This handout is for serotonin syndrome hypertensive crisis (autonomic instability + neuromuscular hyperactivity + altered mental status + htn crisis ± hyperthermia). Your care team identified this based on: serotonergic agent (ssri/snri/maoi/tca/tramadol/triptan/linezolid/methylene-blue/st-john's-wort/mdma/cocaine) added or escalated within 24-72 h + autonomic + neuromuscular features (boyer nejm 2005 pmid 15784664).
Other reasons your team may use this plan: hypertensive crisis + tachycardia + diaphoresis + tremor/clonus (lower-extremity dominant) + agitation/delirium + temperature ≥38°c — serotonin toxidrome; inducible or spontaneous clonus with concurrent bp ≥180/120 — hunter criteria entry trigger.
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 |
|---|---|---|---|---|
| lorazepam | 1-2 mg IV q5-10 min PRN, max 8 mg in 1 h | IV | PRN | Boyer NEJM 2005 PMID 15784664 first-line — benzodiazepine for sympatholysis + neuromuscular control + sedation; titrate to symptom control + sedation level |
| diazepam | 5-10 mg IV q5-10 min | IV | PRN | Boyer NEJM 2005 — alternative to lorazepam; longer half-life advantageous for sustained neuromuscular control |
| cyproheptadine | 12 mg PO/NG load → 2 mg PO/NG q2h until improvement; max 32 mg/24 h then 8 mg PO q6h maintenance | PO/NG | load + q2h titrated | Boyer NEJM 2005 + Gillman Pharmacother 2010 PMID 20429837 — 5-HT2A antagonist; case-series + animal-model evidence; reserved for moderate-severe disease; available only PO/NG (no IV) |
| nicardipine | 5 mg/h IV titrate q5 min by 2.5 mg/h to max 15 mg/h | IV | continuous | AHA 2025 HTN guideline + ACC 2017 — preferred IV agent for HTN crisis; titratable + autoregulation-aware; avoids unopposed alpha concern of pure beta-blockers |
| labetalol | 10-20 mg IV q10 min, max 300 mg cumulative; OR infusion 0.5-2 mg/min titrate | IV | PRN bolus or infusion | AHA 2025 HTN guideline — mixed alpha-beta acceptable in SS HTN crisis (alpha component prevents unopposed alpha; benefit of HR control); avoid pure beta-blocker monotherapy in concurrent stimulant exposure |
| rocuronium | 0.6-1.2 mg/kg IV bolus | IV | as needed for intubation | Preferred over succinylcholine for intubation in SS with rhabdomyolysis (avoids hyperK + ↑K from depolarization); supports active cooling + neuromuscular control in severe SS |
| AVOID droperidol/haloperidol high-dose | AVOID | N/A | N/A | QTc prolongation + dystonia risk; can worsen autonomic instability; antiemetic alternative if needed: ondansetron caution (5-HT3 antagonist — avoid in SS), prefer prochlorperazine or simply benzo |
| AVOID nitroprusside | AVOID | N/A | N/A | Cyanide accumulation worsens with hyperthermia + rhabdo + hepatic dysfunction; nicardipine or labetalol preferred |
| AVOID succinylcholine | AVOID | N/A | N/A | Hyperkalemia from rhabdomyolysis + succinylcholine = arrest risk; use rocuronium for RSI |
| AVOID bromocriptine/dantrolene | AVOID | N/A | N/A | Bromocriptine is dopamine agonist — worsens serotonin syndrome (used for NMS); dantrolene has no role in SS (used for malignant hyperthermia + sometimes NMS); aggressive cooling + benzo + paralysis preferred for severe hyperthermia |
| STOP all serotonergic agents | STOP | N/A | mandatory | Boyer NEJM 2005 + Hunter criteria — mandatory first step; resolution in 70% within 24-48 h after cessation; if MAOI on board, requires 14-d washout before reintroducing serotonergic agent |
Plan: Serotonin syndrome HTN crisis — STOP serotonergic agents; benzodiazepine-first sympatholysis + neuromuscular control; cyproheptadine for refractory severe disease; nicardipine/labetalol for BP; AVOID droperidol/nitroprusside/succinylcholine/bromocriptine
Contact your care team if any of the following happen:
Call 911 or go to the nearest emergency room right away if you have:
Comprehensive medication review + safer alternatives (e.g., switch tramadol to non-serotonergic analgesic; switch SSRI to bupropion if depression amenable); psychiatry consult if depression/SI driver; pharmacy MTM for SS-prevention education; document SS in allergy/ADR list; pain medicine consult if chronic pain driving tramadol use; if MAOI was on board, mandatory 14-d washout before reintroducing serotonergic agent; outpatient PCP follow-up at 1 week
Guideline: Boyer & Shannon NEJM 2005 (PMID 15784664) — landmark serotonin syndrome review + Hunter criteria (Dunkley QJM 2003 PMID 12925718) + 2025 ACC/AHA HTN (Whelton)