The use of atypical antipsychotics in the management of schizophrenia

Long-term drug treatment of schizophrenia with conventional antipsychotics has limitations: an estimated quarter to one third of patients are treatmen t-resistant; conventional antipsychotics have only a modest impact upon neg ative symptoms (poverty of thought, social withdrawal and loss of affect); and adverse effects, particularly extrapyramidal symptoms (EPS). Newer, so- called atypical, antipsychotics such as olanzapine, risperidone, sertindole and clozapine (an old drug which was re-introduced in 1990) are claimed to address these limitations. Atypical agents are, at a minimum, at least as effective as conventional drugs such as haloperidol. They also cause substa ntially fewer extrapyramidal symptoms. However, some other adverse effects are more common than with conventional drugs. For example, clozapine carrie s a significant risk of serious blood disorders, for which special monitori ng is mandatory; it also causes troublesome drowsiness and increased saliva tion more often than conventional agents. Some atypical agents cause more w eight gain or QT prolongation than older agents. The choice of therapy is, therefore, not straightforward. At present, atypical agents represent an ad vance for patients with severe or intolerable EPS. Most published evidence exists to support the use of clozapine, which has also been shown to be eff ective in schizophrenia refractory to conventional agents. However, the nee d for compliance with blood count monitoring and its sedative properties ma ke careful patient selection important. The extent of any additional direct benefit offered by atypical agents on negative symptoms is not yet clear. The lack of a depot formulation for atypical drugs may pose a significant p ractical problem. To date, only two double-blind studies in which atypical agents were compared directly have been published. Neither provides compell ing evidence for the choice of one agent over another. Atypical agents are many times more expensive than conventional drugs. Although drug treatment constitutes only a small proportion of the costs of managing schizophrenia, the additional annual cost of the use of atypical agents in, say, a quarte r of the likely U.K. schizophrenic population would be about pound 56 M. Th ere is only limited evidence of cost-effectiveness. Atypical antipsychotics are not currently licensed for other conditions where conventional antipsy chotics are commonly used, such as behaviour disturbance or dementia in the elderly. Their dose, and place in treatment in such cases have yet to be d etermined.