Treatment of Neuroleptic Malignant Syndrome
Immediately discontinue all antipsychotic medications and initiate aggressive supportive care—this is the cornerstone of NMS management and takes priority over all other interventions. 1
Immediate Actions
Stop the offending agent immediately upon suspicion of NMS, even before diagnostic confirmation, as delays significantly worsen outcomes. 1, 2 This is the single most critical intervention that determines survival.
Supportive Care Measures
Administer benzodiazepines (such as lorazepam) for agitation and muscle rigidity, as these are first-line agents for symptom control. 1, 3
Implement aggressive cooling measures for hyperthermia using external cooling techniques (ice packs, cooling blankets, evaporative cooling). 1
Provide IV fluid resuscitation to address dehydration, autonomic instability, and elevated creatine kinase/rhabdomyolysis. 1, 3
Avoid physical restraints as they exacerbate isometric muscle contractions, worsening hyperthermia and lactic acidosis, thereby increasing mortality. 1
Pharmacologic Interventions for Severe Cases
When supportive care alone is insufficient or the presentation is severe, consider specific pharmacologic agents as second-line therapy:
Bromocriptine (dopamine agonist) at doses typically 2.5-10 mg orally three times daily addresses the underlying dopamine deficiency in severe NMS. 1, 4, 5, 6 The FDA label for amantadine specifically notes that dopamine agonists like bromocriptine are used in NMS treatment. 4
Dantrolene sodium (muscle relaxant) at 1-2.5 mg/kg IV every 6 hours reduces muscle rigidity and hyperthermia by acting directly on skeletal muscle. 1, 5, 6 Maximum daily dose should not exceed 10 mg/kg.
Note: While bromocriptine and dantrolene are widely used, their effectiveness has not been definitively demonstrated in controlled studies, and some case series show no difference in duration or complications compared to supportive care alone. 4, 5 However, given the high mortality risk, their use is reasonable in severe cases.
Critical Care Management
ICU admission is necessary for approximately 25% of NMS patients, particularly those with extreme hyperthermia, severe autonomic instability, or complications. 1
Emergency sedation, neuromuscular paralysis, and intubation are required for extreme hyperthermia (>41.1°C or 106°F). 1
Hemodialysis may be necessary if acute renal failure develops from rhabdomyolysis. 3
Essential Monitoring
Obtain the following laboratory tests immediately and monitor serially:
- Complete blood count (expect leukocytosis 15,000-30,000 cells/mm³) 3
- Creatine kinase (typically elevated ≥4 times upper limit of normal) 1, 3
- Comprehensive metabolic panel including electrolytes, renal function, liver function 1
- Arterial blood gases (watch for metabolic acidosis) 1
- Coagulation studies (monitor for disseminated intravascular coagulation) 1
Electroconvulsive Therapy (ECT)
Consider ECT as a second-line treatment when pharmacologic interventions fail or in life-threatening situations, particularly if the patient has a concurrent psychiatric condition that would benefit from ECT. 7, 8, 6 The American Academy of Child and Adolescent Psychiatry specifically indicates ECT for severe and persistent NMS. 7, 8
Clinical Pitfalls to Avoid
Do not delay discontinuation of antipsychotics while awaiting diagnostic confirmation—clinical suspicion alone warrants immediate cessation. 2
Do not use anticholinergics liberally, as they can worsen hyperthermia and autonomic instability; use judiciously only if needed. 6
Do not restart antipsychotics for at least 2 weeks following complete resolution of NMS symptoms. 2 When rechallenge is necessary, use low-potency agents at minimal doses with gradual titration. 5
Recognize that abrupt discontinuation of dopamine agonists (like amantadine) can precipitate NMS, so taper these agents carefully if they must be stopped. 4
Prognosis
With prompt recognition and aggressive management, mortality has decreased from 76% in the 1960s to less than 10-15% currently. 1, 3 Early intervention is the primary determinant of survival, making high clinical suspicion and immediate action paramount.