Efficacy of the novel antidepressant agomelatine on the circadian rest-activity cycle and depressive and anxiety symptoms in patients with major depressive disorder: a randomized, double-blind comparison with sertraline.
OBJECTIVE
This study evaluates the efficacy of agomelatine, the first antidepressant to be an agonist at MT(1)/MT(2) receptors and an antagonist at 5-HT(2C) receptors, versus sertraline with regard to the amplitude of the circadian rest-activity cycle and depressive and anxiety symptoms in patients with major depressive disorder (MDD).


METHODS
Outpatients with DSM-IV-TR-defined MDD received either agomelatine 25 to 50 mg (n = 154) or sertraline 50 to 100 mg (n = 159) during a 6-week, randomized, double-blind treatment period. The study was conducted from 2005 to 2006. The main outcome measure was the relative amplitude of the individual rest-activity cycles, expressed as change from baseline to week 6 and collected from continuous records using wrist actigraphy and sleep logs. Secondary outcome measures were sleep efficiency and sleep latency, both derived from actigraphy, and efficacy on depression symptoms (17-Item Hamilton Depression Rating Scale total score and Clinical Global Impressions scale scores) and anxiety symptoms (Hamilton Anxiety Rating Scale total score and subscores).


RESULTS
A significant difference in favor of agomelatine compared to sertraline on the relative amplitude of the circadian rest-activity cycle was observed at the end of the first week (P = .01). In parallel, a significant improvement of sleep latency (P <.001) and sleep efficiency (P <.001) from week 1 to week 6 was observed with agomelatine as compared to sertraline. Over the 6-week treatment period, depressive symptoms improved significantly more with agomelatine than with sertraline (P <.05), as did anxiety symptoms (P <.05).


CONCLUSIONS
The favorable effect of agomelatine on the relative amplitude of the circadian rest-activity/sleep-wake cycle in depressed patients at week 1 reflects early improvement in sleep and daytime functioning. Higher efficacy results were observed with agomelatine as compared to sertraline on both depressive and anxiety symptoms over the 6-week treatment period, together with a good tolerability profile. These findings indicate that agomelatine offers promising benefits for MDD patients.


BACKGROUND
www.isrctn.org: ISRCTN49376288.
Kasper
Siegfried
S
Department of Psychiatry and Psychotherapy, Medical University Vienna, MUV, AKH, Währinger Gürtel 18-20, A-1090 Wien, Austria. biol-psychiatry@meduniwien.ac.at
Hajak
Göran
G
Wulff
Katharina
K
Hoogendijk
Witte J G
WJ
Montejo
Angel Luis
AL
Smeraldi
Enrico
E
Rybakowski
Janusz K
JK
Quera-Salva
Maria-Antonia
MA
Wirz-Justice
Anna M
AM
Picarel-Blanchot
Françoise
F
Baylé
Franck J
FJ
D000081:Acetamides / Q000009:adverse effects / Q000627:therapeutic use*; D056044:Actigraphy / Q000379:methods; D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D001007:Anxiety / Q000150:complications / Q000188:drug therapy*; D002940:Circadian Rhythm / Q000187:drug effects*; D003863:Depression / Q000150:complications / Q000188:drug therapy*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects*; D011569:Psychiatric Status Rating Scales; D012146:Rest; D020280:Sertraline / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D012890:Sleep / Q000187:drug effects; D016896:Treatment Outcome; D009281:Naphthalenes
D000081:Acetamides; D000928:Antidepressive Agents; D020280:Sertraline; C084711:agomelatine; D009281:Naphthalenes