Risperidone is useful as a first-line drug for the treatment of all forms of schizophrenia, including residual schizophrenia. (8,,,5 53 and 54' Definitive data are lacking for its efficacy in patients who are neuroleptic resistant or who have failed to respond to olanzapine, quetiapine, or clozapine. (354) Clinical experience is not supportive of widespread efficacy in these groups but there may be some responders. However, risperidone may be useful in patients who fail to tolerate other antipsychotic agents because of side-effects not shared by risperidone. Risperidone is well-tolerated in low doses by the elderly and has been widely used in the United States for the treatment of a variety of senile psychoses/5 56> Its efficacy against haloperidol was established in a series of multicentre trials which demonstrated advantages for risperidone in overall psychopathology in mainly chronic schizophrenic patients in an acute exacerbation at doses in the 6 to 8 mg/day range. (852) However, these doses have proven to be higher than is needed for most patients in clinical practice, possibly reflecting some of the problems in generalizing from controlled clinical trials. The doses for schizophrenia most often used in non-elderly adults are now 3 to 5 mg/day. Some first-episode patients may respond to 1 to 2 mg/day. Some treatment-resistant patients may need doses higher than 6 mg/day. Whether prolonged trials, i.e. up to 6 months, are useful in such patients, as they are in clozapine patients, is not yet known.

Risperidone has more of a tendency to produce extrapyramidal side-effects than any of the other atypical antipsychotics but this can be minimized by using the lowest dose which controls positive symptoms and adding an anticholinergic drug, if necessary.(56> Addition of a typical neuroleptic to risperidone will increase the risk of extrapyramidal side-effects. Risperidone is not well tolerated by patients with Parkinson's disease because of extrapyramidal side-effects. There are some data suggesting the risk of tardive dyskinesia in patients with schizophrenia, and especially the elderly, with risperidone is less than that of the typical neuroleptic drugs. (57)

The issue of whether the improvement in negative symptoms by risperidone and other atypical antipsychotic drugs is due to an effect on so-called primary negative symptoms versus secondary negative symptoms has been much debated. Data from the large multicentre trials of risperidone versus clozapine show an effect on primary negative symptoms as residual change left after adjusting for improvement due to decreases in positive or depressive symptoms and extrapyramidal side-effects.(58> Risperidone has a greater ability to improve cognition in schizophrenia than the typical neuroleptic drugs. (1.7) Improvement in working memory has been the strongest finding. Improvement in attention, executive function, and verbal learning and memory has also been reported.

As with clozapine, risperidone has been used in patients with bipolar mania and psychotic depression. (14) It appears to be at least as effective as typical neuroleptic drugs and is better tolerated. Considering the risk of tardive dyskinesia in such patients, it is clearly a superior choice for these patients. Risperidone is also widely used in treating the agitation, aggression, and paranoia of patients with senile psychoses. Low doses (e.g. 0.5-2 mg/day) are usually adequate.

In summary, risperidone is a highly useful addition to the treatment of schizophrenia and other forms of psychosis. It may produce significant advantages over typical neuroleptic drugs with regard to negative symptoms, cognition, and extrapyramidal side-effects, but it does produce equivalent increases in serum prolactin levels. Its tolerability with regard to extrapyramidal side-effects is highly dose dependent so that it must be used at the lower doses where possible.

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