Treatment of Neuroleptic Malignant Syndrome (NMS)
The primary treatment for neuroleptic malignant syndrome is immediate discontinuation of the precipitating antipsychotic medication and providing aggressive supportive care, including management of hyperthermia, autonomic instability, and rigidity. 1
Initial Management
- Immediately discontinue the offending antipsychotic medication, which is the most critical first step in NMS management 1
- Provide aggressive supportive care to address the life-threatening symptoms 1
- Treat agitation with benzodiazepines to help reduce muscle activity and associated hyperthermia 1, 2
- Implement cooling measures for hyperthermia, as the fever is due to muscular hyperactivity rather than hypothalamic dysregulation (antipyretics are typically not effective) 2, 1
- Administer IV fluids to manage dehydration and electrolyte abnormalities 2, 1
- Monitor for and treat complications such as rhabdomyolysis, metabolic acidosis, renal failure, and coagulation disorders 1
Pharmacologic Interventions
- For severe cases, consider dopaminergic agents such as bromocriptine to address the underlying dopamine deficiency 1, 3
- Dantrolene sodium may be used as a muscle relaxant to reduce rigidity and hyperthermia in severe cases 1, 3, 4
- Low dosages of direct-acting sympathomimetic amines (phenylephrine, norepinephrine, epinephrine) or short-acting drugs (esmolol, nitroprusside) may be used to manage blood pressure fluctuations 2
- Avoid indirect agents like dopamine as they may cause overshooting of the desired effect 2
Management of Severe Cases
- For extreme hyperthermia (>41.1°C), consider emergency sedation, neuromuscular paralysis with nondepolarizing agents (vecuronium, rocuronium), and intubation 2, 1
- Avoid succinylcholine due to risk of complications from hyperkalemia and rhabdomyolysis 2
- Approximately 25% of NMS patients require intensive care unit admission 1
- Avoid physical restraints as they may worsen muscle contractions, hyperthermia, and lactic acidosis 1
Laboratory Monitoring
- Obtain complete blood count (leukocytosis is common, 15,000-30,000 cells/mm³) 2, 1
- Monitor electrolytes, renal function, liver function, creatine kinase (often elevated), arterial blood gases, and coagulation studies 2, 1
- Elevated alkaline phosphatase, lactate dehydrogenase, and transaminases may indicate impaired liver function 2
Alternative Therapies for Refractory Cases
- Electroconvulsive therapy (ECT) should be considered for NMS cases that are refractory to pharmacological interventions 5, 4
- ECT has shown a remission rate of 73.3% in refractory cases and is particularly useful when the underlying condition is also responsive to ECT 5
- Patients typically show early initial response to ECT but may require multiple treatments (average 17.7) to minimize recurrence of symptoms 5
Prognosis and Follow-up
- With proper treatment, mortality from NMS has decreased from 76% in the 1960s to less than 10-15% in recent years 2, 1
- Early recognition and prompt management are crucial for improving outcomes 1, 6
- After resolution of NMS, reassess the need for antipsychotic treatment and wait at least 2 weeks before considering rechallenge with antipsychotics 6
- Educate patients and families about NMS risk factors and symptoms to monitor 6