How to manage a 22-year-old female (fe) patient with Attention Deficit Hyperactivity Disorder (ADHD) who is taking generic Vyvanse (lisdexamfetamine) 30 mg and uses cannabis regularly, but reports that Vyvanse is not effective for her?

Management of Inadequate Vyvanse Response in a 22-Year-Old Female with ADHD and Regular Cannabis Use

Primary Recommendation: Address Cannabis Use First, Then Optimize Stimulant Therapy

The most critical step is to address the patient's regular cannabis use, as this is likely interfering with Vyvanse efficacy and should be discontinued or significantly reduced before making medication changes. 1

Cannabis use can significantly impair executive function and attention, directly counteracting ADHD medication effects and making it impossible to accurately assess whether the stimulant is truly ineffective 1. Additionally, the 30 mg Vyvanse dose is at the lower end of the therapeutic range for adults, suggesting inadequate dosing rather than true treatment failure 2, 3.

Step 1: Evaluate and Address Substance Use

• Screen for cannabis use disorder and assess frequency, quantity, and timing of cannabis use relative to Vyvanse dosing, as substance use can mask medication efficacy and complicate treatment 1
• Educate the patient that cannabis use directly impairs the cognitive domains that ADHD medications are designed to improve (attention, working memory, executive function), making it impossible to determine if Vyvanse is truly ineffective 1
• Implement urine drug screening to objectively monitor cannabis use throughout treatment adjustments 1
• Consider referral to addiction services if the patient meets criteria for cannabis use disorder or is unable to reduce/discontinue use independently 1

Step 2: Optimize Vyvanse Dosing (After Cannabis Reduction/Cessation)

If the patient successfully reduces or stops cannabis use, titrate Vyvanse before switching medications, as 30 mg is subtherapeutic for most adults. 2, 3

• Increase Vyvanse to 40 mg after 1 week of reduced/no cannabis use, then reassess symptoms 2
• Continue weekly titration by 10-20 mg increments up to 70 mg daily (maximum FDA-approved dose) until optimal symptom control is achieved 2, 3
• Target dose range for adults is typically 50-70 mg daily for full therapeutic effect, with efficacy demonstrated at 14 hours post-dose 2, 3
• Monitor for side effects including decreased appetite, insomnia, increased heart rate, anxiety, and irritability at each dose adjustment 2

Step 3: If Vyvanse Remains Ineffective at Optimal Dose

Switch to methylphenidate-based stimulants if Vyvanse fails at 70 mg daily with confirmed cannabis abstinence, as approximately 40% of patients respond to only one stimulant class. 4, 5

• Start with long-acting methylphenidate (OROS-methylphenidate/Concerta 36 mg once daily or extended-release methylphenidate) rather than immediate-release formulations for better adherence 4, 5
• Titrate methylphenidate by 18 mg weekly up to 54-72 mg daily maximum 5
• Combined use of both amphetamine and methylphenidate classes yields >90% response rates when properly dosed, so exhausting both classes is essential before considering non-stimulants 5

Step 4: Monitor for Psychiatric Comorbidities

• Assess for emerging depression or anxiety that may be contributing to perceived ADHD treatment failure, as cannabis use is often self-medication for underlying mood disorders 1
• Screen for bipolar disorder risk factors before continuing stimulant therapy, as stimulants can precipitate manic episodes in vulnerable individuals 1
• If mood symptoms persist after ADHD optimization, consider adding an SSRI to the stimulant regimen rather than switching medications 1

Critical Safety Considerations

• Monitor cardiovascular parameters (blood pressure and heart rate) at baseline and each visit during dose titration 2
• Assess for signs of stimulant misuse or diversion, particularly given the substance use history, though lisdexamfetamine has lower abuse potential than other stimulants due to its prodrug formulation 2, 6, 7
• Avoid MAO inhibitors concurrently or within 14 days of Vyvanse due to hypertensive crisis risk 2
• Monitor for serotonin syndrome if combining with serotonergic agents 2

Common Pitfalls to Avoid

• Do not assume medication failure at 30 mg, as this is a starting dose and most adults require 50-70 mg for optimal effect 2, 3
• Do not switch medications without first addressing cannabis use, as substance use will undermine any ADHD treatment 1
• Do not add multiple medications simultaneously, as this makes it impossible to determine which intervention is effective 1
• Do not prescribe benzodiazepines for anxiety in this population, as they may reduce self-control and have disinhibiting effects, particularly problematic with concurrent substance use 1
• Do not underdose due to substance use history concerns, as proper ADHD treatment may actually reduce substance use by improving executive function and reducing self-medication behaviors 6

Expected Timeline

• Week 1-2: Cannabis reduction/cessation with close monitoring 1
• Week 3-6: Systematic Vyvanse titration to 50-70 mg with weekly dose increases 2
• Week 7-8: Final assessment of Vyvanse efficacy at optimal dose 3
• Week 9+: Switch to methylphenidate class if needed, with similar titration protocol 4, 5