How do Adderall (mixed‑amphetamine salts) and Vyvanse (lisdexamfetamine) differ in formulation, onset, duration, dosing, metabolism, and abuse potential for ADHD?

Adderall vs. Vyvanse: Key Clinical Differences

Both Adderall (mixed amphetamine salts) and Vyvanse (lisdexamfetamine) are first-line amphetamine-based stimulants with comparable 70-80% response rates for ADHD, but they differ critically in formulation, pharmacokinetics, duration, and abuse potential. 1

Formulation & Metabolism

Vyvanse is a prodrug that requires enzymatic conversion to become active, while Adderall contains pre-formed active amphetamine salts. 2, 3

• Vyvanse (lisdexamfetamine): Dextroamphetamine covalently bound to L-lysine; the lysine is cleaved off through rate-limited hydrolysis by enzymes on red blood cells during first-pass metabolism, converting it to active dextroamphetamine 2, 3, 4
• Adderall: Contains a 3:1 ratio of dextroamphetamine to levoamphetamine in immediate-release pellets (for Adderall XR, half release immediately and half after ~4 hours) 5, 6

Onset & Duration

Vyvanse provides slightly longer duration (up to 13 hours) compared to Adderall XR (12 hours), but both have rapid onset within 1.5-2 hours. 3, 5, 4

• Vyvanse: Onset within 1-2 hours post-dose; duration up to 13 hours due to rate-limited enzymatic conversion 3, 4
• Adderall XR: Onset within 1.5 hours; provides 12-hour coverage with bimodal release 5, 6
• Adderall IR: Immediate onset but requires multiple daily doses (typically 2-3 times daily) 1

Dosing Ranges

Adult dosing for Vyvanse ranges from 30-70 mg once daily, while Adderall ranges from 10-50 mg total daily dose (often split into 2-3 doses for IR formulation). 1, 7

• Vyvanse: 30-70 mg once daily in the morning; maximum 70 mg/day 7
• Adderall XR: 10-40 mg once daily; some patients require up to 50 mg total daily dose 1, 2
• Adderall IR: 5-20 mg two to three times daily; typical range 10-50 mg total daily dose 1

Conversion Between Formulations

When converting from Vyvanse 70 mg to Adderall, start with Adderall XR 30 mg once daily or Adderall IR 10-15 mg twice daily (20-30 mg total), then titrate based on clinical response. 2

• The conversion is not 1:1 due to different pharmacokinetic profiles; Vyvanse's prodrug mechanism results in more gradual, sustained release 2
• Monitor for breakthrough symptoms in late afternoon/evening and adjust dosing accordingly 2

Abuse Potential

Vyvanse has demonstrably lower abuse potential than Adderall due to its prodrug formulation, which cannot be activated through intranasal or intravenous routes. 3, 4

• Vyvanse: Nasal or IV administration does not produce significant elevation in "drug liking" scores among known stimulant abusers, as the prodrug must be metabolized enzymatically in the blood 3, 4
• Adderall: Contains pre-formed active amphetamine that can be abused through crushing/snorting or injection 1
• For patients with substance use history, the American Academy of Child and Adolescent Psychiatry recommends long-acting formulations like Vyvanse or Concerta (methylphenidate) with lower abuse potential 1

Side Effect Profile

Both medications share similar adverse effect profiles typical of amphetamine stimulants, with appetite suppression, insomnia, and headache occurring in >10% of patients. 3, 8

• Common adverse effects (>10% incidence): Decreased appetite, insomnia, headache 3, 8
• Cardiovascular effects: Monitor blood pressure and pulse at baseline and regularly during treatment for both medications 1, 2
• Growth effects: Track height and weight, particularly in children and adolescents, as both can affect growth 1

Clinical Selection Algorithm

Choose Vyvanse when:

• Substance abuse history or diversion concerns exist (prodrug formulation reduces abuse potential) 1, 3, 4
• Once-daily dosing is critical for adherence 1, 7
• Slightly longer duration of action (13 vs. 12 hours) is needed 3, 4

Choose Adderall when:

• Cost is a primary concern (generic mixed amphetamine salts available) 1
• Flexible dosing throughout the day is needed (IR formulation allows 2-3 daily doses) 1
• Patient has previously responded well to Adderall formulations 1

Monitoring Requirements

Both medications require identical cardiovascular and growth monitoring protocols. 1, 2

• Baseline: Blood pressure, pulse, height, weight, cardiac history screening 1
• During titration: Weekly symptom ratings and vital signs at each dose adjustment 1, 2
• Maintenance: Quarterly vital signs in adults; at every visit in children/adolescents with annual height/weight tracking 1

Common Pitfalls to Avoid

• Do not assume Vyvanse and Adderall are interchangeable at equivalent doses—the prodrug mechanism of Vyvanse results in different pharmacokinetics requiring individualized titration 2, 3
• Do not prescribe either medication with MAO inhibitors—risk of severe hypertension and cerebrovascular accidents; require 14-day washout 1
• Do not underdose—many patients require higher doses within the therapeutic range (Vyvanse 50-70 mg; Adderall 30-40 mg total daily) for optimal response 1, 2, 7
• Do not overlook late-day symptom coverage—if evening symptoms persist on once-daily dosing, consider adding an afternoon IR dose of Adderall or optimizing Vyvanse timing 1, 2