Combination Therapy for ADHD with Strattera and Vyvanse

Introduction to Combination Therapy

The American Academy of Pediatrics guidelines support the use of atomoxetine as adjunctive therapy with stimulant medications for ADHD treatment on an off-label basis, with limited evidence supporting its efficacy and safety 1
Only extended-release guanfacine and extended-release clonidine have FDA approval for adjunctive use with stimulants, while atomoxetine has been used in combination with stimulants on an off-label basis 1
This combination may be considered when stimulant therapy alone is not fully effective or is limited by side effects 1

Obtain detailed cardiac history including specific cardiac symptoms before initiating combination therapy 1
Obtain family history of sudden death, cardiovascular symptoms, Wolff-Parkinson-White syndrome, hypertrophic cardiomyopathy, and long QT syndrome before initiating combination therapy 1
Monitor heart rate and blood pressure regularly, as stimulants increase HR by 1-2 beats per minute and BP by 1-4 mm Hg on average 1
A subset of patients (5-15%) may experience more substantial increases in HR and BP 1

Start atomoxetine at 40 mg orally once daily, titrate every 7-14 days to 60 mg, then 80 mg daily, with a maximum dose of the lesser of 1.4 mg/kg/day or 100 mg/day 2, 3
Start lisdexamfetamine at 20-30 mg orally once in the morning, increase by 10 mg weekly, with a maximum dose of 70 mg daily 4, 5, 6

Decreased appetite is a common side effect with both medications 1
Insomnia can occur with both, though it is more common with stimulants 1
Cardiovascular changes, such as increased HR and BP, can occur with both medications 1
Initial somnolence and gastrointestinal symptoms can occur with atomoxetine, particularly if the dose is increased too rapidly 1
Rare increase in suicidal thoughts is a potential side effect of atomoxetine, with an FDA black box warning 1
Abdominal pain and headaches are potential side effects of lisdexamfetamine 1

Both medications can affect growth velocity 1
Atomoxetine shows initial growth delays in the first 1-2 years, with return to expected measurements after 2-3 years 1
Stimulants may decrease predicted adult height by 1-2 cm, with effects diminishing by the third year 1

Watch for mood destabilization, especially in patients with a family history of bipolar disorder 2
Monitor for agitation, irritability, hostility, impulsivity, restlessness, or mania, particularly in the first 24-48 hours after initiation or dose changes 2
Vyvanse can be discontinued without specific tapering requirements 4, 5, 6