What are the differences in dosage and side effects between Adderall (amphetamine and dextroamphetamine) and Vyvanse (lisdexamfetamine) for a patient with Attention Deficit Hyperactivity Disorder (ADHD)?

Adderall vs Vyvanse: Dosage and Side Effects for ADHD

Key Differences

Both Adderall (mixed amphetamine salts) and Vyvanse (lisdexamfetamine) are highly effective stimulants for ADHD, but Vyvanse offers a smoother, longer duration of action with potentially lower abuse liability due to its prodrug formulation. 1, 2

Dosing Recommendations

Adderall (Mixed Amphetamine Salts)

Starting and Titration:

• Children (6-12 years): Start at 2.5 mg twice daily (morning and noon), increase by 2.5-5 mg weekly intervals 3
• Adolescents and Adults: Start at 5 mg once or twice daily, titrate upward in 5-10 mg intervals each week 3
• Maximum doses: Up to 40 mg/day for children, or 0.9 mg/kg/day for adults (typically not exceeding 40 mg/day) 3
• Dosing schedule: Typically dosed twice daily (morning and noon), with optional third dose in afternoon for homework/social activities 3

Important dosing considerations:

• Children weighing less than 45 lb (20 kg) should omit the 7.5 mg dose level during titration 3
• Some children may require only once-daily dosing 3

Vyvanse (Lisdexamfetamine)

Starting and Titration:

• Starting dose: 20-30 mg orally once in the morning 3, 4, 1
• Titration: Increase by 10 mg weekly intervals 3, 4, 1
• Maximum dose: 70 mg daily 3, 4, 1
• Dosing schedule: Once daily in the morning only 1

Pharmacokinetic advantages:

• Vyvanse is a prodrug that requires enzymatic hydrolysis in red blood cells to release active dextroamphetamine 1, 2
• Peak effect occurs at approximately 3.5-4.4 hours post-dose 1
• Duration of action is extended throughout the day with single morning dosing 2, 5
• Food delays absorption by approximately 1 hour but does not significantly affect overall exposure 1

Side Effect Profiles

Common Side Effects (Both Medications)

Appetite and Weight:

• Decreased appetite is the most common side effect with both medications 3, 4, 6
• Weight loss occurs frequently 6, 7
• Growth suppression may occur with prolonged use in children (1-2 cm reduction in predicted adult height) 3, 4, 6

Sleep Disturbances:

• Insomnia is common, particularly with Adderall due to multiple daily dosing 3, 4, 6, 7
• Severity ranges from mild (<1 hour delay) to severe (>1.5 hours delay) 3
• Vyvanse may cause less insomnia due to smoother pharmacokinetic profile 2, 5

Gastrointestinal:

• Abdominal pain occurs with both medications 3, 4
• Headaches are common 3, 6

Neuropsychiatric:

• Irritability and restlessness 6, 7
• Mood lability, particularly in preschool-aged children 3
• Rare but serious: hallucinations and psychotic symptoms 3

Cardiovascular Effects (Both Medications)

Monitoring requirements:

• Both increase heart rate by 1-2 beats per minute on average 4
• Both increase blood pressure by 1-4 mm Hg on average 4
• 5-15% of patients may experience more substantial increases 4
• Obtain detailed cardiac history including family history of sudden death, Wolff-Parkinson-White syndrome, hypertrophic cardiomyopathy, and long QT syndrome before initiating 3, 4
• Regular blood pressure and heart rate monitoring required 3, 4

Abuse Potential Differences

Adderall:

• Higher abuse potential due to immediate-release formulation options 8
• Can produce rapid euphoric effects when crushed and snorted or injected 2
• Classified as Schedule II controlled substance 8

Vyvanse:

• Lower abuse liability due to prodrug formulation 2, 5, 9
• Does not produce high dextroamphetamine levels when injected or snorted 2
• Requires enzymatic hydrolysis for activation, preventing rapid euphoric effects 2, 5
• Still classified as Schedule II controlled substance but with reduced likability scores in abuse studies 5, 9

Long-Term Considerations

Tolerance and Effectiveness:

• Effectiveness may decrease with long-term use for both medications 6
• Monitor for signs of tolerance, particularly at higher doses 3
• Children continuing psychostimulants for more than 10 years showed no better symptom reduction than those who discontinued 6

Growth Monitoring:

• Both medications affect growth velocity 4
• Stimulants may decrease predicted adult height by 1-2 cm, with effects diminishing by third year 3, 4
• Regular height and weight monitoring required 3

Clinical Decision-Making Algorithm

Choose Vyvanse when:

• Once-daily dosing is preferred for adherence or to avoid school-based dosing 1
• Concern exists about abuse potential or diversion risk 2, 5, 9
• Smoother, longer duration of effect is desired 2, 5
• Patient has difficulty with multiple daily doses 1

Choose Adderall when:

• Flexible dosing throughout the day is needed 3
• Lower cost is a priority (generic availability) 3
• Shorter duration of action is preferred (e.g., to minimize evening insomnia) 3
• Patient requires dose adjustments at different times of day 3

Critical Monitoring Parameters

Initial evaluation before starting either medication:

• Detailed cardiac history and family history of sudden cardiac death 3, 4
• Baseline blood pressure, heart rate, height, and weight 3
• Screen for personal or family history of bipolar disorder 4

Ongoing monitoring:

• ADHD rating scales from teachers and parents at each dose adjustment 3
• Blood pressure and heart rate at each visit 3, 4
• Height and weight monitoring, particularly in children 3, 4
• Watch for mood destabilization, agitation, or suicidal thoughts (particularly first 24-48 hours after initiation or dose changes) 4

Common Pitfalls to Avoid

• Do not exceed maximum recommended doses without clear documentation that symptoms could not be controlled at lower doses and higher doses are not producing side effects 3
• Do not ignore cardiovascular screening - obtain detailed cardiac history before initiating 3, 4
• Do not rapidly escalate atomoxetine if combining with stimulants, as this increases gastrointestinal side effects 3, 4
• Do not assume all patients respond equally - approximately 70% respond to first stimulant tried, but nearly 90% respond if both stimulant types are tried 3