What is the treatment for neuroleptic malignant syndrome (NMS)?

Treatment of Neuroleptic Malignant Syndrome (NMS)

The immediate management of neuroleptic malignant syndrome requires discontinuation of all antipsychotics, aggressive supportive care, and consideration of specific pharmacological interventions including benzodiazepines, bromocriptine, and dantrolene in severe cases. 1

Immediate Management

1. Discontinue the offending agent

   • Immediately stop all antipsychotic medications 1
   • This is the most critical first step in management

2. Supportive care

   • Continuous monitoring of vital signs and cardiorespiratory status 1
   • Aggressive hydration with intravenous fluids to prevent renal failure from rhabdomyolysis 1
   • Physical cooling measures for hyperthermia 1
   • For hemodynamic instability, use direct-acting vasoactive agents (phenylephrine or norepinephrine) rather than indirect agents like dopamine 1

3. First-line pharmacological treatment

   • Benzodiazepines (diazepam or lorazepam) for agitation and muscle activity reduction 1
   • These medications help manage symptoms while addressing the underlying pathophysiology

Severe or Persistent Cases

For patients with severe or persistent symptoms, additional pharmacological interventions may be necessary:

1. Dantrolene sodium

   • Dosage: 1-2.5 mg/kg IV every 6 hours (maximum 10 mg/kg/day) 1
   • Acts as a direct-acting muscle relaxant to reduce rigidity

2. Bromocriptine

   • Dopaminergic agonist that helps counteract the dopamine blockade that contributes to NMS 1

3. Electroconvulsive therapy (ECT)

   • Consider in cases resistant to pharmacological treatment 1
   • Particularly beneficial when catatonia is a prominent feature 1

Monitoring and Follow-up

• Close monitoring of:

  • Vital signs
  • Mental status
  • Creatine kinase (CK) levels
  • Renal function
  • Serum electrolytes
  • Liver function 1

• Laboratory findings to monitor include:

  • Elevated CK levels
  • Leukocytosis
  • Electrolyte disturbances
  • Elevated liver enzymes
  • Metabolic acidosis
  • Myoglobinuria 1

Long-term Management

• Wait at least 2 weeks after complete symptom resolution before reintroducing antipsychotics 1
• When restarting antipsychotics:
  • Begin with low-potency agents
  • Use gradual dose increases
  • Avoid the original precipitating drug if possible 1

Clinical Pearls and Pitfalls

• Differential diagnosis is crucial: NMS must be distinguished from serotonin syndrome, malignant hyperthermia, lethal catatonia, CNS infections, heat stroke, and anticholinergic toxicity 1

• Risk factors to recognize:

  • Young adult males
  • Concomitant use of multiple psychotropics
  • Rapid dose escalation
  • Dehydration
  • Physical exhaustion
  • Use of long-acting depot antipsychotics
  • Abrupt discontinuation of dopaminergic agents 1

• Recurrence risk: Patients with a history of NMS have an increased risk of recurrence, requiring careful monitoring with any future antipsychotic treatment 1

• Mortality rate: While historically as high as 76% in the 1960s, proper recognition and treatment have reduced mortality to less than 15% currently 1

• All antipsychotics can cause NMS: Both typical and atypical antipsychotics can trigger NMS, with haloperidol being the most frequently reported agent 1