Treatment of Neuroleptic Malignant Syndrome
Immediately discontinue all antipsychotic medications and initiate aggressive supportive care, which forms the cornerstone of NMS management and has reduced mortality from 76% to less than 10-15%. 1
Immediate Actions Upon Suspicion
- Stop the offending agent immediately – this is the single most critical intervention, even before diagnostic confirmation is complete 1, 2
- Avoid physical restraints as they worsen isometric muscle contractions, exacerbating hyperthermia and lactic acidosis, thereby increasing mortality 1
- Admit approximately 25% of patients to the ICU based on severity of presentation 1
Aggressive Supportive Care
Temperature Management
- Implement external cooling measures for hyperthermia using cooling blankets, ice packs, and evaporative cooling 1, 2
- For extreme hyperthermia (>41.1°C), proceed to emergency sedation, neuromuscular paralysis, and intubation 1
Fluid and Metabolic Management
- Administer IV fluids aggressively to address dehydration and prevent rhabdomyolysis from elevated creatine kinase 1, 2
- Hemodialysis may be necessary if renal failure develops 2
Agitation Control
- Use benzodiazepines (lorazepam or alprazolam) as first-line agents for agitation management 1, 2
- Benzodiazepines provide sedation without worsening dopamine blockade 1
Autonomic Stabilization
- Normalize vital signs with IV fluids and other agents to address tachycardia and blood pressure fluctuations 1
Pharmacologic Interventions for Severe Cases
Dopaminergic Agents
- Bromocriptine addresses the underlying dopamine deficiency in severe NMS 1, 3
- Consider bromocriptine when supportive measures alone are insufficient and rigidity/hyperthermia persist 3, 4
Muscle Relaxants
- Dantrolene sodium reduces muscle rigidity and hyperthermia by acting directly on skeletal muscle 1, 5
- Dantrolene has demonstrated efficacy in case reports of NMS induced by antipsychotic monotherapy 5
- Consider dantrolene for severe, prolonged, or refractory cases with prominent rigidity 4, 6
The evidence for bromocriptine and dantrolene remains somewhat controversial, with some sources questioning their merit while others report efficacy 3. However, in severe cases where supportive care is inadequate, these agents represent reasonable adjunctive options 4, 6.
Second-Line Treatment
- Electroconvulsive therapy (ECT) serves as second-line treatment for severe and persistent NMS, particularly when concurrent psychiatric conditions would benefit from ECT 1
- ECT has been used successfully in refractory cases and is particularly useful in post-NMS patients 3, 6
Essential Monitoring
Laboratory Testing
- Complete blood count (monitor for leukocytosis of 15,000-30,000 cells/mm³) 1, 2
- Electrolytes and renal function 1
- Liver function tests 1
- Creatine kinase (often ≥4 times upper limit of normal) 1, 2
- Arterial blood gases 1
- Coagulation studies 1
Complications to Monitor
- Rhabdomyolysis with markedly elevated creatine kinase 1, 2
- Metabolic acidosis 1, 7
- Elevated liver enzymes 1, 2
- Renal failure requiring potential hemodialysis 1, 2
- Seizures 1, 7
- Disseminated intravascular coagulation 1, 7
Critical Pitfalls to Avoid
- Never continue antipsychotics while evaluating for NMS – discontinue immediately upon suspicion 1, 2, 8
- Do not use physical restraints, which worsen the syndrome 1
- Avoid pro re nata (p.r.n.) chemical restraints, which are prohibited 9
- Do not delay treatment waiting for diagnostic confirmation – early recognition and prompt management are crucial for the dramatic improvement in outcomes 1, 8
The diagnosis is clinical without pathognomonic laboratory criteria, so a high index of suspicion based on the tetrad of altered mental status, fever, muscle rigidity, and autonomic dysfunction should trigger immediate intervention 2, 7.