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neuroleptic malignant syndrome

Etiology: - pharmacologic agents a) high potency neuroleptics 1] haloperidol* 2] fluphenazine* 3] trifluoperazine 4] bromperidol 5] domperidone 6] thiothixene 7] molindone b) less potent neuroleptics 1] thioridazine 2] chlorpromazine 3) perphenazine c) other antipsychotics 1] clozapine 2] risperidone d) typical antipsychotics more commonly implicated than atypical antipsychotics [4] e) other agents 1] fluoxetine 2] loxapine 3] tricyclic dibenzodiazepines 4] metoclopramide f) coadministration of neuroleptic with lithium carbonate is a risk factor 4,5] - occurs with any dopamine D2 receptor antagonist [4] - also reported in patients who abruptly discontinue dopaminergic agent, carbidopa/levodopa or dopaminergic receptor agonist [4] - commonly associated with dehydration [4,5] * most common offending agents Pathology: - inhibition of dopamine receptors in the hypothalamus a) increased heat generation b) decreased heat dissipation Clinical manifestations: 1) hyperthermia, temperature may be > 105.8 F (41 C) 2) extramyramidal signs - muscle rigidity (lead pipe) all muscle groups [8] - dystonia [4] - no clonus - hyporeflexia/bradyreflexia 3) autonomic instability a) tachycardia b) tachypnea c) diaphoresis d) blood pressure alterations e) sialorrhea f) normal or hypoactive bowel sounds [8] 4) altered mental status - agitation [4], stupor, mutism, coma [8] 5) seizures 6) cardiac arrhythmias 7) pupils normal [8] 8) rhabdomyolysis - acute renal failure 9) syndrome occurs within 2 weeks of initiation of neuroleptic - onset over days - average 1-3 days Laboratory: 1) complete blood count (CBC) leukocytosis 2) serum creatine kinase: marked increase 3) urine myoglobin: increased Special laboratory: - electrocardiogram: sinus tachycardia Differential diagnosis: - febrile catatonia - malignant hyperthermia as a postoperative reaction to anesthesia - parkinsonian hyperpyrexia syndrome Management: 1) discontinue use of antipsychotic agent (neuroleptic) 2) supportive measures a) ventilation b) cooling c) clinical hydration 3) pharmacologic agents a) benzodiazepine for agitation [4,5] b) dantrolene (direct muscle relaxant) [7] c) bromocryptine 5-15 mg TID or Sinemet 25/100 QID [7] 4) electroconvulsive therapy [7] 5) syndrome resolves over days to weeks - mental status changes resolve first [4] 6) waiting period of at least 2 weeks before restarting antipsychotic - start with low potency agent [4,5] - avoid lithium carbonate - avoid dehydration

Related

neuroleptic

General

drug-induced hyperthermia syndrome

References

  1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 1146
  2. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 88
  3. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 712
  4. Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2009, 2012, 2015, 2018, 2021.
  5. Strawn JR, Keck PE Jr, Caroff SN. Neuroleptic malignant syndrome. Am J Psychiatry. 2007 Jun;164(6):870-6. PMID: 17541044
  6. Gillman PK. Neuroleptic malignant syndrome: mechanisms, interactions, and causality. Mov Disord. 2010 Sep 15;25(12):1780-90. PMID: 20623765
  7. Kuhlwilm L et al. The neuroleptic malignant syndrome - a systematic case series analysis focusing on therapy regimes and outcome. Acta Psychiatr Scand 2020 Jul 13; [e-pub] PMID: 32659853 https://onlinelibrary.wiley.com/doi/full/10.1111/acps.13215
  8. Sinert RH Fast Five Quis: Serotonin Syndrome Medscape. 2121. June 4. https://reference.medscape.com/viewarticle/951841 - Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005 Mar 17;352(11):1112-20 PMID: 15784664 Review https://www.nejm.org/doi/10.1056/NEJMra041867
  9. 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 Sep;72(9):1222-8. PMID: 21733489
  10. NINDS Neuroleptic Malignant Syndrome Information Page https://www.ninds.nih.gov/Disorders/All-Disorders/Neuroleptic-Malignant-Syndrome-Information-Page