title: Network Meta-Analysis and Cost-Effectiveness Analysis of New Generation Antidepressants.
abstract: BACKGROUND
  Major depressive disorder (MDD) impacts health, quality of life and workplace productivity. Antidepressant treatment is the primary therapeutic intervention. This study assessed the efficacy and tolerability of new generation antidepressants and their cost-effectiveness in the Singapore healthcare system.
  
  
  METHODS
  We conducted a systematic search for head-to-head randomised controlled trials on ten antidepressants (agomelatine, duloxetine, escitalopram, fluvoxamine, fluoxetine, mirtazapine, paroxetine, sertraline, trazodone and venlafaxine) employed as monotherapy in acute MDD management. We performed a network meta-analysis to compare their relative efficacy. The outcome measures for efficacy were response and remission rate, and mean change in Hamilton Depression Rating Scale (HDRS) score; and for tolerability, study withdrawal rates due to adverse events. To evaluate their relative cost effectiveness, a decision tree simulating a cohort of MDD patients using antidepressant as monotherapy was constructed from a societal perspective over 6 months. We used effectiveness data from our network meta-analysis and local data on resource use for depression in Singapore. The incremental cost expected for each additional quality-adjusted life-year (QALY) gained was calculated and presented as the incremental cost-effectiveness ratio (ICER).
  
  
  RESULTS
  We identified 76 relevant articles for the network meta-analysis. Of the ten agents included in the analysis, mirtazapine and agomelatine were most efficacious in achieving response and remission, respectively. Mirtazapine and duloxetine resulted in the greatest magnitude of change in the HDRS score. Agomelatine, escitalopram and sertraline were the best tolerated of the drugs analysed, while duloxetine was the least well tolerated drug. Using a composite outcome of efficacy (response and remission rates) and tolerability, agomelatine, escitalopram and mirtazapine were the favoured treatments. In the cost-effectiveness analysis, apart from agomelatine, all the treatments were dominated by mirtazapine. Against mirtazapine, agomelatine was not cost effective given that its ICER exceeded the threshold value.
  
  
  CONCLUSIONS
  Agomelatine, escitalopram and mirtazapine had favourable balance between efficacy and tolerability. In addition, mirtazapine was a cost-effective option in the Singapore healthcare system.
authors: Pharmacy and Therapeutics Office, Group Corporate Development, National Healthcare Group, 3 Fusionopolis Link, #03-08 Nexus@one-north, Singapore, 138543, Singapore. ai_leng_khoo@nhg.com.sg.
authors: Ai Leng
authors: AL
authors: Khoo
authors: Pharmacy and Therapeutics Office, Group Corporate Development, National Healthcare Group, 3 Fusionopolis Link, #03-08 Nexus@one-north, Singapore, 138543, Singapore.
authors: Hui Jun
authors: HJ
authors: Zhou
authors: Pharmacy and Therapeutics Office, Group Corporate Development, National Healthcare Group, 3 Fusionopolis Link, #03-08 Nexus@one-north, Singapore, 138543, Singapore.
authors: Monica
authors: M
authors: Teng
authors: Pharmacy and Therapeutics Office, Group Corporate Development, National Healthcare Group, 3 Fusionopolis Link, #03-08 Nexus@one-north, Singapore, 138543, Singapore.
authors: Liang
authors: L
authors: Lin
authors: Pharmacy and Therapeutics Office, Group Corporate Development, National Healthcare Group, 3 Fusionopolis Link, #03-08 Nexus@one-north, Singapore, 138543, Singapore.
authors: Ying Jiao
authors: YJ
authors: Zhao
authors: Pharmacy Department, Institute of Mental Health, Singapore, Singapore.
authors: Lay Beng
authors: LB
authors: Soh
authors: Department of General Psychiatry, Institute of Mental Health, Singapore, Singapore.
authors: Yee Ming
authors: YM
authors: Mok
authors: Pharmacy and Therapeutics Office, Group Corporate Development, National Healthcare Group, 3 Fusionopolis Link, #03-08 Nexus@one-north, Singapore, 138543, Singapore.
authors: Boon Peng
authors: BP
authors: Lim
authors: Department of General Psychiatry, Institute of Mental Health, Singapore, Singapore.
authors: Kok Peng
authors: KP
authors: Gwee
mesh_terms: D000928:Antidepressive Agents / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D003663:Decision Trees; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000191:economics / Q000503:physiopathology; D006801:Humans; D011569:Psychiatric Status Rating Scales; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D016032:Randomized Controlled Trials as Topic; D012846:Singapore; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents