New trends in schizophrenia treatment

Abstract

Particular features are involved in the atypical antipsychotic concept :efficacity on refractory patients and negative symptoms, lessor noextrapyramidal side effects less tardive dyskinesia and less increase inprolactinemia. The imprecision of the atypical neuroleptic class must beunderlined. In fact, the pharmacological agents who are included in thisclass potentially induce few neurological side effects. These effectsappearing in doses very much higher than in the therapeutical range. Inthis case, atypical should refer to a particularity in the links betweendoses, efficacy and side effects more than to a definition in a specificcategory. Dopaminergic hypothesis is explained more and more by adopaminergic system dysregulation than by a simple dopaminergichyperactivity. This dysregulation might be autonomous or linked to othermonoaminergic systems. These new antipsychotics show affinity fordifferent monoaminergic receptors. After clozapine, several agents arenow available (risperidone) or just about to be (olanzapine, seroquel,sertindole, ziprasidone, zotepine). Therapeutical effects are probablylinked with a dual antagonist effects on 5HT2 and D2 receptors. Theatypical antipsychotic efficacy on negative symptoms remainscontroversial. While very few patients are found to be `'purely''negative, most of the schizophrenic patients will show sooner or latersome negative symptoms mixed with positive ones. The obviousdifficulties in methodological and clinical evaluation of negativesymptoms are at least dual: depressive symptoms; extrapyramidal sideeffects. Secondary negative symptoms usually don't last, while primarynegative symptoms are more permanent. Kraepelin describes them as theavolutionnal syndrom of dementia praecox. Usually negative symptomsimprove during therapeutic trials, including those using classicalneuroleptics. This should not lead us to the conclusion that we havetoday at our disposal pharmacological agents effective on avolutionnalsyndrom or primary negative symptoms. More studies are still necessary.Similarities and differences between the new antipsychotic are not yetevaluated, except partly for clozapine and risperidone. Some newneuroleptics might simplify greatly the therapeutic range. Studiesconcerning risperidone clearly prove its efficacity on a daily dose of 6+/- 2 mg. A daily dose of 10 mg doesn't bring any additionalimprovement. This aspect must be underlined while the efficacy-doseratio of the classical neuroleptics are still questioned. Consequentlytoo many patients might be given insufficient doses and others excessivedoses resulting in side effects and no additional benefits. These newantipsychotics must add a positive modification in schizophrenic care.They might lead to a limited use of additional therapeutics and a betterobservance thus allo wing less relapses and less rehospitalisations.