Recognize
- FEVER + lead-pipe RIGIDITY + AMS + autonomic instability
- Onset days–weeks after starting / increasing antipsychotic (or stopping dopamine agonist in PD)
- Labs: CK markedly ↑ (often > 1000), ↑ WBC, ↑ LFTs, ↓ Fe, metabolic acidosis
- Distinguishing from serotonin syndrome: bradyreflexia + lead-pipe rigidity (not clonus); slower onset
Common offenders
Haloperidol, fluphenazine, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole · also metoclopramide, prochlorperazine, promethazine · withdrawal of levodopa / amantadine in Parkinson's.
Management
- Stop all dopamine antagonists (or restart withdrawn dopamine agonist)
- Aggressive cooling — ice, evaporative, cold IVF; target < 38.5°C
- Benzodiazepines — Lorazepam 1–2 mg IV q4–6h for agitation / mild rigidity
- Dantrolene 1–2.5 mg/kg IV q6h (max 10 mg/kg/day) for severe rigidity / hyperthermia
- Bromocriptine 2.5–5 mg PO/NG q8h (dopamine agonist) — continue 10 days
- IV fluids + bicarb for rhabdo (UOP > 1–2 mL/kg/hr); monitor K, Cr, CK
- Intubate + non-depolarizing paralytic if refractory hyperthermia / rigidity (avoid succinylcholine — hyperK)
- ECT considered for refractory cases
Disposition
- ICU admission — mortality 10–20% if untreated
- Resolution typically 7–14 days; longer for depot antipsychotics
- Psychiatry consult before re-challenging — wait ≥ 2 wk, use lower-potency atypical