The social and economic burden of treatment-resistant schizophrenia: a systematic literature review

Int Clin Psychopharmacol. 2014 Mar;29(2):63-76. doi: 10.1097/YIC.0b013e32836508e6.


Patients with schizophrenia often fail to respond to an initial course of therapy. This study systematically reviewed the societal and economic burden of treatment-resistant schizophrenia (TRS). Studies that described patients with TRS published 1996-2012 were included if they collected primary data on clinical, social, or economic outcomes. All studies were independently reviewed and extracted by at least two investigators. Sixty-five studies were identified. Almost 60% (SD 18%) of patients failed to achieve response after 23 weeks on antipsychotic drug therapy. Patients with TRS had high rates of smoking (56%), alcohol abuse (51%), substance abuse (51%), and suicide ideation (44%). The incidence of severe adverse events to treatment was 4% (SD 7%). Mean quality of life for patients who were unresponsive or intolerant to treatment was ∼20% lower than that of patients in remission. Annual costs for patients with schizophrenia are $15 500-$22 300 and are 3-11-fold higher for patients with TRS. TRS remains common and costly, despite availability of many treatment options, and contributes to a significant loss in patient quality of life. Although estimates in the literature vary greatly, TRS conservatively adds more than $34 billion in annual direct medical costs in the USA.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use
  • Comorbidity
  • Cost of Illness
  • Costs and Cost Analysis
  • Drug Resistance
  • Humans
  • Psychiatric Status Rating Scales
  • Quality of Life
  • Randomized Controlled Trials as Topic
  • Schizophrenia / complications
  • Schizophrenia / economics*
  • Schizophrenia / epidemiology
  • Schizophrenia / therapy
  • Schizophrenic Psychology


  • Antipsychotic Agents