What is the recommended use and dosage of lisdexamfetamine (Vyvanse) for Attention Deficit Hyperactivity Disorder (ADHD) and binge eating disorder?

Lisdexamfetamine: Clinical Use and Dosing

Lisdexamfetamine is FDA-approved for two indications: ADHD in patients aged 6 years and older, and moderate to severe binge eating disorder (BED) in adults, with recommended dosing of 50-70 mg/day for both conditions after initial titration from 30 mg/day. 1

ADHD Treatment

First-Line vs. Second-Line Status

• In the United States, lisdexamfetamine is approved as a first-line therapy for ADHD, while in many European countries it is designated as second-line therapy after methylphenidate failure 2
• Stimulants including lisdexamfetamine demonstrate the largest effect sizes for reducing ADHD core symptoms compared to all other medication classes 2, 3
• If methylphenidate fails to provide adequate benefit after appropriate dosing and duration, lisdexamfetamine should be the preferred next option over non-stimulants 2

Dosing for ADHD

• Start at 30 mg orally once daily in the morning 1, 4
• Titrate in increments of 10-20 mg at weekly intervals to a maximum of 70 mg/day 1
• The therapeutic dose range is typically 30-70 mg/day, with most patients responding to 50-70 mg/day 1
• Once-daily dosing provides "around-the-clock" symptom control, avoiding the rebound effects seen with shorter-acting stimulants 2

Efficacy in ADHD

• Clinical trials demonstrated statistically significant reductions in ADHD-RS-IV scores across all age groups (pediatric 6-17 years and adults 18-55 years) at doses of 30,50, and 70 mg/day compared to placebo 1
• In maintenance studies, only 9% of patients on lisdexamfetamine experienced treatment failure compared to 75% on placebo during a 6-week double-blind withdrawal phase 1
• The prodrug formulation requires enzymatic hydrolysis, which provides decreased liability for misuse and diversion compared to immediate-release amphetamines 4

Binge Eating Disorder Treatment

Indication and Evidence Base

• Lisdexamfetamine is the only FDA-approved medication for moderate to severe BED in adults 1, 5
• The American Psychiatric Association suggests (2C rating) that adults with BED who prefer medication or have not responded to psychotherapy alone be treated with either an antidepressant or lisdexamfetamine 2
• Psychotherapy (cognitive-behavioral therapy or interpersonal therapy) remains first-line treatment; lisdexamfetamine is reserved for patients preferring medication or failing psychotherapy 2

Dosing for BED

• Start at 30 mg once daily in the morning 1
• After 1 week, increase to 50 mg/day 1
• Additional increases to 70 mg/day should be made as tolerated and clinically indicated 1
• The recommended therapeutic dose range is 50-70 mg/day; the 30 mg dose was not statistically different from placebo 1, 6

Efficacy in BED

• In pivotal trials, lisdexamfetamine 50-70 mg/day reduced binge eating days per week by 3.9-4.1 days compared to 2.5-3.3 days with placebo at week 12 1
• Effect sizes ranged from 0.83 to 0.97, which are highly robust 7
• The number needed to treat (NNT) for response was 3, and NNT for remission (4-week binge cessation) was 4 7
• 50% of patients on 70 mg/day achieved 4-week binge cessation compared to 21.3% on placebo 1, 6
• Weight loss of 4.9-5.2 kg occurred with 50-70 mg/day doses, though lisdexamfetamine is not indicated for weight loss 1, 6

Safety and Monitoring

Common Adverse Effects

• Most frequent adverse events (≥10% and greater than placebo): dry mouth (NNH=4), decreased appetite (NNH=11), insomnia (NNH=11), and headache (NNH=19) 2, 7
• Additional common effects include irritability, increased blood pressure and pulse, stomach pain, and weight loss 2
• Most treatment-emergent adverse events are mild to moderate in intensity 5
• Discontinuation due to adverse events is low, with NNH of 44 7

Monitoring Parameters

• Monitor height and weight regularly, particularly in pediatric patients 2
• Check pulse and blood pressure at baseline and during treatment 2
• Assess for suicidality, though recent evidence suggests stimulants may actually decrease suicidal risk in ADHD patients 2
• Cardiovascular screening is prudent, though large registry studies suggest serious cardiovascular events are unlikely causally related to stimulants 2

Critical Contraindications and Warnings

• Lisdexamfetamine is a controlled substance (Schedule II) with potential for abuse and dependence 2
• Not indicated or recommended for weight loss; use of sympathomimetics for weight loss has been associated with serious cardiovascular adverse events 1
• Pediatric patients younger than 6 years experienced more long-term weight loss and should not receive lisdexamfetamine 1
• Avoid in patients with comorbid substance use disorders unless specifically indicated for ADHD treatment 2

Clinical Pearls

Advantages Over Other Formulations

• Prodrug design provides smooth, extended duration of action with reduced abuse potential 4
• Once-daily dosing improves medication adherence compared to multiple daily doses 2
• Rapid onset of treatment effects for ADHD (within 1-4 weeks) 2
• Available as capsules that can be opened and mixed with water for patients unable to swallow pills 1

When to Choose Lisdexamfetamine

• For ADHD: After methylphenidate failure or as first-line in the US 2
• For BED: When psychotherapy fails or patient prefers medication 2
• When comorbid ADHD and BED exist, lisdexamfetamine treats both conditions 8
• When once-daily dosing and lower abuse potential are priorities 4