A patient on lisdexamfetamine (Vyvanse) 30 mg daily has reduced anxiety and better concentration but develops brain fog, fatigue, and a strong desire to sleep after about 2 PM; what management steps are recommended?

Management of Afternoon Crash on Vyvanse 30mg

Add a 5mg dextroamphetamine (Dexedrine) dose at 2:00 PM to cover the afternoon symptom gap, as this timing follows established guidelines for second stimulant dosing and addresses the medication wear-off causing your patient's brain fog and exhaustion. 1, 2, 3

Understanding the Problem

Your patient is experiencing classic lisdexamfetamine wear-off around 2 PM, which occurs because:

• Lisdexamfetamine peaks at approximately 4.4 hours post-dose and gradually declines throughout the day 4
• The prodrug mechanism provides extended coverage but may not last a full day for all patients 5, 6
• Daily use without adequate coverage can lead to depletion of dopamine and norepinephrine reserves, resulting in paradoxical fatigue 1

Recommended Management Strategy

First-Line Approach: Add Afternoon Booster

Add dextroamphetamine 5mg at 2:00 PM to extend symptom control through the afternoon and evening:

• This timing is specifically recommended by the National Comprehensive Cancer Network for second stimulant doses, with explicit guidance that it should be given no later than 2:00 PM to minimize insomnia risk 2, 3
• The combined regimen (Vyvanse 30mg + Dexedrine 5mg at 2:00 PM) totals 35mg dextroamphetamine equivalent daily, well within the 50-70mg maximum daily amphetamine dose for adults 2
• Lisdexamfetamine has demonstrated efficacy up to 14 hours post-dose in some adults, but individual variation exists 5, 6

Alternative Approach: Optimize Morning Dose Timing

Ensure the patient takes Vyvanse as early as possible in the morning (ideally 6:00-7:00 AM):

• Earlier administration can help extend coverage later into the day 1
• Lisdexamfetamine levels peak at 1.5 hours, with d-amphetamine levels peaking at 4.4 hours post-dose 4

If Booster Insufficient: Consider Dose Increase

Increase Vyvanse to 40mg or 50mg if the afternoon booster doesn't adequately address symptoms:

• Titrate weekly in 10mg increments up to a maximum of 70mg/day 1
• Higher doses may provide longer duration of effect 6

Critical Timing Considerations

Never administer the afternoon dose later than 2:00 PM:

• Administration after 2:00 PM significantly increases sleep problems 1, 2, 3
• This is a firm cutoff established across multiple guidelines 2, 3

Monitoring Requirements

Check at follow-up visits:

• Blood pressure and pulse quarterly (small mean increases expected with amphetamine therapy) 2
• Weight at every visit (appetite suppression occurs in 25-39% of patients) 2
• ADHD symptom ratings using standardized scales 2
• Sleep quality and any signs of insomnia 1

Common Pitfalls to Avoid

Do not:

• Increase caffeine intake to compensate for afternoon fatigue (combined use with high caffeine >300mg/day can potentiate cardiovascular effects and worsen rebound fatigue) 1
• Skip medication on weekends thinking it will help (this can actually worsen tolerance issues) 1
• Crush or open Vyvanse capsules attempting faster onset (destroys the prodrug mechanism) 2

When to Consider Alternatives

Switch to methylphenidate, atomoxetine, or guanfacine if:

• Persistent fatigue develops despite optimization of Vyvanse dosing and timing 1
• Cardiovascular side effects become problematic 2
• Patient develops tolerance requiring escalation beyond maximum recommended doses 2