Skip to main navigation menu Skip to main content Skip to site footer

No. 1 (2026)

GENERAL THERAPY QUESTIONS AND REVIEWS

Hematological Adverse Effects of Antipsychotic Therapy

https://doi.org/10.48612/psyph/9nfd-764f-66v1

Published 2026-03-30

  • E.G. Lisina
    • ,
  • A.V. Golenkov

E.G. Lisina
Chuvash State University named after I.N. Ulyanov

A.V. Golenkov
Chuvash State University named after I.N. Ulyanov

Abstract

Background. Hematological adverse effects of antipsychotic therapy are rare but potentially life-threatening complications and include neutropenia, agranulocytosis, thrombocytopenia, anemia, eosinophilia, and, in rare cases, pancytopenia. Although clozapine has been studied most extensively, literature data indicate that other typical and atypical antipsychotics may also cause hematological toxicity.

Aim — to summarize current evidence on hematological adverse effects of antipsychotic drugs, associated mechanisms and risk factors, and to outline principles of clinical monitoring.

Materials and methods. A narrative review of the literature was conducted, covering 75 publications for the period 1978–2025, which were selected according to the criteria of clinical and laboratory verification of hematological disorders associated with antipsychotic therapy.

Results. Hematological complications may occur with both first-generation and second-generation antipsychotics. The most clinically significant reactions are neutropenia and agranulocytosis, predominantly during the early phase of treatment. The largest number of reported cases of cytopenias are associated with the prescription of clozapine, which is the only drug from the antipsychotic group that has approved rules for hematological monitoring. Current concepts of the pathogenesis of drug-induced cytopenias are discussed, distinguishing idiosyncratic immune-mediated reactions from dose-dependent myelotoxic effects. A unified algorithm for hematological monitoring of antipsychotic drugs is proposed. Particular attention is given to polypharmacy, DRESS syndrome, and the perspectives of pharmacogenomics (including HLA associations) as a potential tool for risk stratification.

Conclusion. Hematological safety of antipsychotic therapy requires regular laboratory monitoring, individualized risk assessment, and a multidisciplinary approach, especially when high-risk agents are used and when vulnerability factors are present. Promising strategies to reduce the incidence of severe complications include the development of pharmacogenomic predictors and the optimization of monitoring protocols based on contemporary evidence.

Keywords

antipsychotics, hematological adverse effects, neutropenia, agranulocytosis, clozapine, hematological monitoring

PDF (Русский)

References

  1. Balon R., Berchou R. Hematologic side effects of psychotropic drugs // Psychosomatics. – 1986. – Vol. 27 (2). – Pp. 119–127. – https://doi.org/10.1016/S0033-3182(86)72722-9
  2. Oyesanmi O., Kunkel E.J., Monti D.A., Field H.L. Hematologic side effects of psychotropics // Psychosomatics. – 1999. – Vol. 40 (5). – Pp. 414–421. – https://doi.org/10.1016/S0033-3182(99)71206-5
  3. Flanagan R.J., Dunk L. Haematological toxicity of drugs used in psychiatry // Hum Psychopharmacol. – 2008. – Vol. 23. – Pp. 27–41. – https://doi.org/10.1002/hup.917
  4. Latif Z., Malik M.A., Jabbar F., Ahmed Y., McDonough C. Clozapine-induced late leukopenia // Ir J Med Sci. – 2012. – Vol. 181 (1). – Pp. 139–141. – https://doi.org/10.1007/s11845-010-0587-y
  5. Lu Y., Wu B., Li K., Liu Z., Chen Y., Xu T. Drug-induced agranulocytosis: a disproportionality analysis and umbrella review // Front Pharmacol. – 2025. – Vol. 16. – Art. 1641747. – https://doi.org/10.3389/fphar.2025.1641747
  6. Grover S., Shouan A., Chakrabarti S., Avasthi A. Haematological side effects associated with clozapine: A retrospective study from India // Asian J Psychiatr. – 2020. – Vol. 48. – Art. 101906. – https://doi.org/10.1016/j.ajp.2019.101906
  7. Lambert D., Nothem M.E., Kobylarz Z., Scholcoff C. A medication hiccup: Chlorpromazine-induced agranulocytosis in a 72-year-old male // WMJ: Off Publ State Med Soc Wis. – 2022. – Vol. 121 (3). – Pp. E60–E62.
  8. Korkmaz S., Yıldız S., Korucu T., Gundogan B., Sunbul Z.E., Korkmaz H., Atmaca M. Frequency of anemia in chronic psychiatry patients // Neuropsychiatr Dis Treat. – 2015. – Vol. 22 (11). – Pp. 2737–2741. – https://doi.org/10.2147/NDT.S91581
  9. Buckley P.F., Meltzer H.Y. Treatment of schizophrenia // The Textbook of Psychopharmacology. – 1st Edition. – Edited by A.F. Schatzberg, C.B. Nemeroff. – Washington, DC: American Psychiatric Press, 1995. – P. 627.
  10. Pushpakumara J., Karunarathna P., Sivathiran S., Liyanage A., Indrakumar J. Clozapine induced pancytopenia leading to severe sepsis: An unusual early complication // BMC Res Notes. – 2015. – Vol. 16 (8). – Art. 792. – https://doi.org/10.1186/s13104-015-1777-5
  11. Pang N., Thrichelvam N., Naing K.O. Olanzapine-induced pancytopenia: A rare but worrying complication // East Asian Arch Psychiatry. – 2017. – Vol. 27. – Pp. 35–37.
  12. Goyal L., Acebo R., Islam S., Ajmera K., Kaasam S. A rare case of risperidone-induced hypothermia and thrombocytopenia // Cureus. – 2022. – Vol. 9, no. 14 (5). – e24836. – https://doi.org/10.7759/cureus.24836
  13. Fan K.Y., Chen W.Y., Huang M.C. Quetiapine-associated leucopenia and thrombocytopenia: A case report // BMC Psychiatry. – 2015. – Vol. 7 (15). – Art. 110. – https://doi.org/10.1186/s12888-015-0495-9
  14. Oyewumi L.K. Acquired aplastic anemia secondary to perphenazine // Can J Clin Pharmacol. – 1999. – Vol. 6. – Pp. 169-171.
  15. Stübner S., Grohmann R., Engel R., Bandelow B., Ludwig W.D., Wagner G., Müller-Oerlinghausen B., Möller H.J., Hippius H., Rüther E. Blood dyscrasias induced by psychotropic drugs // Pharmacopsychiatry. – 2004. – Vol. 37, suppl. 1. – Pp. 70–78. – https://doi.org/10.1055/s-2004-815513
  16. Остроумова О.Д., Кочетков А.И., Павлеева Е.Е., Кравченко Е.В. Лекарственно-индуцированные нейтропения и агранулоцитоз // Безопасность и риск фармакотерапии. – 2020. – Т. 8, № 3. – С. 109–122. – https://doi.org/10.30895/2312-7821-2020-8-3-109-122
  17. Тихонов Д.А., Горбунов А.А. Лекарственная нейтропения: возможные механизмы формирования // Экспериментальная и клиническая фармакология. – 2021. – Т. 84, № 10. – С. 37–43. – https://doi.org/10.30906/0869-2092-2021-84-10-37-43
  18. Duggal H.S., Singh I. Psychotropic drug-induced neutropenia // Drugs Today (Barc). – 2005. – Vol. 41 (8). – Pp. 517–526. – https://doi.org/10.1358/dot.2005.41.8.893629
  19. Andrès E., Maloisel F. Idiosyncratic drug-induced agranulocytosis or acute neutropenia // Curr Opin Hematol. – 2008. – Vol. 15. – Pp. 15–21. – https://doi.org/10.1097/MOH.0b013e3282f15fb9
  20. Curtis B.R. Non-chemotherapy drug-induced neutropenia: key points to manage the challenges // Hematology Am Soc Hematol Educ Program. – 2017. – Vol. 1. – Pp. 187–193. – https://doi.org/10.1182/asheducation-2017.1.187
  21. Fabrazzo M., Prisco V., Sampogna G., Perris F., Catapano F., Monteleone A.M., Maj M. Clozapine versus other antipsychotics during the first 18 weeks of treatment: A retrospective study on risk factor increase of blood dyscrasias // Psychiatry Res. – 2017. – Vol. 256. – Pp. 275–282. – https://doi.org/10.1016/j.psychres.2017.06.068
  22. Wiciński M., Węclewicz M.M. Clozapine-induced agranulocytosis/granulocytopenia: Mechanisms and monitoring // Curr Opin Hematol. – 2018. – Vol. 25 (1). – Pp. 22–28. – https://doi.org/10.1097/MOH.0000000000000391
  23. Burckart G.J., Snidow J., Bruce W. Neutropenia following acute chlorpromazine ingestion // Clin Toxicol. – 1981. – Vol. 18 (7). – Pp. 797–801. – https://doi.org/10.3109/15563658108990307
  24. Rahajeng B. Chlorpromazine-induced anemia in schizophrenia patient: A case-report // Proceedings of the International Conference on Sustainable Innovation on Health Sciences and Nursing (ICOSI-HSN 2022). – 2022. – https://doi.org/10.2991/978-94-6463-070-1_13
  25. Husain Z., Reddy B.Y., Schwartz R.A. DRESS syndrome: Part I. Clinical perspectives // J Am Acad Dermatol. – 2013. – Vol. 68 (5). – Pp. 693.e1–14. – https://doi.org/10.1016/j.jaad.2013.01.033
  26. Eshki M., Allanore L., Musette P., Milpied B., Grange A., Guillaume J.C., Chosidow O., Guillot I., Paradis V., Joly P., Crickx B., Ranger-Rogez S., Descamps V. Twelve-year analysis of severe cases of drug reaction with eosinophilia and systemic symptoms: A cause of unpredictable multiorgan failure // Arch Dermatol. – 2009. – Vol. 145 (1). – Pp. 67–72. – https://doi.org/10.1001/archderm.145.1.67
  27. Ghozlane L., Asma J., Ahmed Z., Ons C., Sarrah K., Riadh D., Sihem E.A. Antipsychotics induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: Literature review and a report of a suspected case related to chlorpromazine // Curr Drug Saf. – 2023. – Vol. 18 (4). – Pp. 571–575. – https://doi.org/10.2174/1574886317666220603104837
  28. Gowda S.M., Vijay Kumar K.G., Shilpa K. Chlorpromazine-induced drug reaction with eosinophilia and systemic symptoms syndrome // Indian J Psychol Med. – 2020. – Vol. 6, no. 42 (1). – Pp. 99–101. – https://doi.org/10.4103/IJPSYM.IJPSYM_364_19
  29. Кирилочев О.О. Осложнения терапии клозапином: актуализация информации // Современная терапия психических расстройств. – 2023. – № 3. – С. 12–20. – https://doi.org/10.21265/PSYPH.2023.11.37.002
  30. Atkin K., Kendall F., Gould D., Freeman H., Liberman J., O'Sullivan D. Neutropenia and agranulocytosis in patients receiving clozapine in the UK and Ireland // Br J Psychiatry. – 1996. – Vol. 169 (4). – Pp. 483–488. – https://doi.org/10.1192/bjp.169.4.483
  31. Dunk L.R., Annan L.J., Andrews C.D. Rechallenge with clozapine following leucopenia or neutropenia during previous therapy // Br J Psychiatry. – 2006. – Vol. 188. – Pp. 255–263. – https://doi.org/10.1192/bjp.188.3.255
  32. Li X.H., Zhong X.M., Lu L., Zheng W., Wang S.B., Rao W.W., Wang S., Ng C.H., Ungvari G.S., Wang G., Xiang Y.T. The prevalence of agranulocytosis and related death in clozapine-treated patients: A comprehensive meta-analysis of observational studies // Psychol Med. – 2020. – Vol. 50 (4). – Pp. 583–594. – https://doi.org/10.1017/S0033291719000369
  33. Thome J., Kopf D. Blutbildveränderungen unter Antipsychotika der Zweiten Generation // Psychiatr Prax. – 2005. – Vol. 32 (4). – Pp. 167–171. – https://doi.org/10.1055/s-2004-828330
  34. Peinado A.G., Ruiz P.C., Fraile S.C., Cano M.G., Fajardo G.E.B. Clozapine induced blood dyscrasias and a therapeutical approach // Eur Psychiatry. – 2016. – Vol. 33 (S1). – Art. S613. – https://doi.org/10.1016/j.eurpsy.2016.01.2293
  35. Lambertenghi Deliliers G. Blood dyscrasias in clozapine-treated patients in Italy // Haematologica. – 2000. – Vol. 85 (3). – Pp. 233–237.
  36. Hummer M., Kurz M., Barnas C., Saria A., Fleischhacker W.W. Clozapine-induced transient white blood count disorders // J Clin Psychiatr. – 1994. – Vol. 55. – Pp. 429–432.
  37. Chatterton R. Eosinophilia after commencement of clozapine treatment // Aust N Z J Psychiatry. – 1997. – Vol. 31 (6). – Pp. 874–876. – https://doi.org/10.3109/00048679709065515
  38. Verdoux H., Bittner R.A., Hasan A. et al. The time has come for revising the rules of clozapine blood monitoring in Europe. A joint expert statement from the European Clozapine Task Force // Eur Psychiatry. – 2025. – Vol. 68 (1). – e17. – https://doi.org/10.1192/j.eurpsy.2024.1816
  39. Honigfeld G., Arellano F., Sethi J., Bianchini A., Schein J. Reducing clozapine-related morbidity and mortality: 5 years of experience with the Clozaril National Registry // J Clin Psychiatry. – 1998. – Vol. 59, Suppl. 3. – Pp. 3–7.
  40. Myles N., Myles H., Xia S., Large M., Kisely S., Galletly C., Bird R., Siskind D. Meta-analysis examining the epidemiology of clozapine-associated neutropenia // Acta Psychiatr Scand. – 2018. – Vol. 138 (2). – Pp. 101–109. – https://doi.org/10.1111/acps.12898
  41. Huang W., Lin C., Liao S. Decreased white blood cell count related to haloperidol add-on treatment to olanzapine // Taiwan J Psychiatr. – 2011. – Vol. 25 (2). – Pp. 115–118.
  42. Şahan E. Haloperidol-related neutropenia // Indian J Psychiatry. – 2019. – Vol. 61 (3). – Pp. 307–310. – https://doi.org/10.4103/psychiatry.IndianJPsychiatry_152_18
  43. Jagtiani A., Veigne S., Gandhi R., Rizvi A. Haloperidol decanoate-induced pancytopenia: A case report // Cureus. – 2023. – Vol. 20, no. 15 (10). – e47402. – https://doi.org/10.7759/cureus.47402
  44. Bouvier M.L., Fehsel K., Schmitt A., Meisenzahl-Lechner E., Gaebel W., von Wilmsdorff M. Sex-dependent effects of long-term clozapine or haloperidol medication on red blood cells and liver iron metabolism in Sprague Dawley rats as a model of metabolic syndrome // BMC Pharmacol Toxicol. – 2022. – Vol. 15, no. 23 (1). – Art. 8. – https://doi.org/10.1186/s40360-021-00544-4
  45. Wasti A., Zahid S., Ahmed N. Antipsychotic drugs induced iron deficiency anemia in schizophrenic patients // Int J Advanced Res. – 2013. – Vol. 1 (10). – Pp. 111–118.
  46. Correll C.U., Kim E., Sliwa J.K., Hamm W., Gopal S., Mathews M., Venkatasubramanian R., Saklad S.R. Correction: Pharmacokinetic characteristics of long-acting injectable antipsychotics for schizophrenia: An overview // CNS Drugs. – 2025. – Vol. 39 (1). – Pp. 111–112. – https://doi.org/10.1007/s40263-024-01138-4
  47. Kattalai Kailasam V., Chima V., Nnamdi U., Sharma K., Shah K. Risperidone-induced reversible neutropenia // Neuropsychiatr Dis Treat. – 2017. – Vol. 25 (13). – Pp. 1975–1977. – https://doi.org/10.2147/NDT.S141472
  48. Semba J., Okui S. Risperidone-induced thrombocytopenia: A case report // Gen Hosp Psychiatry. – 2009. – Vol. 31 (1). – Pp. 97–98. – https://doi.org/10.1016/j.genhosppsych.2008.06.005
  49. Chawath S., Ramdurg S., Badiger S., Chaukimath S.P. Risperidone-induced anaemia // Natl Med J India. – 2023. – Vol. 36 (1). – Pp. 22–23. – https://doi.org/10.25259/NMJI_115_20
  50. Cowan C., Oakley C. Leukopenia and neutropenia induced by quetiapine // Prog Neuropsychopharmacol Biol Psychiatry. – 2007. – Vol. 30, no. 31 (1). – Pp. 292–294. – https://doi.org/10.1016/j.pnpbp.2006.07.003
  51. Shankar B.R. Quetiapine-induced leucopenia and thrombocytopenia // Psychosomatics. – 2007. – Vol. 48 (6). – Pp. 530–531. – https://doi.org/10.1176/appi.psy.48.6.530
  52. Oluboka O., Haslam D., Lam T., Bown-Demarco D. Quetiapine-induced leucopenia: Possible dosage-related phenomenon // Can J Psychiatry. – 2003. – Vol. (1). – Pp. 65–66. – https://doi.org/10.1177/070674370304800116
  53. Chih-Jen Wang M.D., Cheng-Chen Chang M.D., Si-Sheng Huang M.D. Leucopoenia induced by quetiapine in a patient with history of clozapine-induced leucopenia // Taiwanese J Psychiatry (Taipei). – 2011. – Vol. 25. – Pp. 191–194.
  54. Buchman N., Strous R.D., Ulman A.M., Lerner M., Kotler M. Olanzapine-induced leukopenia with human leukocyte antigen profiling // Int Clin Psychopharmacol. – 2001. – Vol. 16. – Pp. 55–57. – https://doi.org/10.1097/00004850-200101000-00007
  55. Nooijen P.M., Carvalho F., Flanagan R.J. Haematological toxicity of clozapine and some other drugs used in psychiatry // Hum Psychopharmacol. – 2011. – Vol. 26. – Pp. 112–119. – https://doi.org/10.1002/hup.1181
  56. Malhotra K., Vu P., Wang D.H., Lai H., Faziola L.R. Olanzapine-induced neutropenia // Ment Illn. – 2015. – Vol. 7 (5871). – Pp. 18–20. – https://doi.org/10.4081/mi.2015.5871
  57. Grover S., Hegde A., Agarwal M., Sachdeva M.S. Olanzapine-associated leukopenia and thrombocytopenia managed with lithium in a patient who developed leukopenia with clozapine in the past: A case report // Prim Care Companion CNS Disord. – 2012. – Vol. 14 (6). – PCC.12l01367. – https://doi.org/10.4088/PCC.12l01367
  58. Dernovsek M.Z., Tavcar R. Olanzapine appears haematologically safe in patients who developed blood dyscrasia on clozapine and risperidone // Int Clin Psychopharmacol. – 2000. – Vol. 15 (4). – Pp. 237–238. – https://doi.org/10.1097/00004850-200015040-00008
  59. Pickard L., Fordham N., Koh M. Amisulpride induced agranulocytosis: a case report // Ann Hematol. – 2016. – Vol. 95 (7). – Pp. 1193–1195. – https://doi.org/10.1007/s00277-016-2656-4
  60. Mielczarek Z., Trędzbor B., Piekarska-Bugiel K., Krysta K. Neutropenia in a schizophrenia patient following combined lurasidone and paliperidone therapy: a case report // Postep Psychiatr Neurol. – 2023. – Vol. 32 (3). – Pp. 152–155. – https://doi.org/10.5114/ppn.2023.132474
  61. Sood S. Neutropenia with multiple antipsychotics including dose dependent neutropenia with lurasidone // Clin Psychopharmacol Neurosci. – 2017. – Vol. 15. – Pp. 413–415.
  62. Rafi M., Goyal C., Reddy P., Reddy S. Lurasidon induced thrombocytopenia: Is it a signal of drug induced myelosuppression? // Indian J Psychol Med. – 2018. – Vol. 40. – Pp. 191–192.
  63. Pisciotta V. Drug-induced agranulocytosis // Drugs. – 1978. – Vol. 15 (2). – Pp. 132–143. – https://doi.org/10.2165/00003495-197815020-00003
  64. Мосолов С.Н., Малин Д.И., Рывкин П.В., Сычев Д.А. Лекарственные взаимодействия препаратов, применяемых в психиатрической практике // Современная терапия психических расстройств. – 2019. – № S1. – С. 2–35. – https://doi.org/10.21265/PSYPH.2019.50.40828
  65. Reese J.A., Li X., Hauben M., Aster R.H., Bougie D.W., Curtis B.R., George J.N., Vesely S.K. Identifying drugs that cause acute thrombocytopenia: an analysis using 3 distinct methods // Blood. – 2010. – Vol. 23, no. 116 (12). – Pp. 2127–2133. – https://doi.org/10.1182/blood-2010-03-276691
  66. Aster R.H. Drug-induced thrombocytopenia // Platelets. – 4th ed. – A.D. Michelson, M. Cattaneo, A. Frelinger, P.J. Newman, eds. – Cambridge, MA, USA: Academic Press, 2019. – Pp. 725–739.
  67. Ten Berg M.J., Huisman A., Souverein P.C., Schobben A.F.A.M., Egberts A.C.G., van Solinge W.W., van Den Bemt P.M.L.A. Drug-induced thrombocytopenia: A population study // Drug Saf. – 2006. – Vol. 29. – Pp. 713–721. – https://doi.org/10.2165/00002018-200629080-00008
  68. Vayne C., Guéry E.A., Rollin J., Baglo T., Petermann R., Gruel Y. Pathophysiology and diagnosis of drug-induced immune thrombocytopenia // J Clin Med. – 2020. – Vol. 13, no. 9 (7). – Art. 2212. – https://doi.org/10.3390/jcm9072212
  69. Lundh B., Hasselgren K.H. Hematological side effects from antihypertensive drugs // Acta Med Scand Suppl. – 1979. – Vol. 628. – Pp. 73–75. – https://doi.org/10.1111/j.0954-6820.1979.tb00782.x
  70. Trimble M.A., Sketch M.H. Jr., Mehta R.H. Hemolytic anemia: A rare but potentially serious adverse effect of captopril // Herz. – 2007. – Vol. 32 (1). – Pp. 62–64. – https://doi.org/10.1007/s00059-007-2956-5
  71. Myles N., Myles H., Xia S., Large M., Bird R., Galletly C., Kisely S., Siskind D. A meta-analysis of controlled studies comparing the association between clozapine and other antipsychotic medications and the development of neutropenia // Aust N Z J Psychiatry. – 2019. – Vol. 53 (5). – Pp. 403–412. – https://doi.org/10.1177/0004867419833166
  72. Ali M., Mufti A.A., Razaq A., Zafar Ali H., Deforce D., Gansemans Y., van Nieuwerburgh F. A retrospective study on clozapine-induced blood dyscrasias in the first 20 weeks of therapy // J Psychiatr Res. – 2025. – Vol. 91. – Pp. 491–500. – https://doi.org/10.1016/j.jpsychires.2025.09.081
  73. Alhaj H.A., Samara J., Alnamous A., Karima R., Saber-Ayad M. Advancing drug safety in psychiatry: Insights from pharmacogenomics of hypersensitivity reactions // Front Pharmacol. – 2025. – Vol. 19 (16). – Art. 1651898. – https://doi.org/10.3389/fphar.2025.1651898
  74. Okhuijsen-Pfeifer C., van der Horst M.Z., Luykx J.J. Op naar een gepersonaliseerde clozapinebehandeling // Tijdschr Psychiatr. – 2023. – Vol. 65 (2). – Pp. 107–112.
  75. Islam F., Hain D., Lewis D., Law R., Brown L.C., Tanner J.A., Müller D.J. Pharmacogenomics of Clozapine-induced agranulocytosis: A systematic review and meta-analysis // Pharmacogenomics J. – 2022. – Vol. 22 (4). – Pp. 230–240. – https://doi.org/10.1038/s41397-022-00281-9

Downloads

Download data is not yet available.