22-Aug-2005

Schizophrenia

Summary

It is often forgotten that until the late 1950s there was no treatment for schizophrenia, or for that matter, any other severe enduring mental illness. The majority of patients admitted to asylum care never left: hence the peak occupancy of 150,000 reported in the UK in 1955. As an interesting comparison, this is twice the current UK prison population.

Last Updated: 27-Aug-2010

The discovery of conventional (or typical) antipsychotic drugs made a major contribution to the feasibility of asylum closure, which took place from the mid 1970s. The limitations of these drugs have been well rehearsed: their relatively poor efficacy for disabling negative symptoms; their extrapyramidal side-effects (EPS); their lack of impact on at least 20% of patients who became treatment resistant; and their failure to influence the cognitive deterioration which so often resulted in severe functional impairment.

Even so, it is also frequently forgotten that during the latter part of the last century very large numbers of patients were maintained in stability in the community by virtue of long-acting depot injections. The new class of atypical antipsychotic drugs, with one exception, lack this advantage. Furthermore, their efficacy for positive symptoms is only marginally better than that of the conventional drugs. Although as a group the atypical agents are significantly better for negative symptoms (at least the secondary variety) than conventional drugs, their impact on schizophrenic intellectual impairment is disappointing, and certainly not sufficient to normalise these deficits and their associated functional disabilities.

The main advantage of atypical antipsychotic drugs remains their lack of extrapyramidal, dysphoric and similar unwanted effects, and it is now well established that most patients prefer this type of medication for these reasons. However, marked weight gain with some atypical options remains problematic, and can be a reason for treatment discontinuation.

Although the mechanism of action of atypical antipsychotic drugs is not, unlike the conventional variety, limited to dopamine D2 receptor antagonism, we are in many respects no further forward towards confirming their true therapeutic actions. Clozapine – the only antipsychotic agent licensed for resistant illness – has a low affinity for the D2 receptor. There are some attractive theories regarding short D2 ‘off times’ and regional dopaminergic imbalance. These are supported by limited experimental evidence, but await convincing extrapolation from therapeutic mechanisms of action to aetiopathophysiology. It is tempting to assume that drug actions are germane to pathophysiology in schizophrenia, and we all tend to do it; however, such statements are tantamount to saying that headache is caused by aspirin deficiency.

Despite understandable enthusiasm about atypical antipsychotic drug treatments, their benefits have been compromised by a lack of long-acting formulations alongside an escalating tendency of patients away from adherence, and perhaps most of all, the upsurge in abuse of substances many of which directly antagonise the actions of these drugs. Although the importance of early treatment in the determination of outcome is now recognised, recovery from a first episode of illness remains elusive: only 13% of patients in a recent study had achieved this at 2 years. Can there be, therefore, much enthusiasm about progress in the overall treatment of schizophrenia?

The answer is most likely a qualified ‘yes’. There are very few psychiatrists who would wish to return to the days of asylum care, conventional treatment, no clozapine and no psychological therapy. Patients have vastly increased autonomy and choice in their healthcare preferences, whether we agree with them or not. New early intervention services hope to prevent the accumulation of further cohorts of seriously compromised, treatment-resistant patients, whilst contemporary assertive outreach services may afford patients previously unheard of levels of community resources and support. The development of potential treatments with more mechanisms of action continues, unimpeded by market-share considerations. We hope for the introduction of a drug as effective as clozapine, but devoid of its side-effects, and available in a long-acting form: we continue to attempt to educate the profession and the public about schizophrenia, and to work for the social inclusion of our patients. There is still a long way to go, and we have come much too far to give up now.

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This Editorial has been written by the specialist opinion leader, Professor Ann M Mortimer, Foundation Chair in Psychiatry, University of Hull and published in the latest issue of the serial publication, Drugs in Context.

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