What is the comparative efficacy and safety of Adderall (amphetamine/dextroamphetamine) versus Vyvanse (lisdexamfetamine)?

Comparative Efficacy and Safety of Adderall vs. Vyvanse

Vyvanse (lisdexamfetamine) is generally preferred over Adderall (amphetamine/dextroamphetamine) due to its more consistent release profile, reduced abuse potential, and similar efficacy with potentially fewer side effects.

Pharmacological Differences

• Mechanism of Action:

  • Adderall: Direct-acting mixture of amphetamine salts (75% dextroamphetamine, 25% levoamphetamine)
  • Vyvanse: Prodrug of dextroamphetamine requiring enzymatic hydrolysis to become active 1

• Pharmacokinetics:

  • Vyvanse has a 0.6 ± 0.6 hour longer lag time and reaches peak levels 1.1 ± 1.5 hours later than Adderall 1
  • Both medications achieve similar maximum concentrations and total exposure (AUC) 1
  • Vyvanse provides more consistent blood levels due to rate-limited enzymatic conversion 2

Efficacy Comparison

Both medications are highly effective for ADHD treatment with similar efficacy profiles:

• The American Academy of Pediatrics notes that stimulant medications have an effect size of approximately 1.0 for treating ADHD's core symptoms 3
• Both medications effectively reduce core ADHD symptoms including inattention, hyperactivity, and impulsivity
• Response to either medication is idiosyncratic, with approximately 40% of patients responding to both amphetamine and methylphenidate-based medications, and about 40% responding to only one 3

Safety and Side Effect Profile

Common side effects for both medications include:

• Decreased appetite
• Insomnia
• Irritability
• Cardiovascular effects (increased blood pressure, heart rate)
• Weight loss

However, Vyvanse may offer some advantages:

• More gradual onset and offset of effects may reduce "crash" symptoms
• More predictable duration of action (10-12 hours) compared to immediate-release Adderall (4-6 hours)
• Lower potential for abuse due to prodrug formulation requiring enzymatic activation 2, 4

Abuse Potential

• Vyvanse was specifically designed to have lower abuse potential due to its prodrug formulation 2
• The rate-limited enzymatic conversion means Vyvanse cannot be easily manipulated for rapid absorption 4
• However, a direct comparison study found that oral Vyvanse and D-amphetamine produced similar peak ratings of potentially abuse-related subjective effects 1

Clinical Decision Algorithm

1. For patients with concerns about medication abuse potential:

   • Prefer Vyvanse due to its prodrug formulation 2, 4

2. For patients needing consistent all-day coverage:

   • Vyvanse provides 10-12 hours of coverage with less variability
   • Adderall XR provides 8-10 hours but may have more variability

3. For patients with insurance/cost concerns:

   • Adderall (especially generic versions) is typically less expensive
   • Vyvanse has no generic equivalent yet

4. For patients with difficulty swallowing pills:

   • Vyvanse capsules can be opened and dissolved in water
   • Adderall is available in tablet form that can be split

Dosing Considerations

• Adderall starting dose: 5-10 mg daily, maximum 50 mg daily 5
• Vyvanse starting dose: 30 mg daily, maximum 70 mg daily 4
• Titration should occur gradually with weekly follow-up to assess efficacy and side effects 5

Special Considerations

• Cardiovascular monitoring: Both medications require regular monitoring of blood pressure and heart rate 5
• Growth monitoring: Height and weight should be tracked, especially in children 5
• Timing of administration: Morning dosing is recommended for both medications to minimize sleep disturbances

Conclusion

While both medications are effective for ADHD treatment, Vyvanse offers advantages in terms of consistent drug delivery, potentially smoother side effect profile, and reduced abuse potential. However, individual response varies, and some patients may respond better to one medication than the other.