What is the recommended starting dose and comparison between Vyvanse (lisdexamfetamine) and Adderall (amphetamine and dextroamphetamine) when initiating stimulant therapy?

Starting Stimulant Therapy: Adderall vs Vyvanse

For initiating stimulant therapy, start with Adderall XR 10 mg once daily in the morning for adults or Adderall IR 2.5-5 mg twice daily for children, as this provides the most flexible titration options and established dosing guidelines, though Vyvanse offers advantages in abuse-deterrent properties and longer duration of action that may be preferred in specific clinical scenarios. 1, 2

Initial Dosing Recommendations

Adderall (Amphetamine/Dextroamphetamine)

Immediate-Release (IR) Formulation:

• Children: Start with 2.5 mg twice daily (after breakfast and lunch) 3, 1
• Adults: Start with 5 mg twice daily 3, 1
• Morning administration is critical to minimize sleep disturbances 1, 2

Extended-Release (XR) Formulation:

• Both children and adults: Start with 10 mg once daily in the morning 1, 2
• This formulation provides convenience of once-daily dosing while maintaining flexibility 4

Vyvanse (Lisdexamfetamine)

• Standard starting dose: 30 mg once daily in the morning 5, 6
• Therapeutic range: 30-70 mg daily 5, 6
• Vyvanse is a prodrug that remains inactive until enzymatic conversion in red blood cells to d-amphetamine, providing a smoother pharmacokinetic profile 5, 7

Titration Protocol

Adderall Titration

• Increase by 5 mg weekly increments for both IR and XR formulations based on clinical response and tolerability 1, 2
• Allow at least one week between dose increases to properly evaluate response 1, 2
• Maximum daily dose: 40-50 mg for adults 1, 2
• For children weighing less than 25 kg, single doses should not exceed 10 mg 1

Vyvanse Titration

• Increase by 10 mg weekly increments if symptom control is inadequate 8
• Maximum daily dose: 70 mg 8, 6
• The longer intervals between dose adjustments reflect the prodrug's unique pharmacokinetics 5, 7

Key Differentiating Factors

Abuse Potential and Diversion Risk

Vyvanse has significantly lower abuse potential compared to Adderall, making it the preferred choice in adolescents and adults with substance abuse concerns. 3 The American Academy of Pediatrics specifically identifies lisdexamfetamine as having reduced abuse potential because it requires metabolic activation after ingestion and cannot be effectively extracted for intranasal or intravenous abuse. 3 Human abuse liability studies demonstrate that Vyvanse produces lower drug-liking scores compared to immediate-release d-amphetamine at equivalent doses. 6, 7

Duration of Action

• Vyvanse provides efficacy up to 13-14 hours post-dose in children and adults, extending symptom control into the early evening 5, 9
• Adderall XR typically provides 10-12 hours of coverage 4
• This extended duration makes Vyvanse particularly advantageous for adolescents who drive, as the American Academy of Pediatrics emphasizes the importance of medication coverage during driving hours 3

Pharmacokinetic Profile

• Vyvanse's prodrug mechanism provides more gradual onset and offset, potentially reducing rebound symptoms 5, 7
• The rate-limited hydrolysis creates a smoother pharmacodynamic profile compared to traditional amphetamine formulations 7

Baseline Assessment Requirements

Before initiating either medication, obtain:

• Blood pressure and pulse (critical for detecting undiagnosed hypertension or cardiac arrhythmias) 3, 1, 2
• Height and weight (to monitor growth and appetite suppression) 3, 1, 2
• Substance abuse screening in adolescents and adults before starting treatment 3
• Physical examination to rule out contraindications 3

Monitoring During Titration

Initial Phase (First 4-8 weeks)

• Weekly telephone contact with in-person visits at least monthly until symptoms stabilize 1
• Assess target ADHD symptoms using standardized rating scales at each contact 1, 2
• Evaluate side effects systematically: insomnia, appetite suppression, headaches, irritability, social withdrawal 1

Ongoing Maintenance

• Adults: Check blood pressure and pulse quarterly 3, 1
• Children: Annual vital signs during routine physical examination 3
• Weigh at each visit to detect appetite suppression early 1, 2

Common Pitfalls to Avoid

Starting at excessively high doses leads to unnecessary side effects and medication non-adherence—always begin with the lowest recommended starting dose. 1, 2

Inadequate time between dose increases (less than one week) prevents accurate assessment of therapeutic response and tolerability. 1, 2

Afternoon or evening administration significantly increases insomnia risk—both medications must be given in the morning. 1, 2

Continuing dose escalation beyond maximum recommendations when ineffective—if maximum doses fail to provide adequate symptom control, switch to an alternative medication class rather than exceeding dosing limits. 1, 2

Failing to screen for substance abuse in adolescents and adults before prescribing—this is a critical safety consideration that determines medication selection. 3

Special Clinical Scenarios

Adolescents with Diversion Risk

Choose Vyvanse over Adderall when there are concerns about medication diversion or misuse, as the prodrug formulation makes extraction and abuse significantly more difficult. 3 Monitor prescription refill requests for signs of misuse or diversion. 3

Older Adults

• Start with more conservative dosing (Adderall XR 5 mg or Vyvanse 20 mg) due to age-related pharmacokinetic changes 2
• Increase by 5 mg every 2 weeks instead of weekly to minimize adverse effects 2
• Monitor vital signs more frequently due to increased sensitivity to cardiovascular effects 2

Preschool-Age Children (4-5 years)

• Methylphenidate is preferred over amphetamines in this age group, as amphetamines lack sufficient safety and efficacy evidence for children under 6 years 3
• If amphetamines are used, start with lower doses and increase in smaller increments due to slower metabolism 3

When Maximum Dose Fails

If patients reach maximum recommended doses (Adderall 50 mg or Vyvanse 70 mg) without adequate symptom control:

• Do not exceed maximum dosing—more is not better and increases adverse effect risk 1, 2
• Switch to an alternative stimulant class (methylphenidate-based if on amphetamine, or vice versa) 2
• Consider adding non-stimulant medications such as atomoxetine or extended-release guanfacine 3, 2
• Reevaluate the diagnosis and assess for comorbid conditions affecting treatment response 2