A translational research approach to poor treatment response in patients with schizophrenia: clozapine–antipsychotic polypharmacy

A translational research approach to poor treatment response in patients with schizophrenia: clozapine–antipsychotic polypharmacy

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J Psychiatry Neurosci 2009; 34(6): 433-442

William G. Honer, MD; Ric M. Procyshyn, PhD; Eric Y.H. Chen, MD; G. William MacEwan, MD; Alasdair M. Barr, PhD

Honer, Procyshyn, Barr — BC Mental Health and Addictions Research Institute; Honer, Procyshyn, MacEwan — Department
of Psychiatry, University of British Columbia, Vancouver, BC; Chen — Department of Psychiatry, University of Hong Kong, Hong Kong SAR, China; Barr — Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC

Abstract

Poor treatment response in patients with schizophrenia is an important clinical problem, and one possible strategy is concurrent treatment with more than one antipsychotic (polypharmacy). We analyzed the evidence base for this strategy using a translational research model focused on clozapine–antipsychotic polypharmacy (CAP). We considered 3 aspects of the existing knowledge base and translational research: the link between basic science and clinical studies of efficacy, the evidence for effectiveness in clinical research and the implications of research for the health care delivery system. Although a rationale for CAP can be developed from receptor pharmacology, there is little available preclinical research testing these concepts in animal models. Randomized clinical trials of CAP show minimal or no benefit for overall severity of symptoms. Most studies at the level of health services are limited to estimates of CAP prevalence and some suggestion of increased costs. Increasing use of antipsychotic polypharmacy in general may be a factor contributing to the underutilization of clozapine and long delays in initiating clozapine monotherapy. Translational research models can be applied to clinical questions such as the value of CAP. Better linkage between the components of translational research may improve the appropriate use of medications such as clozapine in psychiatric practice.


Submitted Mar. 6, 2009; Revised Jun. 18, Jul. 31, 2009; Accepted Aug. 2, 2009.

Acknowledgements: Supported by BC Mental Health and Addictions Services and the Michael Smith Foundation for Health Research. Dr. Barr is a CIHR New Investigator.

Competing interests: Dr. Honer reports receiving consulting fees for sitting on paid advisory boards for In-silico, Wyeth, Janssen, Novartis and AstraZeneca; lecture fees from Janssen and AstraZeneca; and educational grant support from Janssen, Eli Lilly and AstraZeneca. Dr. Procyshyn has received consulting or advisory board fees and lecture fees from AstraZeneca, GlaxoSmithKline, Janssen, Pfizer and Eli Lilly. Dr. MacEwan has received consulting or advisory board fees from AstraZeneca, Janssen, Eli Lilly, Pfizer and Novartis; lecture fees from GlaxoSmithKline and Apotex; and grant support from Astra – Zeneca. Dr. Chen reports having received research funding from Astra Zeneca, Janssen-Cilag, Pfizer, Eli Lilly, Sanofi-aventis and Otsuka; has participated in paid advisory boards for Otsuka; and received educational grant/travel support from Janssen. Dr. Barr has acted as a consultant to Eli Lilly Canada.

Contributors: Drs. Honer, Procyshyn, Chen and Barr reviewed the literature, Drs. Honer, Procyshyn, Chen and Barr wrote the article; all authors read and revised the article. All authors gave final approval for the article to be published.

Correspondence to: Dr. W.G. Honer, BC Mental Health and Addictions Research Institute, A3-127, 938 West 28th Ave., Vancouver BC V5Z 4H4; honer@interchange.ubc.ca