Is it safe to use Strattera (atomoxetine) and Guanfacine in combination for the management of Attention Deficit Hyperactivity Disorder (ADHD)?

Combination of Strattera (Atomoxetine) and Guanfacine for ADHD Management

The combination of Strattera (atomoxetine) and guanfacine can be safely used for ADHD management, particularly in patients with inadequate response to monotherapy, with appropriate monitoring of vital signs and side effects. 1

Rationale for Combination Therapy

Atomoxetine and guanfacine work through different mechanisms:

• Atomoxetine: Selectively inhibits presynaptic norepinephrine reuptake in the prefrontal cortex with an effect size of approximately 0.7 1, 2
• Guanfacine: Alpha-2A adrenoceptor agonist with efficacy rate of 58.5% vs. 29.4% for placebo 1, 3

This combination may be particularly beneficial for:

• Patients with partial response to either medication alone
• Those needing coverage for both inattentive and hyperactive/impulsive symptoms
• Patients requiring symptom control throughout the day 1

Clinical Considerations

Efficacy

• The American Academy of Pediatrics guidelines support combination therapy with guanfacine added to other ADHD medications for enhanced efficacy in partial responders 1
• Limited research suggests the combination can extend duration of symptom relief or address a wider range of symptoms than either agent alone 4

Safety Profile

• Cardiovascular effects:

  • Atomoxetine: Mild increases in heart rate and blood pressure 1, 2
  • Guanfacine: Decreases in heart rate and blood pressure 1
  • These opposing cardiovascular effects may partially counterbalance each other, but require careful monitoring

• Common side effects to monitor:

  • Atomoxetine: Appetite loss, abdominal pain, headaches, somnolence, nausea 1, 2
  • Guanfacine: Somnolence, headaches, fatigue 1, 3
  • Combined therapy may increase risk of sedation/somnolence 5

Implementation Strategy

1. Start with monotherapy first:

   • Try optimizing either medication alone before considering combination 1

2. When adding second agent:

   • Start with low dose of the added medication
   • Titrate slowly based on response and tolerability
   • Monitor vital signs regularly (blood pressure, heart rate)

3. Monitoring parameters:

   • Vital signs at each dose change and regularly thereafter
   • Sedation levels
   • Growth parameters
   • Liver function (for atomoxetine)
   • Consider ECG in patients with cardiac risk factors 1

Special Considerations

• Abrupt discontinuation: Avoid sudden discontinuation of guanfacine due to risk of rebound hypertension; requires gradual tapering 1

• Drug interactions: Both medications undergo hepatic metabolism; atomoxetine via CYP2D6 pathway, which can be affected by poor metabolizer status or concomitant medications 2, 6

• Evidence limitations: Published evidence on this combination is limited, with heterogeneous study designs and small sample sizes 5

Clinical Bottom Line

While the combination of atomoxetine and guanfacine appears safe and potentially effective for ADHD management, careful patient selection, dose titration, and monitoring are essential. This approach should be considered for patients who have had inadequate response to optimized monotherapy with either agent.