What is the best course of action for a patient with Attention Deficit Hyperactivity Disorder (ADHD) who is experiencing declining efficacy of Lisdexamfetamine (Vyvanse) 20mg daily, with stable mood and anxiety symptoms on Duloxetine (Cymbalta) 90mg daily?

Increase Lisdexamfetamine to 30 mg Daily

Increasing lisdexamfetamine from 20 mg to 30 mg daily is the appropriate next step for this patient experiencing declining efficacy, as dose optimization through systematic titration is standard practice for stimulant management in ADHD, and the patient has no contraindications or concerning side effects. 1

Rationale for Dose Increase

• The patient's report of faster wear-off and declining efficacy after prolonged use at 20 mg indicates tolerance development, which is best addressed by dose optimization rather than switching medications 1
• Lisdexamfetamine demonstrates dose-dependent efficacy, with 30 mg, 50 mg, and 70 mg doses all showing statistically significant superiority over placebo in adult ADHD trials 2
• The current 20 mg dose is below the typical therapeutic range for adults, where doses of 30-70 mg daily are standard, with many patients requiring 50-70 mg for optimal symptom control 2, 3
• Systematic titration to optimal effect is more important than strict mg/kg calculations, with 70% of patients responding optimally when proper titration protocols are followed 1

Evidence Supporting This Approach

• In controlled adult trials, lisdexamfetamine 30 mg, 50 mg, and 70 mg all produced significantly greater improvements in ADHD-RS total scores compared to placebo after 4 weeks, with mean reductions of -16.2, -17.4, and -18.6 points respectively versus -8.2 for placebo 2
• Higher doses were associated with greater efficacy, with the 70 mg dose showing the largest treatment effect (placebo-subtracted difference of -10.4 points) 2
• Lisdexamfetamine maintains efficacy at 14 hours post-dose in adults, making it suitable for managing ADHD symptoms that extend late into the day 3
• A maintenance study demonstrated that 91% of adults maintained treatment response when continuing lisdexamfetamine versus 25% on placebo, confirming sustained efficacy with ongoing treatment 2

Monitoring During Titration

• Assess ADHD symptom response after 1 week at 30 mg, as significant between-group differences favoring lisdexamfetamine are evident after just 1 week of treatment 4
• Monitor blood pressure and pulse at baseline and regularly during treatment, as mean increases at last on-treatment assessment were pulse rate +7.0 bpm, systolic BP +3.4 mmHg, and diastolic BP +3.2 mmHg 5
• Track appetite and weight at each visit, as decreased appetite occurs in 27% of adults (versus 2% on placebo) and mean weight loss after 4 weeks ranges from 2.8 to 4.3 pounds depending on dose 2
• Monitor sleep quality, as insomnia occurs in 27% of adults on lisdexamfetamine (versus 8% on placebo), though this typically emerges early in treatment with median time to onset of 17 days 2, 5

Further Titration Strategy

• If inadequate response at 30 mg after 1 week, increase to 50 mg daily, as this represents the mid-range therapeutic dose with robust efficacy data 2, 3
• Maximum dose is 70 mg daily, which can be considered if 50 mg provides insufficient symptom control 2, 6
• The American Academy of Child and Adolescent Psychiatry recommends adjusting doses weekly by 5-10 mg increments until symptoms resolve or maximum tolerated dose is reached 1

Interaction with Duloxetine

• There are no significant pharmacokinetic interactions between lisdexamfetamine and duloxetine, making this combination safe to continue 1
• The stable mood and anxiety symptoms on duloxetine 90 mg suggest no need for adjustment of the antidepressant regimen 1
• Continue monitoring for any emergence of anxiety or agitation as the stimulant dose increases, though the patient's current stability on duloxetine provides protection against mood destabilization 1

Common Pitfalls to Avoid

• Do not assume the current 20 mg dose is adequate, as 54-70% of adults with ADHD respond to stimulants when properly titrated to higher doses 1
• Do not switch medication classes prematurely—maximize lisdexamfetamine efficacy first through dose optimization before considering alternatives like methylphenidate 7, 1
• Do not add a second ADHD medication (such as a non-stimulant) before optimizing the stimulant dose, as monotherapy at appropriate doses is preferred over polypharmacy 1
• Do not discontinue duloxetine or assume a single medication can treat both ADHD and mood symptoms, as no single antidepressant is proven for this dual purpose 1