Midlife Women with Major Depressive Disorder: Effects of Quetiapine Extended-release on Mood, Sleep and Menopause-related Symptoms

Abstract

Background:

Recent studies suggest that the menopausal transition may constitute a period of greater risk for the development of new onset/recurrent depressive episodes. In addition, the presence of vasomotor and other menopause-related complaints may adversely affect quality of life and overall functioning. With the long-term safety of hormone therapies being questioned, non-hormonal strategies are needed for the management of symptomatic midlife women. This report is a preliminary analysis of a study investigating the effects of quetiapine extended-release (Seroquel XR) in symptomatic perimenopausal and postmenopausal women with major depressive disorder (MDD).

Methods:

Peri and postmenopausal women, age 40 to 60 years, suffering from MDD and reporting menopause-related symptoms were recruited into a 2-week, placebo lead-in phase, followed by an open trial (8 weeks) with quetiapine extended-release, flexible dose, 150-300 mg/day. The primary outcome measure (i.e. changes in depressive symptoms) was assessed via Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Other measures included: Hamilton Depression Rating Scale (HAM-D), menopause-related symptoms (Greene Climacteric Scale - GCS), Clinical Global Impression (CGI-S), sleep characteristics (Pittsburgh Sleep Quality Index - PSQI) and the impact of hot flashes on daily functioning (Hot Flash-Related Daily Interference Scale (HFRDIS).

Results:

Thirty-nine women (mean age 49.3±4.3 years) were enrolled in the placebo lead-in phase. Of those, 25 were considered eligible for the 8-week trial with quetiapine extended-release. This interim analysis (LOCF) included 18 women who completed 4 to 8 weeks of treatment with quetiapine extended-release (median MADRS total scores at baseline = 28 ±6.1; median final dose of quetiapine extended-release=200 mg/day). At the end of the study, 13 out of 18 (72.2%) participants achieved remission (total MADRS scores < 10). Overall, subjects showed significant reduction in total MADRS (p< 0.001) and HAM-D scores (p< 0.001). Treatment with quetiapine extended-release improved menopause-related symptoms, as shown by a decrease in Greene Climacteric Scale total scores (p< 0.001) and sub-scores for psychological (p< 0.001), vasomotor (p=0.001), and somatic (p=0.001) complaints (Wilcoxon tests). Quetiapine extended-release did affect menopause-related sexual dysfunction (changes in CGS sexual sub-scores, p=0.06). There was a substantial reduction in overall burden associated with vasomotor symptoms, i.e., decreased HFRDIS scores (p< 0.001). Lastly, sleep efficiency, perceived sleep quality, and daily sleep disturbances improved significantly after treatment with quetiapine extended-release (p< 0.001 for all PSQI sub-scores).

Discussion:

This is the first study examining the efficacy of Seroquel XR for the treatment of Major Depressive Disorder in a population of symptomatic peri and postmenopausal women. Treatment with Seroquel XR not only reduced depressive symptomatology but also improved vasomotor symptoms and sleep complaints. Larger randomized, placebo-controlled studies are warranted to better explore the efficacy and predictors of response with quetiapine extended-release for this specific population.