title: A placebo-controlled study of three agomelatine dose regimens (10 mg, 25 mg, 25-50 mg) in patients with major depressive disorder.
abstract: A randomised placebo-controlled "dose relation study" was conducted in 549 patients who met the criteria for major depressive disorder, to evaluate the efficacy and safety of three doses regimens of agomelatine during 6 weeks: low fixed dosage (10 mg/day, n=133), fixed dosage (25 mg/day, n=138) and a flexible dosage with up-titration in case of insufficient improvement at week 2 (25-50 mg/day, n=137). At last post-baseline assessment, there were significant and incremental placebo-agomelatine differences on mean HAM-D₁₇ total scores in favour of each agomelatine dose regimen (2.46 ± 0.76 points, p=0.001 at 10 mg; 4.71+0.75 points, p<0.0001 at 25 mg and 4.92 ± 0.76 points, p<0.0001 at 25-50 mg) with statistically significant differences between 25 mg and 25-50 mg dose regimens compared to the 10 mg dose. The response rate according to HAM-D₁₇ was significantly higher in patients taking agomelatine than those taking placebo (difference of 16.1% at 10 mg p=0.005; 25.9% and 27.4% respectively at 25 mg and 25-50 mg, p<0.0001). The benefit of agomelatine was demonstrated in the subgroup of severely depressed patients in the 25 mg and 25-50 mg/day regimens. Consistent clinical response according to CGI variables and better social functioning were found in patients receiving agomelatine. All dose regimens of agomelatine were well tolerated and no unexpected adverse event was reported. This study provides evidence of a dose effect for agomelatine between 10 mg and the therapeutic dose regimen of agomelatine 25-50 mg: the efficacy of the higher dose regimens being more efficacious than the lowest (10 mg) daily dose. The data support a definitive statement regarding the utility of 25 mg as the threshold dose for initiating agomelatine in depressed patients.
authors: University of Toronto, University Health Network, Canada. Electronic address: Sidney.Kennedy@uhn.ca.
authors: Sidney H
authors: SH
authors: Kennedy
authors: Serbsky State Scientific Center of Social and Forensic Psychiatry, Russia.
authors: Alla
authors: A
authors: Avedisova
authors: Institut de Recherches Internationales Servier (IRIS), 50 rue Carnot, 92284 Suresnes Cedex, France.
authors: Natalia
authors: N
authors: Giménez-Montesinos
authors: Institut de Recherches Internationales Servier (IRIS), 50 rue Carnot, 92284 Suresnes Cedex, France.
authors: Carole
authors: C
authors: Belaïdi
authors: Institut de Recherches Internationales Servier (IRIS), 50 rue Carnot, 92284 Suresnes Cedex, France.
authors: Christian
authors: C
authors: de Bodinat
mesh_terms: D000081:Acetamides / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D011569:Psychiatric Status Rating Scales; D044122:Receptor, Melatonin, MT1 / Q000819:agonists; D044123:Receptor, Melatonin, MT2 / Q000819:agonists; D044405:Receptor, Serotonin, 5-HT2C / Q000737:chemistry; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D012720:Severity of Illness Index; D055815:Young Adult; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D044405:Receptor, Serotonin, 5-HT2C; D058830:Serotonin 5-HT2 Receptor Antagonists; C084711:agomelatine; D009281:Naphthalenes
keywords: Agomelatine; Depression; Dose regimen; Placebo