What is Vyvanse (lisdexamfetamine) and how does it work?

Vyvanse (Lisdexamfetamine): Mechanism of Action and Clinical Use

Vyvanse (lisdexamfetamine dimesylate) is a prodrug stimulant medication that is converted to active dextroamphetamine in the bloodstream, primarily used to treat ADHD and moderate to severe binge eating disorder in adults by blocking the reuptake and increasing the release of dopamine and norepinephrine in the brain. 1

Pharmacology and Mechanism of Action

• Prodrug Design: Lisdexamfetamine is a unique prodrug consisting of dextroamphetamine covalently bound to the amino acid l-lysine 1
• Activation Process: It remains pharmacologically inactive until enzymatically converted to its active form (dextroamphetamine) through a process predominantly associated with red blood cells 2
• Neurotransmitter Effects: Once activated, it works by:
  • Blocking the reuptake of dopamine and norepinephrine by inhibiting their transporters (DAT and NAT)
  • Increasing the release of these neurotransmitters into the synaptic cleft
  • Affecting the vesicular monoamine transporter 2 1, 2

Pharmacokinetic Properties

• Duration of Action: Provides approximately 12 hours of symptom control with once-daily dosing 3
• Absorption: Food prolongs the time to maximum concentration (Tmax) by approximately 1 hour but does not affect overall exposure 1
• Metabolism: The prodrug design creates rate-limited enzymatic biotransformation, contributing to its long-acting profile 3
• Lower Abuse Potential: The prodrug nature may provide additional safety regarding abuse potential compared to immediate-release stimulants 4, 3

Clinical Applications

1. Attention-Deficit/Hyperactivity Disorder (ADHD):

   • FDA-approved for treatment in adults and children 6 years and older 1
   • Helps increase attention and decrease impulsiveness and hyperactivity 1
   • Demonstrated significant improvements in ADHD rating scales and executive function measures 5

2. Binge Eating Disorder (BED):

   • Currently the only FDA-approved medication for moderate to severe BED in adults 6
   • Significantly reduces binge eating days per week compared to placebo 6
   • Not indicated for weight loss or treatment of obesity 1

Dosing and Administration

• Available in multiple strengths: 10mg, 20mg, 30mg, 40mg, 50mg, 60mg, and 70mg capsules 1
• Typically started at lower doses and titrated based on response and tolerability 7
• Administered once daily due to its long-acting properties 1

Common Side Effects

• Most common adverse effects include:
  • Decreased appetite
  • Dry mouth
  • Insomnia
  • Headache
  • Increased blood pressure and heart rate 1
• Most side effects are mild to moderate in intensity 2

Important Precautions

• Abuse and Dependence: Has a high potential for abuse and may lead to physical dependence after prolonged use 1
• Cardiovascular Risks: May increase blood pressure and heart rate; contraindicated in patients with serious heart disease 1
• Psychiatric Effects: May trigger or worsen psychiatric symptoms including psychosis, mania, or aggression 1
• Drug Interactions: Should not be taken with MAOIs or within 14 days of stopping MAOI treatment 1

Special Considerations

• Classified as a Schedule II controlled substance due to its abuse potential 1
• Requires strict distribution control in some countries 2
• May be a viable treatment option for ADHD even in patients with a history of stimulant use disorder, due to its prodrug design and lower abuse potential 4