What is the preferred initial medication and starting dose for an adult patient with Attention Deficit Hyperactivity Disorder (ADHD), comparing Adderall (amphetamine and dextroamphetamine) and Vyvanse (lisdexamfetamine)?

Preferred Initial Medication and Starting Dose for Adult ADHD

For adult ADHD, start with amphetamine-based stimulants (Adderall or Vyvanse) rather than methylphenidate, with Vyvanse 30 mg once daily in the morning as the preferred initial choice due to its once-daily dosing, lower abuse potential, and consistent symptom control throughout the day. 1

Why Amphetamine-Based Stimulants Are Preferred

Amphetamine-based stimulants demonstrate superior efficacy in adults compared to methylphenidate, with comparative studies showing amphetamines are the preferred first-line option for adult ADHD treatment 1. Both medication classes work by enhancing dopamine and norepinephrine in prefrontal cortex networks, but amphetamines consistently show stronger effect sizes in adult populations 2.

• Stimulant medications overall achieve 70-80% response rates in adults with ADHD 1, 3
• Amphetamines improve ADHD symptom severity with a standardized mean difference of -0.72 (95% CI -0.87 to -0.57) 4
• Mixed amphetamine salts (Adderall) specifically increase retention in treatment compared to other amphetamine derivatives 4

Vyvanse vs. Adderall: The Practical Differences

Vyvanse (lisdexamfetamine) offers distinct advantages over immediate-release Adderall that make it the superior initial choice for most adults:

Vyvanse Advantages:

• Once-daily dosing improves medication adherence compared to multiple daily doses, which is critical for adults with executive dysfunction 1, 5
• Prodrug formulation provides consistent, rate-limited release of active dextroamphetamine through enzymatic hydrolysis in the gastrointestinal tract, resulting in lower intrasubject and intersubject pharmacokinetic variability 6, 2
• Reduced abuse potential because it does not produce high dextroamphetamine levels when injected or snorted, with lower likability scores in abuse liability studies 6, 7
• Around-the-clock coverage extending beyond work hours, addressing functional impairment in multiple settings 1

Adderall Considerations:

• Requires 2-3 times daily dosing for immediate-release formulations, though extended-release (Adderall XR) provides once-daily option 8, 3
• Greater effects on appetite and sleep due to longer excretion half-lives compared to methylphenidate 1
• May be preferred if cost is a significant barrier, as generic mixed amphetamine salts are available

Specific Starting Doses and Titration

Vyvanse Starting Protocol:

• Start: 30 mg once daily in the morning 5
• Titration: Increase by 10 mg weekly based on clinical response and tolerability 5
• Therapeutic range: 30-70 mg daily, with 50-70 mg representing the most common maintenance doses 5
• Maximum dose: 70 mg daily 5
• Time to assess response: 2-4 weeks to reach optimal dosing 5

Adderall Alternative Dosing:

• Immediate-release: Start 5 mg once or twice daily, titrate upward in 5-10 mg intervals each week 8
• Adderall XR: Start 10 mg once daily in the morning, titrate by 5 mg weekly up to 50 mg maximum 1
• Typical maintenance: 20-40 mg total daily dose for most adults 3
• Maximum: 40 mg daily (some patients may require up to 0.9 mg/kg or 65 mg with clear documentation) 8

Critical Monitoring During Initiation

Systematic assessment is essential during the first 2-4 weeks:

• Weekly contact (by telephone or visit) during initial titration to assess response and side effects 5
• Blood pressure and pulse at baseline and each dose adjustment 1
• ADHD symptom rating scales from the patient and significant others to objectively track improvement 5
• Specific side effect screening: insomnia, appetite suppression, headaches, weight loss, anxiety 5
• Weight monitoring regularly, as weight loss is common with stimulants 5

When to Choose Adderall Over Vyvanse

Consider starting with Adderall (particularly immediate-release) in these specific scenarios:

• Cost constraints where generic mixed amphetamine salts are necessary
• Need for flexible dosing with ability to add afternoon doses for evening symptom coverage 8
• Previous positive response to immediate-release amphetamines
• Desire for shorter duration if patient needs medication effects to wear off earlier in the evening

Common Pitfalls to Avoid

Do not start at too high a dose, as this leads to unnecessary side effects and decreased medication adherence 5. The 30 mg starting dose for Vyvanse or 5-10 mg for Adderall allows assessment of tolerability before escalation.

Do not fail to systematically assess both benefits and side effects during titration—use structured rating scales rather than relying solely on subjective patient report 5. Adults with ADHD are unreliable reporters of their own behaviors, so obtain collateral information from family members or close contacts when possible 1.

Do not assume inadequate response means treatment failure at lower doses—approximately 70% of patients respond optimally when proper titration protocols are followed 3. Continue titrating to the maximum recommended dose before switching medications.

Do not prescribe to patients with active substance abuse disorder without careful consideration, though long-acting formulations like Vyvanse have lower abuse potential 1, 6. Screen for substance use history at baseline.

Do not use in patients with uncontrolled hypertension, symptomatic cardiovascular disease, or active hyperthyroidism 1. Baseline cardiovascular screening is essential.

If First Stimulant Fails

If inadequate response occurs after adequate treatment with one amphetamine formulation, trial methylphenidate before considering non-stimulants, as approximately 40% of patients respond to both classes and 40% respond to only one 3. Nearly 90% will respond if both stimulant classes are tried 8.

Non-stimulant options (atomoxetine, guanfacine, clonidine) are second-line, reserved for patients with contraindications to stimulants, intolerable side effects, or active substance abuse 1.