Risperidone is a benzisoxazole derivative that was heralded as a major breakthrough in the treatment of schizophrenia on its British launch last year. To what extent does research published in peer reviewed journals support this claim?

How antipsychotic drugs work is not fully understood. Although their ability to block dopamine receptors is important, a substantial proportion of patients respond poorly to neuroleptics - especially those with “negative symptoms” such as apathy and social withdrawal - so theremust be more to the pharmacotherapy of schizophrenia than just an effect on dopaminergic transmission. Other neurotransmitters - for example, 5-hydroxytryptamine possibly acting at 5HT2 receptors, could be involved: in support of this are the antipsychotic properties of clozapine, which has a greater affinity for 5HT2 receptors than dopamine 2 receptors, and the apparent beneficial effect of add on treatment with the potent 5HT2 receptor blocker ritanserin.1

Risperidone blocks catecholamine receptors (mainly dopamine 2 and alpha 1 and alpha 2 adrenoceptors) and 5HT2 receptors. It has antihistamine (H1) activity but no effect on beta adrenoceptors, muscarinic cholinoceptors, or peptidergic receptors.*RF 2-5* Open studies have suggested that it has a therapeutic effect on both positive and negative symptoms of schizophrenia and may be helpful in patients who have not responded to conventional neuroleptics. With lower doses extrapyramidal symptoms do not commonly occur. The results of controlled trials*RF 6-12* have supported these preliminary observations, and …