Is it safe to use Strattera (atomoxetine) and Prozac (fluoxetine) together?

Safety of Using Strattera (Atomoxetine) and Prozac (Fluoxetine) Together

The combination of Strattera (atomoxetine) and Prozac (fluoxetine) should be used with caution due to potential drug interactions through the CYP2D6 pathway, which may increase atomoxetine levels and side effects, though the combination can be used with proper monitoring and dosage adjustments.

Drug Interaction Mechanism

Fluoxetine is a potent inhibitor of CYP2D6, which is the primary enzyme responsible for metabolizing atomoxetine. This interaction has important clinical implications:

• Fluoxetine can significantly increase atomoxetine plasma levels by inhibiting its metabolism 1
• This interaction effectively converts normal "extensive metabolizers" of atomoxetine into "poor metabolizers" 2
• Approximately 7% of the population are already poor CYP2D6 metabolizers naturally, who have slower clearance of atomoxetine 2

Clinical Management Recommendations

Dosage Adjustments

When using this combination:

1. Start with reduced atomoxetine dosing:

   • Consider starting atomoxetine at 50% of the normal dose when combined with fluoxetine
   • The normal starting dose of atomoxetine is 0.5 mg/kg/day for children and adolescents up to 70 kg or 40 mg daily for adults 2

2. Titration strategy:

   • Increase doses more slowly than usual
   • Monitor for side effects for at least 24-48 hours after dosage changes 3
   • Allow longer intervals between dose adjustments (at least 1-2 weeks)

Monitoring Requirements

Patients on this combination should be monitored for:

1. Cardiovascular parameters:

   • Blood pressure and heart rate at each visit
   • Atomoxetine alone can cause statistically significant increases in heart rate and blood pressure 4

2. Mental health status:

   • Watch for signs of serotonin syndrome (confusion, agitation, tremors, hyperreflexia, hyperthermia) 3
   • Monitor for increased anxiety or agitation, especially during the first few weeks
   • Both medications carry warnings about potential suicidal ideation, particularly in children and adolescents 4

3. Side effects:

   • Gastrointestinal symptoms (nausea, decreased appetite)
   • Somnolence or insomnia
   • Dry mouth and other anticholinergic effects

Evidence for Combination Use

There is limited but supportive evidence for using atomoxetine with SSRIs:

• A study examining atomoxetine with fluoxetine for ADHD with comorbid depression or anxiety found the combination was well tolerated, though with greater increases in blood pressure and pulse than atomoxetine alone 5
• Case reports suggest that atomoxetine can be used in combination with other medications when single-agent treatment is inadequate 6
• A systematic review found that combination therapy with atomoxetine and other agents may benefit some patients who have tried several ADHD medications without success 7

Potential Benefits of Combination

This combination may be particularly useful in specific clinical scenarios:

• Patients with comorbid ADHD and depression or anxiety disorders
• Cases where monotherapy with either medication has provided partial but inadequate symptom relief
• Situations where extending duration of symptom control is needed

Cautions and Contraindications

Exercise extreme caution or avoid this combination in patients with:

• Cardiovascular disease or risk factors
• Hepatic impairment (both drugs are metabolized in the liver)
• History of seizures
• Narrow-angle glaucoma
• History of suicidal ideation or behavior

Practical Approach

1. Before starting combination:

   • Establish efficacy and tolerability of each medication individually when possible
   • Consider pharmacogenetic testing for CYP2D6 status if available 1

2. When initiating combination:

   • If patient is already on fluoxetine, start atomoxetine at a reduced dose
   • If patient is already on atomoxetine, reduce the dose before adding fluoxetine
   • Weekly monitoring during initial combination therapy

3. Long-term management:

   • Once stabilized, monthly follow-up is appropriate
   • Regular reassessment of the need for continued combination therapy

While this combination can be used with proper precautions, clinicians should remain vigilant for potential adverse effects and be prepared to adjust treatment as needed.