Lurasidone in the treatment of schizophrenia: a critical evaluation

Antipsychotic medications are the foundation of the pharmacological treatment of schizophrenia and lurasidone is the most recent of the 65 agents around the world to become available. In order to use it optimally, it is important to understand its pharmacological and clinical nature and its comparative effectiveness to other antipsychotic agents in the treatment of schizophrenia.

Following a comprehensive review of the literature, this article summarizes current information about the pharmacology of lurasidone, data about its short- and long-term efficacy and safety/tolerability in the treatment of schizophrenia, its comparative effectiveness to other antipsychotic agents, and guidance about its optimal use in the treatment of individuals with schizophrenia.

Lurasidone is a benzoisothiazole with potent dopamine D2 and serotonin 5HT2A antagonist and serotonin 5HT1A partial agonist properties (like other second-generation antipsychotic agents) with additional potent 5HT7 and alpha2C noradrenergic antagonism. It has little or no activity at the alpha1 and alpha2A noradrenergic, 5HT2C serotonergic, histaminergic and cholinergic receptors. Available only in an oral formulation, it is effective in once-daily dosing (40 - 160 mg/day) and its absorption is affected by food. There is an extensive clinical trial database with short-term and long-term placebo- and antipsychotic-controlled clinical trials evaluating the efficacy and safety/tolerability of lurasidone in the treatment of schizophrenia. It has been found to be efficacious with comparable efficacy to other agents in the treatment of acute psychosis and prevention of relapse in individuals with schizophrenia. The greater antidepressant and cognitive benefits suggested by its receptor profile need substantiation in robust clinical trials. It is less likely to cause metabolic and cardiac adverse effects than most other second-generation agents and is associated with a modest risk of extrapyramidal side-effects, akathisia, and prolactin elevation.