Onset of Action for Vyvanse (Lisdexamfetamine)
Vyvanse begins working approximately 1.5 to 2 hours after oral administration, with peak effects occurring around 3.5 to 4.4 hours post-dose. 1, 2
Pharmacokinetic Timeline
The medication follows a predictable absorption pattern:
- Lisdexamfetamine itself reaches peak plasma concentration at approximately 1 hour after ingestion 1
- Active d-amphetamine (the therapeutic metabolite) reaches peak concentration at 3.5 hours post-dose for capsules and 4.4 hours for chewable tablets 1
- Measurable clinical effects begin as early as 1.5 hours after administration 2
Duration of Effect
Therapeutic effects persist for 13 hours or longer after a single morning dose. 2, 3 In controlled laboratory school studies with children aged 6-12 years, Vyvanse demonstrated statistically significant efficacy at every measurement point from 1.5 hours through 13 hours post-dose compared to placebo 2. In adults, efficacy has been documented up to 14 hours post-dose 3.
Food Effects on Onset
Food delays the time to peak effect by approximately 1 hour but does not reduce overall absorption or efficacy. 1 A high-fat meal shifts the time to maximum d-amphetamine concentration from 3.8 hours (fasted) to 4.7 hours (fed), while yogurt shifts it to 4.2 hours 1. The total drug exposure (AUC) and maximum concentration (Cmax) remain unchanged 1.
Mechanism Explaining Delayed Onset
Vyvanse is a prodrug that requires enzymatic conversion in red blood cells to become pharmacologically active. 1, 4, 5 The parent compound lisdexamfetamine does not bind to dopamine or norepinephrine transporters and has no direct therapeutic activity 1. After oral administration, red blood cells hydrolyze lisdexamfetamine into active d-amphetamine and the amino acid l-lysine 1, 4, 5. This rate-limited conversion process explains why onset is slower compared to immediate-release amphetamine formulations 6, 5.
Clinical Comparison to Immediate-Release Amphetamine
Lisdexamfetamine has a 0.6-hour longer lag time and reaches peak levels 1.1 hours later than equivalent doses of immediate-release d-amphetamine. 6 In a direct comparison study, 100 mg lisdexamfetamine (equimolar to 40 mg d-amphetamine) showed delayed onset but identical peak effects and total exposure 6.
Practical Dosing Recommendations
Administer Vyvanse in the early morning to ensure symptom coverage extends through the entire day and evening. 7 Taking the medication too late shifts the duration curve later, potentially causing insomnia while leaving morning hours uncovered 7. The standard starting dose is 20-30 mg once daily in the morning, with weekly titration in 10 mg increments up to a maximum of 70 mg daily 8, 7.
Common Pitfall to Avoid
Do not expect immediate symptom relief within the first hour after administration. Unlike immediate-release stimulants that may work within 30-60 minutes 8, Vyvanse requires 1.5-2 hours before therapeutic effects become apparent 1, 2. Patients should be counseled about this delayed onset to set appropriate expectations and ensure medication adherence.