title: 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.
abstract: 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.
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University Vienna, MUV, AKH, Währinger Gürtel 18-20, A-1090 Wien, Austria. biol-psychiatry@meduniwien.ac.at
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
authors.forename: Göran
authors.initials: G
authors.lastname: Hajak
authors.forename: Katharina
authors.initials: K
authors.lastname: Wulff
authors.forename: Witte J G
authors.initials: WJ
authors.lastname: Hoogendijk
authors.forename: Angel Luis
authors.initials: AL
authors.lastname: Montejo
authors.forename: Enrico
authors.initials: E
authors.lastname: Smeraldi
authors.forename: Janusz K
authors.initials: JK
authors.lastname: Rybakowski
authors.forename: Maria-Antonia
authors.initials: MA
authors.lastname: Quera-Salva
authors.forename: Anna M
authors.initials: AM
authors.lastname: Wirz-Justice
authors.forename: Françoise
authors.initials: F
authors.lastname: Picarel-Blanchot
authors.forename: Franck J
authors.initials: FJ
authors.lastname: Baylé
mesh_terms: 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
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; D020280:Sertraline; C084711:agomelatine; D009281:Naphthalenes