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Comparison of neuroleptic malignant syndrome induced by first- and second-generation antipsychotics

  • Julian N. Trollor (a1), Xiaohua Chen (a2), Kate Chitty (a3) and Perminder S. Sachdev (a4)
Abstract
Background

Reports of neuroleptic malignant syndrome (NMS) induced by second-generation antipsychotic drugs highlight a propensity for atypical clinical presentations.

Aims

To systematically compare the clinical profile of NMS induced by first- (1G-NMS) and second-generation antipsychotic drugs (2G-NMS).

Method

The Australian Adverse Drug Reaction Advisory Committee (ADRAC) database was searched to identify individuals with NMS reported between April 1994 and September 2010. The clinical characteristics of 208 people with NMS induced by monotherapy with first- or second-generation antipsychotic drugs, as well as presenting features of NMS, were compared.

Results

The individuals with 2G-NMS were younger and more likely to have a psychotic disorder diagnosis. The features of NMS in the two groups were very similar, except that people with 2G-NMS were less likely to present with rigidity or extrapyramidal signs compared with those with 1G-NMS. This difference was due to the lower rates of rigidity in those with clozapine-induced NMS. Mortality was considerably lower for those with 2G-NMS (3.0%) compared with 1G-NMS (16.3%), and the former were more likely to have received supportive treatment.

Conclusions

The clinical profile of 2G-NMS is largely similar to 1G-NMS, with clozapine-induced NMS being differentiated by the relative lack of rigidity as a feature. Mortality is lower for 2G-NMS.

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Copyright
Corresponding author
Julian N. Trollor, 34 Botany St, University of New South Wales, NSW 2052, Australia. Email: J.Trollor@unsw.edu.au
Footnotes
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Declaration of interest

None.

Footnotes
References
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1 Adityanjee, , Aderibigbe, YA, Mathews, T. Epidemiology of neuroleptic malignant syndrome. Clin Neuropharmacol 1999; 22: 151–8.
2 Shalev, A, Hermesh, H, Munitz, H. Mortality from neuroleptic malignant syndrome. J Clin Psychiatry 1989; 50: 1825.
3 Adityanjee, , Sajatovic, M, Munshi, KR. Neuropsychiatric sequelae of neuroleptic malignant syndrome. Clin Neuropharmacol 2005; 28: 197204.
4 Levenson, JL, Fisher, JG. Long-term outcome after neuroleptic malignant syndrome. J Clin Psychiatry 1988; 49: 154–6.
5 Addonizio, G, Susman, VL, Roth, SD. Neuroleptic malignant syndrome: review and analysis of 115 cases. Biol Psychiatry 1987; 22: 1004–20.
6 Caroff, SN, Mann, SC, Campbell, EC. Atypical antipsychotics and neuroleptic malignant syndrome. Psychiatry Ann 2000; 30: 314–21.
7 Kontaxakis, VP, Havaki-Kontaxaki, BJ, Christodoulou, NG, Paplos, KG. Olanzapine-associated neuroleptic malignant syndrome. Prog Neuropsychopharmacol Biol Psychiatry 2002; 26: 897902.
8 Farver, DK. Neuroleptic malignant syndrome induced by atypical antipsychotics. Expert Opin Drug Saf 2003; 2: 2135.
9 Ananth, J, Parameswaran, S, Gunatilake, S, Burgoyne, K, Sidhom, T. Neuroleptic malignant syndrome and atypical antipsychotic drugs. J Clin Psychiatry 2004; 65: 464–70.
10 Trollor, J, Xiaohua, C, Sachdev, P. Neuroleptic malignant syndrome associated with atypical antipsychotic drugs. CNS Drugs 2009; 23: 477–92.
11 Boyd, IW. The role of the Australian Adverse Drug Reactions Advisory Committee (ADRAC) in monitoring drug safety. Toxicology 2002; 181–182: 99102.
12 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.
13 Shalev, A, Munitz, H. The neuroleptic malignant syndrome: agent and host interaction. Acta Psychiatr Scand 1986; 73: 337–47.
14 Naganuma, H, Fujii, I. Incidence and risk factors in neuroleptic malignant syndrome. Acta Psychiatr Scand 1994; 90: 424–6.
15 Sachdev, P, Mason, C, Hadzi-Pavlovic, D. Case-control study of neuroleptic malignant syndrome. Am J Psychiatry 1997; 154: 1156–8.
16 Berardi, D, Amore, M, Keck, PE, Jr Troia, M, Dell'Atti, M. Clinical and pharmacologic risk factors for neuroleptic malignant syndrome: a case-control study. Biol Psychiatry 1998; 44: 748–54.
17 Caroff, SN. The neuroleptic malignant syndrome. J Clin Psychiatry 1980; 41: 7983.
18 Levenson, JL. Neuroleptic malignant syndrome. Am J Psychiatry 1985; 142: 1137–45.
19 Sachdev, P, Kruk, J, Kneebone, M, Kissane, D. Clozapine-induced neuroleptic malignant syndrome: review and report of new cases. J Clin Psychopharmacol 1995; 15: 365–71.
20 Sachdev, PS. A rating scale for neuroleptic malignant syndrome. Psychiatry Res 2005; 135: 249–56.
21 Jaan, MW, Grimsley, SR, Gray, EC, Chang, W-H. Pharamacokinetics and pharmacodynamics of clozapine. Clin Pharmacokinet 1993; 24: 161–76.
22 Coward, DM, Imperato, A, Urwyler, S, White, TG. Biochemical and behavioural properties of clozapine. Psychopharmacology 1989; 99 (suppl): S612.
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  • ISSN: 0007-1250
  • EISSN: 1472-1465
  • URL: /core/journals/the-british-journal-of-psychiatry
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Comparison of neuroleptic malignant syndrome induced by first- and second-generation antipsychotics

  • Julian N. Trollor (a1), Xiaohua Chen (a2), Kate Chitty (a3) and Perminder S. Sachdev (a4)
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eLetters

Atypical Anti-Psychotics and Atypical Presetation of Neuroleptic Malignant Syndrome

K.A.L.A. Kuruppuarachchi, Professor of Psychiatry
05 September 2012

The article on Comparison of neuroleptic malignant syndrome induced by first- and second- generation antipsychotics (Trollor et al. 2012) published in the BJP highlights an important area in contemporary psychiatric practice.

As there is an increasing trend in prescribing psychotropic medication globally for a variety of conditions it is obvious that we aregoing to encounter more and more cases of NMS with varying clinical presentations. It is important to be aware of these diverse pictures and atypical symptom patterns in order to minimize the morbidity and mortalityand to improve the outcomes of NMS.

Since there is a considerable overlap between the symptom pattern of NMS and other conditions such as Serotonin syndrome, Catatonia , Anti - NMDA Receptor Encephalitis there are further problems in early detection of the condition. Marginal to moderate elevation of CPK levels are seen insimilar situations leading to added difficulties in arriving at a conclusion. Such difficulties are highlighted in the recent literature (Chapman et al. 2011).

Patients with atypical presentations of NMS have been reported globally. Cases reported even from developing countries to support the notion that the atypical presentation is more often seen amongst the patients who received second generation antipsychotics. A case with atypical features in presentation of NMS induced by olanzapine has been reported and considered NMS as a spectrum disorder displaying a varying degree of severity of its core-features of rigidity, hyperthermia, autonomic instability and elevated CPK levels (Mishra et al. 2007). It has also been shown that clozapine induced NMS has lesser extrapyramidal symptoms. Atypical presentations of NMS create problems in diagnosis and management since hyperthermia and/or muscle rigidity may be absent or develop slowly over several days(Picard 2008). NMS associated with atypical antipsychotics in paediatric patients has been reviewed and suggested to maintain a high index of suspicion even though it is rare in this population (Croakin 2008). Also cases of NMS without fever following conventional antipsychotics have been reported (Peiris , Kuruppuarachchi . Weerasena et al 2000).

Atypical antipsychotics specially with clozapine associated NMS givesclues to the possible aetiological role of serotonergic and noradrenergicreceptors in the pathophysiology of NMS(Khaldi et al. 2008).

It is also important to pay attention to the area of ethno -psychopharmacology too as the pharmacodynamics and pharmacokinetics are different amongst various ethnic groups which in turn lead to differentvulnerabilities, clinical presentations and outcomes.

The other important area note worthy is the overlap of symptoms of catatonia and NMS creating further difficulties in the diagnosis and management. Since catatonia rating scales are not widely used in our countries there is a possibility of missing or over inclusion of cases.

Most of the work seem to be based on case reports and clinicians reports which cause problems in accuracy. However as the authors in the article mentioned there are difficulties in obtaining information other than depending on already recorded data. It seems that the authors mainly rely on the clinicians judgement in arriving at the diagnosis. Alsothe variation of the CPK levels were not clear. However on the whole the work need to be commended as there is a dearth of such research related toNMS.

We need to do more prospective perhaps multicenter studies to arrive at proper conclusions.

References:

Trollor JN, Chen X, Chitty K, Sachdev PS. Comparison of neuroleptic malignant syndrome induced by first- and second- generation antipsychotics. British Journal of Psychiatry 2012; 201: 52-56.

Chapman MR and Vause HE. Anti-NMDA Receptor Encephalitis : Diagnosis,Psychiatric Presentation and Treatment. Am J Psychiatry 2011; 168(3): 245-251.

Mishra B, Mishra B, Sahoo S, Arora M, Khess C. Atypicality in presentation of neuroleptic malignant syndrome caused by olanzapine. Indian J Med Sci 2007; 61: 570-573.

Picard LS, Lindsay S, Strawn JR, Kaneria RM, Patel NC, Keck PE Jr. Atypical neuroleptic malignant syndrome : diagnostic controversies and considerations. Pharmacotherapy 2008; 28(4): 530-5.

Croakin PE, Emslie GJ, Mayes TL. Neuroleptic malignant syndrome associated with atypical antipsychotics in pediatric patients: a review ofpublished cases. J Clin Psychiatry 2008; 69(7): 1157-65.

Peiris DTS, Kuruppuarachchi KALA, Weerasena LP, Seneviratne SL, Tilakaratna YT, DE Silva HJ , Wijesiriwardena B. Neuroleptic malignant syndrome without fever: a report of three cases. Neurol Neurosurg Psychiatry 2000; 69: 277-278.

Khaldi S, Kornreich C, Choubani Z, Gourevitch R. Neuroleptic malignant syndrome and atypical antipsychotics: a brief rview. Encephale: 2008; 34(6): 618-24.

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Conflict of interest: None declared

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Comparison of NMS induced by first- and second-generation antipsychotics

Gurdaval Singh, ST6 in General Adult Psychiatry
06 August 2012

It was interesting to read the article on comparing neuroleptic malignant syndrome (NMS) induced by first-generation (1G) and second-generation (2G) antipsychotics based on NMS cases extracted from the Australian Adverse Drug Reaction Advisory Committee (ADRAC) database1. As the authors mention, the study was limited by the reporting of adverse events by the clinicians.

The authors state that clinicians may be more likely to report 2G-NMS, especially in the case of clozapine, which is associated with closer monitoring of adverse events. It is possible that since extrapyramidal symptoms (EPS), such as rigidity, are expected to occur more frequently with 1G antipsychotics, clinicians may be less sensitive to report it. Similarly there may be under reporting of 1G-NMS and a greater propensity to report NMS induced by 2G antipsychotics.

The difference in the mortality rate between 1G and 2G antipsychotics(16.3% vs. 3%) is difficult to explain. The authors raise the possibility of a more aggressive management approach with 2G antipsychotics. One possibility is the potential early detection and subsequent management of NMS induced by 2G antipsychotics when something unusual is happening, suchas the presence of rigidity. In 1G NMS, it is possible that the early signs of NMS are overlooked and attributed to benign EPS with the subsequent attempt to treat it using anticholinergic medication. This could simply delay the diagnosis and management of 1G-NMS cases. Hence a high index of suspicion is required not to miss the early signs of NMS both in 1G and 2G cases.

Due to its rarity, some doctors and other healthcare professionals may have never encountered a patient presenting with features suggestive of NMS. For this reason, their lack of clinical experience may lead to a failure of such a condition being detected and appropriately managed. It is important that all clinicians involved in prescribing antipsychotics should be fully aware of the variety of clinical manifestations of NMS (typical and atypical NMS presentations), rather than solely focus on those clinical features of NMS that clinicians are accustomed to eliciting(typical NMS presentations). It also highlights the training needs of clinicians. It would be interesting to see whether simulated clinical stations can be used to become more familiar with such conditions.

There is a significant difference in the underlying diagnosis betweenthe 1G and 2G antipsychotic groups. However, whether it influences the mortality rate is difficult to know. It is also difficult to draw any firmconclusions given that nearly half of the sample did not have the diagnosis mentioned. At least one should be cautious in prescribing antipsychotics in the absence of a primary psychotic disorder as the risk-benefit ratio may not be favourable.

Although the authors attempted to ascertain whether there were any differences in the clinical presentation of NMS between the different 2G antipsychotics, we wondered if there were any differences in the clinical presentation of NMS between 1G antipsychotics. In this study, it could be possible that the relatively small number of 1G-NMS cases (n = 43) or if one particular 1G antipsychotic was over represented may be limiting factors in answering this query.

REFERENCES

1. Troller 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 - 56.

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Conflict of interest: None declared

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