What are the primary pharmacotherapies for Prader Willi Syndrome?

Primary Pharmacotherapies for Prader-Willi Syndrome

Growth hormone therapy is the primary and most effective pharmacotherapy for Prader-Willi syndrome (PWS), improving body composition, motor development, and quality of life, and should be initiated as early as 2-3 months of age in children with PWS. 1

Growth Hormone Therapy

Growth hormone (GH) therapy is considered the cornerstone of pharmacological management for PWS, with multiple benefits:

• Normalizes body habitus and improves lean body mass
• Enhances motor development and physical activity levels
• Improves body composition and reduces fat mass
• Increases linear growth and final height
• Improves cognitive and developmental milestones 2, 1, 3

Administration and Monitoring

• Recommended dosage: 0.5-1 mg/m²/day 4
• Treatment can begin as early as 2-3 months of age 2
• Pre-treatment evaluation must include:
  • Polysomnography (sleep study)
  • Early morning serum ACTH and cortisol
  • IGF-1 levels
  • Head circumference measurement 1
• Follow-up monitoring:
  • Repeat polysomnography 6-10 weeks after starting therapy
  • IGF-1 levels at least twice yearly
  • Head circumference at each visit 2, 1

Contraindications

• Closed epiphyses
• Active malignancy
• Severe obstructive sleep apnea
• Acute critical illness 1

Hormone Replacement Therapies

Human Chorionic Gonadotropin (hCG)

• Indicated for treatment of undescended testes before surgery
• Benefits include increased scrotal size and partial normalization of phallus length
• Helps avoid general anesthesia in infants with low muscle tone 2

Sex Hormone Therapy

• Consider for management of hypogonadism
• Evaluation of pubertal status and referral to pediatric endocrinology is recommended 2

Thyroid Hormone Replacement

• For management of hypothyroidism, which is common in PWS 1

Psychiatric Medications

SSRIs (Selective Serotonin Reuptake Inhibitors)

• Effective for reducing skin picking, compulsivity, and aggressive episodes
• Particularly useful for managing obsessive-compulsive behaviors which are common in PWS 5

Atypical Antipsychotics

• Helpful for individuals with psychotic features or extreme aggression and impulsivity
• Consider for patients with maternal uniparental disomy who have increased risk of psychotic disorders 5

Topiramate

• May be used in severe cases of skin picking that don't respond to behavioral interventions 2

Ineffective Treatments

• CNS stimulants and anorectic agents have not been effective in treating hyperphagia in PWS
• This is because hyperphagia in PWS is attributed to decreased satiation rather than increased hunger 5

Comprehensive Management Approach

While growth hormone is the primary pharmacotherapy, optimal management requires:

1. Strict dietary controls based on phase-specific approach:

   • Addressing poor feeding in infancy
   • Preventing weight gain in early childhood
   • Implementing strict controls for hyperphagia in later stages 1

2. Environmental modifications:

   • Locking cabinets and refrigerators
   • Limiting food exposures
   • Maintaining consistent meal routines 2, 1

3. Behavioral management:

   • Structured, predictable routines
   • Support during transitions
   • Behavioral programming 1, 5

Important Considerations

• Sleep disorders are common in PWS and require careful monitoring, especially when starting GH therapy
• Respiratory vulnerability increases risk of complications; maintain low threshold for respiratory evaluation
• Regular polysomnography is essential to monitor for sleep apnea 2, 1
• Vomiting after binge-eating can be an ominous sign due to high pain tolerance in PWS patients 2

Growth hormone therapy remains the most evidence-based pharmacological intervention for PWS, with substantial benefits for morbidity, mortality, and quality of life when combined with appropriate dietary, behavioral, and environmental interventions.