Cyproheptadine Dosing
For adults with serotonin syndrome, initiate cyproheptadine with a 12 mg loading dose followed by 2 mg every 2 hours for at least 24 hours in severe cases requiring ICU admission, or 4 mg three times daily for milder ward-level cases; for pediatric patients, use 0.25 mg/kg per day as the preferred dosing regimen. 1, 2
Adult Dosing
Serotonin Syndrome
- Severe cases (ICU-level): Loading dose of 12 mg, then 2 mg every 2 hours for at least 24 hours 2
- Moderate cases (ward-level): 4 mg three times daily 2
- Alternative initial dosing: 4-8 mg orally, with repeat dosing if residual symptoms persist after 2 hours 3
- All patients in the retrospective study showed at least partial response within 24 hours, which can serve as a diagnostic indicator of serotonin syndrome 2
Allergic Reactions and Appetite Stimulation
- Therapeutic range: 4-20 mg daily, with most patients requiring 12-16 mg daily 4
- Initial dosing: Start with 4 mg three times daily and adjust based on response 4
- Maximum dose: 32 mg daily for refractory cases, though not to exceed 0.5 mg/kg/day 4
Pediatric Dosing
Serotonin Syndrome
- Recommended dose: 0.25 mg/kg per day, with cyproheptadine being the preferred agent according to the American Academy of Pediatrics 1
Allergic Reactions and Appetite Stimulation
- Ages 2-6 years: 2 mg (½ tablet) two or three times daily, calculated as approximately 0.25 mg/kg/day or 8 mg/m² body surface area 4
- Maximum: 12 mg daily 4
- Ages 7-14 years: 4 mg (1 tablet) two or three times daily 4
- Maximum: 16 mg daily 4
Administration Considerations
Formulation and Routes
- Available as 4 mg tablets that can be divided for smaller doses 1
- Tablets can be crushed and administered via nasogastric tube if needed 1
- Sublingual administration is NOT recommended: Serum concentrations are significantly lower than oral administration (C_max 4.0 vs 30.0 μg/L), making this route unlikely to be effective for serotonin syndrome 5
Clinical Caveats
Important limitations to consider:
- The benefits and indications for cyproheptadine in serotonin syndrome remain uncertain, with an 11-year California Poison Control System review showing no significant differences in serious outcomes or hospitalization rates between patients who received versus did not receive cyproheptadine 6
- Cyproheptadine was not administered in 48% of serotonin syndrome cases primarily due to minimal clinical severity and patient improvement with supportive care alone 6
- Use should be considered an adjunct to supportive care, not a replacement 3
Safety profile:
- Most common adverse effect is drowsiness in both adults and children 7
- Hepatotoxicity is uncommon to rare (estimated frequency 0.27-1.4 per 1000 patients), though very rare cases of liver failure have been reported 7
- Neurological symptoms are the most frequently reported adverse effects (41% of reports), followed by hepatic complications (16%) 7
Response monitoring: