Key Points
- Use the highest‑yield diagnostic test early; do not let testing delay time‑critical therapy.
- Set objective targets and reassess frequently.
- Plan definitive source control or disease‑specific therapy when indicated; document follow‑up and patient education.
Algorithm
- Diagnose using Hunter criteria; stop serotonergic agents.
- Sedate with benzodiazepines; aggressive cooling and IV fluids.
- Add cyproheptadine if moderate–severe; manage complications; ICU if severe.
Clinical Synopsis & Reasoning
Triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities (clonus, hyperreflexia). Stop serotonergic agents, give benzodiazepines for agitation, aggressive cooling for hyperthermia, and cyproheptadine for moderate–severe cases. Avoid antipyretics and succinylcholine.
Treatment Strategy & Disposition
Stabilize ABCs. Initiate guideline‑concordant first‑line therapy with precise dosing and continuous monitoring. Escalate to advanced/procedural interventions based on explicit failure criteria. Define ICU, step‑down, and ward disposition triggers; involve specialty teams early.
Epidemiology / Risk Factors
- Risk varies by comorbidity and precipitants; see citations for condition‑specific data.
Investigations
| Test | Role / Rationale | Typical Findings | Notes |
|---|
| Hunter criteria assessment | Diagnosis | Most specific clinical rule | — |
| BMP/CK/lactate and EKG | Complications | Electrolyte disturbances, rhabdomyolysis | — |
| Drug history (SSRIs, MAOIs, linezolid, tramadol, MDMA) | Etiology | Identify culprit | — |
High-Risk & Disposition Triggers
| Trigger | Why it matters | Action |
|---|
| Hyperthermia >40°C, rigidity, or rapidly worsening vitals | Severe toxicity | ICU; sedation, paralysis, intubation, active cooling |
| MAOI + SSRI/SNRI exposure | High risk | Stop agents; avoid serotonergic meds |
| Rhabdomyolysis or renal failure | Complications | Aggressive fluids; alkalinize urine if indicated |
| Older age or comorbid heart disease | Arrhythmia risk | Telemetry and careful sedation |
| Inadequate response to benzodiazepines | Refractory | Consider cyproheptadine escalation |
Pharmacology
| Medication/Intervention | Mechanism | Onset | Role in Therapy | Limitations |
|---|
| Benzodiazepines (diazepam/lorazepam) | Sedation/muscle relaxation | Minutes | First-line control of agitation and tremor | — |
| External cooling/IV fluids | Supportive | Minutes | Treat hyperthermia and dehydration | — |
| Cyproheptadine 12 mg load then 2 mg q2h to effect; 8 mg q6h maintenance | 5-HT2A antagonist | Hours | Moderate–severe toxicity | Oral/NG only |
| Intubation and paralysis (non-depolarizing) for severe hyperthermia | Airway/heat control | Immediate | Prevent complications | Avoid succinylcholine |
Prognosis / Complications
- Outcome depends on timeliness of diagnosis and definitive therapy; monitor for complications.
Patient Education / Counseling
- Provide red‑flag education, adherence guidance, and explicit return precautions; arrange timely specialty follow‑up.
References
- Toxicology consensus on serotonin syndrome — Link