What are the efficacy, dosing, side‑effect profile, and abuse potential of Vyvanse (lisdexamfetamine) compared with Adderall immediate‑release (mixed amphetamine salts) for children with attention‑deficit/hyperactivity disorder?

Vyvanse vs. Adderall IR in Pediatric ADHD: Clinical Recommendations

Primary Recommendation

For children with ADHD, Vyvanse (lisdexamfetamine) is preferred over Adderall immediate-release due to its lower abuse potential, once-daily dosing that improves adherence, and equivalent efficacy when properly dosed—particularly important in adolescents where diversion risk is highest. 1

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Efficacy Comparison

Equivalent Therapeutic Response

• Both medications demonstrate approximately 70% response rates as monotherapy when systematically titrated, with nearly 90% of patients responding when both are tried sequentially if the first agent fails 1
• Lisdexamfetamine reduces ADHD rating scale scores by approximately 27 points in children aged 6–12 years, demonstrating robust symptom control 2
• The prodrug design of lisdexamfetamine provides consistent therapeutic effect throughout the day (up to 12–13 hours) with less intersubject variability in drug levels compared to immediate-release formulations 3, 4

Age-Specific Considerations

• For school-aged children (6–11 years), methylphenidate or amphetamines are first-line, with over 70% responding to methylphenidate and >90% responding to at least one stimulant class when both are systematically trialed 5
• For adolescents (12–18 years), Vyvanse is explicitly preferred due to concerns about medication diversion and substance misuse, which are critically important in this age group 1, 5

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Dosing Algorithms

Vyvanse (Lisdexamfetamine)

• Starting dose: 20–30 mg once daily in the morning 1
• Titration: Increase by 10 mg weekly based on symptom response 1
• Maximum dose: 70 mg daily 1
• Onset: 1–2 hours post-dose with duration up to 13 hours 3
• Mechanism: Prodrug requiring enzymatic hydrolysis in red blood cells to convert to active d-amphetamine, making it therapeutically inactive until metabolized 1, 3

Adderall Immediate-Release

• Starting dose (children/adolescents): 2.5 mg twice daily (after breakfast and lunch) 5
• Titration: Increase by 2.5–5 mg per dose weekly if symptom control is inadequate 5
• Maximum dose: 40 mg total daily (children <25 kg should not receive single doses >10 mg) 5
• Administration: Requires multiple daily doses (typically 2–3 times daily), which reduces adherence and increases abuse potential 4, 6

Critical Dosing Principle

• Systematic titration to maximum symptom reduction (not just "some improvement") is essential, with approximately 70% achieving optimal response when proper protocols are followed 5
• Do not rely on mg/kg calculations; titrate based on symptom response and tolerability using standardized rating scales from parents, teachers, and patients 5

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Side-Effect Profile

Common Adverse Effects (Both Medications)

• Appetite suppression, insomnia, headache occur in >10% of patients 2, 6
• Abdominal pain, irritability, mood changes are frequent dose-limiting effects 5
• Growth suppression of approximately 1–2 cm from predicted adult height with chronic use at higher doses 5

Vyvanse-Specific Considerations

• Greater appetite suppression and sleep disturbance compared to methylphenidate due to longer elimination half-life 5
• Fewer adverse events overall due to avoidance of rapid plasma concentration spikes from the prodrug design 4
• Less intersubject variability in pharmacokinetics (coefficient of variation 15.3–21.6% for Vyvanse vs. 42.8–52.8% for mixed amphetamine salts XR) 4

Adderall IR-Specific Concerns

• Rebound symptoms when medication wears off between doses 6
• Peak-related side effects (jitteriness, irritability) due to rapid absorption 1
• In-school dosing requirement creates embarrassment and compliance issues 5

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Abuse Potential: The Critical Differentiator

Vyvanse's Abuse-Deterrent Properties

• Prodrug formulation is therapeutically inactive until enzymatically converted in the body, making intranasal or intravenous administration ineffective 1, 3
• In adult stimulant abusers, oral lisdexamfetamine produced significantly lower abuse-related "liking" scores compared to immediate-release d-amphetamine (p=0.039) 4, 7
• Rate-limited enzymatic biotransformation prevents the rapid "high" associated with immediate-release formulations 2, 3

Adderall IR's Higher Risk

• Immediate-release formulations have higher abuse potential due to rapid onset and peak effects 1
• The American Academy of Pediatrics explicitly recommends Vyvanse over immediate-release amphetamines in adolescents and young adults specifically because of diversion concerns 1

Clinical Imperative for Adolescents

• Screen for substance abuse symptoms before initiating treatment in all adolescents 5
• Monitor prescription-refill requests for signs of misuse or diversion 1
• College-age patients face significant peer pressure for stimulant diversion, making Vyvanse's abuse-deterrent properties particularly valuable 1

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Monitoring Requirements

Baseline Assessment (Both Medications)

• Blood pressure and pulse 5
• Height and weight 5
• Cardiac history (personal and family history of syncope, arrhythmias, structural heart disease) 8
• Substance abuse screening in adolescents 5

During Titration

• Weekly symptom ratings from parents, teachers, and adolescent self-reports using standardized scales 5
• Vital signs at each dose adjustment 5
• Weight monitoring at every visit to objectively track appetite suppression 5
• Systematic assessment for insomnia, anorexia, headaches, social withdrawal, and mood changes 5

Maintenance Phase

• Quarterly visits once stable 8
• Ongoing growth monitoring (height/weight) 5
• Cardiovascular parameters at regular intervals 5

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Clinical Decision Algorithm

Choose Vyvanse When:

1. Adolescent or young adult (diversion/abuse risk is highest) 1
2. Adherence concerns exist (once-daily dosing improves compliance) 1, 6
3. All-day symptom coverage is needed (12–13 hour duration) 1, 3
4. Family history of substance use disorder 1
5. Patient cannot manage multiple daily doses (school setting) 5

Choose Adderall IR When:

1. Flexible dosing throughout the day is required (e.g., only morning coverage needed) 1
2. Fine-tuning individual doses for specific time periods 1
3. Initial titration in younger children where precise dose adjustments are needed 5
4. Cost is prohibitive for long-acting formulations (though this should not override safety concerns in high-risk populations) 1

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Common Pitfalls to Avoid

Do Not:

• Assume both medications are interchangeable in adolescents—the abuse potential difference is clinically significant 1
• Prescribe immediate-release formulations when extended-release options are available in populations at risk for diversion 1
• Underdose stimulants—community practice often uses lower doses than optimal, resulting in inferior outcomes 5
• Ignore the social context—college-age patients face peer pressure for stimulant sharing 1
• Dose after 4:00–5:00 PM with Adderall IR, as this creates sleep disruption that worsens overall ADHD symptoms 5

Do:

• Titrate systematically to maximum symptom reduction (not just "some improvement") 5
• Use standardized rating scales from multiple informants (parents, teachers, self-report) at each dose level 5
• Consider adding a short-acting booster (5–10 mg methylphenidate or 5 mg dextroamphetamine at 3:00–4:00 PM) if Vyvanse wears off too early, rather than switching entirely to IR formulations 5
• Integrate behavioral therapy with medication—combination treatment allows lower stimulant doses and produces superior functional outcomes 5

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Special Populations

Preschool-Aged Children (4–5 Years)

• Methylphenidate is the only medication with adequate evidence (though off-label) 5
• Consider only if symptoms persisted ≥9 months, dysfunction exists in multiple settings, behavioral therapy failed, and moderate-to-severe impairment is present 5

Adolescents with Driving Concerns

• Provide medication coverage during after-school driving hours using longer-acting formulations or late-afternoon short-acting doses 5
• Adolescents with ADHD have inherent driving risks requiring symptom control while operating vehicles 5

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Bottom Line

Vyvanse is the superior choice for most children and adolescents with ADHD due to its once-daily dosing, lower abuse potential, and equivalent efficacy. Adderall IR retains a role for initial titration in younger children or when flexible dosing is specifically needed, but should be avoided in adolescents and young adults where diversion risk is substantial. 1, 5, 3