Neuroleptic malignant syndrome

(Redirected from NMS)

Background

File:NMS clinical features.jpg
Patient exhibiting NMS symptoms: hyperthermia, significant extrapyramidal symptoms, various autonomic symptoms, and impaired consciousness.
  • Life-threatening neurologic emergency associated with dopamine receptor blockade[1]
  • Can occur with single dose, dose increase, or stable chronic dosing
  • Onset typically 1-3 days after exposure (but can occur weeks later)
  • Causative agents:
    • "Typical" high-potency antipsychotics: haloperidol (most common), chlorpromazine, fluphenazine
    • "Atypical" antipsychotics: risperidone, olanzapine, quetiapine, aripiprazole[2]
    • Antiemetics: metoclopramide, promethazine, droperidol
    • Withdrawal of dopaminergic agents (levodopa, bromocriptine) in Parkinson's disease
  • Mortality: 5-20%[3]
  • Most deaths from complications of severe muscle rigidity (rhabdomyolysis → renal failure, respiratory failure)

Clinical Features

  • Develops over 1-3 days (distinguishes from serotonin syndrome which is more acute)
  • Classic tetrad[4]:

1. Altered Mental Status

  • Agitated delirium progressing to stupor and coma
  • May be earliest feature

2. Muscle Rigidity

  • Generalized "lead-pipe" rigidity (distinguishing feature from serotonin syndrome)
  • May cause chest wall rigidity → respiratory failure

3. Hyperthermia

  • >38°C in 87% of cases; >40°C in 40%
  • Can exceed 42°C

4. Autonomic Instability

  • Tachycardia, labile blood pressure, diaphoresis
  • Sialorrhea (drooling), urinary incontinence

Complications

Differential Diagnosis

Feature NMS Serotonin syndrome Malignant hyperthermia Anticholinergic toxicity
Onset Days Hours Minutes (OR) Hours
Rigidity Lead-pipe Clonus/hyperreflexia Generalized Absent
Skin Diaphoresis Diaphoresis Mottled/diaphoresis Dry, flushed
CK >1000 Mildly elevated Markedly elevated Normal
Pupils Normal Mydriasis Normal Mydriasis
Bowel sounds Normal/decreased Hyperactive Normal Absent

Template:Altered mental status and fever DDX

Evaluation

  • CK: typically >1000 IU/L; correlates with degree of rigidity; may exceed 100,000
  • CBC: leukocytosis (WBC >10K typical, may exceed 40K)
  • BMP: hypocalcemia, hypomagnesemia, hyperkalemia, metabolic acidosis
  • LFTs: transaminitis common
  • Serum iron: low iron level supports NMS diagnosis (distinguishes from serotonin syndrome)
  • Urinalysis: myoglobinuria from rhabdomyolysis
  • Coagulation studies: DIC screening
  • Blood cultures: rule out sepsis
  • CT head/LP: rule out CNS infection; CSF may show mildly elevated protein

NMS vs Serotonin Syndrome

  • History of neuroleptic drug → NMS; serotonergic drug → serotonin syndrome
  • NMS: lead-pipe rigidity, slow onset (days), elevated CK, low iron
  • SS: clonus/hyperreflexia, rapid onset (hours), hyperactive bowel sounds, diarrhea

Management

Immediate

  • Stop all dopamine-blocking agents immediately
  • If precipitated by withdrawal of dopaminergic therapy (levodopa): restart at lower dose
  • Aggressive IV fluid resuscitation (goal UOP >1-2 mL/kg/hr for rhabdomyolysis)
  • Active cooling measures for hyperthermia >40°C

Agitation and Rigidity

  • Benzodiazepines first-line:
    • Lorazepam 2 mg IV q5min until agitation and muscle rigidity resolve
  • For severe cases with respiratory failure or chest wall rigidity:
    • Intubation with NON-DEPOLARIZING paralytic (rocuronium, vecuronium)
    • AVOID succinylcholine (risk of hyperkalemia from rhabdomyolysis)

Directed Medical Therapy

  • Efficacy controversial — limited to case reports/series[5]
  • Dantrolene (skeletal muscle relaxant):
    • Consider for severe rigidity with hyperthermia >40°C
    • 0.25-2 mg/kg IV q6-12h (max 10 mg/kg/day)
    • Monitor LFTs (hepatotoxicity risk)
  • Bromocriptine (dopamine agonist):
    • 2.5 mg PO/NGT q6-8h (max 40 mg/day)
    • Continue for 10 days after NMS resolves to prevent relapse
  • Amantadine (alternative to bromocriptine):
    • 100 mg PO initially; titrate to 200 mg q12h

Electroconvulsive Therapy

  • Consider for refractory NMS unresponsive to pharmacotherapy[6]

Monitoring

  • Serial CK, renal function, electrolytes
  • Continuous cardiac monitoring
  • Treat hyperkalemia aggressively if present

Disposition

  • Admit to ICU for all suspected cases
  • Symptoms typically resolve over 7-10 days (longer with depot antipsychotics — up to 2-4 weeks)
  • After recovery, cautious rechallenge with a different, low-potency antipsychotic may be attempted after 2 weeks
  • Psychiatric consultation for medication management

See Also

References

  1. ↑ Su YP, et al. Retrospective chart review on exposure to psychotropic medications associated with neuroleptic malignant syndrome. Acta Psychiatr Scand. 2014;130(1):52-60. PMID 24256459
  2. ↑ Trollor JN, et al. Neuroleptic malignant syndrome associated with atypical antipsychotic drugs. CNS Drugs. 2009;23(6):477-92. PMID 19480467
  3. ↑ Shalev A. Mortality from neuroleptic malignant syndrome. J Clin Psychiatry. 1989;50(1):18-25. PMID 2562951
  4. ↑ Gurrera RJ, et al. A validation study of the international consensus diagnostic criteria for NMS. J Clin Psychopharmacol. 2013;33(6):747-54. PMID 24100788
  5. ↑ Addonizio G, et al. Neuroleptic malignant syndrome: review and analysis of 115 cases. Biol Psychiatry. 1987;22(8):1004-20. PMID 3620091
  6. ↑ Morcos N et al. Electroconvulsive therapy for neuroleptic malignant syndrome: a case series. J ECT. 2019;35(4):225-230. PMID 31651674
  • Strawn JR, et al. Neuroleptic malignant syndrome. Am J Psychiatry. 2007;164(6):870-876. PMID 17541044
  • Berman BD. Neuroleptic malignant syndrome: a review for neurohospitalists. Neurohospitalist. 2011;1(1):41-47. PMID 23983836
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