Short-term efficacy and safety of desvenlafaxine in a randomized, placebo-controlled study of perimenopausal and postmenopausal women with major depressive disorder.
BACKGROUND
The risk for major depressive disorder (MDD) increases during the menopausal transition. Nonetheless, no large, placebo-controlled studies have prospectively assessed the efficacy of antidepressants in perimenopausal or postmenopausal women. This randomized, double-blind, placebo-controlled trial evaluated the short-term efficacy and safety of desvenlafaxine (administered as desvenlafaxine succinate) in perimenopausal and postmenopausal women with DSM-IV-defined MDD.


METHODS
387 depressed perimenopausal and postmenopausal women aged 40 to 70 years were randomly assigned to placebo or desvenlafaxine (100 or 200 mg/d at the discretion of the investigator) in an 8-week, flexible-dose trial conducted from September 2006 to June 2008. The primary efficacy variable was change from baseline in 17-item Hamilton Depression Rating Scale (HDRS(17)) total score, analyzed using a mixed-effects model for repeated-measures analysis. Safety data were collected throughout the trial.


RESULTS
The reduction in adjusted HDRS17 total scores from baseline to week 8 (mean daily dose after titration, 162 to 176 mg/d) was significantly greater for desvenlafaxine (-12.64) compared with placebo (-8.33; P < .001). Statistical separation from placebo was observed at week 1 and was sustained through week 8. Both the perimenopausal and postmenopausal subgroups achieved significant reductions in HDRS(17) total scores with desvenlafaxine treatment (perimenopausal, P = .003; postmenopausal, P < .001). Response (58.6%) and remission (38.2%) rates were significantly higher for desvenlafaxine compared with placebo (31.6% [P < .001] and 22.4% [P = .008], respectively). In all, 19/256 (7.4%) desvenlafaxine-treated patients and 4/125 (3.2%) placebo-treated patients discontinued due to adverse events. Treatment-emergent adverse events were reported by 94/125 (75.2%) placebo-treated patients and 218/256 (85.2%) desvenlafaxine-treated patients.


CONCLUSIONS
Short-term treatment with desvenlafaxine was effective and generally well tolerated in perimenopausal and postmenopausal women with MDD.


BACKGROUND
clinicaltrials.gov Identifier: NCT00369343.
Kornstein
Susan G
SG
Department of Psychiatry and Institute for Women's Health, Virginia Commonwealth University, Richmond, VA 23209-0710, USA. skornstein@mcvh-vcu.edu
Jiang
Qin
Q
Reddy
Sujana
S
Musgnung
Jeff J
JJ
Guico-Pabia
Christine J
CJ
D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D003511:Cyclohexanols / Q000009:adverse effects* / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy; D000069468:Desvenlafaxine Succinate; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008297:Male; D008593:Menopause / Q000187:drug effects / Q000523:psychology*; D008875:Middle Aged; D017698:Postmenopause / Q000187:drug effects / Q000523:psychology*; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome
D000928:Antidepressive Agents; D003511:Cyclohexanols; D000069468:Desvenlafaxine Succinate