[Treatment of negative symptoms in schizophrenia by amisulpride. Review of the literature].

The deficit forms of schizophrenia have given rise to important research and controversy for the last 15 years. It is now recognized that some negative symptoms in schizophrenia are part of a pure and primary deficit syndrome which could be related to decreased dopaminergic function and which is not well improved by standard antipsychotic drugs. Amisulpride is a substituted benzamide neuroleptic with an original pharmacologic profile. Prescription of high doses (600-1 200 mg/day) yields to an usual antipsychotic activity on positive symptoms, through the blockage of post-synaptic dopamine receptors. At low doses, amisulpride preferentially blocks presynaptic dopamine autoreceptors, with a poor affinity for striatal sites. Three recent double-blind placebo controlled studies have suggested an efficacy of low doses (50-300 mg/day) of amisulpride in deficit forms of schizophrenia. The first study was carried out in young never-treated schizophrenic patients, and showed a significant improvement of negative symptoms with a 6-week amisulpride treatment. In the second study, subjects with a long-course deficit schizophrenia were included after a 6-week wash-out period. Reduction of scores of negative symptoms (Andreasen's scale) was about twice as important in the amisulpride group compared to the placebo group, whereas positive symptoms, modest at inclusion, remained unchanged. Finally, the efficacy of amisulpride was shown in another double-blind long-term study over 6 months in patients with predominantly negative symptoms. The overall safety profile of amisulpride in these studies was good, in particular with a low incidence of extrapyramidal symptoms. Thus, amisulpride at low doses appeared to be a well tolerated treatment for various deficit forms of schizophrenia, with a short-term and long-term efficacy.