Clozapine v. first- and second-generation antipsychotics in treatment-refractory schizophrenia: systematic review and meta-analysis

Br J Psychiatry. 2016 Nov;209(5):385-392. doi: 10.1192/bjp.bp.115.177261. Epub 2016 Jul 7.


Background: Although clozapine is the 'gold standard' for treatment-refractory schizophrenia, meta-analyses of clozapine for this condition are lacking.

Aims: We conducted a systematic review and meta-analysis of clozapine treatment for people with treatment-refractory schizophrenia.

Method: We searched the Cochrane Schizophrenia Group's trial register, PubMed and EMBASE and hand-searched key papers for randomised controlled trials of clozapine for treatment-refractory schizophrenia.

Results: Twenty-one papers with 25 comparisons were included. The number needed to treat was 9. Clozapine was superior for positive symptoms in both the short and long term. In the short term only clozapine was superior for total and negative symptoms, with higher response rates. Both funding source and dosage affected results. Higher baseline psychosis scores predicted better outcomes for clozapine in a meta-regression.

Conclusions: Clozapine is superior for treatment-refractory disorder but if there is no response by 6 months medications with lower adverse reactions should be considered.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antipsychotic Agents / pharmacology*
  • Clozapine / pharmacology*
  • Humans
  • Schizophrenia / drug therapy*


  • Antipsychotic Agents
  • Clozapine