What is the difference between Vyvanse (lisdexamfetamine) and Adderall (amphetamine and dextroamphetamine) for the treatment of Attention Deficit Hyperactivity Disorder (ADHD)?

Vyvanse vs Adderall for ADHD Treatment

Both Vyvanse (lisdexamfetamine) and Adderall (mixed amphetamine salts) are highly effective first-line stimulants for ADHD, but Vyvanse offers distinct advantages in abuse potential, duration of action, and consistency of effect, making it preferable in adolescents at risk for diversion and adults requiring all-day coverage. 1

Key Pharmacological Differences

Mechanism and Formulation

• Vyvanse is a prodrug that requires enzymatic hydrolysis in red blood cells to convert to active d-amphetamine, making it therapeutically inactive until metabolized in the body 1, 2, 3
• Adderall is a mixture of immediate-release amphetamine salts (75% dextroamphetamine and 25% levoamphetamine) that is active upon ingestion 1
• Vyvanse cannot produce high amphetamine levels when crushed, injected, or snorted, conferring lower abuse potential 1, 3

Duration and Dosing

• Vyvanse: Once-daily dosing with effects lasting up to 13 hours; start at 20-30 mg, titrate by 10 mg weekly to maximum 70 mg daily 1, 2
• Adderall XR: Once-daily extended release; start at 10 mg, titrate by 5 mg weekly to maximum 50 mg daily 1
• Adderall IR: Requires twice or thrice daily dosing; start at 5 mg BID, increase by 5 mg weekly 1

Clinical Efficacy

Comparative Effectiveness

• Both medications demonstrate equivalent efficacy for core ADHD symptoms when dosed appropriately 1, 4
• Vyvanse provides more consistent plasma levels throughout the day due to its prodrug formulation, avoiding the biphasic release pattern of some extended-release formulations 2, 4
• Response rates are approximately 70% for either medication as monotherapy; nearly 90% respond if both are tried sequentially 1

Duration of Effect

• Vyvanse provides full-day coverage through 6 PM based on parent ratings, making it advantageous for homework completion and evening activities 4
• Adderall XR typically provides 8-12 hours of coverage; IR formulations require afternoon dosing for extended coverage 1

Abuse and Diversion Considerations

Special Populations at Risk

In adolescents and young adults, Vyvanse is specifically recommended over immediate-release amphetamines due to lower abuse potential 1:

• The prodrug mechanism prevents extraction of active drug for non-oral routes of administration 1, 3
• Human abuse liability studies show lower drug-liking scores compared to equivalent doses of immediate-release d-amphetamine 4
• Particularly important for patients with comorbid substance use disorders 5

Patients with Stimulant Use Disorder

• Vyvanse has been successfully used to treat ADHD in patients with methamphetamine use disorder, actually reducing cravings for illicit stimulants 5
• The once-daily dosing and prodrug formulation make it feasible for this high-risk population 5

Dosing Algorithms

Starting Vyvanse

1. Begin at 20-30 mg once daily in the morning 1
2. Increase by 10 mg weekly based on symptom response 1
3. Maximum dose: 70 mg daily 1, 2
4. Food delays Tmax by approximately 1 hour but does not affect overall exposure 2

Starting Adderall

1. XR formulation: Start 10 mg once daily, increase by 5 mg weekly to maximum 50 mg 1
2. IR formulation: Start 5 mg BID (after breakfast and lunch), increase by 5 mg weekly 1
3. Consider third afternoon dose for homework/evening activities 1

Safety Profile

Common Adverse Effects (Both Medications)

• Decreased appetite, insomnia, upper abdominal pain, headache, irritability, weight loss 1, 4
• Monitor blood pressure, pulse, height, and weight at each visit 1
• Monitor infants for irritability, insomnia, and feeding difficulty if breastfeeding (both L3 lactation risk) 1

Pregnancy Considerations

• Both medications carry similar fetal risks: possible small increased risk for gastroschisis (aOR 3.0), preeclampsia (aRR 1.29), and preterm birth (aRR 1.30) when continued in second half of pregnancy 1
• Neither is associated with major congenital malformations or cardiac defects 1

Clinical Decision-Making

Choose Vyvanse When:

• Adolescent or young adult with diversion concerns 1
• History of substance use disorder, particularly stimulants 5
• Need for consistent all-day coverage including evening activities 4
• Preference for once-daily dosing to improve adherence 6
• Previous inadequate response to methylphenidate 1, 6

Choose Adderall When:

• Need for flexible dosing throughout the day 1
• Immediate-release formulation needed for titration or specific timing 1
• Cost considerations favor generic mixed amphetamine salts 1
• Patient has responded well previously to amphetamine-based medications 1

Important Caveats

• Preschool children (4-5 years): Limited evidence for amphetamines in this age group; methylphenidate has more safety data 1
• Driving safety: Both provide coverage for adolescent driving when dosed appropriately; consider timing of dose for afternoon/evening driving 1
• Treatment-naïve vs. experienced patients: Vyvanse shows similar response rates regardless of previous ADHD medication exposure 6
• Controlled substance status: Both are Schedule II controlled substances requiring careful monitoring for signs of misuse or diversion 1