Neuroleptic Malignant Syndrome - review of pathophysiology, clinical presentation, differentiation and management
DOI:
https://doi.org/10.12775/JEHS.2024.67.49175Keywords
NMS, neuroleptic malignant symptom, adverse effect, neurolepticsAbstract
Introduction and purpose: The number of invented and produced medications has increased over recent years. Besides their positive impact on health, they invariably provide various kinds of side effects. This review is focused on malignant neuroleptic syndrome, a rare condition with no fully confirmed pathogenesis, which at least partially can be explained as an adverse effect of blocking dopamine receptors. Even though it usually affects psychiatric or neurological patients, doctors of all medical specializations should stay alert, as the condition can often lead to premature death.
Brief description of knowledge: The main symptoms associated with NMS are hypertonia, hyperpyrexia, autonomic instability and altered consciousness. They can appear in any configuration, sometimes followed by less characteristic manifestations. It should be primarily differentiated from serotonin syndrome, malignant hyperpyrexia and catatonia, mostly through the interview of those who have taken medications and undergone surgeries, as there are not any specific lab tests available. Fundamental treatment methods consist of neuroleptic withdrawal, intensive supportive care, drug administration and eventually ECT.
Summary: NMS is an uncommon, severe disease that should be carefully considered in patients treated with neuroleptics. Due to its rarity and sudden onset, it appears to be problematic to conduct widespread research and studies, so there are still no concrete, consistent and unquestioned guidelines on recognizing and treating the condition.
References
Pelonero AL, Levenson JL, Pandurangi AK. Neuroleptic malignant syndrome: a review. Psychiatr Serv. 1998;49(9):1163-1172. doi:10.1176/ps.49.9.1163
Barnes TR, Drake R, Paton C, et al. Evidence-based guidelines for the pharmacological treatment of schizophrenia: Updated recommendations from the British Association for Psychopharmacology. J Psychopharmacol (Oxford). 2020;34(1):3-78. doi:10.1177/0269881119889296
Pileggi DJ, Cook AM. Neuroleptic Malignant Syndrome. Ann Pharmacother. 2016;50(11):973-981. doi:10.1177/1060028016657553
Buckley PF, Hutchinson M. Neuroleptic malignant syndrome. J Neurol Neurosurg Psychiatr. 1995;58(3):271-273. doi:10.1136/jnnp.58.3.271
Strawn JR, Keck PE, Caroff SN. Neuroleptic malignant syndrome. Am J Psychiatry. 2007;164(6):870-876. doi:10.1176/ajp.2007.164.6.870
Ossowska K. Neuronal basis of neuroleptic-induced extrapyramidal side effects. Pol J Pharmacol. 2002;54(4):299-312.
Kyotani Y, Zhao J, Nakahira K, Yoshizumi M. The role of antipsychotics and other drugs on the development and progression of neuroleptic malignant syndrome. Sci Rep. 2023;13(1):18459. doi:10.1038/s41598-023-45783-z
Tse L, Barr A, Scarapicchia V, Vila-Rodriguez F. Neuroleptic Malignant Syndrome: A Review from a Clinically Oriented Perspective. CN. 2015;13(3):395-406. doi:10.2174/1570159X13999150424113345
Adnet P, Lestavel P, Krivosic-Horber R. Neuroleptic malignant syndrome. Br J Anaesth. 2000;85(1):129-135. doi:10.1093/bja/85.1.129
Berman BD. Neuroleptic malignant syndrome: a review for neurohospitalists. Neurohospitalist. 2011;1(1):41-47. doi:10.1177/1941875210386491
Su YP, Chang CK, Hayes RD, et al. Retrospective chart review on exposure to psychotropic medications associated with neuroleptic malignant syndrome. Acta Psychiatr Scand. 2014;130(1):52-60. doi:10.1111/acps.12222
Misawa F, Okumura Y, Takeuchi Y, Fujii Y, Takeuchi H. Neuroleptic malignant syndrome associated with long-acting injectable versus oral second-generation antipsychotics: Analyses based on a spontaneous reporting system database in Japan. Schizophr Res. 2021;231:42-46. doi:10.1016/j.schres.2021.02.016
Berardi D, Amore M, Keck PE, Troia M, Dell’Atti M. Clinical and pharmacologic risk factors for neuroleptic malignant syndrome: a case-control study. Biol Psychiatry. 1998;44(8):748-754. doi:10.1016/s0006-3223(97)00530-1
Keck PE, Pope HG, Cohen BM, McElroy SL, Nierenberg AA. Risk factors for neuroleptic malignant syndrome. A case-control study. Arch Gen Psychiatry. 1989;46(10):914-918. doi:10.1001/archpsyc.1989.01810100056011
Langan Martin J, Martin DJ. Neuroleptic Malignant Syndrome. In: Life-Threatening Effects of Antipsychotic Drugs. Elsevier; 2016:223-240. doi:10.1016/B978-0-12-803376-0.00010-1
Viejo LF, Morales V, Puñal P, Pérez JL, Sancho RA. Risk factors in neuroleptic malignant syndrome. A case-control study. Acta Psychiatr Scand. 2003;107(1):45-49. doi:10.1034/j.1600-0447.2003.02385.x
Kuno S, Mizuta E, Yamasaki S. Neuroleptic malignant syndrome in parkinsonian patients: risk factors. Eur Neurol. 1997;38 Suppl 2:56-59. doi:10.1159/000113484
Oruch R, Pryme IF, Engelsen BA, Lund A. Neuroleptic malignant syndrome: an easily overlooked neurologic emergency. Neuropsychiatr Dis Treat. 2017;13:161-175. doi:10.2147/NDT.S118438
Gurrera RJ. A systematic review of sex and age factors in neuroleptic malignant syndrome diagnosis frequency. Acta Psychiatr Scand. 2017;135(5):398-408. doi:10.1111/acps.12694
Velamoor R. Neuroleptic malignant syndrome: A neuro-psychiatric emergency: Recognition, prevention, and management. Asian J Psychiatr. 2017;29:106-109. doi:10.1016/j.ajp.2017.05.004
Otani K, Horiuchi M, Kondo T, Kaneko S, Fukushima Y. Is the predisposition to neuroleptic malignant syndrome genetically transmitted? Br J Psychiatry. 1991;158:850-853. doi:10.1192/bjp.158.6.850
Ortiz JF, Wirth M, Eskander N, Cozar JC, Fatade O, Rathod B. The genetic foundations of serotonin syndrome, neuroleptic malignant syndrome, and malignant hyperthermia: is there a genetic association between these disorders? Cureus. 2020;12(9):e10635. doi:10.7759/cureus.10635
Suzuki A, Kondo T, Otani K, et al. Association of the TaqI A polymorphism of the dopamine D(2) receptor gene with predisposition to neuroleptic malignant syndrome. Am J Psychiatry. 2001;158(10):1714-1716. doi:10.1176/appi.ajp.158.10.1714
Mihara K, Kondo T, Suzuki A, et al. Relationship between functional dopamine D2 and D3 receptors gene polymorphisms and neuroleptic malignant syndrome. Am J Med Genet B Neuropsychiatr Genet. 2003;117B(1):57-60. doi:10.1002/ajmg.b.10025
Velamoor VR, Norman RM, Caroff SN, Mann SC, Sullivan KA, Antelo RE. Progression of symptoms in neuroleptic malignant syndrome. J Nerv Ment Dis. 1994;182(3):168-173. doi:10.1097/00005053-199403000-00007
Wadoo O, Ouanes S, Firdosi M. Neuroleptic malignant syndrome: a guide for psychiatrists. BJPsych Advances. 2021;27(6):373-382. doi:10.1192/bja.2020.71
Modi S, Dharaiya D, Schultz L, Varelas P. Neuroleptic malignant syndrome: complications, outcomes, and mortality. Neurocrit Care. 2016;24(1):97-103. doi:10.1007/s12028-015-0162-5
Ngo V, Guerrero A, Lanum D, et al. Emergent treatment of neuroleptic malignant syndrome induced by antipsychotic monotherapy using dantrolene. CPCEM. 2019;3(1):16-23. doi:10.5811/cpcem.2018.11.39667
Gambassi G, Capurso S, Tarsitani P, Liperoti R, Bernabei R. Fatal neuroleptic malignant syndrome in a previously long-term user of clozapine following its reintroduction in combination with paroxetine. Aging Clin Exp Res. 2006;18(3):266-270. doi:10.1007/BF03324659
Schönfeldt-Lecuona C, Kuhlwilm L, Cronemeyer M, et al. Treatment of the neuroleptic malignant syndrome in international therapy guidelines: A comparative analysis. Pharmacopsychiatry. 2020;53(2):51-59. doi:10.1055/a-1046-1044
Levenson JL. Neuroleptic malignant syndrome. Am J Psychiatry. 1985;142(10):1137-1145. doi:10.1176/ajp.142.10.1137
Margetić B, Aukst-Margetić B. Neuroleptic malignant syndrome and its controversies. Pharmacoepidemiol Drug Saf. 2010;19(5):429-435. doi:10.1002/pds.1937
Velamoor VR. Neuroleptic malignant syndrome. Recognition, prevention and management. Drug Saf. 1998;19(1):73-82. doi:10.2165/00002018-199819010-00006
Scotton WJ, Hill LJ, Williams AC, Barnes NM. Serotonin syndrome: pathophysiology, clinical features, management, and potential future directions. Int J Tryptophan Res. 2019;12:1178646919873925. doi:10.1177/1178646919873925
Stevens DL. Association between selective serotonin-reuptake inhibitors, second-generation antipsychotics, and neuroleptic malignant syndrome. Ann Pharmacother. 2008;42(9):1290-1297. doi:10.1345/aph.1L066
Ware MR, Feller DB, Hall KL. Neuroleptic malignant syndrome: diagnosis and management. Prim Care Companion CNS Disord. 2018;20(1). doi:10.4088/PCC.17r02185
Guinart D, Misawa F, Rubio JM, et al. A systematic review and pooled, patient-level analysis of predictors of mortality in neuroleptic malignant syndrome. Acta Psychiatr Scand. 2021;144(4):329-341. doi:10.1111/acps.13359
Collard HR, Saint S, Matthay MA. Prevention of ventilator-associated pneumonia: an evidence-based systematic review. Ann Intern Med. 2003;138(6):494-501.
Bienvenu OJ, Neufeld KJ, Needham DM. Treatment of four psychiatric emergencies in the intensive care unit. Crit Care Med. 2012;40(9):2662-2670. doi:10.1097/CCM.0b013e31825ae0f8
van Rensburg R, Decloedt EH. An approach to the pharmacotherapy of neuroleptic malignant syndrome. Psychopharmacol Bull. 2019;49(1):84-91.
Rogers JP, Oldham MA, Fricchione G, et al. Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology. J Psychopharmacol (Oxford). 2023;37(4):327-369. doi:10.1177/02698811231158232
Kuhlwilm L, Schönfeldt-Lecuona C, Gahr M, Connemann BJ, Keller F, Sartorius A. The neuroleptic malignant syndrome-a systematic case series analysis focusing on therapy regimes and outcome. Acta Psychiatr Scand. 2020;142(3):233-241. doi:10.1111/acps.13215
Trollor JN, Sachdev PS. Electroconvulsive treatment of neuroleptic malignant syndrome: a review and report of cases. Aust N Z J Psychiatry. 1999;33(5):650-659. doi:10.1080/j.1440-1614.1999.00630.x
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Karolina Strus, Magdalena Madera, Natalia Dąbrowska, Sylwia Mazur, Roksana Zdunek, Agata Mazur, Emilia Nagórska, Krzysztof Marcinkowski, Aleksy Bizan, Aleksandra Kublińska
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 321
Number of citations: 0