Neuroleptic malignant syndrome

(Redirected from NMS)


  • Life threatening neurologic emergency associated with the use of neuroleptic agents[1][2]
  • Develops over 1-3 days
  • Majority of deaths occur from complications of muscle rigidity
  • Mortality rates up to 5 to 20% [4]

Clinical Features

Patient exhibiting NMS symptoms: hyperthermia, significant extrapyramidal symptoms, various autonomic symptoms, and impaired consciousness.


Differential Diagnosis

  • Serotonin Syndrome
    • Serotonin syndrome more likely to have hyperreflexia, myoclonus, ataxia, nausea and vomiting, diarrhea
    • Rigidity and hyperthermia, if present, is less severe than in NMS; more commonly presents with clonus and hyperreflexia
  • Malignant Hyperthermia
    • Distinguish by clinical setting (use of inhalational anesthetics or sux)
    • Hyperthermia, muscle rigidity, and dysautonomia is similar to NMS though more fulminant
  • Anticholinergic Toxicity
    • Diaphoresis, rigidity, elevated CK are absent
    • Flushing, mydriasis, bladder distension are common
  • Sympathomimetics
    • Rigidity is not seen

Movement Disorders and Other Abnormal Contractions

Altered mental status and fever


Serotonin syndrome vs Neuroleptic malignant syndrome

  • History of a new serotonergic drug or a dose increase of a serotonergic drug are helpful
  • Serotonin syndrome is usually much more acute in onset than NMS which may develop over days or weeks
  • Presence of ‘lead pipe’ rigidity is typical of NMS, while serotonin syndrome typically manifests with tremor and hyperreflexia
  • Elevations in CK, LFTs, and WBC, coupled with a low iron level, distinguishes NMS from serotonin syndrome among patients taking both neuroleptic and serotonin agonist medications simultaneously


  • The causative agent should be stopped
  • Discontinue all dopamine blocking agents
  • If precipitant is a dopaminergic therapy (L-dopa or Carbidopa) it can be restarted later at lower doses as an outpatient

Supportive Care

  • Agitation should be controlled with Benzodiazepines
    • Lorazepam 2 mg IV q5 min until agitation and muscle rigidity resolves
  • Fluid resuscitation
  • Cooling measures
  • Intubation and paralysis for severe cases, chest wall rigidity or respiratory failure
    • Use NON-DEPOLARIZING paralytic agent

Directed Medical Therapy[6]

Controversial with unclear and disputed efficacy

  • Dantrolene (skeletal muscle relaxant) - Consider only in patients with severe rigidity
    • May cause hepatotoxicity in patients with liver disease
    • 0.25-2mg/kg IV q6-12hr, max dose 10mg/kg/day
  • Bromocriptine (dopamine agonist)
    • 2.5mg PO q6-8hr, max dose 40mg/day
  • Amantadine (alternative to bromocriptine)
    • 100mg PO initially; titrate up as needed to max dose 200mg q12hr

Electroconvulsive Therapy

  • Limited case series suggest that ECT can be effective in NMS refractory to pharmacotherapy[7]


  • Admit, usually to ICU

See Also


  1. 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. Nov 15 2013
  2. Trollor JN, Chen X, Sachdev PS. Neuroleptic malignant syndrome associated with atypical antipsychotic drugs. CNS Drugs. 2009;23(6):477-92
  3. Dunkley, E. J. C., Isbister, G. K., Sibbritt, D., Dawson, A. H. and Whyte, I. M. (2003) ‘The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity’, QJM, 96(9), pp. 635–642. doi: 10.1093/qjmed/hcg109
  4. Shalev A. Mortality from neuroleptic malignant syndrome. J Clin Psychiatry. 1989;50(1):18-25.
  5. Gurrera RJ, Velamoor V, Cernovsky ZZ. A Validation Study of the International Consensus Diagnostic Criteria for Neuroleptic Malignant Syndrome. J Clin Psychopharmacol. Aug 22 2013
  6. Addonizio G, Susman VL, Roth SD. Neuroleptic malignant syndrome: review and analysis of 115 cases. Biol Psychiatry. Aug 1987;22(8):1004-20
  7. Morcos N et al., Electroconvulsive therapy for neuroleptic malignant syndrome: a case series. J ECT. 2019.