Lumateperone: A Novel Antipsychotic for Schizophrenia

Abstract

Objective: To provide a concise review of the new Food and Drug Administration (FDA)-approved antipsychotic, lumateperone, for use in schizophrenia. Data Sources: A literature search of PubMed was performed (January 2000 to May 2020) using the following key terms: lumateperone, Caplyta, and ITI-007. Abstracts from conferences, review articles, clinical trials, and drug monographs were reviewed. Study Selection and Data Extraction: Relevant English-language monographs and studies conducted in humans were considered. Data Synthesis: Lumateperone was FDA approved for the treatment of schizophrenia in December 2019 based on 2 published randomized, double-blind, placebo-controlled trials. Lumateperone’s pharmacology is consistent with that of other second-generation antipsychotics in that it has a higher affinity for the serotonin (5-HT2A) receptors compared with dopamine (D2) receptors but with lower affinities for α-1 and histaminergic receptors. In addition, it serves as a presynaptic dopamine partial agonist, serotonin reuptake inhibitor, and an indirect modulator of glutamatergic systems. Based on the 4-week clinical trials, lumateperone was well tolerated. Most common treatment-emergent adverse events were headache, somnolence, and dizziness. Relevance to Patient Care and Clinical Practice: At this time, lumateperone had a statistically significant reduction in Positive and Negative Syndrome Scale when compared with placebo and was not significantly associated with the extrapyramidal symptoms (EPS) and metabolic adverse effects commonly seen with other antipsychotics. Conclusions: Lumateperone has the potential to benefit individuals with schizophrenia who are intolerant to the EPSs or metabolic adverse effects of other antipsychotics. However, further head-to-head trials with commercially available antipsychotics are still required to assist in establishing its role in treatment.

Lumateperone tosylate, A Selective and Concurrent Modulator of Serotonin, Dopamine, and Glutamate, in the Treatment of Schizophrenia

“…72,74 Ingestion of a high-fat meal leads to an approximate decrease in C max of 33%, and T max is extended to approximately 2 hours. 73,79 Dosages at 120 mg/day have not been shown to produce any statistically significant improvement in efficacy. When taken with a high-fat meal, the area under the plasma-concentration-time curve (AUC) increases by 9%.…”

“…72 Also, the use of lumateperone with UGT inhibitors should be avoided as coadministration can lead to increased exposure of lumateperone and its metabolites. 79…”

“…When taken orally, 58% radiolabeled lumateperone is excreted in the urine, and 29% is excreted in the feces. 79 Less than 1% of the dose is excreted in the urine unchanged. 73,79 The metabolites of lumateperone are water-soluble.…”

“…79 Less than 1% of the dose is excreted in the urine unchanged. 73,79 The metabolites of lumateperone are water-soluble. Thus they are entirely excreted in the urine.…”

“…71 PHASE II CLINICAL TRIALS FDA approval was given for lumateperone for the treatment of schizophrenia based on two randomized, double-blind, placebo-controlled trials: a phase II trial (ITI-007-500; NCT01499563) and a phase III trial (ITI-007-301; NCT00282761). 79 In ITI-007-500; NCT01499563, patients ranging in age from 18-55 years with acute exacerbation of psychosis were given 60 mg ITI-007, 120 mg ITI-007, risperidone 4 mg, or placebo once daily for four weeks. The primary endpoint was the measurement of the PNSS total score with secondary analyses performed on symptom subscales.…”