Should the dose of atomoxetine be lower when combining with Vyvanse (lisdexamfetamine)?

Atomoxetine Dosing When Combined with Lisdexamfetamine (Vyvanse)

When combining atomoxetine with lisdexamfetamine (Vyvanse), the atomoxetine dose should be reduced to approximately 0.5-0.7 mg/kg/day (half the standard dose) to minimize side effects while maintaining efficacy.

Rationale for Dose Reduction

• The standard maximum recommended dosage of atomoxetine is 1.4 mg/kg/day or 100 mg/day (whichever is lower) when used as monotherapy 1
• When combining with stimulants like lisdexamfetamine, a lower atomoxetine dose (approximately 0.5-0.7 mg/kg/day) is recommended to reduce the risk of additive side effects while maintaining therapeutic benefit 2
• Studies have shown that lower maintenance doses of atomoxetine (0.5 mg/kg/day) can be effective after initial response to standard doses, suggesting reduced dosing is viable when used in combination therapy 2

Potential Side Effects of Combination Therapy

• Both medications can affect cardiovascular parameters, with atomoxetine potentially increasing heart rate and blood pressure 3
• Lisdexamfetamine (Vyvanse) is also associated with cardiovascular effects, creating potential for additive impact on vital signs 3
• Combined therapy may increase the risk of:
  • Appetite suppression and weight loss 4
  • Sleep disturbances 4
  • Increased heart rate and blood pressure 3

Implementation Strategy

• Start with a lower atomoxetine dose (0.5 mg/kg/day) when initiating combination therapy 2
• Consider split dosing of atomoxetine (morning and evening) to reduce side effects during the initial titration period 5
• Monitor vital signs (heart rate and blood pressure) more frequently during the initial combination period 3
• Titrate atomoxetine slowly if needed, with smaller incremental increases than would be used in monotherapy 5

Monitoring Recommendations

• Assess cardiovascular parameters (heart rate and blood pressure) at each visit during the initial combination period 3
• Monitor for signs of excessive stimulation, sleep disturbances, or appetite suppression 4
• Evaluate the therapeutic response after 6-8 weeks, as atomoxetine has a delayed onset of action compared to stimulants 1
• Be vigilant for any signs of mood changes or irritability, as both medications can affect mood 6

Clinical Pearls

• The combination of atomoxetine with lisdexamfetamine may provide more consistent 24-hour symptom control than either medication alone 1
• This combination may be particularly beneficial for patients who have partial response to either medication alone 7
• Approximately 75% of responders to stimulants like lisdexamfetamine will also respond to atomoxetine, making the combination potentially effective for many patients 7
• The lower dose of atomoxetine in combination therapy may help reduce the risk of side effects while maintaining efficacy 2

Special Considerations

• Obtain personal and family cardiac history before initiating combination therapy 3
• Consider performing an ECG if there are any cardiac risk factors 3
• Be aware that atomoxetine is metabolized by CYP2D6, and poor metabolizers may require even lower doses when combining with stimulants 4
• The combination may be particularly useful for patients with comorbid anxiety or tics, as atomoxetine has shown benefits in these populations 4