What is the comparison between Vyvanse (lisdexamfetamine) and dextroamphetamine for treating Attention Deficit Hyperactivity Disorder (ADHD)?

Vyvanse vs Dextroamphetamine for ADHD Treatment

For most patients with ADHD, lisdexamfetamine (Vyvanse) offers advantages over dextroamphetamine due to its prodrug formulation providing more consistent plasma levels throughout the day, reduced abuse potential, and once-daily dosing convenience, though both medications have similar efficacy in treating ADHD symptoms. 1, 2

Pharmacological Differences

Mechanism of Action

• Lisdexamfetamine (Vyvanse): Prodrug consisting of dextroamphetamine covalently bonded to L-lysine amino acid 1

  • Enzymatically hydrolyzed primarily in the blood to active dextroamphetamine 1
  • Conversion unaffected by gastrointestinal pH and transit times 3
  • Parent drug is therapeutically inactive 1

• Dextroamphetamine: Direct-acting stimulant medication 4

  • Both medications ultimately work through the same active molecule (dextroamphetamine)
  • Both block reuptake of norepinephrine and dopamine and increase release of these monoamines 1

Pharmacokinetics

• Lisdexamfetamine:

  • Delayed onset: Peak plasma levels reached approximately 1.1 hours later than dextroamphetamine 2
  • Extended duration of action: 13 hours in children, 14 hours in adults 3
  • Consistent plasma concentrations throughout the day 3
  • Low inter-subject (<25%) and intra-subject (<8%) variability 1

• Dextroamphetamine:

  • Faster onset of action 2
  • Shorter duration requiring multiple daily doses for immediate-release formulations
  • More variable blood levels throughout the day

Clinical Efficacy

Both medications demonstrate robust efficacy for ADHD symptoms, with no clear evidence that one is superior to the other in terms of symptom control 3, 5. The American Academy of Pediatrics recommends stimulants (including both dextroamphetamine and lisdexamfetamine) as first-line medication treatment for ADHD due to their strong evidence base (effect size 1.0) 6.

Practical Considerations

Dosing Convenience

• Lisdexamfetamine: Once-daily dosing 3
• Dextroamphetamine: Immediate-release forms typically require multiple daily doses; extended-release formulations are available

Abuse Potential

• Lisdexamfetamine: Designed with reduced abuse potential 4

  • Does not produce high dextroamphetamine levels when injected or snorted 4
  • However, research shows similar peak ratings of abuse-related subjective effects when taken orally compared to dextroamphetamine 2

• Dextroamphetamine: Higher potential for misuse and diversion 4

Side Effect Profile

Both medications have similar side effect profiles typical of stimulants 5:

• Decreased appetite
• Insomnia
• Abdominal pain
• Irritability
• Cardiovascular effects (increased blood pressure, heart rate)

Patient Selection Considerations

Factors Favoring Lisdexamfetamine:

• Concerns about medication adherence (once-daily dosing)
• Risk of medication diversion or misuse
• Need for consistent coverage throughout the day
• Patients who require more predictable blood levels

Factors Favoring Dextroamphetamine:

• Need for more flexible dosing
• Cost considerations (generic dextroamphetamine may be less expensive)
• Patients who may benefit from shorter duration of action

Monitoring and Follow-up

For both medications, the American Academy of Pediatrics recommends 6:

• Regular monitoring every 3-4 weeks during dose titration
• Once stabilized, follow-up every 3-6 months
• Monitor vital signs, weight, sleep quality, appetite, and symptom control at each visit

Common Pitfalls to Avoid

• Failing to recognize ADHD as a chronic condition requiring ongoing management 6
• Overlooking comorbidities that can worsen symptoms 6
• Treating only ADHD symptoms while neglecting anxiety or depression 6
• Not considering the patient's daily schedule and medication coverage needs
• Ignoring potential for medication diversion in high-risk settings

While head-to-head comparisons between lisdexamfetamine and dextroamphetamine are limited 5, the available evidence suggests lisdexamfetamine offers practical advantages in terms of consistent drug delivery and convenience, while both medications provide similar efficacy for ADHD symptom control.