How does Lisdexamphetamine (Vyvanse) work for weight loss?

How Lisdexamfetamine Works for Weight Loss

Lisdexamfetamine (Vyvanse) causes weight loss primarily by decreasing appetite and increasing satiety through its effects on dopamine and norepinephrine neurotransmission in the brain, though it is not FDA-approved for weight loss purposes.

Mechanism of Action

Lisdexamfetamine is a prodrug that works through a unique mechanism:

• It is pharmacologically inactive until metabolized in the body 1
• After oral ingestion, it undergoes enzymatic hydrolysis predominantly in red blood cells 2
• This process converts lisdexamfetamine to:
  • Active d-amphetamine (the therapeutic component)
  • L-lysine (a naturally occurring amino acid) 1

The resulting d-amphetamine affects weight through several pathways:

1. Appetite suppression: Increases levels of norepinephrine and dopamine in the brain, which reduces hunger sensations and food cravings
2. Enhanced satiety: Promotes feelings of fullness, leading to decreased food intake
3. Increased energy expenditure: May slightly increase metabolic rate

Clinical Evidence for Weight Effects

While not FDA-approved for weight management, weight loss is a documented effect:

• In children with ADHD and obesity, lisdexamfetamine showed significant BMI reductions over a 2-year period:

  • Children with severe obesity: BMI Z-score decreased by -0.41
  • Children with mild-moderate obesity: BMI Z-score decreased by -0.44 3

• The FDA label explicitly states: "Lisdexamfetamine dimesylate capsules are not indicated or recommended for weight loss" 4

Important Considerations

Safety Concerns

• The FDA label warns: "Use of other sympathomimetic drugs for weight loss has been associated with serious cardiovascular adverse events" 4
• Common side effects include:
  • Decreased appetite
  • Insomnia
  • Upper abdominal pain
  • Headache
  • Irritability
  • Weight loss
  • Nausea 5

Abuse Potential

• Lisdexamfetamine carries a boxed warning regarding abuse and dependence potential 4
• The prodrug formulation may provide some abuse-deterrent properties compared to immediate-release amphetamines 1
• Pre-treatment screening for cardiac disease is required 4

Clinical Context

Lisdexamfetamine is FDA-approved for:

1. ADHD in adults and children 6 years and older
2. Moderate to severe binge eating disorder (BED) in adults 4

For BED, lisdexamfetamine (50-70 mg/day) has shown efficacy in reducing binge eating episodes 6, with weight loss occurring as a secondary effect.

Key Takeaway

While lisdexamfetamine can cause weight loss through appetite suppression and increased satiety, it should not be prescribed specifically for weight management due to safety concerns, abuse potential, and lack of FDA approval for this indication. Its weight-reducing effects should be considered only in the context of its approved uses for ADHD and binge eating disorder.