[Show abstract][Hide abstract] ABSTRACT:
In this 8-week double-blind multicenter trial, we evaluated the efficacy and safety of 2 fixed doses of agomelatine in patients with moderate to severe major depressive disorder. Primary efficacy variable was the change in 17-item Hamilton Depression Rating Scale (HAM-D17) total score from baseline to week 8/end of treatment. Secondary efficacy assessment compared the improvements in clinical response and remission (HAM-D17), Clinical Global Impression--Improvement Score, Clinical Global Impression--Severity Score, Hospital Anxiety and Depression (HAD), sleep (Leeds Sleep Evaluation Questionnaire), disability (Sheehan Disability Scale), and overall Quality of Life in Depression Scale between the agomelatine and placebo groups. Eligible patients (n = 511; baseline mean HAM-D17 score = 27.0) were randomized (1:1:1) to once-daily agomelatine, 25 mg; agomelatine, 50 mg; or placebo. Agomelatine 50 mg provided a statistically significant improvement in HAM-D17 score from first baseline visit through week 8 compared with placebo (week 8 treatment difference, 2.5; P = 0.004), whereas agomelatine 25 mg did not show (P = 0.505) a significant improvement. Treatment differences for all secondary efficacy variables were also statistically significant for agomelatine 50 mg versus placebo: Clinical Global Impression--Improvement (P = 0.012); Clinical Global Impression--Severity difference (P = 0.003); improvement in HAD total score, 2.2 (P = 0.014); patients' ability to get sleep (P < 0.001); quality of sleep (P = 0.002). Both doses of agomelatine were well tolerated relative to placebo. However, clinically notable transient aminotransferase elevations were observed in 4.5% of the patients in the agomelatine 50 mg group. The results showed significant antidepressant efficacy of agomelatine 50 mg/d, including a positive effect on sleep compared with placebo in outpatients with moderate to severe major depressive disorder.
[Show abstract][Hide abstract] ABSTRACT:
To evaluate the efficacy, safety, and tolerability of fixed-dose agomelatine 25 and 50 mg/d in the treatment of outpatients with moderate-to-severe major depressive disorder (MDD) compared to placebo.
In this 8-week, multicenter, double-blind, parallel-group trial, patients with DSM-IV-defined MDD were randomly assigned (1:1:1) to receive a once-daily dose of agomelatine 25 mg, agomelatine 50 mg, or placebo. The primary efficacy measure was the change from baseline to week 8 in the clinician-rated 17-item Hamilton Depression Rating Scale (HDRS(17)); other efficacy measures were the clinical remission and response rates (measured by HDRS(17)), Clinical Global Impressions scales, Hospital Anxiety and Depression Scale (HADS) score, subjective measures on sleep, and the overall quality of life. The study was conducted between December 2006 and January 2008.
Agomelatine 25 mg/d was more efficacious based on the HDRS(17) total score (P = .01) compared to placebo throughout the treatment period, whereas for agomelatine 50 mg/d, statistically significant reduction in HDRS(17) total score could be observed from weeks 2 to 6 but not at week 8 (P = .144). A higher proportion of patients receiving agomelatine 25 mg/d showed clinical response (P = .013), clinical remission (P = .07), and improvement according to the Clinical Global Impressions-Improvement scale (P = .065) compared to those receiving placebo. No statistically significant difference between patients receiving agomelatine 50 mg/d compared to placebo on clinical response (P = .116) or clinical remission (P =. 457) was observed. HADS score, quality of sleep, and quality of life significantly improved with agomelatine 25 mg/d compared to placebo. Both agomelatine doses were safe and well tolerated, although clinically notable aminotransferase elevations were observed transiently in the agomelatine 50 mg/d group.
Agomelatine 25 mg/d was effective in the treatment of patients with moderate-to-severe MDD and was safe and well tolerated. Agomelatine 50 mg/d provided evidence for its antidepressant efficacy until week 6 and was also safe and well tolerated.
clinicaltrials.gov Identifier: NCT00411242.
The Journal of Clinical Psychiatry 03/2010; 71(5):616-26. DOI:10.4088/JCP.09m05471blu · 5.14 Impact Factor