What is the use of Cyproheptadine (antihistamine) as an appetite stimulant in pediatric patients, particularly those with a history of chronic illness?

Cyproheptadine as an Appetite Stimulant in Children

Cyproheptadine is the first-line appetite stimulant for pediatric patients with poor appetite and weight loss, particularly in chronic illness, with a typical starting dose of 0.25 mg/kg/day divided 2-3 times daily, not exceeding 12 mg/day in children 2-6 years or 16 mg/day in children 7-14 years. 1, 2

Evidence-Based Recommendations

Primary Indication and Efficacy

• The European Society for Clinical Nutrition and Metabolism (ESPEN) and European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) recommend cyproheptadine as the first-line appetite stimulant for pediatric patients with poor appetite and weight loss, particularly in cystic fibrosis, based on moderate-grade evidence showing improvements in weight and BMI z-scores. 1

• In cystic fibrosis patients specifically, cyproheptadine demonstrated significant weight gain (mean 3.45 kg over 12 weeks) compared to placebo (1.1 kg), with improvements in BMI percentiles, ideal body weight/height ratios, and both fat and fat-free mass. 3

• Long-term efficacy is maintained over 9 months, with patients continuing to gain or maintain previously gained weight without loss of effectiveness. 4

• In pediatric oncology patients with cancer-related cachexia, 76% (50/66) responded to cyproheptadine with an average weight gain of 2.6 kg and mean weight-for-age z-score improvement of 0.35 (P=0.001). 5

Dosing Algorithm

For children 2-6 years: 2

• Start with 2 mg (0.5 tablet) two to three times daily
• Calculate based on 0.25 mg/kg/day or 8 mg/m² body surface area
• Maximum dose: 12 mg/day

For children 7-14 years: 2

• Start with 4 mg (1 tablet) two to three times daily
• Adjust based on size and response
• Maximum dose: 16 mg/day

Titration approach: Begin at the lower end of the dosing range and increase gradually based on response over 4 weeks, as most studies evaluated efficacy at this interval. 3, 5

Safety Profile and Side Effects

• Mild sedation is the most common side effect (16% of patients), followed by irritability/behavioral changes (6%), increased appetite/weight gain (5%), and abdominal pain (2.5%). 6

• Only 2.5% of patients discontinued therapy due to side effects, indicating excellent tolerability. 6

• No life-threatening alterations have been observed even with accidental overdoses ranging from 0.3-6.15 mg/kg, though symptoms like somnolence, excitation, hallucinations, ataxia, and tachycardia can occur and typically resolve within 6-12 hours. 7

• Cyproheptadine has atropine-like anticholinergic effects (dry mouth, constipation) that are generally well-tolerated but require caution in patients with bronchial asthma, increased intraocular pressure, hyperthyroidism, cardiovascular disease, or hypertension. 2

Clinical Predictors of Response

Better response rates are seen in: 6

• Younger children (multivariate analysis P=0.04)
• Female patients (P=0.03)
• Early vomiting (within 1 hour of meals) versus late vomiting (P=0.03)
• Retching after Nissen fundoplication (86% response rate)

Evaluate response at 4 weeks: If no response to cyproheptadine after 4 weeks, consider switching to megestrol acetate as second-line therapy, though this carries significant risks including adrenal suppression requiring cortisol monitoring and thromboembolic events. 1, 5

Important Contraindications and Precautions

• Contraindicated in children under 2 years of age due to lack of established safety and efficacy. 2

• Avoid concurrent use with MAO inhibitors, which prolong and intensify anticholinergic effects. 2

• Use caution with CNS depressants (alcohol, sedatives, tranquilizers) due to additive effects. 2

• Warn caregivers that antihistamines may diminish mental alertness or paradoxically cause excitation in young children. 2

Advantages Over Alternative Agents

Cyproheptadine is preferred over megestrol acetate because: 1

• Megestrol acetate causes adrenal suppression requiring cortisol monitoring and stress-dose steroids during illness
• Thromboembolic events are a significant concern with megestrol acetate
• Cyproheptadine has a more favorable safety profile suitable for prolonged use

Avoid dronabinol, metoclopramide, nandrolone, pentoxifylline, and hydrazine sulfate in pediatrics due to insufficient evidence or lack of demonstrated appetite-stimulating effects. 1

Monitoring Parameters

• Weight measurements at 4-week intervals initially, then quarterly for long-term therapy 4, 3
• Height and BMI percentiles 3
• Prealbumin and nutritional markers in oncology patients 5
• Assess for side effects, particularly sedation and behavioral changes 6
• No specific laboratory monitoring required unless switching to alternative agents 1