What is a good adjunct to Vyvanse (lisdexamfetamine) for managing afternoon irritability?

Adjunctive Medications for Managing Afternoon Irritability with Vyvanse

Guanfacine extended-release is the best adjunctive medication to Vyvanse for managing afternoon irritability, as it can be used alongside stimulants with fewer gastrointestinal side effects than other options. 1

Understanding Afternoon Irritability with Vyvanse

Vyvanse (lisdexamfetamine) is a prodrug stimulant that converts to d-amphetamine in the blood after oral administration 2. While it has a long duration of action (up to 14 hours in adults) 3, some patients experience irritability in the afternoon as the medication's effects begin to wane.

This irritability can be understood as either:

• A rebound effect as stimulant levels decrease
• A manifestation of returning ADHD symptoms
• A side effect of the stimulant itself

First-Line Adjunctive Options

1. Guanfacine Extended-Release

• Mechanism: Alpha-2 adrenergic agonist
• Benefits:
  • Can be used as monotherapy or adjunctive to stimulants
  • Side effect profile features somnolence/fatigue rather than gastrointestinal symptoms
  • May specifically help with irritability and emotional dysregulation
• Dosing: Start low and titrate gradually

2. Atomoxetine

• Mechanism: Selective norepinephrine reuptake inhibitor
• Benefits:
  • Different side effect profile than stimulants
  • Lower effects on appetite compared to stimulants
  • May provide smoother coverage throughout the day
• Dosing: 1.2 mg/kg/day (up to 100mg daily)
• Caveat: Takes 6-12 weeks for full therapeutic effect versus days for stimulants 1

Alternative Approaches

3. Bupropion

• Mechanism: Norepinephrine-dopamine reuptake inhibitor
• Benefits:
  • Activating; possible rapid improvement of energy level
  • May help with afternoon transition
• Dosing: Start with 37.5 mg every morning, then increase by 37.5 mg every 3 days; maximum 150 mg twice daily
• Caution: Should not be used in agitated patients or those with seizure disorders
• Timing: To minimize risk of insomnia, give second dose before 3 p.m. 4

4. Stimulant Dosing Adjustments

• Adding a small afternoon dose of immediate-release methylphenidate
• Overlapping stimulant dosing pattern
• Switching to longer-acting stimulants
• Combining immediate-release with sustained release 4

Practical Implementation Algorithm

1. First, assess the pattern of irritability:

   • If occurring just after medication administration: Consider peak effect irritability
   • If occurring late afternoon: Consider rebound effect

2. For rebound irritability:

   • Try guanfacine extended-release as first-line adjunctive treatment
   • Start with low dose and titrate based on response

3. If guanfacine is ineffective or poorly tolerated:

   • Consider atomoxetine as an alternative non-stimulant option
   • Remember longer onset of action (6-12 weeks)

4. For stimulant adjustment approach:

   • Consider adding small afternoon dose of immediate-release stimulant
   • Ensure second dose is given before 3 p.m. to avoid sleep disturbance

Monitoring and Follow-up

• Regular assessment of symptom control throughout the day
• Monitor for side effects of both medications
• Assess vital signs, particularly with guanfacine (potential for hypotension)
• Evaluate sleep quality, as poor sleep can worsen irritability

Important Considerations and Pitfalls

• Avoid unnecessary polypharmacy; start with one adjunctive medication
• Rule out other causes of irritability (hunger, sleep issues, comorbid conditions)
• Consider that irritability may be a manifestation of returning ADHD symptoms rather than medication side effect
• Be cautious with timing of additional stimulant doses to avoid sleep disruption
• Remember that behavioral interventions can complement pharmacological approaches

By following this approach, afternoon irritability associated with Vyvanse can be effectively managed while maintaining the benefits of the primary ADHD treatment.