were randomized in the study (Figure 1). Of those, 484 subjects (85.4%) completed at least 1 on-therapy evaluation for primary efficacy endpoints and were included in the ITT population. Overall, 393 of 484 subjects (81.2%) completed 12 weeks of therapy, and 368 of 484 subjects (76.0%) completed the 26-week study. More desvenlafaxine-treated subjects discontinued from the study compared with placebo (P = .009); the

Comment

The results of this randomized, double-blind, placebo-controlled trial indicate that desvenlafaxine is an effective therapy for moderate to severe VMS associated with menopause. The 100 and 150 mg desvenlafaxine doses significantly reduced the number and severity of HFs when compared with placebo after 4 and 12 weeks of treatment. Statistical separation over placebo was demonstrated as early as the first week of therapy.

Both desvenlafaxine doses achieved significant reductions in the number of

Acknowledgments

A list of the Study 319 investigators is included in an appendix. The authors thank Drs Kathleen Dorries and Mary Hanson for assistance in the preparation of the manuscript.

References (33)

  • Treatment of menopause-associated vasomotor symptoms: position statement of the North American Menopause Society

    Menopause

    (2004)
  • D.C. Deecher

    Physiology of thermoregulatory dysfunction and current approaches to the treatment of vasomotor symptoms

    Expert Opin Investig Drugs

    (2005)
  • G.B. Karkanias et al.

    Estradiol regulation of alpha 1b-adrenoceptor mRNA in female rat hypothalamus-preoptic area

    J Neuroendocrinol

    (1996)
  • C.L. Loprinzi et al.

    Phase III evaluation of fluoxetine for treatment of hot flashes

    J Clin Oncol

    (2002)
  • V. Stearns et al.

    Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial

    JAMA

    (2003)
  • V. Stearns et al.

    Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial

    J Clin Oncol

    (2005)
  • Cited by (0)

    This study was supported in part by Wyeth Research. Dr David Archer is a consultant for Wyeth Research and has received Grants and honoraria from the Wyeth Speakers Bureau. Dr Caroline DuPont participated in a Wyeth Consultant Board meeting in 2006. Drs Ginger Constantine, James Pickar, and Sophie Olivier are employed by Wyeth Research. The research described in this manuscript was supported by Wyeth Research.

    Cite this article as: Archer DF, Dupont CM, Constantine GD, et al. Desvenlafaxine for the treatment of vasomotor symptoms associated with menopause: a double-blind, randomized, placebo-controlled trial of efficacy and safety. Am J Obstet Gynecol 2009;200:238.e1-238.e10.

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