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Sustained efficacy and safety of agomelatine versus placebo over 24 weeks in elderly out-patients suffering from major depressive disorder

Collection

  • Depression and Mood Disorders

Author(s)

Document Type

Published Date

  • 2014

Abstract

  • With an increasingly ageing population, there is a growing need to develop novel ways to treat depression in the elderly. Few published placebo-controlled study results in elderly depressed patients reached a clinical difference of at least 2 points vs placebo on the HAM-D total score, while no positive trial in patients older than 75 years has been published yet [1-3]. The present analysis assesses the 24-week antidepressant efficacy and safety of agomelatine 25-50 mg versus placebo in elderly out-patients suffering from moderate to severe Major Depressive Disorder (MDD). Agomelatine being indicated in patients aged less than 75 years, results in this sub-population are presented. In this phase III, international, randomized, double-blind trial, 222 patients aged of at least 65 years were randomized to receive agomelatine 25-50 mg (n = 151) or placebo (n = 71). Among the 146 patients who entered the 18-week double-blind extension period (109 on agomelatine and 37 on placebo), 116 completed the 24 week treatment period (88 on agomelatine and 28 on placebo). In the FAS (N = 218), the mean HAM-D17 total score significantly decreased from baseline to endpoint with agomelatine (from 26.9+2.8 to 12.3+8.9) vs placebo (from 26.8+3.2 to 15.3+8.9) with a significant difference in favor of agomelatine of 2.90 (SE = 1.20), p = 0.017. In the more severe patients (HAM-D17 total score >25 and CGI-S >5 at baseline), the clinical benefit was reinforced with a significant difference in favor of agomelatine of 3.67 (SE = 1.57), p = 0.022. In patients <75 years (N = 149), the observed difference vs placebo was 3.57 (1.51), p = 0.019. The response rate to treatment (decrease in HAM-D17 total score from baseline of at least 50%) was significantly higher with agomelatine than with placebo: 61% vs 43% respectively in the FAS (p = 0.013), 69% vs 49% respectively in the more severe patients (p = 0.024) and 63% vs 41% in patients <75 years (p = 0.010). More patients were remitters (HAM-D17 total score <7) with agomelatine than with placebo 34% vs 23% respectively in the FAS (NS), 38% vs 24% respectively in the more severe patients (NS) and 40% vs 22% in patients <75 years, p = 0.034. In terms of functional outcome there was a significant improvement in the agomelatine group as compared to placebo with a difference on the SDS total score of: 3.23 (1.15), p = 0.006 in the FAS, 3.43 (1.42), p = 0.021 in the more severe patients and 3.53 (1.42), p = 0.015 in patients <75 years. The most frequent emergent adverse events (in at least 5% of patients) were: somnolence (6.6%), headache (6.0%) and diarrhea (5.3%) on agomelatine, nasopharyngitis (7.0%), headache, dizziness and fatigue (5.6% each) on placebo. Two patients in agomelatine group (1 aged >75 years) with normal liver enzyme values at baseline had potentially clinically significant transaminases increase (>3ULN). All values normalized after agomelatine discontinuation. These results demonstrate the long-term antidepressant efficacy of agomelatine combined with a good tolerability profile and social functioning benefits in elderly MDD patients over 24 weeks
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