Efficacy and Safety of Agomelatine vs Paroxetine Hydrochloride in Chinese Han Patients with Major Depressive Disorder: A Multicentre, Double-Blind, Noninferiority, Randomized Controlled Trial.

PURPOSE

The purpose of this study is to investigate the efficacy, safety, and tolerability of agomelatine and paroxetine in Chinese Han patients with major depressive disorder (MDD).

METHODS

A 8-week, double-blind, randomized, parallel study was conducted in 14 medical centers in mainland China from December 2011 to September 2012. A total of 264 subjects with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of MDD were randomly assigned to receive agomelatine 25-50 mg/d (n = 132) or paroxetine 20-40 mg/d (n = 132). The primary efficacy was evaluated by the decrease of Hamilton Depression Rating Scale (HAM-D17) scores. The secondary measurements of efficacy included Hamilton Anxiety Rating Scale, Montgomery-Asberg Depression Rating Scale, Sheehan Disability Scale, Clinical Global Impressions-Severity, and Clinical Global Impressions-Improvement. The laboratory test abnormity, and observed and self-reported adverse events were all assessed as the measurements of safety and tolerability.

RESULTS

Both the agomelatine and paroxetine groups showed significant improvement from baseline to the end point (P < 0.05) without between-group differences (P > 0.05). The mean decrease of HAM-D17 of agomelatine group was not inferior to the paroxetine group over the 8-week treatment (agomelatine 15.26 ± 6.44 vs paroxetine 14.87 ± 5.89, δ = 2.0; μA-μB 95% confidence interval, -1.13 to 1.91). The percentage of responders at the last postbaseline assessment was similar in the 2 groups on both HAM-D17 (agomelatine 66.15% vs paroxetine 63.49%) and Clinical Global Impressions-Improvement (agomelatine 79.09% vs paroxetine 80.36%). The anxiety (Hamilton Anxiety Rating Scale) and sleep symptoms (sleep items of HAM-D17) of the patients were improved significantly in the 2 groups at week 8 without between-group differences (P > 0.05). The incidence of overall adverse events was similar in the 2 groups (agomelatine 49.62% vs paroxetine 56.15%, P > 0.05). The incidence of adverse events in skin and subcutaneous tissue was higher in the paroxetine group than in the agomelatine group (none in agomelatine and 4.62% in paroxetine, P = 0.0144).

CONCLUSIONS

Agomelatine showed equivalent antidepressant efficacy to paroxetine in treating MDD patients after 8 weeks of treatment with an acceptable safety.