Exciting claims about what 'atypical' antipsychotic drugs can do are marred by the poor quality of much of the research evidence, say Paul Wilson, Simon Gilbody and Anne-Marie Bagnall

Schizophrenia is one of the most common of the severe mental illnesses. Drug treatment forms the main element of effective management but should be used alongside a range of psychosocial interventions.

Antipsychotics form the main class of drugs used to treat or manage schizophrenia. Antipsychotics - also known as neuroleptics, anti-schizophrenia drugs and, inaccurately, as major tranquillisers - revolutionised the treatment of schizophrenia in the 1950s. The antipsychotic action of these drugs is more than just the promotion of sedation and probably depends upon specific receptors in the brain.

Adverse side-effects

But adverse effects associated with antipsychotics are common. These include troublesome and socially disabling movement disorders that resemble the symptoms of Parkinson's disease.

Involuntary facial movements (tardive dyskinesia) also occur in over 20 per cent of those using 'typical' drugs and do not necessarily recede once the antipsychotic is stopped or reduced. Other troublesome side-effects include sedation, dry mouth, blurred vision, constipation, weight gain and, occasionally, impotence.

While conventional drugs are generally an effective treatment for many of the symptoms of schizophrenia, these side-effects can limit their use for a significant portion of people with schizophrenia. Continual medication is often necessary during periods of relative wellness, and poor compliance can precipitate relapse and necessitate (costly) rehospitalisation.

Poor compliance

It has been suggested that the side-effect profile of older drugs has contributed to poor patient compliance and relapsing illness following discharge into the community ('revolving door' patients). The recent shift to community based models of service provision has made the question of continued compliance with drugs when unsupervised all the more important.

One approach has been to promote the use of long-term injectable (depot) forms of conventional medication that need only be given once fortnightly. But injectable forms of medication still have the side-effects described above and a significant proportion of people fail to respond to conventional drugs.

'Typical' and 'atypical' drugs

More than a decade ago, with the reintroduction of the drug clozapine into common use, older drugs began to be labelled as 'typical' in their propensity to cause movement disorders.

Clozapine was 'atypical' in that it did not seem to cause these side-effects as readily. In truth, rather than such a dichotomy of 'typical' and 'atypical', there is a continuum, and some inexpensive older drugs may have an 'atypical' profile.

Examples of some of the recently introduced new or 'atypical' drugs include risperidone, olanzapine, sertindole and ziprasidone.

The increased cost of these drugs will have a major impact on drug budgets, and should be justified by robust evidence of clinical and cost-effectiveness.

Evidence of effectiveness

The latest issue of Effective Health Care draws upon evidence from systematic reviews carried out by the Cochrane schizophrenia group.

The bulletin summarises the evidence on the effectiveness of the main drugs used in the treatment of schizophrenia, covering areas of drug management that may concern managers and clinicians in the UK.

The development of the new 'atypical' antipsychotic drugs may offer scope for improving the effectiveness of treatment.

They may cause fewer adverse effects and be more acceptable to those with schizophrenia than other older drugs.

But at present, all statements on the effects of 'atypical' antipsychotics must be qualified. The claims being made are exciting, but take place in the context of ever greater conflicts of interest, both academic and monetary. The quality of much of the research evidence, as measured by clear reporting and clinical applicability, is poor.

The drug trials are, on average, small, short, include participants who are not typical of everyday practice, randomise care regimens that are difficult to generalise, have high attrition rates, and report outcomes that are of dubious clinical value. This often limits the conclusions that can be drawn.

Financial implications

It has been estimated that 'atypical' antipsychotics could add up to£210m to the annual UK drug budget if prescribed for all patients with schizophrenia, and£54m if restricted to those with treatment-resistant schizophrenia. Speculation that direct drug costs are offset by decreases in hospitalisation, indirect costs and intangible savings is not based on reliable data.

Additionally, the quantity and quality of economic evidence is not sufficient to enable decision-makers to choose between the drugs with any certainty. This is likely to have contributed to considerable regional variations in access to newer drugs.

The new framework

The Department of Health has recently outlined policy initiatives to improve and standardise the care of schizophrenia in the national service framework for mental health.

The framework says that, from next year, the government will ensure extra resources are made available to help meet the greatly increased demands on limited drug budgets.

The 'atypical' antipsychotics may be a further refinement, but not a revolution, in the care of those with schizophrenia.

If the NHS is to fund 'atypical' antipsychotics in full, their use should be justified by trial data clearly supportive of use in everyday practice. Large, long-term randomised drug trials with participants, interventions and primary outcomes familiar to health professionals who treat people with schizophrenia are long overdue.

Given the nature of the available evidence, those involved in the care of people with schizophrenia need to maintain up-to date knowledge of research on antipsychotics. Guides to practice should be appraised for bias and everyday applicability. Clinical use of relevant up-to-date information must, where possible, be in collaboration with clients and carers and tailored to their needs.

Key issues

The development of the new 'atypical' antipsychotic drugs may offer scope for improving the effectiveness of treatment.

If the NHS is to fully fund 'atypical' antipsychotics, their use should be justified by reliable research evidence demonstrating their use in everyday practice.

Large, long-term, randomised drug trials with participants, interventions and primary outcomes familiar to health professionals who treat people with schizophrenia are long overdue.

Those involved in the care of people with schizophrenia need to maintain their knowledge of current research evidence on antipsychotics.


1 Drug treatments for schizophrenia. Effective Health Care 1999; 5(6).

2 Department of Health. A National Service Framework for Mental Health. DoH, 1999.

Paul Wilson, Simon Gilbody and Anne-Marie Bagnall are all research fellows at the NHS centre for rev iews and dissemination, York University.

Effective Health Care is an independent report based on systematic reviews of research evidence, produced by the NHS centre for reviews and dissemination, York University. The bulletin aims to provide NHS decision makers with information on the effectiveness of interventions and the delivery and organisation of healthcare. For more information, phone 01904-433648 or e-mail revdis@york.ac.uk