neuroleptic malignant syndrome
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Etiology
- pharmacologic agents
- high potency neuroleptics
- haloperidol*
- fluphenazine*
- trifluoperazine
- bromperidol
- domperidone
- thiothixene
- molindone
- less potent neuroleptics
- high potency neuroleptics
- perphenazine
- other antipsychotics
- typical antipsychotics more commonly implicated than atypical antipsychotics[4]
- other agents
- 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
- increased heat generation
- decreased heat dissipation
Clinical manifestations
- hyperthermia, temperature may be > 105.8 F (41 C)
- extramyramidal signs
- muscle rigidity (lead pipe) all muscle groups[8]
- dystonia[4]
- no clonus
- hyporeflexia/bradyreflexia
- autonomic instability
- tachycardia
- tachypnea
- diaphoresis
- blood pressure alterations
- sialorrhea
- normal or hypoactive bowel sounds[8]
- altered mental status
- seizures
- cardiac arrhythmias
- pupils normal[8]
- rhabdomyolysis
- syndrome occurs within 2 weeks of initiation of neuroleptic
- onset over days - average 1-3 days
Laboratory
- complete blood count (CBC) leukocytosis
- serum creatine kinase: marked increase
- urine myoglobin: increased
Diagnostic procedures
Differential diagnosis
- febrile catatonia
- malignant hyperthermia as a postoperative reaction to anesthesia
- parkinsonian hyperpyrexia syndrome
Management
- discontinue use of antipsychotic agent (neuroleptic)
- supportive measures
- ventilation
- cooling
- clinical hydration
- pharmacologic agents
- benzodiazepine for agitation[4][5]
- dantrolene (direct muscle relaxant)[7]
- bromocryptine 5-15 mg TID or Sinemet 25/100 QID[7]
- electroconvulsive therapy[7]
- syndrome resolves over days to weeks
- mental status changes resolve first[4]
- waiting period of at least 2 weeks before restarting antipsychotic
- start with low potency agent[4][5]
- avoid lithium carbonate
- avoid dehydration
More general terms
Additional terms
References
- ↑ Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 1146
- ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 88
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 712
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 4.9 Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2009, 2012, 2015, 2018, 2021.
- ↑ 5.0 5.1 5.2 5.3 Strawn JR, Keck PE Jr, Caroff SN. Neuroleptic malignant syndrome. Am J Psychiatry. 2007 Jun;164(6):870-6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17541044
- ↑ Gillman PK. Neuroleptic malignant syndrome: mechanisms, interactions, and causality. Mov Disord. 2010 Sep 15;25(12):1780-90. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20623765
- ↑ 7.0 7.1 7.2 7.3 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: https://www.ncbi.nlm.nih.gov/pubmed/32659853 https://onlinelibrary.wiley.com/doi/full/10.1111/acps.13215
- ↑ 8.0 8.1 8.2 8.3 8.4 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: https://www.ncbi.nlm.nih.gov/pubmed/15784664 Review https://www.nejm.org/doi/10.1056/NEJMra041867 - ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/21733489
- ↑ NINDS Neuroleptic Malignant Syndrome Information Page https://www.ninds.nih.gov/Disorders/All-Disorders/Neuroleptic-Malignant-Syndrome-Information-Page