Das maligne neuroleptische Syndrom (MNS) – Eine systematische Übersicht

Zusammenfassung

Hintergrund: Beim malignen neuroleptischen Syndrom (MNS) handelt es sich um ein potenziell lebensbedrohliches medikamenteninduziertes Krankheitsbild. Die Kernsymptomatik besteht aus Hyperthermie ohne Infektnachweis, Diaphorese (Schwitzen), Rigor der Skelettmuskulatur, wechselnder Bewusstseinsstörung und Erhöhung der Kreatinkinase im Blut. Ferner besteht eine vegetative Dysfunktion mit Herzfrequenz- und Blutdruckschwankungen.

Ziel dieser Übersichtsarbeit ist es, die aktuelle Studienlage zusammenzufassen und die Diagnosestellung des MNS bzw. die Abgrenzung von anderen Syndromen zu erleichtern. Darüber hinaus werden die therapeutischen Optionen, die beim MNS zu Verfügung stehen, erörtert.

Methode: Es wurde eine systematische Literaturrecherche durchgeführt. Es wurden Bücher, Fallberichte und Leitlinien eingeschlossen.

Ergebnisse: In dieser Übersichtsarbeit werden die aktuell gängigen diagnostischen Kriterien, die Differenzialdiagnose, die vermutete Ätiopathogenese und mögliche therapeutische Interventionen dargestellt.

Schlussfolgerung: Das frühe klinische Erscheinungsbild ist heterogen und macht die Diagnostik nicht leicht. Dabei ist eine frühe Behandlung wichtig für eine gute Prognose und rasche Rückbildung. Die Therapieoptionen richten sich nach der bisherigen klinischen Erfahrung auf der Basis von Einzelfallberichten und Expertenmeinungen. Bei der Diagnosestellung sollten die Kernsymptome beachtet werden: Einnahme von Dopamin-Antagonisten, Hyperthermie, Diaphorese, Rigor, Bewusstseinsstörungen, CK-Erhöhung und vegetative Dysregulation.

Abstract

Background: Neuroleptic malignant syndrome (NMS) is a rare but potentially life-threatening medication-induced syndrome. Core symptoms are hyperthermia, diaphoresis, rigidity, impaired consciousness, and creatinine kinase elevation. Additionally, patients show vegetative dysregulation including blood pressure fluctuations. The purpose of this paper is to summarize current findings, to facilitate diagnostics and to distinguish NMS from other syndromes.

Methods: We performed a systematic review of the literature. We included scientific publications, books and guidelines.

Results: In this review we summarize the current diagnostic criteria, differential diagnosis, pathogenesis and therapeutic options.

Conclusion: Clinical symptoms of NMS are heterogeneous and it is difficult to diagnose early states. Early interventions are important to ensure fast and complete recovery. Since NMS is a rare condition, publications on NMS-therapy are based on single-case reports, meta-analysis or expert opinions. Core symptoms should be considered: Exposure to dopamine-antagonists, hyperthermia, diaphoresis, rigidity, mental status alteration, creatinine kinase elevation, and vegetative dysregulation.

Schlüsselwörter

malignes neuroleptisches Syndrom - Antipsychotika - Neuroleptika - Hyperthermie - akinetische Krise - Katatonie

Key words

neuroleptic malignant syndrome - antipsychotics - neuroleptics - hyperthermia - akinetic crisis - catatonia

• Literatur

• 1 Ayd Jr FJ. Fatal hyperpyrexia during chlorpromazine therapy. J Clin Exp Psychopathol 1956; 17: 189-192
• 2 Delay J, Pichot P, Lemperiere T et al. A non-phenothiazine and non-reserpine major neuroleptic, haloperidol, in the treatment of psychoses. Ann Med Psychol (Paris) 1960; 118 (01) 145-152
• 3 Haddad PM. Neuroleptic malignant syndrome. May be caused by other drugs. BMJ 1994; 308: 200
• 4 Ananth J, Parameswaran S, Gunatilake S et al. Neuroleptic malignant syndrome and atypical antipsychotic drugs. J Clin Psychiatry 2004; 65: 464-470
• 5 Bottlender R, Jager M, Hofschuster E et al. Neuroleptic malignant syndrome due to atypical neuroleptics: three episodes in one patient. Pharmacopsychiatry 2002; 35: 119-121
• 6 Trollor JN, Chen X, Chitty K et al. Comparison of neuroleptic malignant syndrome induced by first- and second-generation antipsychotics. Br J Psychiatry 2012; 201: 52-56
• 7 Assion HJ, Volz HP. Malignes neuroleptisches Syndrom. 1. Aufl. Stuttgart: Thieme; 2004
• 8 American Psychiatric Association. DSM-5 Task Force. Diagnostic and statistical manual of mental disorders: DSM-5. 5th. Aufl. Arlington: VA: American Psychiatric Association; 2013
• 9 Chang CK, Harrison S, Lee W et al. Ascertaining instances of neuroleptic malignant syndrome in a secondary mental healthcare electronic medical records database: the SLAM BRC Case Register. Ther Adv Psychopharmacol 2012; 2: 75-83
• 10 Haddad PM, Mattey VS Hrsg Neurological complications of antipsycotic drugs. 3. Aufl. Bethesda: Wiley-Blackwell; 2011
• 11 Addonizio G, Susman VL, Roth SD. Neuroleptic malignant syndrome: review and analysis of 115 cases. Biol Psychiatry 1987; 22: 1004-1020
• 12 Caroff SN, Mann SC. Neuroleptic malignant syndrome. Med Clin North Am 1993; 77: 185-202
• 13 Levenson JL. Neuroleptic malignant syndrome. Am J Psychiatry 1985; 142: 1137-1145
• 14 Strawn JR, Keck Jr PE, Caroff SN. Neuroleptic malignant syndrome. Am J Psychiatry 2007; 164: 870-876
• 15 Woodbury MM, Woodbury MA. Neuroleptic-induced catatonia as a stage in the progression toward neuroleptic malignant syndrome. J Am Acad Child Adolesc Psychiatry 1992; 31: 1161-1164
• 16 Gurrera RJ, Caroff SN, Cohen A et al. An international consensus study of neuroleptic malignant syndrome diagnostic criteria using the Delphi method. J Clin Psychiatry 2011; 72: 1222-1228
• 17 Stubner S, Rustenbeck E, Grohmann R et al. Severe and uncommon involuntary movement disorders due to psychotropic drugs. Pharmacopsychiatry 2004; 37 (Suppl. 01) S54-S64
• 18 Nielsen RE, Wallenstein Jensen SO, Nielsen J. Neuroleptic malignant syndrome-an 11-year longitudinal case-control study. Can J Psychiatry 2012; 57: 512-518
• 19 Shalev A, Hermesh H, Munitz H. Mortality from neuroleptic malignant syndrome. J Clin Psychiatry 1989; 50: 18-25
• 20 Nakamura M, Yasunaga H, Miyata H et al. 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: 427-430
• 21 Caroff SN, Hurford I, Lybrand J et al. Movement disorders induced by antipsychotic drugs: implications of the CATIE schizophrenia trial. Neurol Clin 2011; 29: 127-148 , viii
• 22 Panagariya A, Sharma B, Singh R et al. The neuroleptic malignant syndrome: a report of 14 cases from North India. Neurol India 2007; 55: 166-168
• 23 Tural U, Onder E. Clinical and pharmacologic risk factors for neuroleptic malignant syndrome and their association with death. Psychiatry Clin Neurosci 2010; 64: 79-87
• 24 Caroff SN. The neuroleptic malignant syndrome. J Clin Psychiatry 1980; 41: 79-83
• 25 Margetic B, Aukst-Margetic B. Neuroleptic malignant syndrome and its controversies. Pharmacoepidemiol Drug Saf 2010; 19: 429-435
• 26 Moscovich M, Novak FT, Fernandes AF et al. Neuroleptic malignant syndrome. Arq Neuropsiquiatr 2011; 69: 751-755
• 27 Viejo LF, Morales V, Punal P et al. Risk factors in neuroleptic malignant syndrome. A case-control study. Acta Psychiatr Scand 2003; 107: 45-49
• 28 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: 52-60
• 29 Langan J, Martin D, Shajahan P et al. Antipsychotic dose escalation as a trigger for neuroleptic malignant syndrome (NMS): literature review and case series report. BMC Psychiatry 2012; 12: 214
• 30 Guze BH, Baxter Jr LR. Current concepts. Neuroleptic malignant syndrome. N Engl J Med 1985; 313: 163-166
• 31 Mann SC, Auriacombe M, Macfadden W et al. Lethal catatonia: clinical aspects and therapeutic intervention. A review of the literature. Encephale 2001; 27: 213-216
• 32 Argyriou AA, Drakoulogona O, Karanasios P et al. Lithium-induced fatal neuroleptic malignant syndrome in a patient not being concomitantly treated with commonly offending agents. J Pain Symptom Manage 2012; 44: e4-e6
• 33 Shalev A, Hermesh H, Munitz H. The role of external heat load in triggering the neuroleptic malignant syndrome. Am J Psychiatry 1988; 145: 110-111
• 34 Ziegenbein M, Kropp S, Hillemacher T et al. Genetic predisposition to neuroleptic malignant syndrome in siblings. Ann Pharmacother 2006; 40: 574-575
• 35 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: 1714-1716
• 36 Carroll BT, Lee JW. Catatonia is a risk factor for neuroleptic malignant syndrome. J Clin Psychiatry 2004; 65: 1722-1723
• 37 Assion HJ, Heinemann F, Laux G. Neuroleptic malignant syndrome under treatment with antidepressants? A critical review. Eur Arch Psychiatry Clin Neurosci 1998; 248: 231-239
• 38 Toro-Chico P, Gil Navarro I, Perez Encinas M. Neuroleptic malignant syndrome in association with tricyclic antidepressants. Farm Hosp 2006; 30: 261-262
• 39 Gurrera RJ. Sympathoadrenal hyperactivity and the etiology of neuroleptic malignant syndrome. Am J Psychiatry 1999; 156: 169-180
• 40 Haddow AM, Harris D, Wilson M et al. Clomipramine induced neuroleptic malignant syndrome and pyrexia of unknown origin. BMJ 2004; 329: 1333-1335
• 41 Pelonero AL, Levenson JL, Pandurangi AK. Neuroleptic malignant syndrome: a review. Psychiatr Serv 1998; 49: 1163-1172
• 42 O'Dwyer AM, Sheppard NP. The role of creatine kinase in the diagnosis of neuroleptic malignant syndrome. Psychol Med 1993; 23: 323-326
• 43 Calmeil LF. Dictionnarie de medicine ou repertoire general des sciences. Medicales sous le rapport therorique et practique. In: 2nd ed. Paris: Bechet; 1832
• 44 Fink M, Shorter E, Taylor MA. Catatonia is not schizophrenia: Kraepelin’s error and the need to recognize catatonia as an independent syndrome in medical nomenclature. Schizophr Bull 2010; 36: 314-320
• 45 Mann SC, Caroff SN, Bleier HR et al. Lethal catatonia. Am J Psychiatry 1986; 143: 1374-1381
• 46 Koch M, Chandragiri S, Rizvi S et al. Catatonic signs in neuroleptic malignant syndrome. Compr Psychiatry 2000; 41: 73-75
• 47 Fink M, Taylor MA. Neuroleptic malignant syndrome is malignant catatonia, warranting treatments efficacious for catatonia. Prog Neuropsychopharmacol Biol Psychiatry 2006; 30: 1182-1183 ; author reply 1184–1185
• 48 Fink M. Neuroleptic malignant syndrome and catatonia: one entity or two?. Biol Psychiatry 1996; 39: 1-4
• 49 Fink M. Toxic serotonin syndrome or neuroleptic malignant syndrome?. Pharmacopsychiatry 1996; 29: 159-161
• 50 Northoff G. Catatonia and neuroleptic malignant syndrome: psychopathology and pathophysiology. J Neural Transm 2002; 109: 1453-1467
• 51 Kipps CM, Fung VS, Grattan-Smith P et al. Movement disorder emergencies. Mov Disord 2005; 20: 322-334
• 52 Sternbach H. The serotonin syndrome. Am J Psychiatry 1991; 148: 705-713
• 53 Onofrj M, Thomas A. Acute akinesia in Parkinson disease. Neurology 2005; 64: 1162-1169
• 54 Munhoz RP, Moscovich M, Araujo PD et al. Movement disorders emergencies: a review. Arq Neuropsiquiatr 2012; 70: 453-461
• 55 Douglas A, Morris J. It was not just a heatwave! Neuroleptic malignant-like syndrome in a patient with Parkinson’s disease. Age Ageing 2006; 35: 640-641
• 56 Keyser DL, Rodnitzky RL. Neuroleptic malignant syndrome in Parkinson’s disease after withdrawal or alteration of dopaminergic therapy. Arch Intern Med 1991; 151: 794-796
• 57 Mizuno Y, Takubo H, Mizuta E et al. Malignant syndrome in Parkinson’s disease: concept and review of the literature. Parkinsonism Relat Disord 2003; 9 (Suppl. 01) S3-S9
• 58 Vincent A. Autoimmune encephalitis. J Neurol Neurosurg Psychiatry 2014; 85: e3
• 59 Henderson VW, Wooten GF. Neuroleptic malignant syndrome: a pathogenetic role for dopamine receptor blockade?. Neurology 1981; 31: 132-137
• 60 Osman AA, Khurasani MH. Lethal catatonia and neuroleptic malignant syndrome. A dopamine receptor shut-down hypothesis. Br J Psychiatry 1994; 165: 548-550
• 61 Gillman PK. Neuroleptic malignant syndrome: mechanisms, interactions, and causality. Mov Disord 2010; 25: 1780-1790
• 62 Kornhuber J, Weller M, Riederer P. Glutamate receptor antagonists for neuroleptic malignant syndrome and akinetic hyperthermic parkinsonian crisis. J Neural Transm Park Dis Dement Sect 1993; 6: 63-72
• 63 Nisijima K, Shioda K, Iwamura T. Neuroleptic malignant syndrome and serotonin syndrome. Prog Brain Res 2007; 162: 81-104
• 64 Kontaxakis VP, Havaki-Kontaxaki BJ, Christodoulou NG et al. Olanzapine-associated neuroleptic malignant syndrome: Is there an overlap with the serotonin syndrome?. Ann Gen Hosp Psychiatry 2003; 2: 10
• 65 Rosebush PI, Mazurek MF. Serum iron and neuroleptic malignant syndrome. Lancet 1991; 338: 149-151
• 66 Anglin RE, Rosebush PI, Mazurek MF. Neuroleptic malignant syndrome: a neuroimmunologic hypothesis. CMAJ 2010; 182: E834-E838
• 67 Rosebush PI, Anglin RE, Richards C et al. Neuroleptic malignant syndrome and the acute phase response. J Clin Psychopharmacol 2008; 28: 459-461
• 68 Ferentinos P, Dikeos D. Genetic correlates of medical comorbidity associated with schizophrenia and treatment with antipsychotics. Curr Opin Psychiatry 2012; 25: 381-390
• 69 Velamoor VR, Norman RM, Caroff SN et al. Progression of symptoms in neuroleptic malignant syndrome. J Nerv Ment Dis 1994; 182: 168-173
• 70 Nisijima K, Shioda K. Temporal changes in serum creatine kinase concentration and degree of muscle rigidity in 24 patients with neuroleptic malignant syndrome. Neuropsychiatr Dis Treat 2013; 9: 853-859
• 71 Caroff SN, Mann SC Hrsg. Neuroleptic malignant syndrome. 2. Aufl. Washington D. C: American Psychiatric Publishing; 2003: 1-44
• 72 Francis A, Chandragiri S, Rizvi S et al. Is Lorazepam a treatment for neuroleptic malignant syndrome?. CNS Spectr 2000; 5: 54-57
• 73 Reulbach U, Dutsch C, Biermann T et al. Managing an effective treatment for neuroleptic malignant syndrome. Crit Care 2007; 11: R4
• 74 Trollor JN, Sachdev PS. Electroconvulsive treatment of neuroleptic malignant syndrome: a review and report of cases. Aust N Z J Psychiatry 1999; 33: 650-659
• 75 Ambulkar RP, Patil VP, Moiyadi AV. Neuroleptic malignant syndrome: A diagnostic challenge. J Anaesthesiol Clin Pharmacol 2012; 28: 517-519