Vyvanse and Adderall: Comparative Efficacy for ADHD
Both Vyvanse (lisdexamfetamine) and Adderall (mixed amphetamine salts) are equally effective first-line treatments for ADHD, achieving 70-80% response rates with comparable efficacy, so the choice should be based on practical factors: Vyvanse offers once-daily dosing and lower abuse potential due to its prodrug design, while Adderall XR allows more flexible dose titration starting at lower increments. 1, 2
Core Efficacy Evidence
Both medications work through identical mechanisms—inhibiting dopamine and norepinephrine transporters—and produce equivalent reductions in ADHD symptom severity when properly titrated. 3, 2
Amphetamine-based stimulants as a class demonstrate effect sizes of approximately 1.0, the largest among all ADHD medications, with 70-80% of patients achieving good clinical response. 1, 2
A direct crossover trial comparing lisdexamfetamine (up to 70 mg/day) versus immediate-release mixed amphetamine salts (up to 45 mg/day) found response rates of approximately 80% for both medications, with significant and equal reductions in clinician-rated ADHD symptoms. 4
Key Differentiating Factors
Dosing Flexibility
Adderall XR can be initiated at 5-10 mg daily, allowing finer dose adjustments in patients who may be sensitive to stimulants or require lower starting doses. 1
Vyvanse requires a minimum starting dose of 20 mg, which may be too high for some patients needing more gradual titration. 1
Adderall XR is titrated in 5 mg weekly increments up to a maximum of 50 mg daily, while Vyvanse is titrated in 10 mg weekly increments up to a maximum of 70 mg daily. 1, 3
Duration of Action
Vyvanse provides 13-14 hours of symptom control in a single daily dose, with consistent plasma concentrations throughout the day due to its prodrug conversion in the blood. 5
Adderall XR delivers approximately 10-12 hours of coverage, which may require supplemental afternoon dosing in some patients with evening symptom breakthrough. 3
Abuse Potential
Vyvanse is an inactive prodrug that must be enzymatically hydrolyzed in the blood to release active dexamphetamine, making it resistant to manipulation for abuse (crushing, snorting, or injection produces no immediate euphoric effect). 6, 5, 7
This prodrug design results in lower abuse liability compared to immediate-release or even extended-release formulations of mixed amphetamine salts, which can be manipulated. 6, 7
Adderall XR, while extended-release, can still be crushed or manipulated to release the active drug more rapidly, presenting higher diversion risk in patients with substance use concerns. 1
Pharmacokinetic Considerations
Vyvanse's conversion is unaffected by gastrointestinal pH or variations in transit time, providing more predictable absorption compared to Adderall, which can be affected by acidifying agents (vitamin C, citrus juices) that decrease amphetamine levels. 3, 5
Patients taking Vyvanse do not need to avoid acidic foods or supplements, whereas Adderall absorption may require dose adjustments if acidifying agents are consumed. 3
Clinical Decision Algorithm
Choose Vyvanse when:
- Once-daily dosing is a priority for adherence
- Substance abuse history or diversion concerns exist
- Consistent 13-14 hour coverage is needed
- Patient can tolerate a minimum 20 mg starting dose
Choose Adderall XR when:
- Lower starting doses (5-10 mg) are needed for titration
- More flexible dose adjustments in 5 mg increments are required
- Cost is a significant factor (generic mixed amphetamine salts are available)
- Patient requires shorter duration of action (10-12 hours)
Safety and Monitoring
Both medications share identical adverse effect profiles: decreased appetite, insomnia, headache, and modest increases in blood pressure and pulse occur in >10% of patients. 1
Baseline and ongoing cardiovascular monitoring (blood pressure and pulse) is required for both medications at each visit during titration and quarterly during maintenance. 1
Both are absolutely contraindicated with MAO inhibitors (14-day washout required), symptomatic cardiovascular disease, uncontrolled hypertension, and active psychosis. 1
Common Pitfalls
Do not assume Vyvanse is "better" simply because it is newer or a prodrug—efficacy is equivalent when both are properly dosed. 2, 4
Do not underdose either medication—systematic titration to 70-80% response requires reaching therapeutic ranges (Adderall XR 20-40 mg daily; Vyvanse 50-70 mg daily for most adults). 1, 2
Do not switch between medications without completing an adequate trial of the first agent at optimal doses for 4-6 weeks, as approximately 40% of patients respond to both stimulant classes. 1