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<article xsi:noNamespaceSchemaLocation="http://jats.nlm.nih.gov/publishing/1.1/xsd/JATS-journalpublishing1-mathml3.xsd" dtd-version="1.1" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"><front><journal-meta><journal-id journal-id-type="publisher-id">HPR</journal-id><journal-title-group><journal-title>Health Psychology Research</journal-title></journal-title-group><issn>TBA</issn><eissn>2420-8124</eissn><publisher><publisher-name>Health Psychology Research</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.52965/001c.24932</article-id><article-categories><subj-group subj-group-type="heading"><subject>General</subject></subj-group></article-categories><title>Lumateperone tosylate, A Selective and Concurrent Modulator of  Serotonin, Dopamine, and Glutamate, in the Treatment of  Schizophrenia </title><url>https://healthpr.org/journal/HPR/9/1/10.52965/001c.24932</url><author>MainiKunal,W. HollierJanice,GouldHaley,BollichVictoria,LaForgeJohn,M. CornettElyse,N. EdinofAmber,M. KayeAdam,D. KayeAlan</author><pub-date pub-type="publication-year"><year>2021</year></pub-date><volume>9</volume><issue>1</issue><history><date date-type="pub"><published-time>2021-06-18</published-time></date></history><abstract>Purpose of Review
This is a comprehensive review of the literature regarding the use of Lumateperone tosylate for schizophrenia. This review presents the background, evidence, and indications for the use of lumateperone tosylate in the treatment of schizophrenia.
Recent Findings
Schizophrenia is a chronic mental health disorder that affects approximately 3.3 million people in the United States. Its symptoms, which must be present more than six months, are comprised of disorganized behavior and speech, a diminished capacity to comprehend reality, hearing voices unheard by others, seeing things unseen by others, delusions, decreased social commitment, and decreased motivation. The majority of these symptoms can be managed with antipsychotic medication.Lumateperone is a selective and concurrent modulator of serotonin, dopamine, and glutamate, which all mediate or modulate serious mental illness.
Summary
Schizophrenia is a complex, severe mental illness that affects how the brain processes information. There are many medications used to treat schizophrenia. One antipsychotic agent, lumateperone tosylate, is a newer agent that the FDA recently approved. The most common adverse effects are shown to be mild such as somnolence, constipation, sedation, and fatigue, with the 42 mg recommended dose. Lumateperone tosylate is an FDA-approved drug that can be given only at the 42mg dose once daily with no titration requirements.</abstract><keywords>caplyta, lumateperone tosylate, schizophrenia treatment, schizophrenia</keywords></article-meta></front><body/><back><ref-list><ref id="B1" content-type="article"><label>1</label><element-citation publication-type="journal"><p>1. Kahn RS, Sommer IE, Murray RM, et al. Schizophrenia. Nature Reviews Disease Primers. 2015;1. doi:10.1038/nrdp.2015.672. Strauss GP, Sandt AR, Catalano LT, Allen DN. Negative symptoms and depression predict lower psychological well-being in individuals with schizophrenia. Comprehensive Psychiatry. 2012;53(8):1137-1144. doi:10.1016/j.comppsych.2012.05.0093. Nuechterlein KH, Barch DM, Gold JM, Goldberg TE, Green MF, Heaton RK. Identification of separable cognitive factors in schizophrenia. In: Schizophrenia Research. Vol 72. Schizophr Res; 2004:29-39. doi:10.1016/j.schres.2004.09.0074. Provencher HL, Mueser KT. Positive and negative symptom behaviors and caregiver burden in the relatives of persons with schizophrenia. Schizophrenia Research. 1997;26(1):71-80. doi:10.1016/S0920-9964(97)00043-15. Kahn RS, Keefe RSE. Schizophrenia is a cognitive illness: Time for a change in focus. JAMA Psychiatry. 2013;70(10):1107-1112. doi:10.1001/jamapsychiatry.2013.1556. Hafner H, Maurer K, Loffler W, et al. The epidemiology of early schizophrenia. Influence of age and gender on onset and early course. In: British Journal of Psychiatry. Vol 164. Royal College of Psychiatrists; 1994:29-38. doi:10.1192/s00071250002927147. Saha S, Chant D, Welham J, McGrath J. A systematic review of the prevalence of schizophrenia. PLoS Medicine. 2005;2(5):0413-0433. doi:10.1371/journal.pmed.00201418. Laursen TM, Nordentoft M, Mortensen PB. Excess Early Mortality in Schizophrenia. Annual Review of Clinical Psychology. 2014;10(1):425-448. doi:10.1146/annurev-clinpsy-032813-1536579. Harvey PD. Assessing disability in schizophrenia: tools and contributors. The Journal of clinical psychiatry. 2014;75(10):e27. doi:10.4088/JCP.13049tx5c10. Green MF, Hellemann G, Horan WP, Lee J, Wynn JK. From perception to functional outcome in schizophrenia: Modeling the role of ability and motivation. Archives of General Psychiatry. 2012;69(12):1216-1224. doi:10.1001/archgenpsychiatry.2012.65211. Jones MT, Strassnig MT, Harvey PD. Emerging 5-HT receptor antagonists for the treatment of Schizophrenia. Expert Opinion on Emerging Drugs. 2020;25(2):189-200. doi:10.1080/14728214.2020.177379212. Kapur S, Remington G. Dopamine D2 receptors and their role in atypical antipsychotic action: Still necessary and may even be sufficient. In: Biological Psychiatry. Vol 50. Biol Psychiatry; 2001:873-883. doi:10.1016/S0006-3223(01)01251-313. Lieberman JA, Scott Stroup T, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. New England Journal of Medicine. 2005;353(12):1209-1223. doi:10.1056/NEJMoa05168814. Meftah AM, Deckler E, Citrome L, Kantrowitz JT. New discoveries for an old drug: a review of recent olanzapine research. Postgraduate Medicine. 2020;132(1):80-90. doi:10.1080/00325481.2019.170182315. Strauss GP, Cohen AS. A Transdiagnostic Review of Negative Symptom Phenomenology and Etiology. Schizophrenia Bulletin. 2017;43(4):712-729. doi:10.1093/schbul/sbx06616. Vyas P, Hwang BJ, Bra&amp;scaron;ić JR. An evaluation of lumateperone tosylate for the treatment of schizophrenia. Expert Opinion on Pharmacotherapy. 2020;21(2):139-145. doi:10.1080/14656566.2019.169577817. Ceskova E, Silhan P. Novel treatment options in depression and psychosis. Neuropsychiatric Disease and Treatment. 2018;14:741-747. doi:10.2147/NDT.S15747518. McGrath J, Saha S, Chant D, Welham J. Schizophrenia: A concise overview of incidence, prevalence, and mortality. Epidemiologic Reviews. 2008;30(1):67-76. doi:10.1093/epirev/mxn00119. Epidemiology and risk factors of schizophrenia. PubMed. Accessed July 26, 2020. https://pubmed.ncbi.nlm.nih.gov/26994378/20. Palmer BA, Pankratz VS, Bostwick JM. The lifetime risk of suicide in schizophrenia: A reexamination. Archives of General Psychiatry. 2005;62(3):247-253. doi:10.1001/archpsyc.62.3.24721. Murray RM, Lewis SW. Is schizophrenia a neurodevelopmental disorder? BMJ. 1988;296(6614):63-63. doi:10.1136/bmj.296.6614.6322. McCutcheon RA, Reis Marques T, Howes OD. Schizophrenia - An Overview. JAMA Psychiatry. 2020;77(2):201-210. doi:10.1001/jamapsychiatry.2019.336023. Bramon E, Walshe M, McDonald C, et al. Dermatoglyphics and Schizophrenia: A meta-analysis and investigation of the impact of obstetric complications upon a&amp;ndash;b ridge count. Schizophrenia Research. 2005;75(2-3):399-404. doi:10.1016/j.schres.2004.08.02224. M&amp;auml;ki P, Veijola J, Jones PB, et al. Predictors of schizophrenia - A review. British Medical Bulletin. 2005;73-74:1-15. doi:10.1093/bmb/ldh04625. Cannon M, Jones PB, Murray RM. Obstetric complications and schizophrenia: Historical and meta-analytic review. American Journal of Psychiatry. 2002;159(7):1080-1092. doi:10.1176/appi.ajp.159.7.108026. Leask SJ, Done DJ, Crow TJ. Adult psychosis, common childhood infections and neurological soft signs in a national birth cohort. British Journal of Psychiatry. 2002;181(NOV.):387-392. doi:10.1192/bjp.181.5.38727. Mart&amp;iacute;nez-Ortega JM, Carretero MD, Guti&amp;eacute;rrez-Rojas L, D&amp;iacute;az-Atienza F, Jurado D, Gurpegui M. Winter birth excess in schizophrenia and in non-schizophrenic psychosis: Sex and birth-cohort differences. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2011;35(7):1780-1784. doi:10.1016/j.pnpbp.2011.07.00228. Davies G, Welham J, Chant D, Torrey EF, McGrath J. A Systematic Review and Meta-analysis of Northern Hemisphere Season of Birth Studies in Schizophrenia. Schizophrenia Bulletin. 2003;29(3):587-593. doi:10.1093/oxfordjournals.schbul.a00703029. Brown AS, Schaefer CA, Wyatt RJ, et al. Paternal age and risk of schizophrenia in adult offspring. American Journal of Psychiatry. 2002;159(9):1528-1533. doi:10.1176/appi.ajp.159.9.152830. Malaspina D, Harlap S, Fennig S, et al. Advancing paternal age and the risk of schizophrenia. Archives of General Psychiatry. 2001;58(4):361-367. doi:10.1001/archpsyc.58.4.36131. Messias EL, Chen CY, Eaton WW. Epidemiology of Schizophrenia: Review of Findings and Myths. Psychiatric Clinics of North America. 2007;30(3):323-338. doi:10.1016/j.psc.2007.04.00732. Sipos A, Rasmussen F, Harrison G, et al. Paternal age and schizophrenia: A population based cohort study. British Medical Journal. 2004;329(7474):1070-1073. doi:10.1136/bmj.38243.672396.5533. Morgan C, Fisher H. Environment and schizophrenia: Environmental factors in schizophrenia: Childhood trauma - A critical review. Schizophrenia Bulletin. 2007;33(1):3-10. doi:10.1093/schbul/sbl05334. Dvir Y, Denietolis B, Frazier JA. Childhood Trauma and Psychosis. Child and Adolescent Psychiatric Clinics of North America. 2013;22(4):629-641. doi:10.1016/j.chc.2013.04.00635. Zammit S, Allebeck P, Andreasson S, Lundberg I, Lewis G. Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: Historical cohort study. British Medical Journal. 2002;325(7374):1199-1201. doi:10.1136/bmj.325.7374.119936. Boydell J. Risk factors for schizophrenia. Expert Review of Neurotherapeutics. 2001;1(2):183-191. doi:10.1586/14737175.1.2.18337. Murray RM, Paparelli A, Morrison PD, Marconi A, Di Forti M. What can we learn about schizophrenia from studying the human model, drug-induced psychosis? American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 2013;162(7):661-670. doi:10.1002/ajmg.b.3217738. Tandon R, Keshavan MS, Nasrallah HA. Schizophrenia, &amp;ldquo;Just the Facts&amp;rdquo; What we know in 2008. 2. Epidemiology and etiology. Schizophrenia Research. 2008;102(1-3):1-18. doi:10.1016/j.schres.2008.04.01139. Sullivan PF, Kendler KS, Neale MC. Schizophrenia as a Complex Trait: Evidence from a Meta-analysis of Twin Studies. Archives of General Psychiatry. 2003;60(12):1187-1192. doi:10.1001/archpsyc.60.12.118740. MacIntyre DJ, Blackwood DHR, Porteous DJ, Pickard BS, Muir WJ. Chromosomal abnormalities and mental illness. Molecular Psychiatry. 2003;8(3):275-287. doi:10.1038/sj.mp.400123241. Blackwood DHR, Fordyce A, Walker MT, St Clair DM, Porteous DJ, Muir WJ. Schizophrenia and affective disorders - Cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: Clinical and P300 findings in a family. American Journal of Human Genetics. 2001;69(2):428-433. doi:10.1086/32196942. Bassett AS, Chow EWC. Schizophrenia and 22q11.2 deletion syndrome. Current Psychiatry Reports. 2008;10(2):148-157. doi:10.1007/s11920-008-0026-143. Henriksen MG, Nordgaard J, Jansson LB. Genetics of schizophrenia: Overview of methods, findings and limitations. Frontiers in Human Neuroscience. 2017;11. doi:10.3389/fnhum.2017.0032244. Osimo EF, Beck K, Reis Marques T, Howes OD. Synaptic loss in schizophrenia: a meta-analysis and systematic review of synaptic protein and mRNA measures. Molecular Psychiatry. 2019;24(4):549-561. doi:10.1038/s41380-018-0041-545. Lewis DA. Inhibitory neurons in human cortical circuits: Substrate for cognitive dysfunction in schizophrenia. Current Opinion in Neurobiology. 2014;26:22-26. doi:10.1016/j.conb.2013.11.00346. Guillozet-Bongaarts AL, Hyde TM, Dalley RA, et al. Altered gene expression in the dorsolateral prefrontal cortex of individuals with schizophrenia. Molecular Psychiatry. 2014;19(4):478-485. doi:10.1038/mp.2013.3047. Kaalund SS, Newburn EN, Ye T, et al. Contrasting changes in DRD1 and DRD2 splice variant expression in schizophrenia and affective disorders, and associations with SNPs in postmortem brain. Molecular Psychiatry. 2014;19(12):1258-1266. doi:10.1038/mp.2013.16548. Piskulic D, Addington J, Cadenhead KS, et al. Negative symptoms in individuals at clinical high risk of psychosis. Psychiatry Research. 2012;196(2-3):220-224. doi:10.1016/j.psychres.2012.02.01849. Peter R. H. Synaptic density in human frontal cortex - Developmental changes and effects of aging. Brain Research. 1979;163(2):195-205. doi:10.1016/0006-8993(79)90349-450. Feinberg I. Schizophrenia: Caused by a fault in programmed synaptic elimination during adolescence? Journal of Psychiatric Research. 1982;17(4):319-334. doi:10.1016/0022-3956(82)90038-351. Fusar-Poli P, Radua J, McGuire P, Borgwardt S. Neuroanatomical maps of psychosis onset: Voxel-wise meta-analysis of antipsychotic-naive vbm studies. Schizophrenia Bulletin. 2012;38(6):1297-1307. doi:10.1093/schbul/sbr13452. Alekseichuk I, Turi Z, Amador De Lara G, Antal A, Paulus Correspondence W, Paulus W. Spatial Working Memory in Humans Depends on Theta and High Gamma Synchronization in the Prefrontal Cortex Article Spatial Working Memory in Humans Depends on Theta and High Gamma Synchronization in the Prefrontal Cortex. Current Biology. 2016;26:1513-1521. doi:10.1016/j.cub.2016.04.03553. Uhlhaas PJ, Singer W. Abnormal neural oscillations and synchrony in schizophrenia. Nature Reviews Neuroscience. 2010;11(2):100-113. doi:10.1038/nrn277454. Selvaraj S, Bloomfield PS, Cao B, Veronese M, Turkheimer F, Howes OD. Brain TSPO imaging and gray matter volume in schizophrenia patients and in people at ultra high risk of psychosis: An [11C]PBR28 study. Schizophrenia Research. 2018;195:206-214. doi:10.1016/j.schres.2017.08.06355. Selvaraj S, Arnone D, Cappai A, Howes O. Alterations in the serotonin system in schizophrenia: A systematic review and meta-analysis of postmortem and molecular imaging studies. Neuroscience and Biobehavioral Reviews. 2014;45:233-245. doi:10.1016/j.neubiorev.2014.06.00556. Dean B, Copolov D, Scarr E. Understanding the pathophysiology of schizophrenia: Contributions from the Melbourne Psychiatric Brain Bank. Schizophrenia Research. 2016;177(1-3):108-114. doi:10.1016/j.schres.2016.04.03757. Dean B. The cortical serotonin2A receptor and the pathology of schizophrenia: A likely accomplice. Journal of Neurochemistry. 2003;85(1):1-13. doi:10.1046/j.1471-4159.2003.01693.x58. McGorry PD, Purcell R, Hickie IB, Yung AR, Pantelis C, Jackson HJ. Clinical staging: a heuristic model for psychiatry and youth mental health. Medical Journal of Australia. 2007;187(S7):S40-S42. doi:10.5694/j.1326-5377.2007.tb01335.x59. Stępnicki P, Kondej M, Kaczor AA. Current concepts and treatments of schizophrenia. Molecules. 2018;23(8). doi:10.3390/molecules2308208760. Creese I, Burt DR, Snyder SH. Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science. 1976;192(4238):481-483. doi:10.1126/science.3854461. Kapur S, Seeman P. Antipsychotic agents differ in how fast they come off the dopamine D2 receptors. Implications for atypical antipsychotic action. Journal of Psychiatry and Neuroscience. 2000;25(2):161-166.62. Farde L, Nordstr&amp;ouml;m AL, Wiesel FA, Pauli S, Halldin C, Sedvall G. Positron Emission Tomographic Analysis of Central D1 and D2 Dopamine Receptor Occupancy in Patients Treated with Classical Neuroleptics and Clozapine: Relation to Extrapyramidal Side Effects. Archives of General Psychiatry. 1992;49(7):538-544. doi:10.1001/archpsyc.1992.0182007003200563. Nordstr&amp;ouml;m AL, Farde L, Wiesel FA, et al. Central D2-dopamine receptor occupancy in relation to antipsychotic drug effects: A double-blind PET study of schizophrenic patients. Biological Psychiatry. 1993;33(4):227-235. doi:10.1016/0006-3223(93)90288-O64. Miyamoto S, Miyake N, Jarskog LF, Fleischhacker WW, Lieberman JA. Pharmacological treatment of schizophrenia: A critical review of the pharmacology and clinical effects of current and future therapeutic agents. Molecular Psychiatry. 2012;17(12):1206-1227. doi:10.1038/mp.2012.4765. Kim DH, Stahl SM. Antipsychotic drug development. Current Topics in Behavioral Neurosciences. 2010;4:124-139. doi:10.1007/7854_2010_4766. Kondej M, Stępnicki P, Kaczor AA. Multi-target approach for drug discovery against schizophrenia. International Journal of Molecular Sciences. 2018;19(10):3105. doi:10.3390/ijms1910310567. Mocci G, Jim&amp;eacute;nez-S&amp;aacute;nchez L, Adell A, Cort&amp;eacute;s R, Artigas F. Expression of 5-HT2A receptors in prefrontal cortex pyramidal neurons projecting to nucleus accumbens. Potential relevance for atypical antipsychotic action. Neuropharmacology. 2014;79:49-58. doi:10.1016/j.neuropharm.2013.10.02168. Li P, L. Snyder G, E. Vanover K. Dopamine Targeting Drugs for the Treatment of Schizophrenia: Past, Present and Future. Current Topics in Medicinal Chemistry. 2016;16(29):3385-3403. doi:10.2174/156802661666160808483469. Meltzer HY, Matsubara S, Lee JC. Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin2 pKi values. Journal of Pharmacology and Experimental Therapeutics. 1989;251(1).70. Miyamoto S, Duncan GE, Marx CE, Lieberman JA. Treatments for schizophrenia: A critical review of pharmacology and mechanisms of action of antipsychotic drugs. Molecular Psychiatry. 2005;10(1):79-104. doi:10.1038/sj.mp.400155671. Davis RE, Correll CU. ITI-007 in the treatment of schizophrenia: from novel pharmacology to clinical outcomes. Expert Review of Neurotherapeutics. 2016;16(6):601-614. doi:10.1080/14737175.2016.117457772. Correll CU, Davis RE, Weingart M, et al. Efficacy and Safety of Lumateperone for Treatment of Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. 2020;77(4):349-358. doi:10.1001/jamapsychiatry.2019.437973. Blair HA. Lumateperone: First Approval. Drugs. 2020;80(4):417-423. doi:10.1007/s40265-020-01271-674. FDA Label. Lumateperone Drug Prescribing and Safety Information. Accessed July 20, 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209500s000lbl.pdf75. Vanover KE, Davis RE, Zhou Y, et al. Dopamine D2 receptor occupancy of lumateperone (ITI-007): a Positron Emission Tomography Study in patients with schizophrenia. Neuropsychopharmacology. 2019;44(3):598-605. doi:10.1038/s41386-018-0251-176. Kantrowitz JT. The Potential Role of Lumateperone - Something Borrowed? Something New? JAMA Psychiatry. 2020;77(4):343-344. doi:10.1001/jamapsychiatry.2019.426577. Corponi F, Fabbri C, Bitter I, et al. Novel antipsychotics specificity profile: A clinically oriented review of lurasidone, brexpiprazole, cariprazine and lumateperone. European Neuropsychopharmacology. 2019;29(9):971-985. doi:10.1016/j.euroneuro.2019.06.00878. Snyder GL, Vanover KE, Zhu H, et al. Functional profile of a novel modulator of serotonin, dopamine, and glutamate neurotransmission. Psychopharmacology. 2015;232(3):605-621. doi:10.1007/s00213-014-3704-179. Greenwood J, Acharya RB, Marcellus V, Rey JA. Lumateperone: A Novel Antipsychotic for Schizophrenia. Annals of Pharmacotherapy. Published online June 26, 2020:106002802093659. doi:10.1177/106002802093659780. Lieberman JA, Davis RE, Correll CU, et al. ITI-007 for the Treatment of Schizophrenia: A 4-Week Randomized, Double-Blind, Controlled Trial. Biological Psychiatry. 2016;79(12):952-961. doi:10.1016/j.biopsych.2015.08.02681. Kane JM, Vanover KE, Durgam S, et al. P.671 Efficacy and safety of lumateperone tosylate 42mg in the treatment of schizophrenia: A pooled analysis of phase 2 and 3 studies. European Neuropsychopharmacology. 2019;29:S453-S454. doi:10.1016/j.euroneuro.2019.09.64282. Meyer JM. Lumateperone for schizophrenia. Current Psychiatry. 2020;19(2):33-39.</p><pub-id pub-id-type="doi"/></element-citation></ref></ref-list></back></article>
