Optimisation of prescription in patients with long-term treatment-resistant schizophrenia

Australas Psychiatry. 2013 Oct;21(5):446-8. doi: 10.1177/1039856213492862. Epub 2013 Jul 19.


Objective: The aim of this clinical review was to investigate the effectiveness and safety of the practice of antipsychotic poly-pharmacy (AP) in the long-term management of hospitalised patients with insufficient response to antipsychotic monotherapy.

Method: The databases Medline, PsycINFO, Embase and Scopus were searched. Studies were required to include inpatients with long-term, treatment-resistant schizophrenia on maintenance AP. The search was restricted to systematic review studies.

Results: The review yielded four studies of interest that showed no categorical advantage for maintenance AP for the population of interest. However, clozapine combination faired marginally well. Particular weaknesses of the present literature are low number of participants, and inadequate monitoring of potential adverse effects. The evidence on the risks and benefits of maintenance AP is not generally considered adequate to warrant a recommendation for its use in routine clinical practice in psychiatry.

Conclusions: This review provides a synthesis of the evidence on the maintenance use of AP for hospitalised patients with long-term, treatment-resistant schizophrenia. The results show both no support for AP with some marginal benefit for clozapine combination therapy, and methodological weaknesses of the included studies. These findings have clinical implications for treatment decisions and suggest that sufficiently powered studies are needed.

Keywords: combination-therapy; poly-pharmacy; schizophrenia.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Clozapine / adverse effects
  • Clozapine / therapeutic use
  • Drug Resistance* / drug effects
  • Drug Therapy, Combination / adverse effects
  • Humans
  • Long-Term Care
  • Polypharmacy*
  • Schizophrenia / drug therapy*


  • Antipsychotic Agents
  • Clozapine