How should Vyvanse (lisdexamfetamine) be initiated and titrated in children aged 6‑12 years and adults, including starting dose, weekly dose increments, maximum dose, monitoring parameters, contraindications, and alternative treatments if adequate response is not achieved?

Vyvanse (Lisdexamfetamine) Titration Protocol

Starting Dose

Begin lisdexamfetamine at 30 mg once daily in the morning for both children aged 6–12 years and adults. 1, 2, 3 An alternative starting dose of 20 mg may be considered for patients who are more sensitive to stimulant medications or have tolerability concerns. 1

• Administer the medication in the early morning to provide coverage throughout the school or work day and minimize sleep disturbances. 1, 2, 3
• The prodrug formulation requires in vivo hydrolysis to gradually release active d-amphetamine, with onset of action within 1.5–2 hours post-dose. 4, 5, 6

Titration Schedule

Increase the dose by 10 mg or 20 mg increments at approximately weekly intervals until optimal symptom control is achieved. 1, 2, 3

• Use standardized ADHD rating scales (such as ADHD-RS-IV) from both parents and teachers before each dose increase to objectively assess response. 2
• Weekly telephone contact can be maintained during dose adjustments to guide titration decisions. 1, 2
• Continue titration until optimal symptom control is achieved without adverse effects. 2

Maximum Dose

The maximum approved daily dose is 70 mg for both children and adults. 1, 3

• If the maximum recommended dose (70 mg) does not provide adequate symptom control, switch to a different medication class rather than exceeding the maximum dose. 1
• Do not assume that higher doses will provide better efficacy; if 70 mg is insufficient, consider changing the drug or adding environmental/psychosocial interventions. 7

Monitoring Parameters

Cardiovascular Monitoring

Assess blood pressure and pulse at baseline and at each visit during treatment. 1, 2, 3

• Lisdexamfetamine is contraindicated in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease. 3
• Avoid use in patients with uncontrolled hypertension or symptomatic cardiovascular disease. 7, 3

Growth Monitoring

Track height and weight regularly, as stimulants can affect growth in pediatric patients. 1, 2, 3

• Pediatric patients younger than 6 years experienced more long-term weight loss than patients 6 years and older. 3
• Closely monitor growth; pediatric patients not growing or gaining height or weight as expected may need to have their treatment interrupted. 3

Symptom Assessment

Assess target ADHD symptoms through parent and teacher reports during the initial titration phase. 1

• Efficacy is maintained from 1.5 hours up to 13 hours post-dose in school-aged children. 5
• Monthly follow-up appointments are appropriate once symptoms are stabilized on a maintenance dose. 1
• More frequent appointments are warranted if side effects emerge, comorbid psychiatric conditions are present, or adherence concerns arise. 1

Common Side Effects

Monitor for decreased appetite, insomnia, upper abdominal pain, headache, irritability, weight loss, and nausea. 1, 3, 8

• Most treatment-emergent adverse events are mild to moderate in severity and consistent with those commonly reported with amphetamine products. 4, 8
• Screen for suicidality and clinical worsening, particularly when comorbid psychiatric conditions exist. 7

Contraindications

Absolute contraindications include: 3

• Known hypersensitivity to amphetamine products or other ingredients in lisdexamfetamine
• Use with monoamine oxidase (MAO) inhibitor, or within 14 days of the last MAO inhibitor dose
• Known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease

Relative contraindications and special precautions: 7, 3

• History of substance use disorder (consider long-acting formulations with lower abuse potential)
• Seizure disorder (ensure stability on anticonvulsant therapy first)
• Unstable mood disorder (stabilize mood first)
• Active psychosis or mania

Alternative Treatments if Inadequate Response

If lisdexamfetamine at maximum dose (70 mg) does not provide adequate symptom control, follow this algorithm: 1, 7

1. Switch to a different stimulant class (methylphenidate-based products), as approximately 40% of patients respond to only one stimulant class. 7

2. If two or more stimulants have failed, consider second-line non-stimulant options: 7

   • Atomoxetine (60–100 mg daily; requires 6–12 weeks for full effect)
   • Extended-release guanfacine (1–4 mg daily; particularly useful for comorbid tics, sleep disturbances, or oppositional behaviors)
   • Extended-release clonidine

3. If ADHD symptoms improve but comorbid mood or anxiety symptoms persist, add an SSRI to the stimulant regimen rather than switching medications. 7

4. Combine pharmacotherapy with evidence-based psychosocial interventions, including cognitive-behavioral therapy and parent training in behavior management. 7

Special Considerations

• The prodrug formulation of lisdexamfetamine provides lower abuse potential compared to other amphetamines, which becomes increasingly relevant as children approach adolescence. 2, 4, 6
• Lisdexamfetamine is not indicated for weight loss; use of sympathomimetic drugs for weight loss has been associated with serious cardiovascular adverse events. 3
• In severe renal impairment, the maximum dose is 50 mg/day; in end-stage renal disease, the maximum dose is 30 mg/day. 3