Comparative Study: Olanzapine and Lumateperone as Antipsychotic Drugs
Vasudha S Bavadekar1*, Angha M Joshi1, Manasi Wagdarikar2, Keren Jadhav3, Pratiksha Khandare3
1Department of Pharmaceutical Chemistry, SCES’s Indira College of Pharmacy, Tathawade, Pune-411033, India
1Savitribai Phule Pune University, Pune, Maharashtra, India
2Indira University’s School of Pharmacy, Pune, Maharashtra, India
3Department of Pharmacy Practice, Modern College of Pharmacy, Nigdi, Pune-411044, Maharashtra, India
Received: 6th May, 2025; Revised: 13th Jul 2025; Accepted: 8th Aug, 2025; Available Online: 25th Sep, 2025
ABSTRACT
A new antipsychotic drug called Lumateperone has shown promise in the treatment of bipolar disorder and schizophrenia. It works by modulating dopaminergic, serotonergic, and glutamatergic neurotransmission. One characteristic that sets this dual-acting drug apart from other antipsychotics is its intermediate affinity for D 2 receptors and high affinity for 5- HT2A receptors. According to clinical research, Lumateperone effectively reduces the symptoms of schizophrenia while having a relatively low risk of extrapyramidal symptoms and metabolic abnormalities. Notably, Lumateperone pharmacokinetic profile is characterized by extensive metabolism and low bioavailability, underscoring the significance of cautious dosage and possible medication interactions. Comparative research with the well-known antipsychotic Olanzapine has shown that Lumateperone is more tolerable and has a lower risk of weight gain and negative metabolic consequences. Clarifying Lumateperone effects on neurotransmitter systems and investigating for the clinical features of schizophrenia are two future research directions. The ultimate goal is precision medicine techniques that are adjusted to meet the needs of each patient. Lumateperone, with its distinct therapeutic profile and enhanced tolerability as antipsychotic drug.
Keywords: Lumateperone, Olanzapine, Comparative research, antipsychotic, pharmacokinetic profile
How to cite this article: Vasudha S Bavadekar, Angha M Joshi, Manasi Wagdarikar, Keren Jadhav, Pratiksha Khandare. Comparative Study: Olanzapine and Lumateperone as Antipsychotic Drugs. International Journal of Drug Delivery Technology. 2025;15(3):1417-25. doi: 10.25258/ijddt.15.3.65
REFERENCES
- 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: 1080/00325481.2019.1701823
- Prommer E. Olanzapine: Palliative Medicine Update. American Journal of Hospice and Palliative Medicine. 2012;30(1):75-82. DOI: 1177/1049909112441241
- Bymaster FP, Calligaro DO, Falcone JF, Marsh RD, Moore NA, Tye NC, Seeman P, Wong DT. Radioreceptor Binding Profile of the Atypical Antipsychotic Olanzapine. Neuropsychopharmacology. 1996;14(2):87-96
- Elsayem A, Bush SH, Munsell MF. Subcutaneous Olanzapine for Hyperactive or Mixed Delirium in Patients with Advanced Cancer: A Preliminary Study. Journal of Pain and Symptom Management. 2010;40(5):774-82. DOI: 1016/j.jpainsymman.2010.02.024
- Callaghan JT, Bergstrom RF, Ptak LR, Beasley CM. Olanzapine: Pharmacokinetic and Pharmacodynamic Profile. Clinical Pharmacokinetics. 1999;37(3):177-93. DOI: 2165/00003088-199937030-00001
- Conley RR, Meltzer HY. Adverse Events Related to Olanzapine. The Journal of Clinical Psychiatry. 2000;61(8)(supplement 8):26-9; discussion 30. https://pubmed.ncbi.nlm.nih.gov/10811240
- Bhana N, Foster RH, Olney R, Plosker GL. Olanzapine: An Updated Review of Its Use in the Management of Schizophrenia. Drugs. 2001;61(1):111-61. DOI: 2165/00003495-200161010-00011
- Matza LS, Baker TM, Revicki DA. Efficacy of Olanzapine and Ziprasidone for the Treatment of Schizophrenia: A Systematic Review. CNS Drugs. 2005;19(6):499-515. DOI: 2165/00023210-200519060-00003
- DePietro T. Lumateperone: A Truly Innovative Antipsychotic Medication? American Journal of Psychiatry Residents’ Journal. 2023;18(3):18-20. DOI: 1176/appi.ajp-rj.2023.180306
- Snyder GL, Vanover KE, Zhu H, et al. Functional Profile of a Novel Modulator of Serotonin, Dopamine, and Glutamate Neurotransmission. Psychopharmacology. 2015;232(3):605-21. DOI: 1007/s00213-014-3704-1
- Calabrese JR, Durgam S, Satlin A. Efficacy and Safety of Lumateperone for Major Depressive Episodes Associated with Bipolar I or Bipolar II Disorder: A Phase 3 Randomized Placebo-Controlled Trial. American Journal of Psychiatry. 2021;178(11):1098-106. DOI: 1176/appi.ajp.2021.20071006
- Jawad MY, Alnefeesi Y, Ceban F, et al. Lumateperone for the Treatment of Adults with Schizophrenia: A Systematic Review. Current Psychiatry Reports. 2022;24(8):359-68. DOI: 1007/s11920-022-01344-1
- Thomas K, Saadabadi A. Olanzapine. StatPearls Publishing, 2023. Available on: https://pubmed.ncbi.nlm.nih.gov/30422498/
- Kantrowitz JT, Citrome L. Olanzapine: Review of Safety 2008. Expert Opinion on Drug Safety. 2008 Nov;7(6):761-9. DOI: 1517/14740330802423234
- Citrome L, Holt RI, Walker DJ, Hoffmann VP. Weight Gain and Changes in Metabolic Variables Following Olanzapine Treatment in Schizophrenia and Bipolar Disorder. Clinical Drug Investigation. 2011;31(7):455-82. DOI: 2165/11589060-000000000-00000
- Detke HC, DelBello MP, Landry J, Hoffmann VP, Heinloth A, Dittmann RW. A 52-Week Study of Olanzapine with a Randomized Behavioral Weight Counseling Intervention in Adolescents with Schizophrenia or Bipolar I Disorder. Journal of Child and Adolescent Psychopharmacology. 2016;26(10):922-34. DOI: 1089/cap.2016.0010
- Schulz C, Haight RJ. Safety of Olanzapine Use in Adolescents. Expert Opinion on Drug Safety. 2013;12(5):777-82. DOI: 1517/14740338.2013.815164
- Citrome L, McEvoy JP, Todtenkopf MS, McDonnell D, Weiden PJ. A Commentary on the Efficacy of Olanzapine for the Treatment of Schizophrenia: The past, Present, and Future. Neuropsychiatric Disease and Treatment. 2019;15:2559-69. DOI: 2147/NDT.S209284
- McDonnell DP, Landry J, Detke HC. Long-Term Safety and Efficacy of Olanzapine Long-Acting Injection in Patients with Schizophrenia or Schizoaffective Disorder: A 6-Year, Multinational, Single-Arm, Open-Label Study. International Clinical Psychopharmacology. 2014;29(6):322-31. DOI: 1097/YIC.0000000000000038
- Kolli P, Kelley G, Rosales M, Faden J, Serdenes R. Olanzapine Pharmacokinetics: A Clinical Review of Current Insights and Remaining Questions. Pharmacogenomics and Personalized Medicine. 2023;16(1):1097-108. DOI: 2147/PGPM.S391401
- Cooper D, Lumateperone GV. StatPearls Publishing, 2023. Available on: https://www.ncbi.nlm.nih.gov/books/NBK560844/
- Greenwood J, Acharya RB, Marcellus V, Rey JA. Lumateperone: A Novel Antipsychotic for Schizophrenia. The Annals of Pharmacotherapy. 2021;55(1):98-104. DOI: 1177/1060028020936597
- Snyder GL, Vanover KE, Davis RE, Li P, Fienberg A, Mates S. A Review of the Pharmacology and Clinical Profile of Lumateperone for the Treatment of Schizophrenia. Advances in Pharmacology. 2021;90:253-76. DOI: 1016/bs.apha.2020.09.001
- Sowa-Kućma M, Pańczyszyn-Trzewik P, Jaeschke RR. Exploring the Pharmacological and Clinical Features of Lumateperone: A Promising Novel Antipsychotic. International Journal of Molecular Sciences. 2024;25(24):13289. DOI: 3390/ijms252413289
- 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. Schizophrenia Research. 2021;228:198-205. DOI: 1016/j.schres.2020.12.006
- Correll CU, Davis RE, Weingart M, Saillard J, O’Gorman C, Kane JM, Lieberman JA, Tamminga CA, Mates S, Vanover KE. Efficacy and Safety of Lumateperone for Treatment of Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. 2020;77(4):349-58. DOI: 1001/jamapsychiatry.2019.4379
- Tarzian M, Ndrio M, Chique B, Serai J, Thalackal B, Lau J, Fakoya AO. Illuminating Hope for Mental Health: A Drug Review on Lumateperone. Cureus. 2023;15(9):e46143. DOI: 7759/cureus.46143
- Longo G, Cicolini A, Orsolini L, Volpe U. The Novel Antipsychotic Lumateperone (ITI-007) in the Treatment of Schizophrenia: A Systematic Review. Brain Sciences. 2023;13(12):1641. DOI: 3390/brainsci13121641
- Fulton B, Goa KL. Olanzapine A Review of Its Pharmacological Properties and Therapeutic Efficacy in the Management of Schizophrenia and Related Psychoses. Drugs. 1997;53(2):281-98. DOI: 2165/00003495-199753020-00007
- Wojtasik-Bakalarz K, Siwek M. New Antipsychotic Medication. Pharmacotherapy in Psychiatry and Neurology. 2023;39(1):19-38. DOI: 5114/fpn.2022.124608
- Syed AB, Brašić JR. The Role of Lumateperone in the Treatment of Schizophrenia. Therapeutic Advances in Psychopharmacology. 2021;11:20451253211034019. DOI: 1177/20451253211034019
- Tsapakis EM, Diakaki K, Miliaras A, Fountoulakis KN. Novel Compounds in the Treatment of Schizophrenia: A Selective Review. Brain Sciences. 2023;13(8):1193. DOI: 3390/brainsci13081193
- Haddad PM, Correll CU. The Acute Efficacy of Antipsychotics in Schizophrenia: A Review of Recent Meta-analyses. Therapeutic Advances in Psychopharmacology. 2018;8(11):303-18. DOI: 1177/2045125318781475
- Lumateperone BHA. First Approval. Drugs. 2020;80:417-23. DOI: 1007/s40265-020-01278-5
- Stephenson CM, Pilowsky LS. Psychopharmacology of Olanzapine. A Review. The British Journal of Psychiatry. Supplement. 1999;(38):52-8. https://pubmed.ncbi.nlm.nih.gov/10884900
- Vyas P, Hwang BJ, Brašić JR. An Evaluation of Lumateperone Tosylate for the Treatment of Schizophrenia. Expert Opinion on Pharmacotherapy. 2020;21(2):139-45. DOI: 1080/14656566.2019.1695778
- Kaczmarek A, Szymajda W, Dettlaff K. Lumateperone in the Treatment of Psychiatric Disorders – A Review of the Literature. Pharmacotherapy in Psychiatry and Neurology. 2023;39(1):39-52. DOI: 5114/fpn.2023.127423
- Tazi A, Errachidi F, Sonawane D, Tahri G, Rao S, Mehta S. An Economic Model to Understand the Cost-Effectiveness of Olanzapine Orally Dispersible Tablets (ODT) and Olanzapine Film Coated Tablets as A Group Compared with Other Oral Atypical Antipsychotics for Treating Schizophrenia in Morocco. Annals of General Psychiatry. 2024 Sep 18;23(1). https://annals-general-psychiatry.biomedcentral.com/articles/10.1186/s12991-024-00516-y:33
- Chen J, Ascher-Svanum H, Nyhuis AW, Case MG, Phillips GA, Schuh KJ, Hoffmann VP. Reasons for Continuing or Discontinuing Olanzapine in the Treatment of Schizophrenia from the Perspectives of Patients and Clinicians. Patient Preference and Adherence. 2011;5:547-54. DOI: 2147/PPA.S23255
- Tollefson GD, Kuntz AJ. Review of Recent Clinical Studies with Olanzapine. The British Journal of Psychiatry. Supplement. 1999;174(37):30-5. https://pubmed.ncbi.nlm.nih.gov/10211139
- Bymaster F, Perry KW, Nelson DL, Wong DT, Rasmussen K, Moore NA, Calligaro DO. Olanzapine: A Basic Science Update. The British Journal of Psychiatry. Supplement. 1999;(37):36-40. https://pubmed.ncbi.nlm.nih.gov/10211140
- Chue P, Chue J. A Review of Olanzapine Pamoate. Expert Opinion on Pharmacotherapy. 2012;13(11):1661-70. DOI: 1517/14656566.2012.686169
- Edinoff A, Wu N, deBoisblanc C et al. Lumateperone for the Treatment of Schizophrenia. Psychopharmacology Bulletin. 2020;50(4):32-59. https://pubmed.ncbi.nlm.nih.gov/33012872
- Kantrowitz JT. The Potential Role of Lumateperone – Something Borrowed? JAMA Psychiatry. 2020;77(4):343-4. DOI: 1001/jamapsychiatry.2019.4265
- Suppes T, Durgam S, Kozauer SG et al. Adjunctive Lumateperone (ITI‐007) in the Treatment of Bipolar Depression: Results from a Randomized Placebo-Controlled Clinical Trial. Bipolar Disorders. 2023;25(6):478-88. DOI: 1111/bdi.13310
- Mohamed W. In: Essential Guide to Neurodegenerative Disorders Mechanistic, Diagnostic and Therapeutic Advances Atypi. Cal Antipsychotic Lumateperone Beyond Schizophrenia: Seeking Clarity in A Time of Uncertainty. Elsevier, London. pp. 461-7