Current use of atypical antipsychotics

Abstract

In terms of the phenomenology of schizophrenia, there are four targets for drug treatments: positive symptoms, negative symptoms, affective dysfunction, and cognitive dysfunction. Because of the side-effects of both conventional antipsychotics and the new atypicals, there still is a need to search for better-tolerated antipsychotics. Conventional antipsychotics have two principal limitations: 30-40% of patients have an insufficient response to them, and they have a large variety of adverse effects. Side-effects will reduce patients' compliance with treatment, as well as their immediate quality of life, and may therefore unfavorably affect rehabilitation. Four principal features differentiate atypical from conventional antipsychotics, yet have not been established for all atypicals: fewer extrapyramidal side-effects, greater efficacy in the treatment of negative symptoms, specific pharmacological receptor binding profiles, and greater selective effect on the mesolimbic dopamine neurons than on nigrostriatal neurons. The pharmacological profile of amisulpride is completely different to that of other atypical antipsychotics. It has a high selectivity for D2 and D3 dopamine receptors, and thus would be expected to be devoid of unwanted side-effects associated with action on other neurotransmitter systems. It acts preferentially on the mesocortical and mesolimbic systems. It has an earlier onset of action than haloperidol. Amisulpride is a compound with a dual mode of action. At low doses it blocks presynaptic dopamine autoreceptors, inducing an increased dopaminergic neurotransmission, and at high doses it blocks postsynaptic dopaminergic activity. It is at least as effective as haloperidol, flupenthixol, and risperidone in controlling positive symptoms, as well as having efficacy for negative symptoms. It has less propensity to induce weight gain than do other atypical antipsychotics. For the 60-80% of patients with schizophrenia who require long-term treatment, drug tolerability is crucially important, as it will improve compliance, and therefore reduce relapse rate.