title: Comparison of agomelatine and selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors in major depressive disorder: A meta-analysis of head-to-head randomized clinical trials.
abstract: OBJECTIVE
  Agomelatine is a new antidepressant with unique melatonin receptor type 1A (MTNR1A) and 1B ( MTNR1B) agonism and serotonergic receptor 5-hydroxytryptamine receptor 2C (5-HT-2C) antagonism. Several studies of patients with major depressive disorder (MDD) have confirmed the superior efficacy and safety of agomelatine in comparison with established treatments, such as selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). This meta-analysis comprehensively shows the efficacy, acceptability, and safety of agomelatine in comparison with SSRIs and SNRIs used as antidepressants in MDD.
  
  
  METHODS
  Comprehensive electronic database searches were performed to identify reports of head-to-head randomized controlled trials that have compared agomelatine with SSRIs or SNRIs in terms of efficacy/effectiveness in treating MDD. Response and remission rates at both acute (6-12 weeks) and follow-up (24 weeks) phases, Clinical Global Impression-Improvement Scale response and remission rates, changes in depression scale scores, improvements in subjective sleep, dropout rates, and side effect rates were extracted and analysed.
  
  
  RESULTS
  The meta-analysis included six head-to-head trials involving 1871 patients. In the acute phase, agomelatine had higher response rates (relative risk (RR) 1.08, 95% confidence interval (CI) 1.02-1.15) compared to SSRIs and SNRIs. In the remission analysis, only acute remission rates (RR 1.12, 95% CI 1.01-1.24) significantly differed. The action of agomelatine was superior on the Leeds Sleep Evaluation Questionnaire-Quality of Sleep score (mean difference 4.05, 95% CI 0.61-7.49). Discontinuation due to inefficacy did not differ between agomelatine and SSRIs/SNRIs (RR 0.74, 95% CI 0.42-1.28). Compared to SSRIs and SNRIs, however, agomelatine revealed a lower rate of discontinuation due to side effects (RR 0.38, 95% CI 0.25-0.57).
  
  
  CONCLUSIONS
  Agomelatine has significantly higher efficacy and potential acceptability compared to SSRIs and SNRIs when treating MDD. However, the difference in efficacy is not considered clinically relevant. Because of its unique chronobiotic effects, agomelatine may be useful for the management of some MDD patients with circadian disturbance.
authors.affiliation: Department of Pharmacy, Mackay Memorial Hospital, Taiwan.
authors.forename: Kai-Lin
authors.initials: KL
authors.lastname: Huang
authors.affiliation: Department of Pharmacy, Mackay Memorial Hospital, Taiwan.
authors.forename: Wan-Chen
authors.initials: WC
authors.lastname: Lu
authors.affiliation: Department of Pharmacy, Mackay Memorial Hospital, Taiwan.
authors.forename: Ying-Yue
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Department of Rehabilitation Medicine, Mackay Memorial Hospital, Taiwan.
authors.forename: Gwo-Chi
authors.initials: GC
authors.lastname: Hu
authors.affiliation: Department of Pharmacy, Mackay Memorial Hospital, Taiwan.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Lu
authors.affiliation: Department of Pharmacy, Mackay Memorial Hospital, Taiwan.
authors.forename: Wei-Ying
authors.initials: WY
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, Mackay Memorial Hospital, Taiwan hsuchienchi@gmail.com.
authors.forename: Chien-Chi
authors.initials: CC
authors.lastname: Hsu
mesh_terms: D000081:Acetamides / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; D017367:Selective Serotonin Reuptake Inhibitors; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors; C084711:agomelatine; D009281:Naphthalenes
keywords: Acceptability; agomelatine; efficacy; major depressive disorder; meta-analysis; safety