Duration of Action of Vyvanse (Lisdexamfetamine)
Vyvanse provides approximately 13-14 hours of therapeutic effect when taken once daily in the morning, making it the longest-acting ADHD stimulant medication currently available. 1, 2
Pharmacokinetic Profile and Duration
Lisdexamfetamine reaches peak plasma concentrations approximately 3 hours after oral administration, with d-amphetamine (the active metabolite) achieving mean peak levels around 3.0 hours post-dose at steady state. 3
The therapeutic effect extends through 14 hours post-dose in adults, as demonstrated in controlled trials measuring ADHD symptom control late into the day. 1
In pediatric patients (ages 6-12), efficacy is maintained throughout the entire school day and into early evening (approximately 6 PM), based on parent ratings conducted in morning, afternoon, and early evening timepoints. 4, 5
The prodrug mechanism provides a duration of approximately 12 hours according to multiple sources, though clinical trials demonstrate effects extending beyond this timeframe. 2, 6
Comparison to Other Stimulants
Vyvanse's 13-14 hour duration significantly exceeds other long-acting stimulants: extended-release mixed amphetamine salts (Adderall XR) provide only 8-9 hours, OROS-methylphenidate (Concerta) provides 12 hours, and immediate-release methylphenidate provides only 4-6 hours. 7
The extended duration eliminates the need for afternoon dosing in most patients, addressing compliance issues associated with in-school medication administration. 7
Clinical Implications for Dosing Schedule
Administer Vyvanse once daily in the morning to maximize daytime coverage while minimizing insomnia risk. 8, 9
The single daily dose covers the full school/work day plus evening activities (homework, social interactions) without requiring supplemental afternoon stimulant doses in most cases. 5
For patients requiring extended evening coverage beyond 14 hours or experiencing inadequate late-day symptom control, consider adding a short-acting stimulant (e.g., immediate-release dextroamphetamine 5-10 mg) in early-to-mid afternoon, but schedule no later than 2-3 PM to avoid insomnia. 9, 10
Pharmacokinetic Details
Steady-state d-amphetamine concentrations are reached by day 5 of daily dosing, with 95% of d-amphetamine eliminated within 48 hours following the final dose. 3
The prodrug itself (lisdexamfetamine) is completely eliminated approximately 6 hours post-dose, while the active d-amphetamine metabolite persists much longer to provide the extended therapeutic effect. 3
The rate-limited enzymatic conversion in red blood cells creates a gradual, sustained release of active d-amphetamine, explaining the extended duration despite the prodrug's rapid elimination. 2, 6
Common Pitfall to Avoid
- Do not assume inadequate total daily dosing when patients report late-afternoon symptom return—Vyvanse's 13-14 hour duration should cover most patients' needs, so breakthrough symptoms may indicate suboptimal morning dose rather than true wearing-off, requiring dose titration upward (in 10-20 mg increments weekly to maximum 70 mg) before adding afternoon supplementation. 9