This handout is for neuroleptic malignant syndrome (nms) — toxidrome from antipsychotic d2 blockade (strawn ajp 2007 pmid 17541055; levenson ajp 1985 pmid 2862613; dsm-5-tr 2022); stop ap immediately + icu + supportive (cooling + iv hydration) + dantrolene 1-2.5 mg/kg iv q6h + bromocriptine 2.5 mg po tid + ect for refractory; avoid succinylcholine + re-introduction of offending ap + abrupt clozapine discontinuation. Your care team identified this based on: antipsychotic (typical / atypical / lai depot / clozapine) initiated, dose-escalated, switched, or new agent added within 72 h to 2 weeks (strawn ajp 2007 pmid 17541055; dsm-5-tr 2022).
Other reasons your team may use this plan: tetrad of severe lead-pipe muscle rigidity + hyperthermia (often > 41°c) + autonomic instability (labile bp, tachycardia, diaphoresis) + altered mental status (stupor / mutism / catatonic — not agitation) (strawn ajp 2007); lead-pipe muscle rigidity (generalized) + hyporeflexia in patient on antipsychotic (strawn ajp 2007; distinguishes from serotonin syndrome which has clonus + hyperreflexia); ck > 1000 (often > 10× uln) + ap exposure within 72 h to 2 weeks → presumptive nms (levenson ajp 1985 pmid 2862613).
Take these medications exactly as prescribed. Do not stop or change a dose without talking to your provider.
| Medication | Starting dose | How | When | What it does |
|---|---|---|---|---|
| STOP all antipsychotics | discontinue immediately | NA | immediate | Strawn AJP 2007 PMID 17541055 — mandatory first step; for LAI depot AP washout is not possible — supportive duration extended by weeks; for dopamine-agonist withdrawal NMS, RESTART agonist (different pivot) |
| lorazepam | 1-2 mg IV q 4-6 h (also serves as lorazepam challenge for catatonia-NMS continuum per Fink + Taylor 2003) | IV | q 4-6 h PRN | Strawn AJP 2007 — benzodiazepine first-line for agitation + neuromuscular control + serves as lorazepam challenge for catatonia-NMS continuum (Fink + Taylor Lancet 2003); lorazepam preferred for predictable hepatic metabolism (no active metabolite); 2 mg IV challenge for catatonia-NMS continuum diagnosis |
| IV crystalloid (NS or LR) | 500-1000 mL bolus then maintenance 100-150 mL/h with UOP target > 1 mL/kg/h for rhabdo prophylaxis | IV | continuous | Strawn AJP 2007 — volume + rhabdo prophylaxis; UOP target > 1 mL/kg/h; isotonic crystalloid first-line (NS or LR); consider sodium bicarbonate for urinary alkalinization if CK > 5000 |
| passive + active cooling (cooling blankets, ice packs, evaporative, cold IV fluids) | NA — supportive | NA | continuous until T < 38.5°C | Strawn AJP 2007 — temperature control foundational; passive cooling (remove blankets, fans) for T > 38.5°C; aggressive cooling (ice packs, evaporative, surface cooling, cold IV fluids) + intubation + paralysis (rocuronium, AVOID succinylcholine) for T > 41°C; mortality correlates with peak temperature |
Plan: NMS treatment ladder — STOP AP + ICU + supportive (cooling + IV fluids) → benzo (lorazepam) → dantrolene 1-2.5 mg/kg IV q6h → bromocriptine 2.5 mg PO TID titrate to 7.5 mg TID → amantadine 100 mg PO BID adjunct → ECT for refractory or catatonia-NMS continuum; AVOID succinylcholine + re-introduction of offending AP + abrupt clozapine discontinuation + parenteral AP during NMS + dopamine antagonist anti-emetics during acute NMS (Strawn AJP 2007 PMID 17541055; Levenson AJP 1985 PMID 2862613; Velamoor 2017)
Use these zones to know what to do based on how you feel.
Call 911 or go to the nearest emergency room right away if you have:
Comprehensive medication review at discharge + alternative AP regimen counselling (atypical preferred if typical was trigger; low-potency preferred if high-potency was trigger; clozapine sometimes used as the lowest-NMS-risk agent for required AP; 2-week wash-out + low starting dose + slow titration); psychiatry consult for AP regimen continuation if psychosis / bipolar / treatment-resistant depression with adjunctive AP; pharmacy MTM for NMS-prevention education; document NMS in EHR allergy/ADR list + chart-flag permanent (recurrence ~ 30%); pain medicine consult NOT required (NMS is not chronic pain); if Parkinson disease, restart dopamine agonist post-resolution; outpatient PCP / psychiatry follow-up at 1 week + 1 month + q 1-3 months; patient + caregiver education on NMS recognition + 24-h ED return precaution; recurrence-prevention counselling (alternative AP regimen, slow titration, chart-flag at every visit) (Strawn AJP 2007; Pope 1991)
Guideline: Strawn + Keck + Caroff Am J Psychiatry 2007 PMID 17541055 (canonical NMS update review + management algorithm) + Levenson Am J Psychiatry 1985 PMID 2862613 (initial cardinal description + Levenson criteria) + Caroff + Mann Med Clin North Am 1993 (NMS clinical syndrome anchor; PMID NEEDS_SOURCE_REVIEW) + Caroff + Mann Psychiatr Clin North Am 1988 (Caroff + Mann criteria; PMID candidate 3349602 NEEDS_SOURCE_REVIEW) + DSM-5-TR 2022 (current diagnostic criteria) + Velamoor Asian J Psychiatry 2017 (modern management synthesis) + Pope J Clin Psychiatry 1991 (recurrence ~ 30% on AP re-challenge cohort) + Fink + Taylor Lancet 2003 (catatonia-NMS continuum framework) + FDA AP class boxed warnings (typical + atypical)