What is the difference in treatment between Neuroleptic Malignant Syndrome (NMS) and Serotonin Syndrome?

Treatment Differences Between Neuroleptic Malignant Syndrome and Serotonin Syndrome

The primary treatment difference between Neuroleptic Malignant Syndrome (NMS) and Serotonin Syndrome (SS) is that dantrolene is recommended for severe rigidity and hyperthermia in NMS, while cyproheptadine is the medication of choice for moderate to severe SS. 1

Key Diagnostic Differences

Before discussing treatment, it's important to recognize the diagnostic differences:

Neuroleptic Malignant Syndrome (NMS)

• Causative agents: Dopamine antagonists (antipsychotics) or withdrawal of dopamine agonists within 3 days 1
• Key features:
  • Hyperthermia
  • Lead-pipe muscle rigidity
  • Mental status alteration
  • Elevated creatine kinase
  • Autonomic instability
  • Leukocytosis 1

Serotonin Syndrome (SS)

• Causative agents: Serotonergic medications (SSRIs, MAOIs) within past 5 weeks 1
• Key features (Hunter criteria):
  • Muscle rigidity
  • Temperature >38°C
  • Ocular clonus
  • Inducible clonus
  • Tremor
  • Hyperreflexia 1

Treatment Algorithm

1. Immediate discontinuation of offending agents - This is the most critical first step for both conditions 1, 2

2. Supportive care (for both conditions):

   • IV fluid administration
   • External cooling for hyperthermia
   • Cardiac monitoring
   • Respiratory support if needed 1
   • Benzodiazepines for agitation control 1

3. Specific pharmacologic interventions:

   • For NMS: Dantrolene (1-2.5 mg/kg IV) for severe rigidity and hyperthermia 1, 3
   • For SS: Cyproheptadine (initial dose 12 mg orally, followed by 2 mg every 2 hours until clinical response) 1, 4

4. For mixed or unclear presentations:

   • Provide supportive care and withdraw all potentially offending agents
   • Consider treating for both disorders initially - cyproheptadine for SS and dantrolene for NMS
   • Avoid bromocriptine initially (contraindicated in SS)
   • Avoid chlorpromazine initially (contraindicated in NMS) 2
   • Add bromocriptine when clinical presentation becomes consistent with NMS 2

Important Treatment Considerations

• Mortality rates: NMS mortality has decreased from 76% in the 1960s to <10-15% currently due to early recognition and prompt treatment 1
• SS mortality: Approximately 11% for untreated cases 1
• Laboratory distinctions: Elevations in creatine kinase, liver function tests, and white blood cell count, with low serum iron levels, are more characteristic of NMS than SS 4
• Treatment duration: A 2-week washout of neuroleptic medication is recommended to minimize NMS recurrence 4

Common Pitfalls to Avoid

1. Misdiagnosis: NMS and SS share many clinical features, making differentiation difficult, especially with polypharmacy 5, 6

2. Inappropriate medication use:

   • Bromocriptine is contraindicated in SS
   • Chlorpromazine is contraindicated in NMS 2

3. Delayed recognition: Particularly challenging in pediatric patients who may present atypically compared to adults 6

4. Failure to consider mixed presentations: Patients on multiple psychotropic medications may present with features of both syndromes 2, 6

5. Overlooking the importance of immediate discontinuation: The most critical first step in management is discontinuing the offending agent(s) 1, 2