OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Lumateperone – Caplyta®

DRUG CLASS

Antipsychotic Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULAS AND STRUCTURES

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Lumateperone	313368-91-1	C24-H28-F-N3-O
Paliperidone	144598-75-4	C23-H27-F-N4-O3

ANNOTATED BIBLIOGRAPHY

References updated: June 6, 2023

• Meyer JM. Pharmacotherapy of psychosis and mania. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 279-302.

  (Textbook of pharmacology and therapeutics).
• FDA. https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2019/209500Orig1s000MultidisciplineR.pdf.

  (FDA website with product labels and the multidispline review of lumateperone that supported its approval for use in schizophrenia mentions ALT elevations arose in 2% of patients taking lumateperone vs 1% of controls and that 6 of 595 patients in one study developed ALT elevations above 3 times ULN during therapy, but all were less than 5 times ULN and most were self-limited and none were accompanied by jaundice).
• Correll CU, Davis RE, Weingart M, Saillard J, O'Gorman C, Kane JM, Lieberman JA, et al. Efficacy and safety of lumateperone for treatment of schizophrenia: a randomized clinical trial. JAMA Psychiatry. 2020;77(4):349–358. [PMC free article: PMC6990963] [PubMed: 31913424]

  (Among 450 adults with an acute exacerbation of schizophrenia treated with lumateperone [28 or 42 mg] or placebo once daily for 28 days, symptomatic response rates were higher with lumateperone [36% and 37% than placebo 26%] as were adverse event rates [57% and 65% vs 50%] including somnolence, sedation, fatigue and constipation; no mention of ALT elevations or hepatotoxicity).
• Lumateperone (Caplyta) for schizophrenia. Med Lett Drugs Ther. 2020;62(1603):113–116. [PubMed: 32728011]

  (Concise review of the mechanism of action, clinical efficacy, safety and cost of lumateperone shortly after its approval for use in the US mentions common side effects of somnolence, nausea, dry mouth and elevations in serum aminotransferases).
• Greenwood J, Acharya RB, Marcellus V, Rey JA. Lumateperone: a novel antipsychotic for schizophrenia. Ann Pharmacother. 2021;55(1):98–104. [PubMed: 32590907]

  (Review of the mechanism of action, clinical efficacy and safety of lumateperone mentions that it has high affinity for the serotonin 2A receptor, moderate affinity for dopamine 1 receptor, and may also act as a serotonin-reupdate inhibitor; in two short term clinical trials, lumateperone improved both negative and positive symptoms of schizophrenia, but long term results with comparisons to other second generation antipsychotics have not been reported).
• Correll CU, Vanover KE, Davis RE, Chen R, Satlin A, Mates S. Safety and tolerability of lumateperone 42 mg: an open-label antipsychotic switch study in outpatients with stable schizophrenia. Schizophr Res. 2021;228:198–205. [PubMed: 33453691]

  (Among 301 adults with stable schizophrenia who were switched from another atypical antipsychotic to lumateperone for 6 weeks, symptom scores were stable while 31% developed a drug related adverse event which were mostly mild-to-moderate somnolence [7%], headache [5%] and dry mouth [5%], and among the severe adverse events [3%], none were liver related; no mention of ALT elevations).
• D'Souza I, Durgam S, Satlin A, Davis RE, Kozauer SG, Chen R, Mates S, et al. Lumateperone (ITI-007) in the treatment of bipolar depression: results from a randomized clinical trial. CNS Spectrums. 2021;26:150. Not in PubMed. [PubMed: 36779257]

  (Abstract only: among 377 adults with bipolar disorders experiencing a manic episode treated with lumateperone [42 mg] vs placebo daily for 6 weeks, remission rates were 51% vs 37% at day 43, and therapy was “generally well tolerated”; no information on ALT levels or hepatotoxicity).
• Kane JM, Durgam S, Satlin A, Vanover KE, Chen R, Davis R, Mates S. Safety and tolerability of lumateperone for the treatment of schizophrenia: a pooled analysis of late-phase placebo- and active-controlled clinical trials. Int Clin Psychopharmacol. 2021;36:244–250. [PMC free article: PMC8322041] [PubMed: 34054112]

  (Pooled results from 3 randomized, double-blind controlled trials of lumateperone [n=406] vs risperidone [n=255] and placebo [n=411] for 4 or 6 weeks, overall adverse event rates were 66%, 69% and 55% and there were no deaths and no liver related discontinuations or serious adverse events, and while there were minor average increases in ALT, AST and Alk P on lumateperone therapy, there were no instances of liver injury with jaundice).
• Calabrese JR, Durgam S, Satlin A, Vanover KE, Davis RE, Chen R, Kozauer SG, et al. Efficacy and safety of lumateperone for major depressive episodes associated with bipolar I or bipolar II disorder: a phase 3 randomized placebo-controlled trial. Am J Psychiatry. 2021;178:1098–1106. [PubMed: 34551584]

  (Among 377 adults with bipolar disorders experiencing a major depressive episode enrolled in a randomized controlled trial for 6 weeks, symptom scores improved more with lumateperone [42 mg daily] than placebo and adverse events arose in 55% vs 50%, but there were no serious hepatic adverse events; no mention of ALT elevations or hepatotoxicity).
• Lumateperone (Caplyta) for bipolar depression. Med Lett Drugs Ther. 2022;64(1656):126–128. [PubMed: 35921078]

  (Concise review of the mechanism of action, clinical efficacy, safety, and cost of lumateperone shortly after its approval in the US for treatment of bipolar depression; does not mention ALT elevations or hepatotoxicity).
• Suppes T, Durgam S, Kozauer SG, Chen R, Lakkis HD, Davis RE, Satlin A, et al. Adjunctive lumateperone (ITI-007) in the treatment of bipolar depression: Results from a randomized placebo-controlled clinical trial. Bipolar Disord. 2023 Feb 13; In Press. [PubMed: 36779257]

  (Among 529 adults with bipolar I and II disorder on valproate or lithium to which was added lumateperone [28 or 42 mg] or placebo once daily for 6 weeks, depression symptom scores improved more with lumateperone than placebo [-16.2 and -16.9 vs -14.5], while total adverse event rates were similar and side effects more frequent with lumateperone included somnolence, dizziness and nausea; no mention of ALT elevations or hepatotoxicity).