Is it safe to use Straterra (atomoxetine) and Vyvanse (lisdexamfetamine) in combination?

Combination of Strattera (Atomoxetine) and Vyvanse (Lisdexamfetamine)

Yes, combining Strattera (atomoxetine) and Vyvanse (lisdexamfetamine) is safe and can be used together for ADHD treatment, with atomoxetine having limited evidence supporting its use as adjunctive therapy with stimulant medications on an off-label basis. 1

Evidence for Combination Therapy

The American Academy of Pediatrics guidelines specifically address adjunctive therapy for ADHD, noting that:

• Only extended-release guanfacine and extended-release clonidine have FDA approval for adjunctive use with stimulants 1
• Atomoxetine has been used in combination with stimulants on an off-label basis, with some limited evidence supporting both efficacy and safety of this combination 1
• This combination may be considered when stimulant therapy alone is not fully effective or is limited by side effects 1

Cardiovascular Monitoring Requirements

Both medications affect cardiovascular parameters and require careful monitoring:

Before Initiating Combination Therapy

• Obtain detailed cardiac history including specific cardiac symptoms 1
• Obtain family history of sudden death, cardiovascular symptoms, Wolff-Parkinson-White syndrome, hypertrophic cardiomyopathy, and long QT syndrome 1
• If any risk factors are present, obtain an ECG and consider referral to a pediatric cardiologist if abnormal 1

During Treatment

• 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
• Atomoxetine also causes statistically (but not clinically) significant increases in both heart rate and blood pressure 2

Dosing Approach

Atomoxetine (Strattera)

• Start at 40 mg orally once daily 3, 4
• Titrate every 7-14 days to 60 mg, then 80 mg daily 3, 4
• Maximum dose: lesser of 1.4 mg/kg/day or 100 mg/day 3, 4

Lisdexamfetamine (Vyvanse)

• Start at 20-30 mg orally once in the morning 1
• Increase by 10 mg weekly 1
• Maximum dose: 70 mg daily 1

Common Side Effects to Monitor

Overlapping Side Effects (Monitor Closely)

• Decreased appetite (common with both medications) 1, 2
• Insomnia (can occur with both, though more common with stimulants) 1, 2
• Cardiovascular changes (both can increase HR and BP) 1, 2

Atomoxetine-Specific Side Effects

• Initial somnolence and gastrointestinal symptoms (particularly if dose increased too rapidly) 1
• Rare increase in suicidal thoughts (FDA black box warning) 1, 2
• Extremely rare hepatitis 1

Vyvanse-Specific Side Effects

• Abdominal pain and headaches 1
• Monitor for irritability, insomnia, and feeding difficulty 1

Growth Monitoring

• Both medications can affect growth velocity 1, 2
• 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

Special Considerations

Mood Monitoring

• Watch for mood destabilization, especially in patients with family history of bipolar disorder 3
• Monitor for agitation, irritability, hostility, impulsivity, restlessness, or mania, particularly in the first 24-48 hours after initiation or dose changes 3

Drug Interactions

• CYP2D6 inhibitors (such as paroxetine) significantly affect atomoxetine pharmacokinetics, leading to greater exposure similar to poor metabolizers 2
• Poor CYP2D6 metabolizers have greater exposure and slower elimination of atomoxetine 2

Discontinuation

• Atomoxetine can be stopped abruptly without tapering (no rebound symptoms or discontinuation syndrome) 2, 5
• Vyvanse can also be discontinued without specific tapering requirements 1