[New chemotherapy approaches to psychoses].Encephale 1997; 23 Spec No 2:2-9E
Particular features are involved in the atypical antipsychotic concept: efficacity on refractory patients and negative symptoms, less or no extrapyramidal side effects, less tardive dyskinesia and less increase in prolactinemia. The imprecision of the atypical neuroleptic class must be underlined. In fact, the pharmacological agents who are included in this class potentially induce few neurological side effects. These effects appearing in doses very much higher than in the therapeutical range. In this case, atypical should refer to a particularity in the links between doses, efficacy and side effects more than to a definition in a specific category. Dopaminergic hypothesis is explained more and more by a dopaminergic system dysregulation than by a simple dopaminergic hyperactivity. This dysregulation might be autonomous or linked to other monoaminergic systems. These new antipsychotics show affinity for different monoaminergic receptors. After clozapine, several agents are now available (risperidone) or just about to be (olanzapine, seroquel, sertindole, ziprasidone, zotépine). Therapeutical effects are probably linked with a dual antagonist effects on 5HT2 and D2 receptors. The atypical antipsychotic efficacy on negative symptoms remains controversial. While very few patients are found to be "purely" negative, most of the schizophrenic patients will show sooner or later some negative symptoms mixed with positive ones. The obvious difficulties in methodological and clinical evaluation of negative symptoms are at least dual: depressive symptoms; extrapyramidal side effects. Secondary negative symptoms usually don't last, while primary negative symptoms are more permanent. Kraepelin describes them as the avolutionnal syndrome of dementia praecox. Usually negative symptoms improve during therapeutic trials, including those using classical neuroleptics. This should not lead us to the conclusion that we have today at our disposal pharmacological agents effective on avolutionnal syndrome or primary negative symptoms. More studies are still necessary. Similarities and differences between the new antipsychotic are not yet evaluated, except partly for clozapine and risperidone. Some new neuroleptics might simplify greatly the therapeutic range. Studies concerning risperidone clearly prove its efficacity on a daily dose of 6 +/- 2 mg. A daily dose of 10 mg doesn't bring any additional improvement. This aspect must be underlined while the efficacy-dose ratio of the classical neuroleptics are still questioned. Consequently too many patients might be given insufficient doses and others excessive doses resulting in side effects and no additional benefits. These new antipsychotics must add a positive modification in schizophrenic care. They might lead to a limited use of additional therapeutics and a better observance thus allowing less relapses and less rehospitalisations.