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Post hoc analysis of the efficacy and safety of desvenlafaxine 50 mg/day in a randomized, placebo-controlled study of perimenopausal and postmenopausal women with major depressive disorder

Kornstein, Susan G. MD1; Clayton, Anita MD2; Bao, Weihang PhD3; Guico-Pabia, Christine J. MD, MBA, MPH3

Menopause:
doi: 10.1097/GME.0000000000000178
Original Articles
Editorial
Abstract

Objective: This post hoc analysis assessed the efficacy of desvenlafaxine 50 mg/day for treating major depressive disorder in perimenopausal versus postmenopausal women enrolled in a 10-week, double-blind, placebo-controlled study.

Methods: Perimenopausal and postmenopausal women (40-70 y) diagnosed with major depressive disorder were randomly assigned to receive desvenlafaxine 50 mg/day or placebo. Changes from baseline in the primary efficacy variable (17-item Hamilton Rating Scale for Depression [HAM-D17] score, week 8) and in other secondary efficacy variables (Sheehan Disability Scale and Menopause Rating Scale) were analyzed using analysis of covariance with treatment, region, and baseline in the model. Clinical Global Impressions—Improvement Scale was analyzed with the Cochran-Mantel-Haenszel test. Response and remission rates were evaluated using logistic regression with treatment, region, and baseline HAM-D17 in the model.

Results: Of 426 women (desvenlafaxine, n = 216; placebo, n = 210) included in this analysis, 135 (32%) were perimenopausal and 291 (68%) were postmenopausal at baseline. In both subgroups, improvement from baseline in HAM-D17 scores was significantly greater for desvenlafaxine 50 mg/day than for placebo. Menopause status and time since menopause did not significantly affect HAM-D17 total score. The drug-placebo difference in Sheehan Disability Scale scores was significant in perimenopausal women (−9.3 vs −5.1, P < 0.001) but not in postmenopausal women (−8.8 vs −8.1). Menopause Rating Scale and Clinical Global Impressions—Improvement Scale scores were significantly improved with desvenlafaxine in postmenopausal women.

Conclusions: Desvenlafaxine 50 mg/day is effective in treating depression in both perimenopausal and postmenopausal women. Placebo response on measures of functional impairment is lower in perimenopausal women than in postmenopausal women, resulting in a greater apparent treatment benefit with desvenlafaxine among perimenopausal women.

Author Information

From the 1Institute for Women’s Health, Virginia Commonwealth University, Richmond, VA; 2University of Virginia, Charlottesville, VA; and 3Pfizer Inc, Collegeville, PA.

Received March 22, 2013; revised and accepted October 31, 2013.

In September 2011, Pfizer received a Complete Response Letter from the US Food and Drug Administration on its application for approval to market desvenlafaxine for the treatment of moderate to severe vasomotor symptoms associated with menopause. The Complete Response Letter states that the data included in the application are not sufficient to establish an acceptable risk/benefit profile for the treatment of vasomotor symptoms in the general population of postmenopausal women and that, therefore, desvenlafaxine is not approved for the treatment of vasomotor symptoms in the United States at this time. This decision does not impact desvenlafaxine’s approval for the treatment of major depressive disorder in adults.

Funding/support: This study was sponsored by Pfizer. Medical writing support was provided by Ann Sherwood, PhD, of Peloton Advantage and was funded by Pfizer.

Financial disclosure/conflicts of interest: C.J.G.-P. was a Pfizer employee at the time this study was conducted. A.C. has received grants from Biosante Pharmaceuticals, Palatin Technologies, Pfizer, and Takeda; has served as advisory board member/consultant for Bayer, Dey Pharma, Eli Lilly, Euthymics, Forest, GlaxoSmithKline, Palatin Technologies, Pfizer, Takeda, and Valeant; and has received royalties for and has copyright to Changes in Sexual Functioning Questionnaire by Guilford Publications. S.G.K. has received research support from Pfizer, Bristol-Myers Squibb, Otsuka, Euthymics, Rexahn, Lilly, Boehringer-Ingelheim, and Forest, and has served as consultant for Pfizer, Bristol-Myers Squibb, Lilly, Takeda, Trovis, Rexahn, Dey Pharma, and PGx Health. W.B. is a Pfizer employee.

Address correspondence to: Susan G. Kornstein, MD, Institute for VCU Women’s Health, Virginia Commonwealth University, PO Box 980319, Richmond, VA 23298-0319. E-mail: skornste@vcu.edu

© 2014 by The North American Menopause Society.