Comparative efficacy and tolerability of pharmacological and somatic interventions in adult patients with treatment-resistant depression: a systematic review and network meta-analysis

Curr Med Res Opin. 2017 Apr;33(4):701-711. doi: 10.1080/03007995.2016.1277201. Epub 2017 Feb 6.


Objective: Major depressive disorder (MDD) affects about 10-15% of the general population in a lifetime. A considerable number of patients fail to achieve full symptom remission despite adequate treatment and are considered treatment resistant (TRD). The current study compared the relative efficacy and tolerability of pharmacological and somatic TRD interventions by means of a Bayesian network meta-analysis.

Research design and methods: An electronic literature search of MEDLINE, MEDLINE In-Process, EMBASE, PsycInfo, EconLit and Cochrane Library databases for trials published between September 2003 and September 2014 was conducted. Key outcomes extracted were disease severity change from baseline, response and remission rates at various timepoints and discontinuation due to adverse events.

Results: Of the 3876 abstracts identified, 31 publications/randomised controlled trials (RCTs) were included in the analysis; 19 RCTs investigating 13 pharmacological interventions and 12 RCTs investigating electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS). The evidence synthesis investigating efficacy outcomes of TRD treatments demonstrated superior efficacy for ketamine compared to pharmacological and somatic interventions at 2 weeks after treatment initiation. At 4, 6 and 8 weeks, quetiapine augmentation (800 mg/day) and risperidone augmentation were found to be the first and second best treatments, respectively. Networks were small for response rate and remission rate outcomes at most timepoints. The most tolerable treatment was lamotrigine augmentation showing a comparable profile to placebo/sham.

Conclusions: This analysis revealed scarcity of long-term data on sustained remission that would allow a comparative long-term efficacy assessment. Key limitations of the analysis can be considered the search timeframe and the use of mapping formula for the depression scores.

Keywords: Antidepressant effect; Bayesian hierarchical model; Disease severity; Network meta-analysis; Ranking; Treatment-resistant depression.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Bayes Theorem
  • Depressive Disorder, Major* / diagnosis
  • Depressive Disorder, Major* / drug therapy
  • Depressive Disorder, Major* / psychology
  • Depressive Disorder, Treatment-Resistant / diagnosis
  • Humans
  • Psychotropic Drugs / therapeutic use*
  • Remission Induction / methods
  • Time
  • Transcranial Magnetic Stimulation / methods*
  • Treatment Outcome


  • Psychotropic Drugs