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Drug information update. Atypical antipsychotics and neuroleptic malignant syndrome: Nuances and pragmatics of the association

  • Siddharth Sarkar (a1) and Nitin Gupta (a2)

Summary

Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal adverse event associated with the use of antipsychotics. Although atypical antipsychotics were initially considered to carry no risk of NMS, reports have accumulated over time implicating them in NMS causation. Almost all atypical antipsychotics have been reported to be associated with NMS. The clinical profile of NMS caused by certain atypical antipsychotics such as clozapine has been reported to be considerably different from the NMS produced by typical antipsychotics, with diaphoresis encountered more commonly, and rigidity and tremor encountered less frequently. This article briefly discusses the evidence relating to the occurrence, presentation and management of NMS induced by atypical antipsychotics.

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Copyright

This is an open-access article published by the Royal College of Psychiatrists and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Corresponding author

Correspondence to Nitin Gupta (nitingupta659@yahoo.co.in)

Footnotes

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Declaration of interest

None.

Footnotes

References

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1 Trollor, JN, Chen, X, Chitty, K, Sachdev, PS. Comparison of neuroleptic malignant syndrome induced by first- and second-generation antipsychotics. Br J Psychiatry 2012; 201: 52–6.
2 Langan, J, Martin, D, Shajahan, P, Smith, DJ. Antipsychotic dose escalation as a trigger for neuroleptic malignant syndrome (NMS): literature review and case series report. BMC Psychiatry 2012; 12: 214.
3 Strawn, JR, Keck, PE, Caroff, SN. Neuroleptic malignant syndrome. Am J Psychiatry 2007; 164: 870–6.
4 Gurrera, RJ, Caroff, SN, Cohen, A, Carroll, BT, DeRoos, F, Francis, A, et al. An international consensus study of neuroleptic malignant syndrome diagnostic criteria using the Delphi method. J Clin Psychiatry 2011; 72: 1222–8.
5 Adityanjee, , Sajatovic, M, Munshi, KR. Neuropsychiatric sequelae of neuroleptic malignant syndrome. Clin Neuropharmacol 2005; 28: 197204.
6 Modi, S, Dharaiya, D, Schultz, L, Varelas, P. Neuroleptic malignant syndrome: complications, outcomes, and mortality. Neurocritical Care 2016; 24: 97103.
7 Nakamura, M, Yasunaga, H, Miyata, H, Shimada, T, Horiguchi, H, Matsuda, S. Mortality of neuroleptic malignant syndrome induced by typical and atypical antipsychotic drugs: a propensity-matched analysis from the Japanese Diagnosis Procedure Combination database. J Clin Psychiatry 2012; 73: 427–30.
8 Tarsy, D, Baldessarini, RJ, Tarazi, FL. Effects of newer antipsychotics on extrapyramidal function. CNS Drugs 2002; 16: 2345.
9 Belvederi Murri, M, Guaglianone, A, Bugliani, M, Calcagno, P, Respino, M, Serafini, G, et al. Second-generation antipsychotics and neuroleptic malignant syndrome: systematic review and case report analysis. Drugs RD 2015; 15: 4562.
10 Trollor, JN, Chen, X, Sachdev, PS. Neuroleptic malignant syndrome associated with atypical antipsychotic drugs. CNS Drugs 2009; 23: 477–92.
11 Pope, HG, Cole, JO, Choras, PT, Fulwiler, CE. Apparent neuroleptic malignant syndrome with clozapine and lithium. J Nerv Ment Dis 1986; 174: 493–5.
12 Patel, NC, Crismon, ML, Hoagwood, K, Johnsrud, MT, Rascati, KL, Wilson, JP, et al. Trends in the use of typical and atypical antipsychotics in children and adolescents. J Am Acad Child Adolesc Psychiatry 2005; 44: 548–56.
13 Verdoux, H, Tournier, M, Bégaud, B. Antipsychotic prescribing trends: a review of pharmacoepidemiological studies. Acta Psychiatr Scand 2010;121: 410.
14 Buckley, PF. Broad therapeutic uses of atypical antipsychotic medications. Biol Psychiatry 2001; 50: 912–24.
15 Geddes, J, Freemantle, N, Harrison, P, Bebbington, P. Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis. BMJ 2000; 321: 1371–6.
16 Owens, DC. How CATIE brought us back to Kansas: a critical re-evaluation of the concept of atypical antipsychotics and their place in the treatment of schizophrenia. Adv Psychiatr Treat 2008; 14: 1728.
17 Ananth, J, Parameswaran, S, Gunatilake, S, Burgoyne, K, Sidhom, T. Neuroleptic malignant syndrome and atypical antipsychotic drugs. J Clin Psychiatry 2004; 65: 464–70.
18 Jann, MW, Grimsley, SR, Gray, EC, Chang, WH. Pharmacokinetics and pharmacodynamics of clozapine. Clin Pharmacokinet 1993; 24: 161–76.
19 Amore, M, Zazzeri, N, Berardi, D. Atypical neuroleptic malignant syndrome associated with clozapine treatment. Neuropsychobiology 1997; 35: 197–9.
20 Karagianis, JL, Phillips, LC, Hogan, KP, LeDrew, KK. Clozapine-associated neuroleptic malignant syndrome: two new cases and a review of the literature. Ann Pharmacother 1999; 33: 623–30.
21 Licup, N, Baumrucker, SJ. Olanzapine for nausea and vomiting. Am J Hosp Palliat Care 2010; 27: 432–4.
22 Musshoff, F, Doberentz, E, Madea, B. Lethal neuroleptic malignant syndrome due to amisulpride. Forensic Sci Med Pathol 2013; 9: 218–20.
23 Tsai, JH, Yang, P, Yen, JY, Chen, CC, Yang, MJ. Zotepine-induced catatonia as a precursor in the progression to neuroleptic malignant syndrome. Pharmacotherapy 2005; 25: 1156–9.
24 Horacek, J, Bubenikova-Valesova, V, Kopecek, M, Palenicek, T, Dockery, C, Mohr, P, et al. Mechanism of action of atypical antipsychotic drugs and the neurobiology of schizophrenia. CNS Drugs 2006; 20: 389409.
25 Detweiler, MB, Sullivan, K, Sharma, TR, Kim, KY, Detweiler, JG. Case reports of neuroleptic malignant syndrome in context of quetiapine use. Psychiatr Q 2013; 84: 523–41.
26 Chen, Y-T, Su, K-P, Chang, JP-C. Early detection and management of atypical neuroleptic malignant syndrome secondary to aripiprazole. Schizophr Res 2011; 132: 97–8.
27 Tseng, PT, Chang, YC, Chang, CH, Wang, HY, Cheng, YS, Wu, CK, et al. Atypical neuroleptic malignant syndrome in patients treated with aripiprazole and clozapine: a case-series study and short review. Int J Psychiatry Med 2015; 49: 3543.
28 Leibold, J, Patel, V, Hasan, RA. Neuroleptic malignant syndrome associated with ziprasidone in an adolescent. Clin Therapeut 2004; 26: 1105–8.
29 Ozen, ME, Yumru, M, Savas, HA, Cansel, N, Herken, H. Neuroleptic malignant syndrome induced by ziprasidone on the second day of treatment. World J Biol Psychiatry 2007; 8: 42–4.
30 Mantas, C, Kalabokis, G, Goulia, P, Tourlakopoulos, A, Hyphantis, T, Mavreas, V. Possible neuroleptic malignant syndrome during paliperidone administration: a case report. J Clin Psychopharmacol 2010; 30: 8991.
31 Teng, PR, Lane, HY. Emergence of neuroleptic malignant syndrome while switching between risperidone and paliperidone. J Neuropsychiatry Clin Neurosci 2011; 23: E16.
32 Hsu, W-C, Lin, S-T, Chen, C-C, Tsang, H-Y, Huang, M-F. A self-limiting case of atypical neuroleptic malignant syndrome associated with zotepine. J Clin Psychopharmacology 2011; 31: 667–9.
33 Guanci, N, Aggarwal, R, Schleifer, S. Atypical neuroleptic malignant syndrome associated with iloperidone administration. Psychosomatics 2012; 53: 603–5.
34 Ohoyama, K, Tanii, H, Motomura, E, Konishi, Y, Nakagawa, M, Matsumoto, T, et al. Neuroleptic malignant syndrome induced by blonanserin. J Neuropsychiatry Clin Neurosci 2011; 23: E13.
35 Patel, MK, Brunetti, L. Neuroleptic malignant syndrome secondary to aripiprazole initiation in a clozapine-intolerant patient. Am J Health Syst Pharm 2010; 67: 1254–9.
36 Borovicka, MC, Bond, LC, Gaughan, KM. Ziprasidone- and lithium-induced neuroleptic malignant syndrome. Ann Pharmacother 2006; 40: 139–42.
37 Su, YP, Chang, CK, Hayes, RD, Harrison, S, Lee, W, Broadbent, M, et al. Retrospective chart review on exposure to psychotropic medications associated with neuroleptic malignant syndrome. Acta Psychiatr Scand 2014; 130: 5260.
38 Picard, LS, Lindsay, S, Strawn, JR, Kaneria, RM, Patel, NC, Keck, PE Jr. Atypical neuroleptic malignant syndrome: diagnostic controversies and considerations. Pharmacotherapy 2008; 28: 530–5.
39 Caroff, SN, Mann, SC. Atypical antipsychotics and neuroleptic malignant syndrome. Psychiatr Ann 2000; 30: 314–21.
40 Levenson, JL. Neuroleptic malignant syndrome. Am J Psychiatry 1985; 142: 1137–45.
41 Addonizio, G, Susman, VL, Roth, SD. Symptoms of neuroleptic malignant syndrome in 82 consecutive inpatients. Am J Psychiatry 1986; 143: 1587–90.
42 Odagaki, Y. Atypical neuroleptic malignant syndrome or serotonin toxicity associated with atypical antipsychotics? Cure Drug Saf 2009; 4: 8493.
43 Susman, VL. Clinical management of neuroleptic malignant syndrome. Psychiatr Q 2001; 72: 325–36.
44 Frucht, SJ. Treatment of movement disorder emergencies. Neurotherapeutics 2014; 11: 208–12.
45 Anbalagan, E, Ithman, M, Lauriello, J. Rechallenging clozapine after neuroleptic malignant syndrome. Psychiatr Q 2014; 85: 345–8.
46 Manu, P, Sarpal, D, Muir, O, Kane, JM, Correll, CU. When can patients with potentially life-threatening adverse effects be rechallenged with clozapine? A systematic review of the published literature. Schizophr Res 2012; 134: 180–6.
47 Mendhekar, DN, Jiloha, RC, Mehndiratta, MM, War, L. Challenge with atypical antipsychotic drugs in risperidone induced neuroleptic malignant syndrome: a case report. In J Psychiatry 2002; 44: 387–90.
48 Ross, C. Successful clozapine rechallenge following clozapine-induced neuroleptic malignant syndrome. Ment Health Clin 2015; 5: 8890.

Drug information update. Atypical antipsychotics and neuroleptic malignant syndrome: Nuances and pragmatics of the association

  • Siddharth Sarkar (a1) and Nitin Gupta (a2)

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Drug information update. Atypical antipsychotics and neuroleptic malignant syndrome: Nuances and pragmatics of the association

  • Siddharth Sarkar (a1) and Nitin Gupta (a2)
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eLetters

Soft Diagnosis, Guidelines, and Hard choices

Karol Antczak, Registrar in Psychiatry, Cluain Mhuire Mental Health Service
Elizabeth Cummings, Consultant Psychiatrist, Cluain Mhuire Mental Health Service
06 September 2017

Thank you for this excellent and concise article outlining the complexities involved in Neuroleptic Malignant Syndrome in association with atypical antipsychotics.(1) It serves as a reminder of how guidelines and diagnostic criteria can, for all their clarity, lead to vexing and imperfect choices.

This article brings to mind recent clinical cases where empiric treatment of a soft NMS diagnosis led to challenging decisions. The trouble lay in following guidelines in a patient with very clear treatment resistant schizophrenia who had improved with clozapine. After the withdrawal of the causative agent, the duration for which antipsychotic treatment should be withheld is not completely clear. There are recognised guidelines indicating at least 5 days and monitoring for symptom resolution, while other guidelines say to wait 2 weeks after symptoms have settled.(2,3) As well the atypical presentation of clozapine associated NMS itself, as shown in this article, can lead to uncertainty and serves as a frustrating obstacle which clouds the process of decision making.(1) Moving forward, the recommendation to avoid the precipitating antipsychotic does not provide a clear answer in further management of such a patient on clozapine where other options have proved insufficient or inadequate.(4)

Further difficulty then may arise in persuading someone that the medication, which is associated with such an unpleasant clinical experience, is the correct choice. Particularly when recurrence of NMS on rechallenge with antipsychotics was found to be between 30 and 50%.(4)

In clinical practice there often is no perfect answer and rarely does the right one present itself as the easy choice. An article such as this serves to highlight the challenges present in applying uniform guidelines to complex presentations.

1. Sarkar S, Gupta N. Drug information update. Atypical antipsychotics and neuroleptic malignant syndrome: nuances and pragmatics of the association. BJPsych Bull. 2017 Feb 9:pb-bp.

2. Semple D. Oxford handbook of psychiatry. Oxford University Press; 2013 Feb 28. 957p.

3. Taylor D, Paton C, Kapur S. The Maudsley prescribing guidelines in psychiatry. John Wiley & Sons; 2015 Feb 23. 102p

4. Bhanushali MJ, Tuite PJ. The evaluation and management of patients with neuroleptic malignant syndrome. Neurologic clinics. 2004 May 1;22(2):389-411.

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Conflict of interest: None Declared

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