What is the best Selective Serotonin Reuptake Inhibitor (SSRI) to use in conjunction with Strattera (atomoxetine)?

Best SSRI to Use with Strattera (Atomoxetine)

Escitalopram is the preferred SSRI to use in combination with Strattera (atomoxetine) due to its favorable side effect profile, minimal drug interactions, and efficacy in treating comorbid anxiety disorders.

Rationale for SSRI Selection with Strattera

When selecting an SSRI to combine with Strattera, several factors must be considered:

1. Drug-Drug Interaction Potential

   • Atomoxetine is primarily metabolized by CYP2D6 enzyme
   • SSRIs vary significantly in their inhibition of CYP enzymes
   • Escitalopram and citalopram have minimal effect on major CYP isoforms 1
   • Fluoxetine and paroxetine are potent CYP2D6 inhibitors that could increase atomoxetine levels 1

2. Safety Profile

   • The combination should minimize overlapping side effects
   • Avoid SSRIs that significantly increase cardiovascular risks when combined with atomoxetine
   • Escitalopram has a higher safety and tolerability profile compared to other options 2

Specific SSRI Recommendations

First Choice: Escitalopram

• Minimal CYP2D6 inhibition, reducing risk of atomoxetine level elevation
• Effective for anxiety disorders with onset of action as early as 1-2 weeks 2
• Recommended dosing: 10mg daily initially, increasing to 20mg daily after at least one week 2
• Common side effects include dry mouth, nausea, diarrhea, headache, and somnolence 2

Second Choice: Sertraline

• Moderate CYP2D6 inhibitor (less potent than fluoxetine/paroxetine) 1
• Fewer patients discontinue sertraline due to adverse effects compared to other SSRIs 3
• Good option if escitalopram is not tolerated or unavailable

SSRIs to Avoid with Atomoxetine

• Fluoxetine: Potent CYP2D6 inhibitor with long half-life (1-3 days) and active metabolite norfluoxetine (half-life 7 days) 4, 1
• Paroxetine: Potent CYP2D6 inhibitor with higher reports of suspected reactions 3, 1
• Fluvoxamine: Potent inhibitor of multiple CYP enzymes (CYP1A2, CYP2C19) with higher incidence of adverse events 3, 1

Clinical Evidence for Combination Therapy

Research has shown that atomoxetine combined with an SSRI can be effective and well-tolerated:

• A study examining atomoxetine with fluoxetine found the combination was well-tolerated, though with greater increases in blood pressure and pulse than atomoxetine monotherapy 5
• When combining an SSRI with atomoxetine, monitor for:
  • Increased blood pressure and heart rate
  • Serotonin syndrome (mental status changes, autonomic instability)
  • Potential weight and height changes in pediatric patients 6

Monitoring Recommendations

When using escitalopram with atomoxetine:

• Assess vital signs at baseline and regularly during treatment
• Monitor for side effects every 1-2 weeks initially
• Watch for suicidal ideation/behavior, especially during medication initiation or dose changes
• Use standardized scales to track anxiety and ADHD symptoms
• Evaluate for potential drug interactions if other medications are added

Special Considerations

• For patients with comorbid anxiety disorders, escitalopram is particularly beneficial 2
• For patients with insomnia, consider timing of atomoxetine administration in the morning
• For patients with cardiovascular concerns, more careful monitoring of vital signs is needed
• In cases of treatment resistance, consider adjunctive therapies like CBT

The combination of atomoxetine with escitalopram provides an effective approach for patients with ADHD and comorbid depression or anxiety, with minimal risk of clinically significant drug interactions.