Schizophrenia is associated with a tremendous individual and societal burden. The disease is characterized by a complex set of symptoms including psychosis, hallucinations, delusions and related positive symptoms combined with social function deficits, cognitive disturbances and, often, devastating mood disorder, such as comorbid depression. Management of the disease often requires lifelong pharmacotherapy. However, many pharmacotherapies do not improve all symptoms (e.g., social withdrawal, depression, cognitive deficits) and can be associated with intolerable side effects such as weight gain and metabolic disturbances, motor dysfunction and endocrine dysregulation. Lumateperone (ITI-007, CAPLYTA™) is a novel antipsychotic agent, discovered and developed by Intra-Cellular Therapies, Inc. (ITCI) and approved for treatment of schizophrenia in adults in December 2019. Lumateperone simultaneously modulates serotonin, dopamine and glutamate neurotransmission, three key neurotransmitters implicated in schizophrenia. It achieves efficacy with a favorable safety profile. The clinical development program included 20 clinical trials with over 1900 individuals exposed to lumateperone. The program demonstrated the efficacy for lumateperone in two positive well controlled trials in patients with schizophrenia. The unique pharmacology of lumateperone supports the observed benefits across a wide range of symptoms, including social function and depression, and supports its favorable safety profile. Here, we review the discovery of lumateperone's unique biological effects and its clinical actions in the treatment of schizophrenia.
Keywords: Antipsychotic; Depression; Dopamine D2 receptors; Partial agonism; Positron emission tomography; Serotonin; Serotonin transporter.
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