## Serotonin Syndrome: Acute Management **Key Point:** Cyproheptadine is the first-line pharmacological agent for acute serotonin syndrome, acting as a non-selective serotonin antagonist (5-HT1A and 5-HT2A receptor antagonist) and H1 antagonist. ### Mechanism of Action Cyproheptadine blocks serotonin receptors peripherally and centrally, rapidly counteracting excess serotonergic activity. It also has antihistamine properties that provide sedation and reduce agitation. ### Dosing in Serotonin Syndrome - **Loading dose:** 12 mg orally or via nasogastric tube - **Maintenance:** 2 mg every 2 hours (or 4–8 mg every 6 hours) for 24–48 hours - Onset of symptom relief: typically within 30–60 minutes ### Management Algorithm ```mermaid flowchart TD A[Serotonin Syndrome Suspected]:::outcome --> B[Discontinue serotonergic agents]:::action B --> C[Supportive care: IV fluids, cooling measures]:::action C --> D{Severity?}:::decision D -->|Mild-Moderate| E[Cyproheptadine 12 mg loading]:::action D -->|Severe with hyperthermia| F[ICU admission + aggressive cooling]:::action E --> G[Maintenance: 2 mg Q2H or 4-8 mg Q6H]:::action F --> G G --> H[Monitor for resolution over 24-48 hrs]:::outcome ``` **High-Yield:** Cyproheptadine is the ONLY serotonin antagonist available in clinical practice for this indication. It is not a symptomatic treatment—it addresses the underlying pathophysiology. ### Supportive Measures (Concurrent) - Discontinue all serotonergic agents immediately - IV hydration for rhabdomyolysis prevention - Active cooling for hyperthermia (ice packs, cooling blankets) - Benzodiazepines (lorazepam) for agitation and seizure prophylaxis—adjunctive, not primary - Monitor CK, myoglobin, renal function **Clinical Pearl:** In mild cases, discontinuation of the offending agent and supportive care alone may suffice. Cyproheptadine is reserved for moderate-to-severe presentations or when symptoms persist despite withdrawal. [cite:Kaplan & Sadock's Synopsis of Psychiatry 11e Ch 28]
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