26. Approaches to Treatment-Resistant Patients

  1. Daniel R. Weinberger MD6 and
  2. Paul J. Harrison MA, BM, BCh, DM(Oxon), FRCPsych7
  1. Stephan Leucht MD1,
  2. Christoph U. Correll MD2,3,4 and
  3. John M. Kane MD3,4,5

Published Online: 8 MAR 2011

DOI: 10.1002/9781444327298.ch26

Schizophrenia, Third Edition

Schizophrenia, Third Edition

How to Cite

Leucht, S., Correll, C. U. and Kane, J. M. (2011) Approaches to Treatment-Resistant Patients, in Schizophrenia, Third Edition (eds D. R. Weinberger and P. J. Harrison), Wiley-Blackwell, Oxford, UK. doi: 10.1002/9781444327298.ch26

Editor Information

  1. 6

    Genes, Cognition and Psychosis Program, Clinical Studies Section, Clinical Brain Disorders Branch, National Institute of Health, Bethesda, MD, USA

  2. 7

    Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK

Author Information

  1. 1

    Department of Psychiatry and Psychotherapy, Technische Universit ät München, Klinikum rechts der Isar, Munich, Germany

  2. 2

    Recognition and Prevention (RAP) Program, The Zucker Hillside Hospital, Glen Oaks, NY, USA

  3. 3

    Albert Einstein College of Medicine, Bronx, NY, USA

  4. 4

    The Feinstein Institute for Medical Research, Manhasset, NY, USA

  5. 5

    Department of Psychiatry, The Zucker Hillside Hospital, Psychiatry Research, North Shore—Long Island Jewish Health System, Glen Oaks, NY, USA

Publication History

  1. Published Online: 8 MAR 2011
  2. Published Print: 10 DEC 2010

ISBN Information

Print ISBN: 9781405176972

Online ISBN: 9781444327298



  • treatment resistance;
  • refractory patients;
  • non-response;
  • clozapine


Resistance to antipsychotic drugs is a frequent problem in schizophrenia. In part due to the lack of a uniformly accepted definition of treatment refractoriness, the exact epidemiology is unclear, but most practice guidelines currently consider treatment resistance after two unsuccessful trials with different antipsychotic drugs of 4–6 weeks' duration. Before non-response to treatment can be assumed, a number of factors such as non-adherence, side effects, insufficient doses or ultra-rapid metabolism need to be ruled out. There is increasing evidence that non-response can be detected early in treatment, suggesting that non-responders at 2 weeks may benefit from a change of treatment, but controlled trials are needed to investigate whether switching or any other strategy is effective. There is little evidence-based guidance as to whether a dose increase or a switch of medication is more efficacious in cases of initial non-response. For persistent refractoriness, clozapine remains the gold standard, while there is no convincing evidence for the efficacy of most augmentation strategies such as mood stabilizers, benzodiazepines, antipsychotic combinations or ECT.