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

Treatment of Neuroleptic Malignant Syndrome

Immediately discontinue all antipsychotic medications and initiate aggressive supportive care—this is the cornerstone of NMS management and takes absolute priority over any pharmacologic intervention. 1, 2

Immediate Actions (First-Line Treatment)

Discontinue the offending agent as the single most critical intervention, regardless of psychiatric status. 1, 3

Initiate aggressive supportive care with the following specific measures:

• Benzodiazepines for agitation management rather than physical restraints, which worsen isometric muscle contractions, hyperthermia, and lactic acidosis, thereby increasing mortality 1
• External cooling measures for hyperthermia using ice packs, cooling blankets, and evaporative cooling techniques 1, 2
• Intravenous fluid resuscitation to address dehydration, support renal function, and prevent rhabdomyolysis-induced renal failure 1, 2
• Normalize vital signs with agents to control blood pressure fluctuations and tachycardia 1

Pharmacologic Interventions (Adjunctive Therapy)

Use these agents in severe cases with significant muscle rigidity and hyperthermia:

Dopaminergic agents:

• Bromocriptine addresses the underlying dopamine deficiency in severe NMS 1, 4
• Consider levodopa-carbidopa as an alternative dopaminergic strategy 5
• Anticholinergic drugs like benztropine may enhance bromocriptine effectiveness 5

Muscle relaxants:

• Dantrolene sodium reduces muscle rigidity and hyperthermia in severe cases 1, 5
• Note: The FDA label indicates dantrolene is not officially indicated for NMS treatment, and patients may expire despite its use; however, it remains widely used in clinical practice 6
• Administer intravenously with caution regarding pulmonary edema risk from diluent volume 6

Advanced Interventions for Life-Threatening Cases

For extreme hyperthermia (>41.1°C):

• Emergency sedation 1
• Neuromuscular paralysis 1
• Intubation and mechanical ventilation 1

ICU admission is necessary for approximately 25% of NMS patients 1

Electroconvulsive therapy (ECT) serves as second-line treatment for severe and persistent NMS, particularly when concurrent psychiatric conditions would benefit from ECT 1, 4

Essential Monitoring

Laboratory testing must include:

• Complete blood count (watch for leukocytosis 15,000-30,000 cells/mm³) 1, 2
• Creatine kinase (typically ≥4 times upper limit of normal) 1, 2
• Electrolytes and renal function 1, 2
• Liver function tests 1, 2
• Arterial blood gases 1
• Coagulation studies 1

Monitor for life-threatening complications:

• Rhabdomyolysis with acute renal failure (may require hemodialysis) 1, 2
• Metabolic acidosis 1, 3
• Seizures 1, 3
• Disseminated intravascular coagulation 1, 3

Critical Pitfalls to Avoid

Never use physical restraints, as they exacerbate isometric muscle contractions, worsening hyperthermia and lactic acidosis, directly increasing mortality 1

Do not delay treatment waiting for diagnostic confirmation—NMS is a clinical diagnosis without pathognomonic laboratory findings, and early intervention has reduced mortality from 76% in the 1960s to less than 10-15% currently 1, 2, 3

Avoid passive treatment approaches—active, aggressive management is required to prevent fatalities 5

Treatment Hierarchy Based on Severity

Mild cases: Discontinue antipsychotic + supportive care + benzodiazepines 1, 2

Moderate cases: Add bromocriptine and/or dantrolene to the above regimen 1, 5

Severe cases with extreme hyperthermia or complications: Add ICU admission, consider neuromuscular paralysis/intubation, and ECT if persistent 1

Post-resolution management: Wait at least 2 weeks before considering antipsychotic rechallenge, obtain informed consent after risk-benefit discussion, and educate patient and family about the episode 7