Health Psychology Research / HPR / Volume 9 / Issue 1 / DOI: 10.52965/​001c.24932
GENERAL

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

Kunal Maini1 Janice W. Hollier1 Haley Gould2 Victoria Bollich2 John LaForge2 Elyse M. Cornett3 Amber N. Edinof1* Adam M. Kaye4 Alan D. Kaye3
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1 Department of Psychiatry and Behavioral Medicine, Louisiana State University Shreveport, LA
2 Louisiana State University Shreveport School of Medicine, Shreveport, LA
3 Department of Anesthesiology, Louisiana State University Shreveport, LA
4 Department of Pharmacy Practice, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA
Submitted: 1 June 2021 | Accepted: 16 June 2021 | Published: 18 June 2021
© 2021 by the Author(s). Licensee Health Psychology Research, USA. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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.

Keywords
caplyta
lumateperone tosylate
schizophrenia treatment
schizophrenia
References

1. Kahn RS, Sommer IE, Murray RM, et al. Schizophrenia. Nature Reviews Disease Primers. 2015;1. doi:10.1038/nrdp.2015.67
2. 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.2012.05.009
3. 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.2004.09.007
4. 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)00043-1
5. 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.2013.155
6. 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/s0007125000292714
7. 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.0020141
8. 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-032813-153657
9. Harvey PD. Assessing disability in schizophrenia: tools and contributors. The Journal of clinical psychiatry. 2014;75(10):e27. doi:10.4088/JCP.13049tx5c
10. 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.2012.652
11. 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:10.1080/14728214.2020.1773792
12. 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)01251-3
13. 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/NEJMoa051688
14. 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:10.1080/00325481.2019.1701823
15. Strauss GP, Cohen AS. A Transdiagnostic Review of Negative Symptom Phenomenology and Etiology. Schizophrenia Bulletin. 2017;43(4):712-729. doi:10.1093/schbul/sbx066
16. Vyas P, Hwang BJ, Brašić JR. An evaluation of lumateperone tosylate for the treatment of schizophrenia. Expert Opinion on Pharmacotherapy. 2020;21(2):139-145. doi:10.1080/14656566.2019.1695778
17. Ceskova E, Silhan P. Novel treatment options in depression and psychosis. Neuropsychiatric Disease and Treatment. 2018;14:741-747. doi:10.2147/NDT.S157475
18. 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/mxn001
19. 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.62.3.247
21. Murray RM, Lewis SW. Is schizophrenia a neurodevelopmental disorder? BMJ. 1988;296(6614):63-63. doi:10.1136/bmj.296.6614.63
22. McCutcheon RA, Reis Marques T, Howes OD. Schizophrenia - An Overview. JAMA Psychiatry. 2020;77(2):201-210. doi:10.1001/jamapsychiatry.2019.3360
23. Bramon E, Walshe M, McDonald C, et al. Dermatoglyphics and Schizophrenia: A meta-analysis and investigation of the impact of obstetric complications upon a–b ridge count. Schizophrenia Research. 2005;75(2-3):399-404. doi:10.1016/j.schres.2004.08.022
24. Mäki P, Veijola J, Jones PB, et al. Predictors of schizophrenia - A review. British Medical Bulletin. 2005;73-74:1-15. doi:10.1093/bmb/ldh046
25. 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.159.7.1080
26. 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.181.5.387
27. Martínez-Ortega JM, Carretero MD, Gutiérrez-Rojas L, Díaz-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.2011.07.002
28. 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.a007030
29. 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.159.9.1528
30. 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.58.4.361
31. 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.2007.04.007
32. 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.38243.672396.55
33. 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/sbl053
34. 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.2013.04.006
35. 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.325.7374.1199
36. Boydell J. Risk factors for schizophrenia. Expert Review of Neurotherapeutics. 2001;1(2):183-191. doi:10.1586/14737175.1.2.183
37. 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.32177
38. Tandon R, Keshavan MS, Nasrallah HA. Schizophrenia, “Just the Facts” What we know in 2008. 2. Epidemiology and etiology. Schizophrenia Research. 2008;102(1-3):1-18. doi:10.1016/j.schres.2008.04.011
39. 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.60.12.1187
40. 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.4001232
41. 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:10.1086/321969
42. Bassett AS, Chow EWC. Schizophrenia and 22q11.2 deletion syndrome. Current Psychiatry Reports. 2008;10(2):148-157. doi:10.1007/s11920-008-0026-1
43. 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.2017.00322
44. 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/s41380-018-0041-5
45. 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.2013.11.003
46. 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.2013.30
47. 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.2013.165
48. 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.2012.02.018
49. 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)90349-4
50. 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)90038-3
51. 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/sbr134
52. 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.2016.04.035
53. Uhlhaas PJ, Singer W. Abnormal neural oscillations and synchrony in schizophrenia. Nature Reviews Neuroscience. 2010;11(2):100-113. doi:10.1038/nrn2774
54. 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.2017.08.063
55. 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.2014.06.005
56. 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.2016.04.037
57. 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.x
58. 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.x
59. Stępnicki P, Kondej M, Kaczor AA. Current concepts and treatments of schizophrenia. Molecules. 2018;23(8). doi:10.3390/molecules23082087
60. 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.38544
61. 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, Nordström 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.1992.01820070032005
63. Nordström 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-O
64. 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.2012.47
65. Kim DH, Stahl SM. Antipsychotic drug development. Current Topics in Behavioral Neurosciences. 2010;4:124-139. doi:10.1007/7854_2010_47
66. 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/ijms19103105
67. Mocci G, Jiménez-Sánchez L, Adell A, Cortés 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.2013.10.021
68. 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:10.2174/1568026616661608084834
69. 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.4001556
71. 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:10.1080/14737175.2016.1174577
72. 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.2019.4379
73. Blair HA. Lumateperone: First Approval. Drugs. 2020;80(4):417-423. doi:10.1007/s40265-020-01271-6
74. FDA Label. Lumateperone Drug Prescribing and Safety Information. Accessed July 20, 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209500s000lbl.pdf
75. 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/s41386-018-0251-1
76. Kantrowitz JT. The Potential Role of Lumateperone - Something Borrowed? Something New? JAMA Psychiatry. 2020;77(4):343-344. doi:10.1001/jamapsychiatry.2019.4265
77. 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.2019.06.008
78. 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/s00213-014-3704-1
79. Greenwood J, Acharya RB, Marcellus V, Rey JA. Lumateperone: A Novel Antipsychotic for Schizophrenia. Annals of Pharmacotherapy. Published online June 26, 2020:106002802093659. doi:10.1177/1060028020936597
80. 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.2015.08.026
81. 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.2019.09.642
82. Meyer JM. Lumateperone for schizophrenia. Current Psychiatry. 2020;19(2):33-39.


Conflict of interest
None of the authors of this manuscript have any conflicts of interest
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