A systematic review of atypical antipsychotic drugs in schizophrenia


This project compared the clinical effectiveness, safety and cost-effectiveness of 'atypical' antipsychotic drugs in schizophrenia with conventional antipsychotic drugs, placebo and other atypical antipsychotic drugs. As secondary objectives, the response was investigated in those with 'treatment-resistant' schizophrenia, with predominantly negative symptoms or experiencing their first episode of schizophrenia.


The evidence for the effectiveness of the new atypical antipsychotic drugs was, in general, of poor quality, based on short-term trials and difficult to generalise to the whole population with schizophrenia. Thus all conclusions are based on limited evidence and should be treated with caution. Further research is needed.

However, individuals with schizophrenia may have found new atypical antipsychotic drugs (except for zotepine and ziprasidone) more acceptable than their typical comparators as, in general, fewer of them left trials early. Apart from clozapine for those with treatment-resistant illness, none of the new atypical antipsychotic drugs stands out as being more effective than the others. They all seemed to have slightly different side-effect profiles, which may have varying importance for those with schizophrenia and their carers.

Given the uncertainty about the validity of the clinical data for typical antipsychotic drugs and what is an acceptable cost/QALY, it was not possible to reach any definite conclusions as to whether the additional costs and benefits represent value for money.

Conducted by: A-M Bagnall1, L Jones1, L Ginnelly2, R Lewis1, J Glanville1, S Gilbody3, L Davies4, D Torgerson2, J Kleijnen1

1 NHS Centre for Reviews and Dissemination, University of York; 2 Centre for Health Economics, University of York; 3 Academic Department of Psychiatry and Behavioural Sciences, School of Medicine, University of Leeds; 4 School of Psychiatry and Behavioural Sciences, University of Manchester

Further details

Project page on NIHR HTA Programme website

Related guidance

Commissioned to inform NICE Technology Appraisal 43: The clinical effectiveness and cost effectiveness of newer atypical antipsychotic drugs for schizophrenia. London: National Institute for Clinical Excellence; 2002. NB: This guidance has been updated and replaced by CG82 Schizophrenia.


Bagnall A-M, Jones L, Ginnelly L, Lewis R, Glanville J, Gilbody S, Davies L, Torgerson D, Kleijnen J. A systematic review of atypical antipsychotic drugs in schizophrenia. Health Technol Assess. 2003;7(13):1-214


AM Bagnall, L Jones, J Kleinen. A systematic review of atypical antipsychotic drugs in schizophrenia. International Society of Technology Assessment in Health Care Conference 2002. Berlin, Germany. 9 June 2002.


Bagnall A-M. What happens to adverse events data in the systematic review/TAR process. Fourth InterTASC Information Specialists' Working Group Meeting; 2003 December; York, UK

Bagnall A-M, Jones L, Glanville J, Kleijnen J. Assessing adverse events in a systematic review of atypical antipsychotics for schizophrenia. Systematic Reviews Symposium; 2002 July; Oxford, UK


Commissioned by the HTA Programme on behalf of NICE's Technology Assessment Report (TAR) process