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psych.serotonin-syndrome.v1

Serotonin syndrome — toxidrome from serotonergic exposure (Hunter 2003 PMID 12925718; Boyer NEJM 2005 PMID 15784664); STOP serotonergic + benzo + cyproheptadine + cooling; severe → ICU + intubation + paralysis (rocuronium); AVOID bromocriptine + succinylcholine

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Serotonin syndrome dossier — Boyer NEJM 2005 PMID 15784664 (canonical clinical review + management algorithm) + Dunkley QJM 2003 PMID 12925718 (Hunter Serotonin Toxicity Criteria — sens 84% spec 97%) + Gillman Pharmacother 2010 PMID 20429837 (cyproheptadine evidence) + Iqbal Ochsner J 2012 PMID 23230406 (ED management synthesis) + FDA 2011 linezolid + methylene blue boxed warnings + FDA 2006 SSRI + triptan boxed warning + APA MDD 2023; authored 2026-05-15 as Phase C wave 11 NEW dossier. Step 1 (mandatory): STOP all serotonergic agents (SSRI/SNRI/MAOI/linezolid/methylene blue/tramadol/triptan/fentanyl/DXM/MDMA/St John's wort/5-HTP/lithium augmentation) + lorazepam 1-2 mg IV q 5-10 min PRN + IV crystalloid 500-1000 mL bolus + passive/active cooling for T > 38.5°C; resolution in 70% within 24-48 h after offending agent cessation (Mason Medicine Baltimore 2000). Step 2: cyproheptadine 12 mg PO/NG load → 2 mg PO/NG q 2 h until improvement; max 32 mg/24 h then 8 mg PO q 6 h maintenance; 5-HT2A + H1 antagonist; PO/NG only — no IV formulation; reserved for moderate-severe disease per Boyer NEJM 2005 + Gillman Pharmacother 2010 PMID 20429837. Step 3 (severe): ICU + intubation + paralysis (rocuronium 0.6-1.2 mg/kg IV bolus then 0.3-0.6 mg/kg/h infusion — AVOID succinylcholine in rhabdomyolysis hyperK) + active cooling + benzo infusion (midazolam) + cyproheptadine NG continued. Anti-patterns: (1) AVOID bromocriptine — pro-serotonergic; reserved for NMS rescue (the key NMS-vs-SS pharmacological pivot); (2) AVOID succinylcholine in severe SS with rhabdomyolysis — use rocuronium; (3) AVOID droperidol / haloperidol for SS agitation — QTc + dopaminergic worsening; benzo first-line; (4) AVOID routine dantrolene — limited evidence in SS (used for NMS / malignant hyperthermia); (5) AVOID re-initiation of trigger serotonergic agent without 14-d MAOI washout (5-wk fluoxetine washout); (6) AVOID linezolid with SSRI — FDA 2011 boxed warning; alternative antibiotic OR 2-wk SSRI washout; (7) AVOID methylene blue with SSRI intraoperatively — FDA 2011 surgical warning; reschedule surgery; (8) AVOID delaying diagnosis pending labs — Hunter criteria + serotonergic exposure are bedside clinical diagnosis. Hunter Serotonin Toxicity Criteria (Dunkley QJM 2003 PMID 12925718) = serotonergic agent exposure + ONE of: spontaneous clonus / inducible clonus + agitation OR diaphoresis / ocular clonus + agitation OR diaphoresis / tremor + hyperreflexia / hypertonia + T > 38°C + ocular OR inducible clonus; sens 84%, spec 97%; LR+ ≈ 28; preferred over Sternbach 1991. NMS overlap differential: AP exposure + lead-pipe rigidity + hyporeflexia + stupor + ↑↑ CK + days-weeks onset → NMS; treatment = STOP AP + bromocriptine 2.5 mg PO/NG TID + dantrolene 1-2.5 mg/kg IV q 6 h + ECT urgent if catatonic features (Strawn AJP 2007); routes to psych.first-episode-psychosis / psych.bipolar-disorder / psych.catatonia for longitudinal management; the NMS-vs-SS pharmacological pivot is the most important diagnostic + therapeutic distinction in toxidrome differential. Common SS trigger combinations (Werneke Pharmacopsychiatry 2016): SSRI + tramadol (single most-reported); SSRI + linezolid (FDA 2011 boxed warning — linezolid is reversible MAOI); SSRI + MAOI (phenelzine / tranylcypromine / selegiline transdermal); SSRI + triptan (FDA 2006 boxed warning — consider gepants — rimegepant / ubrogepant — as SS-safe alternative for migraine); SSRI + methylene blue intraoperative (FDA 2011 surgical warning — reschedule surgery if SSRI on board for parathyroidectomy / NIRS perfusion mapping); SSRI + DXM / MDMA / cocaine / St John's wort / 5-HTP / lithium augmentation. Severity triggers (10 total): severe_serotonin_syndrome_with_hyperthermia (life_threatening — ICU + intubation + paralysis + cooling + benzo + cyproheptadine), moderate_serotonin_syndrome (severe — discontinue offending + benzo + cyproheptadine + monitor), hunter_criteria_positive (severe — diagnostic gate), polypharmacy_serotonergic_combinations (severe — review all drugs incl. OTC + supplements), nms_overlap_differential (life_threatening — pivot to dantrolene + bromocriptine for NMS; routes to AP-driven dossiers), avoid_succinylcholine_rhabdomyolysis (severe — use rocuronium for paralysis), avoid_bromocriptine_in_serotonin (severe — pro-serotonergic; NMS only), depression_with_history_of_serotonin_syndrome (moderate — review meds + chart-flag + alternative regimen + slow titration), linezolid_with_ssri_combination (severe — alternative antibiotic or 2-wk wash-out from SSRI), recurrence_after_re_initiation (moderate — clear chart-flag + slow titration + alternative agent if possible). Setting playbooks (4): ED (recognition + Hunter criteria + STOP offending + benzo + cooling + ICU/inpatient disposition); ICU (severe SS — intubation + paralysis (rocuronium) + active cooling + cyproheptadine NG + benzo infusion + continuous monitoring); inpatient (moderate SS continued cyproheptadine + benzo + medication reconciliation + psych consult + chart-flag); outpatient (recurrence prevention — chart-flag + medication review at every visit + alternative regimen counselling + slow titration if re-initiation + patient + caregiver education). Cross-dossier routing: psych.first-episode-psychosis.core.v1 (NMS converging differential — AP-driven syndrome); psych.bipolar-disorder.core.v1 (lithium + SSRI augmentation high-risk; NMS converging differential if AP exposure); psych.depression.core.v1 (chronic SSRI exposure — post-resolution alternative regimen counselling); psych.catatonia.core.v1 (catatonia + NMS overlap can converge with SS-like presentation); cardio.hypertensive-emergency.serotonin-syndrome-related.v1 (sister dossier authored 2026-05-15 for SS + HTN crisis — cardio variant owns BP control; this psych variant owns toxidrome management); workup.hyperthermic_toxidromes umbrella (foundational toxidrome differential); workup.encephalopathy umbrella (organic AMS reversibles workup); future tox.serotonin-syndrome.v1 if pure-tox engine later authored; future peds.serotonin-syndrome.v1 (out-of-scope this wave). PRODUCTION blockers / open gaps: (1) RxCUIs not yet validated via scripts/research/rxnav-validate.ts (lorazepam 6470 cross-ref OK; diazepam 3322 cross-ref OK; cyproheptadine 2598 cross-ref OK; rocuronium 203128 cross-ref OK; bupropion 42347 cross-ref OK; midazolam 6960 cross-ref OK; rimegepant 2599960 placeholder; acetaminophen 161 placeholder); (2) dedicated psych.serotonin-syndrome.v1.ts seed manifest not yet authored — manifest field repointed to psych.depression.core.v1.ts per parallel precedent (psych.catatonia / psych.bipolar / psych.first-episode-psychosis / psych.alcohol_withdrawal / psych.suicidality); (3) Hunter Serotonin Toxicity Criteria + Sternbach 1991 Criteria not yet calc.* entries in clinical-tools-registry — referenced inline in setting_playbooks and severity_triggers; (4) cyproheptadine + lorazepam IV challenge protocols not registered protocol.* atoms — referenced inline; (5) panel.uds not registered — UDS pursued via inline lab orders + setting_playbooks required_assessments; (6) no targeted dossier test file — relies on dossier-contract.test.ts; (7) several PMIDs flagged NEEDS_SOURCE_REVIEW pending Stage-A PubMed verification (Sternbach 1991, Caroff + Mann 1993, Strawn AJP 2007, Werneke 2016, Pedavally 2014, Volpi-Abadie 2013, Mason 2000, Buckley 2014, Frank 2008); (8) _registry.ts import not added this pass per Phase C wave 11 refined pattern (DO NOT touch _registry.ts); (9) paediatric SS out-of-scope — flagged for future peds.serotonin-syndrome.v1; (10) ICD-10 codes referenced are toxicity / extrapyramidal codes — formal SS-specific code is T43.225A (Adverse effect of selective serotonin and norepinephrine reuptake inhibitors, initial encounter); SNOMED 51316009 (serotonin syndrome) verified. Bayesian linkage (Hunter Serotonin Toxicity Criteria sens 84% spec 97% per Dunkley QJM 2003 PMID 12925718 → LR+ ≈ 28, LR− ≈ 0.16 — primary §5.5.2 anchor; Sternbach 1991 sens 75% spec 96% → LR+ ≈ 19 — superseded; serotonergic exposure + autonomic + clonus + agitation triad pre-test moderate-high + positive Hunter → post-test > 95%; spontaneous clonus pathognomonic in serotonergic exposure context LR+ approaching ∞; AP exposure + lead-pipe rigidity + hyporeflexia + stupor high LR+ for NMS differential; linezolid + SSRI combination high pre-test for SS per FDA 2011; T_diagnose = Hunter positive + exposure; T_treat = SS suspected → STOP offending + benzo IV + IV fluids + cooling if T > 38.5°C; T_cyproheptadine = moderate-severe SS after Step 1 OR refractory at 1-2 h; T_ICU = T > 41°C OR rigidity + multi-organ OR refractory autonomic OR intubation requirement; cross-dossier routing to psych.depression.core.v1 / psych.bipolar-disorder.core.v1 / psych.first-episode-psychosis.core.v1 / psych.catatonia.core.v1 / cardio.hypertensive-emergency.serotonin-syndrome-related.v1 / workup.hyperthermic_toxidromes umbrella) is documented in the co-located _research-bundles/psych.serotonin-syndrome.v1.md. Phenotype matrix (severity × trigger × onset × Hunter criteria × host × re-initiation × comorbid syndromes) is encoded indirectly via severity_triggers + setting_playbooks + sibling_differentiation. First-class TS field for phenotype matrix is schema-blocked (parallel-precedent with psych.first-episode-psychosis / psych.catatonia).

Entry points (7)

  • history
    Serotonergic agent (SSRI / SNRI / MAOI / linezolid / methylene blue / tramadol / triptan / fentanyl / DXM / MDMA / St John's wort / 5-HTP / lithium augmentation) initiated, dose-escalated, or added to existing regimen within 24-72 h (Boyer NEJM 2005 PMID 15784664)
    serotonergic_drug_exposure_within_24_72h
  • symptom
    Triad of autonomic instability (tachycardia + diaphoresis + mydriasis + hyperthermia) + neuromuscular hyperactivity (clonus + hyperreflexia + tremor — lower-extremity dominant) + altered mental status (agitation / confusion) (Boyer NEJM 2005)
    serotonin_toxidrome_triad
  • symptom
    Spontaneous clonus OR inducible clonus + agitation / diaphoresis (Hunter criteria; Dunkley QJM 2003 PMID 12925718)
    spontaneous_or_inducible_clonus
  • symptom
    Tremor + hyperreflexia in patient on serotonergic agent (Hunter criteria; Dunkley QJM 2003)
    tremor_with_hyperreflexia
  • history
    Polypharmacy — multiple serotonergic agents on med rec (e.g., SSRI + tramadol; SSRI + linezolid; SSRI + triptan; SSRI + MAOI; SSRI + methylene blue) (Werneke Pharmacopsychiatry 2016)
    polypharmacy_serotonergic
  • history
    Recent dose escalation OR re-initiation of serotonergic agent in patient with prior SS history (Boyer NEJM 2005)
    recent_dose_change_or_re_initiation
  • history
    Illicit (MDMA / cocaine / DXM) OR supplement (St John's wort / 5-HTP / L-tryptophan) use in patient on SSRI / SNRI / MAOI (Boyer NEJM 2005)
    illicit_or_supplement_serotonergic_use

Required inputs (19)

  • agerequired
    demographic • used at CONTEXT
    Geriatric + serotonergic polypharmacy = highest SS risk (tramadol + SSRI common in elderly); paediatric out-of-scope (peds.serotonin-syndrome.v1 future)
  • sex_and_pregnancy_statusrequired
    demographic • used at CONTEXT
    Pregnancy on SSRI presenting with SS — STOP SSRI + supportive + reproductive psychiatry consult; sertraline preferred per APA 2023 if continuation post-recovery needed
  • current_meds_full_serotonergic_reviewrequired
    medication • used at CONTEXT
    Full medication reconciliation incl. OTC (dextromethorphan, St John's wort), supplements (5-HTP, L-tryptophan), illicit (MDMA, cocaine), recently discontinued (MAOI 14-d washout; fluoxetine 5-wk washout), and intraoperative (methylene blue) — mandatory for diagnosis (Hunter criteria gate; Boyer NEJM 2005)
  • temperaturerequired
    vital • used at RED_FLAGS
    T > 38°C with ocular / inducible clonus = Hunter criterion 5 (severe); T > 41°C = life-threatening — ICU + intubation + paralysis + aggressive cooling (Boyer NEJM 2005)
  • heart_raterequired
    vital • used at RED_FLAGS
    Sinus tachycardia universal in moderate-severe SS; > 120 with HTN drives benzo escalation (Boyer NEJM 2005)
  • sbprequired
    vital • used at RED_FLAGS
    Hypertension common in moderate-severe SS from sympathetic surge; SBP > 180 + serotonergic exposure → routes to cardio.hypertensive-emergency.serotonin-syndrome-related.v1 sister dossier
  • dbprequired
    vital • used at RED_FLAGS
    Component of MAP; DBP > 120 supports crisis criterion + autonomic severity
  • clonus_inducible_or_spontaneousrequired
    symptom • used at INITIAL_WORKUP
    Hunter criterion 1 cornerstone — spontaneous clonus = SS; inducible clonus + agitation/diaphoresis = SS; ocular clonus + agitation/diaphoresis = SS (Dunkley QJM 2003 PMID 12925718)
  • neuromuscular_exam_hyperreflexia_rigidityrequired
    symptom • used at INITIAL_WORKUP
    Hyperreflexia (lower > upper extremity), tremor, rigidity (severe) — distinguish from NMS (lead-pipe rigidity + hyporeflexia) (Boyer NEJM 2005)
  • mental_status_agitation_confusionrequired
    symptom • used at INITIAL_WORKUP
    Agitation / confusion / coma in severe SS — discriminator from NMS (stupor / mutism / catatonic) (Boyer NEJM 2005)
  • autonomic_features_diaphoresis_mydriasis_diarrhearequired
    symptom • used at INITIAL_WORKUP
    Diaphoresis + mydriasis + diarrhoea + hyperactive bowel sounds — distinguish from NMS (normal pupils + no diarrhoea) (Boyer NEJM 2005)
  • ecg_12_leadrequired
    imaging • used at INITIAL_WORKUP
    QTc baseline before any benzo / antiemetic / sedative; QTc prolongation risk from serotonergic + antiemetic combinations; baseline for droperidol AVOID decision
  • creatine_kinaserequired
    lab • used at INITIAL_WORKUP
    Rhabdomyolysis common in severe SS (neuromuscular hyperactivity + hyperthermia); CK > 5000 → aggressive IV fluids + alkalinization
  • creatininerequired
    lab • used at INITIAL_WORKUP
    Rhabdomyolysis-AKI risk; drives fluid + dose adjustment for renal-cleared agents; eGFR baseline
  • bmprequired
    lab • used at INITIAL_WORKUP
    Electrolyte derangement (hyperK in rhabdo-AKI, hyperNa from diaphoresis dehydration) + acid-base (lactic acidosis if severe)
  • cbcrequired
    lab • used at INITIAL_WORKUP
    Baseline + leukocytosis common in severe SS; rule out infection differential
  • lft
    lab • used at INITIAL_WORKUP
    Hepatic clearance baseline; serotonergic agents are CYP-metabolised; rule out hepatic encephalopathy differential
  • udsrequired
    lab • used at INITIAL_WORKUP
    Urine drug screen mandatory — illicit serotonergic co-ingestants (MDMA / cocaine / DXM) common in young-adult presentations; informs trigger drug identification
  • lactate
    lab • used at INITIAL_WORKUP
    Hyperthermia + neuromuscular activity → lactate elevation; tracks severity + response to cooling / paralysis

12-phase flow (12)

  1. 1FRAME
    Serotonin syndrome = drug-induced toxidrome from excess 5-HT2A agonism via serotonergic monotherapy or polypharmacy (SSRI/SNRI/MAOI/linezolid/methylene blue/tramadol/triptan/fentanyl/DXM/MDMA/St John's wort/5-HTP/lithium augmentation). Triad = autonomic instability + neuromuscular hyperactivity (clonus dominant) + AMS. Diagnosis via Hunter Serotonin Toxicity Criteria 2003 (sens 84% spec 97%) preferred over Sternbach 1991. Pharmacology pivot: STOP all serotonergic agents IMMEDIATELY; BENZODIAZEPINE FIRST for sympatholysis + neuromuscular control + sedation; cyproheptadine (5-HT2A antagonist) for moderate-severe disease; cooling for hyperthermia; AVOID bromocriptine (pro-serotonergic, reserved for NMS), succinylcholine (rhabdo hyperK), droperidol / haloperidol (QTc + dopaminergic worsening), routine dantrolene (limited SS evidence) (Boyer NEJM 2005 PMID 15784664).
    inputs: temperature, heart_rate, sbp, current_meds_full_serotonergic_review
    advance: SS diagnosis confirmed by Hunter criteria + serotonergic exposure documented (Dunkley QJM 2003 PMID 12925718)
  2. 2ENTRY
    Recognise toxidrome (autonomic + clonus + agitation + hyperthermia + serotonergic exposure within 24-72 h); IV access + cardiac monitor + STOP all serotonergic agents (mandatory first step per Boyer NEJM 2005)
    inputs: age, temperature, current_meds_full_serotonergic_review
    advance: Serotonergic agents discontinued + benzo IV administered + IV fluids started + cooling initiated if T > 38.5°C
  3. 3CONTEXT
    Comprehensive medication reconciliation incl. OTC (DXM, St John's wort), supplements (5-HTP, L-tryptophan), illicit (MDMA, cocaine, DXM abuse), intraoperative (methylene blue parathyroidectomy / NIRS), recently discontinued (MAOI 14-d washout; fluoxetine 5-wk washout to MAOI), and antibiotic class (linezolid = reversible MAOI per FDA 2011 boxed warning); duration of therapy + recent dose changes + co-morbidities (depression, chronic pain, migraine, bipolar on lithium); pregnancy status (reproductive psychiatry consult if continuing SSRI post-recovery — sertraline preferred per APA 2023); SS recurrence history (chart-flag in EHR allergy/ADR list)
    inputs: age, sex_and_pregnancy_status, current_meds_full_serotonergic_review
    advance: Complete med rec + Hunter criteria scored + trigger drugs identified (Boyer NEJM 2005)
  4. 4RED_FLAGS
    Hyperthermia > 41°C → aggressive cooling + intubation + paralysis (rocuronium, AVOID succinylcholine) + benzo infusion (life-threatening; mortality 10-15% if untreated). Refractory clonus / seizures → escalating benzo + intubation. Rhabdomyolysis-AKI → IV fluids + alkalinization + renal replacement therapy if needed. Concurrent MI / dissection from sympathetic surge. NMS overlap suspected (recent AP exposure + rigidity + hyperthermia + AMS) → workup.hyperthermic_toxidromes umbrella + route to AP-driven sibling dossiers. Suicidality screen if patient on SSRI for depression
    inputs: temperature, sbp, creatine_kinase, creatinine
    actions: workup.hyperthermic_toxidromes, workup.suicide_risk
    advance: RED flags screened + life-threats addressed + diagnosis differentiated from NMS / anticholinergic / sympathomimetic / malignant hyperthermia (Boyer NEJM 2005)
  5. 5INITIAL_WORKUP
    Hunter criteria scoring + complete neuromuscular exam (clonus inducibility, rigidity vs hyperreflexia, ocular clonus); ECG (QTc baseline); CK + Cr + lactate + BMP + Mg + glucose + CBC + LFT; UA dipstick (myoglobinuria); CT head if focal deficit (exclude ICH from HTN sympathetic surge); UDS to identify illicit serotonergic co-ingestants (MDMA / cocaine / DXM)
    inputs: ecg_12_lead, creatine_kinase, creatinine, clonus_inducible_or_spontaneous, neuromuscular_exam_hyperreflexia_rigidity, mental_status_agitation_confusion, autonomic_features_diaphoresis_mydriasis_diarrhea, uds
    actions: workup.encephalopathy
    advance: Workup documented + Hunter criteria scored + alternative diagnoses (NMS, anticholinergic, sympathomimetic, malignant hyperthermia, sepsis) excluded (Boyer NEJM 2005; Iqbal Ochsner J 2012 PMID 23230406)
  6. 6BRANCHING_WORKUP
    Mild-moderate SS (no hyperthermia OR T 38-40°C with manageable clonus): supportive + benzo + observation 24 h. Severe SS (T > 41°C, refractory clonus, autonomic instability, multi-organ involvement): ICU + cyproheptadine NG + paralysis (rocuronium) + intubation + active cooling. NMS overlap suspected: parallel NMS workup + bromocriptine + dantrolene + ECT if catatonic features. Autoimmune encephalitis differential if subacute (workup.encephalopathy umbrella). Sepsis differential if fever + leukocytosis + procalcitonin (panel.inflammation)
    advance: Severity stratified + parallel diagnostic workup obtained when triggered (Boyer NEJM 2005)
  7. 7DIFFERENTIAL
    SS vs NMS (AP exposure + lead-pipe rigidity + hyporeflexia + stupor + ↑↑ CK + days-weeks onset) vs anticholinergic toxidrome (mydriasis + dry skin + urinary retention + delirium WITHOUT clonus) vs sympathomimetic (MDMA / cocaine / methamphetamine — mydriasis + tachy + HTN + agitation WITHOUT clonus dominant) vs malignant hyperthermia (volatile anaesthetic exposure + masseter rigidity + ↑↑↑ CK + ↑↑↑ EtCO2) vs sepsis-driven encephalopathy (procalcitonin + culture + lactate) vs heat stroke (environmental + exertional history) vs thyroid storm (panel.thyroid TSH suppressed + Burch-Wartofsky) (Boyer NEJM 2005; Iqbal 2012)
    advance: Working diagnosis assigned + alternative diagnoses excluded (Boyer NEJM 2005)
  8. 8RISK_STRATIFICATION
    Severity tier: mild (autonomic + tremor; no hyperthermia) → outpatient observation after STOP offending; moderate (T 38-40°C + clonus + agitation) → ED → inpatient with cyproheptadine + benzo; severe (T > 41°C + rigidity + rhabdo + multi-organ) → ICU + intubation + paralysis + cyproheptadine NG. Hunter criteria positive → SS diagnosis confirmed (sens 84% spec 97% per Dunkley QJM 2003 PMID 12925718). Suicidality (C-SSRS) if patient on SSRI for depression (Posner 2011)
    inputs: temperature, creatine_kinase
    advance: Severity tier + safety level + treatment selection documented (Boyer NEJM 2005)
  9. 9TREATMENT
    STEP 1 — STOP ALL serotonergic agents (mandatory; resolution within 24-48 h after cessation in 70% per Mason 2000). STEP 2 — Benzodiazepine IV (lorazepam 1-2 mg IV q5-10 min OR diazepam 5-10 mg IV q5-10 min) for sympatholysis + neuromuscular control + sedation (Boyer NEJM 2005 first-line). STEP 3 — IV crystalloid (NS or LR 500-1000 mL bolus then maintenance) for volume + rhabdo prophylaxis. STEP 4 — Cooling: passive (remove blankets, fans) for T > 38.5°C; active (ice packs, evaporative, surface cooling) + intubation + paralysis if T > 41°C. STEP 5 — Cyproheptadine 12 mg PO/NG load → 2 mg PO/NG q2h until improvement; max 32 mg/24 h then 8 mg PO q6h maintenance (5-HT2A antagonist; Gillman Pharmacother 2010 PMID 20429837; reserved for moderate-severe disease per Boyer NEJM 2005; PO/NG only — no IV). STEP 6 — Severe + refractory: ICU + intubation + paralysis (rocuronium, AVOID succinylcholine if rhabdo hyperK) + active cooling + benzo infusion + cyproheptadine NG. AVOID bromocriptine (pro-serotonergic; reserved for NMS), droperidol / haloperidol (QTc + dystonia + dopaminergic worsening), routine dantrolene (limited SS evidence — used in NMS / MH).
    inputs: temperature, heart_rate, sbp, dbp
    advance: Serotonergic agents stopped + benzo titrated + IV fluids running + temp < 38.5°C + clonus improving + Hunter criteria resolving (Boyer NEJM 2005)
  10. 10DISPOSITION
    ICU for severe SS (hyperthermia > 41°C, autonomic instability, severe clonus, intubation, cyproheptadine NG). Inpatient psychiatry / med-psych for moderate SS resolving with benzo + cyproheptadine + medication reconciliation + psych consult for depression management + chart-flag. ED observation 24 h for mild SS resolving with benzo + STOP offending. Outpatient follow-up at 1 week with primary psychiatry / PCP for medication review + alternative regimen counselling + chart-flag in EHR allergy/ADR list
    advance: Level of care set + chart-flag in EHR for recurrence prevention (Boyer NEJM 2005)
  11. 11MONITORING
    Continuous ECG + telemetry; q 15-30 min BP + temp until stable; serial neuromuscular exam q 2-4 h (clonus + hyperreflexia resolution); CK q 6 h if rhabdo; UOP target > 1 mL/kg/h if rhabdo; mental status reassessment q 1 h initially; cyproheptadine effect at 2 h post-load; sedation level + airway protection assessment q 2 h if intubated. Resolution criteria: T < 38°C + clonus resolved + autonomic features resolved + AMS resolved (Boyer NEJM 2005)
    inputs: temperature, heart_rate
    advance: BP at target + temp normal + clonus resolved + CK trending down + mental status improving (Boyer NEJM 2005)
  12. 12FOLLOWUP
    Comprehensive medication review at discharge + alternative regimens (e.g., switch tramadol to non-serotonergic analgesic — paracetamol / NSAID / non-tramadol opioid; switch SSRI to bupropion if depression amenable to NDRI; switch sumatriptan to gepant — rimegepant / ubrogepant — for migraine; switch linezolid to alternative gram-positive coverage if SSRI required); psychiatry consult if depression / SI driver; pharmacy MTM for SS-prevention education; document SS in EHR allergy/ADR list + chart-flag; pain medicine consult if chronic pain driving tramadol use; if MAOI was on board, mandatory 14-d washout before reintroducing serotonergic agent (5-wk for fluoxetine due to norfluoxetine metabolite); outpatient PCP / psychiatry follow-up at 1 week + 1 month; patient + caregiver education on SS recognition + 24-h ED return precaution (Boyer NEJM 2005; APA MDD 2023)
    advance: Medication regimen revised + ADR documented + chart-flag in EHR + follow-up booked + patient/caregiver education completed (Boyer NEJM 2005)