Efficacité et tolérance à court terme de la lurasidone dans la prise en charge de la schizophrénie

Lurasidone is a new second-generation antipsychotic approved in October 2010 by the Food and Drug Administration and in March 2014 by the European Medicines Agency for the treatment of schizophrenia. Like other second-generation antipsychotics, lurasidone is an antagonist of D2 dopamine and 5HT2A serotonin receptors, but differs from the other second-generation antipsychotics in its action profile for certain receptors. Lurasidone is the second-generation antipsychotic with the greatest affinity for 5HT7 receptors and has a low affinity for α1 and α2C-adrenergic and 5HT2C serotonin receptors, and no affinity for histaminergic H1 or muscarinic M1 receptors. Lurasidone has demonstrated its efficacy in several short-term studies in acute schizophrenia with significantly reducing total scores of Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) compared with placebo. Early improvement was observed by days 3-7 for the 80-160 mg/day doses. Two studies with several methodological limitations showed that lurasidone might be involved in the improvement of cognitive performance in schizophrenic patients. Post hoc analysis of four pooled short-term studies showed significantly better effects on improving depressive symptoms associated with schizophrenia in patients treated with lurasidone as compared to patients treated with placebo. Lurasidone differs from the other second-generation antipsychotics by a good tolerability profile, in particular in terms of metabolic and cardiovascular profiles. Although results of the preclinical studies suggested that lurasidone had a low potential for causing clinically significant extrapyramidal symptoms, these were observed with a higher frequency than expected. It seems to have a significant though moderate link with the occurrence of akathisia, extrapyramidal symptoms, and hyperprolactinemia during initiation of treatment. This new tolerance profile greatly broadens the scope of second-generation antipsychotics and supports the view of some authors that the term second-generation antipsychotic is now outdated. Other therapeutic perspectives of lurasidone have been assessed, in particular in bipolar depression.