Can a patient be on both atomoxetine (Strattera) and sertraline (Zoloft) simultaneously?

Can a Patient Be on Both Atomoxetine and Sertraline?

Yes, a patient can be on both atomoxetine and sertraline simultaneously, but this combination requires careful monitoring due to pharmacokinetic interactions and a theoretical risk of serotonin syndrome.

Key Pharmacokinetic Interaction

The primary concern with this combination is that sertraline inhibits CYP2D6, which is the main enzyme responsible for metabolizing atomoxetine 1. This interaction will:

• Increase atomoxetine plasma concentrations significantly 2
• Convert extensive CYP2D6 metabolizers into a pharmacokinetic profile similar to poor metabolizers 2
• Result in approximately 10-fold higher steady-state atomoxetine concentrations 2
• Prolong atomoxetine half-life from 5.2 hours to approximately 21.6 hours 2

When combining these medications, start atomoxetine at a lower dose than usual and titrate more slowly 1. If atomoxetine is already established and sertraline is being added, consider reducing the atomoxetine dose 1.

Serotonin Syndrome Risk Assessment

While atomoxetine is primarily a norepinephrine reuptake inhibitor, it does have some affinity for SERT 3. However:

• Atomoxetine inhibits SERT only minimally even at high doses (40% inhibition at 80 mg/d) 3
• This level of SERT inhibition is not clinically significant 3
• The American Academy of Child and Adolescent Psychiatry guidelines note that caution should be exercised when combining two or more serotonergic drugs, but this is not an absolute contraindication 4

The practical risk of serotonin syndrome with this combination is low, as atomoxetine does not meaningfully inhibit serotonin reuptake at therapeutic doses 3. However, monitor for serotonin syndrome symptoms (mental status changes, neuromuscular hyperactivity, autonomic hyperactivity) especially in the first 24-48 hours after starting the combination or increasing doses 4.

Cardiovascular Monitoring

Both medications can affect cardiovascular parameters:

• Atomoxetine causes small but statistically significant increases in heart rate and blood pressure 5
• Sertraline can interact with drugs metabolized by CYP2D6, potentially affecting cardiovascular medications 1
• Monitor blood pressure and heart rate at baseline and periodically during treatment 5
• The cardiovascular effects of atomoxetine are generally minimal and well-tolerated 5

Clinical Implementation Algorithm

1. If starting atomoxetine in a patient already on sertraline:

   • Begin atomoxetine at 25-40% of the usual starting dose 1
   • Titrate more slowly than usual (every 2-3 weeks instead of weekly) 2
   • Monitor for increased atomoxetine side effects (nausea, decreased appetite, somnolence) 6

2. If adding sertraline to established atomoxetine:

   • Consider reducing atomoxetine dose by 25-50% when initiating sertraline 1
   • Start sertraline at a low dose and increase slowly 4
   • Monitor closely for 24-48 hours after each dose change 4

3. Ongoing monitoring:

   • Assess for serotonin syndrome symptoms at each visit, particularly early in treatment 4
   • Monitor blood pressure and heart rate 5
   • Watch for atomoxetine toxicity signs (excessive sedation, cardiovascular effects) 6, 2

Common Pitfalls to Avoid

• Do not use standard atomoxetine dosing when combined with sertraline—the CYP2D6 inhibition will result in excessive atomoxetine exposure 1, 2
• Do not assume this combination is contraindicated—it is not, unlike MAOIs with serotonergic drugs 4
• Do not forget to adjust atomoxetine dosing if sertraline is discontinued—atomoxetine dose may need to be increased when sertraline is withdrawn 1

Special Populations

In children and adolescents, this combination is explicitly discussed in guidelines as requiring caution but not prohibition 4. The same monitoring principles apply, with particular attention to:

• Behavioral activation or agitation (can occur with SSRIs) 4
• Suicidal ideation (black box warning for atomoxetine) 6
• Growth parameters (atomoxetine can affect height and weight initially) 6