What is the recommended dosing and titration regimen of cyproheptadine for migraine prophylaxis in a 20‑kg child who cannot swallow tablets?

Cyproheptadine Dosing for Migraine Prophylaxis in a 20-kg Child

For a 20-kg child who cannot swallow tablets, cyproheptadine should be initiated at 2 mg (½ tablet crushed) twice daily, with titration up to a maximum of 12 mg per day based on response. 1

Initial Dosing Strategy

• Start with 2 mg (½ tablet) twice daily for children aged 2-6 years, which applies to most children weighing approximately 20 kg 1
• The FDA-approved dosing is based on 0.25 mg/kg/day, which for a 20-kg child equals 5 mg daily total, typically divided into 2-3 doses 1
• Tablets can be crushed and mixed with food or liquid for children unable to swallow whole tablets 2

Titration Protocol

• Adjust dosing every 1-2 weeks based on headache frequency reduction and tolerability 3
• The usual effective range is 4-8 mg daily divided into 2-3 doses 1
• Maximum daily dose is 12 mg for children in this age group (under 7 years) 1
• If the child is 7 years or older, the maximum increases to 16 mg daily 1

Evidence for Efficacy

Cyproheptadine demonstrates solid efficacy in pediatric migraine prophylaxis, though the evidence base is more limited compared to other agents. In a retrospective study of 30 pediatric patients, cyproheptadine reduced mean headache frequency from 8.4 to 3.75 attacks per month (55% reduction) with an 83% overall positive response rate 3. A more recent prospective study showed significant reductions in headache duration, frequency, and severity over 3 months of treatment 4.

Cyproheptadine is specifically recommended for younger children who cannot swallow tablets, making it the preferred first-line agent in this clinical scenario 5. While amitriptyline shows higher efficacy (62% reduction in headache frequency), it is typically reserved for older children who can manage once-daily tablet dosing 3, 5.

Practical Administration

• Formulation: Each tablet contains 4 mg and can be divided or crushed 1
• Dosing schedule: Administer twice or three times daily with meals to minimize gastrointestinal upset 1
• Alternative calculation: Can also dose based on body surface area at 8 mg/m² 1

Expected Side Effects

• Most common: Increased appetite (30%) and drowsiness (5%) 6
• Weight gain is frequently reported and should be monitored 4
• Sedation typically diminishes after the first 1-2 weeks of treatment 3

Monitoring and Duration

• Assess response at 4-6 weeks by tracking headache frequency, duration, and severity using a headache diary 3
• Continue treatment for 6 months if effective, then consider tapering 3
• If inadequate response after 2 months at maximum tolerated dose, switch to alternative prophylactic agent 5

Clinical Pitfalls to Avoid

• Do not exceed maximum daily dose of 12 mg in children under 7 years, as higher doses increase side effects without additional benefit 1
• Avoid abrupt discontinuation after prolonged use; taper over 2-4 weeks 3
• Do not use as monotherapy for acute attacks; ensure appropriate acute treatment (ibuprofen 7.5-10 mg/kg) is prescribed concurrently 7, 5
• Monitor for excessive sedation during the first week, which may require dose reduction or timing adjustment 6