What is the management of Neuroleptic Malignant Syndrome (NMS) and Serotonin Syndrome?

Management of Neuroleptic Malignant Syndrome (NMS) and Serotonin Syndrome

The management of both Neuroleptic Malignant Syndrome (NMS) and Serotonin Syndrome requires immediate discontinuation of the offending agent, aggressive supportive care, and syndrome-specific pharmacological interventions based on symptom severity. 1, 2

Diagnosis and Differentiation

Neuroleptic Malignant Syndrome (NMS)

• Key diagnostic features:
  • Exposure to dopamine antagonist or withdrawal of dopamine agonist within 3 days
  • Hyperthermia (>100.4°F on ≥2 occasions)
  • Muscle rigidity ("lead pipe")
  • Mental status alteration
  • Elevated creatine kinase (≥4 times upper limit of normal)
  • Autonomic instability (blood pressure fluctuations, diaphoresis)
  • Leukocytosis (15,000-30,000 cells/mm³) 1

Serotonin Syndrome

• Hunter Criteria (diagnostic standard):
  • Patient must have taken a serotonergic drug within past 5 weeks
  • Plus one or more of:
    • Spontaneous clonus
    • Inducible clonus with agitation or diaphoresis
    • Ocular clonus with agitation or diaphoresis
    • Tremor and hyperreflexia
    • Muscle rigidity, temperature >38°C, and ocular or inducible clonus 2

Management Algorithm

Step 1: Immediate Actions for Both Syndromes

• Discontinue all potentially offending agents
• Implement supportive care:
  • Secure airway and provide oxygen if needed
  • IV fluid administration
  • External cooling for hyperthermia
  • Cardiac monitoring 1, 2

Step 2: Syndrome-Specific Treatments

For Neuroleptic Malignant Syndrome:

1. Supportive care:

   • IV fluids for dehydration
   • Cooling measures for hyperthermia
   • Benzodiazepines for agitation (first-line)
   • Hemodialysis if renal failure occurs 1

2. Pharmacological interventions:

   • Dantrolene: For severe rigidity and hyperthermia
   • If NMS was triggered by withdrawal of anti-Parkinsonism drug, consider reintroduction 1, 3

For Serotonin Syndrome:

1. Supportive care:

   • IV fluids
   • Benzodiazepines for agitation control (first-line)
   • External cooling for hyperthermia 2

2. Pharmacological interventions:

   • Cyproheptadine: For moderate to severe cases (1-2 mg IV) 2, 3

Step 3: For Mixed or Unclear Presentation

• If features of both syndromes are present:
  1. Provide supportive care and withdraw all potentially offending agents
  2. Consider treatment for both disorders initially:
     • Cyproheptadine for SS
     • Dantrolene for NMS
  3. Do not use bromocriptine initially (contraindicated in SS)
  4. Do not use chlorpromazine initially (contraindicated in NMS)
  5. Add bromocriptine only when clinical presentation becomes clearly consistent with NMS 4

Monitoring and Follow-up

• Monitor vital signs, mental status, and muscle rigidity
• Follow laboratory values: creatine kinase, liver function tests, renal function, electrolytes
• Observe patients for at least 24 hours after symptom resolution 2
• For NMS, allow a minimum 2-week washout period before reintroducing any antipsychotic medication 5, 6

Pitfalls and Caveats

• Mixed presentations are common with polysubstance ingestions
• Serotonin syndrome may be prolonged if the serotonergic agent has a long half-life
• Using bromocriptine in serotonin syndrome or chlorpromazine in NMS can worsen symptoms
• Physical restraint without sedation should be avoided in sympathomimetic toxidromes 2, 4
• The mortality rate for both syndromes can reach approximately 11% without proper treatment, primarily due to respiratory failure 2