The role of lumateperone in the treatment of schizophrenia

Abstract

Schizophrenia is a devastating mental disorder resulting in marked morbidity and mortality despite the optimal use of all currently available interventions. For this reason, the release of lumateperone (CaptylaR), also known as ITI-007, an orally administered, atypical antipsychotic provided a welcome novel tool for clinicians to utilize precision medicine to tailor an optimal treatment plan to the specific needs of each person with schizophrenia. To generate a foundation for clinicians to assess the risks and benefits of lumateperone in relation to other interventions for schizophrenia, we conducted a search of items for ‘ITI-007’ and ‘lumateperone’ on PubMed, ScienceDirect, Web of Science, Google Scholar, and www.clinicaltrials.gov . We present a critical evaluation of the limited information about lumateperone for schizophrenia, its use approved by the US Food and Drug Administration. Lumateperone merits consideration for patients with treatment-resistant schizophrenia and for patients with schizophrenia who are vulnerable to developing metabolic dysfunction and movement disorders. On the other hand, lumateperone should not be used for (a) women who are pregnant or breastfeeding, children, adolescents, and elderly patients with dementia-related psychosis, (b) patients who are at risk for cerebrovascular diseases, (c) patients who use inducers and moderate or strong inhibitors of the cytochrome P450-3A4 (CYP3A4) isozyme, and (d) patients who use alcohol and other sedating agents. Clinical trials from multiple centers without financial conflicts of interest to market lumateperone are needed to directly compare and contrast lumateperone and other antipsychotic agents to generate trustworthy evidence to be assessed objectively by clinicians treating patients with schizophrenia. Future investigations will provide the foundations to identify the evidence for comprehensive evaluations of the role of lumateperone in the treatment of people with schizophrenia and other conditions.

The Role of Childhood Trauma in Psychosis and Schizophrenia: A Systematic Review

“…Based on the dopamine hypothesis, positive symptoms are related to the hyperfunctionality of dopamine D2 receptor neurotransmission in limbic and subcortical brain regions. Hypoactivity of D1 receptor neurotransmission contributes to negative and cognitive symptoms of SCZ [ 2 ]. An alteration in dopamine function is strongly associated with the onset of psychotic symptoms.…”

Third-generation antipsychotics in patients with schizophrenia and non-responsivity or intolerance to clozapine regimen: What is the evidence?

“…Lumateperone, on the other hand, may present pharmacokinetic interactions with clozapine due to its metabolization partially via CYP1A2 isoforms ( 63 ). However, other CYP450 isoenzymes are involved in the lumateperone metabolization (3A4, 2C8), therefore, alternate pathways are available ( 63 , 64 ).…”

“…Lumateperone, on the other hand, may present pharmacokinetic interactions with clozapine due to its metabolization partially via CYP1A2 isoforms ( 63 ). However, other CYP450 isoenzymes are involved in the lumateperone metabolization (3A4, 2C8), therefore, alternate pathways are available ( 63 , 64 ). The safety profile of lumateperone was evaluated in large clinical trials as good, with no clinically significant motor, endocrine, or cardiometabolic adverse events, which allows for optimism in the case of patients with schizophrenia and comorbid metabolic diseases, either primary or secondary to antipsychotic medication ( 64 ).…”

New synthesis of a late-stage tetracyclic key intermediate of lumateperone

“…Lumateperone ( 1 ) is a recently launched drug marketed for the treatment of schizophrenia and developed for further neuropsychiatric and neurological disorders [ 1 – 6 ] ( Figure 1 ).…”