NEW ANTIPSYCHOTICS IN SCHIZOPHRENIA - THE FRENCH EXPERIENCE

Since the beginning of the neuroleptics in 1952, French psychiatrists have proposed a classification of neuroleptics, taking into account th e pharmacological and therapeutic differences between these drugs. The y distinguished 3 different clinical effects of neuroleptics: sedative effects, effects on the positive symptoms of schizophrenia and effect s on the negative symptoms. The effect of some neuroleptics on negativ e symptoms is recognized by the international community, which conside rs clozapine to be effective. In France, in most cases, the indication of clozapine is still refractory paranoid schizophrenia. The effect o f this atypical neuroleptic on other types of schizophrenic patient is not well known. Remoxipride appears to be as effective in treating ps ychotic symptoms and to have fewer side effects than haloperidol. Remo xipride is effective for both positive and negative symptoms. Loxapine has been prescribed in France since 1980. Its pharmacological profile is close to that of clozapine: it has dopamine (D-2), histamine (H-1) , serotonin (5-HT2) and adrenergic (alpha(1))-blocking activities. Its best indication seems to be paranoid schizophrenia, although some dat a suggest bipolar action. The bipolar action of some new neuroleptics is illustrated by amisulpride, a substitute benzamide derivative. The originality of this molecule lies in its two opposite actions at two d istinct doses. Doses of 600-1200 mg/day are effective against positive symptoms; 50-150 mg/day improves negative symptoms. This latter effec t could be mediated by activation of the dopamine system. Risperidone binds to 5-HT2, D-2, alpha(1), and H-1 receptors. At a daily dose of 5 mg, risperidone would probably act on both negative and positive symp toms, inducing fewer extrapyramidal symptoms than classical neurolepti cs. Carpipramine is neither antidepressant nor neuroleptic; carpiprami ne is a specific 5-HT2 antagonist and is the only known disinhibitor d rug. The St. Anne Hospital School, following Deniker, recommends its u se for hebephrenic patients. Amineptine is a very potent dopaminergic antidepressant that can be effective on negative symptoms such as loss of affect and anergia. All the drugs are empirically prescribed. Thei r use would be justified by a serotonin and/or dopamine hypothesis of schizophrenia.