Is it safe to use Strattera (Atomoxetine) and Sertraline (Selective Serotonin Reuptake Inhibitor) together?

Safety of Using Strattera (Atomoxetine) and Sertraline Together

Caution should be exercised when combining Strattera (atomoxetine) and sertraline due to the potential risk of serotonin syndrome, though the combination can be used with proper monitoring and dose adjustment.

Potential Risks and Interactions

• Sertraline is a selective serotonin reuptake inhibitor (SSRI) that can increase serotonin levels, while atomoxetine is a selective norepinephrine reuptake inhibitor that primarily affects norepinephrine but may have some minor serotonergic effects 1

• When combining two or more serotonergic drugs (including SSRIs like sertraline), caution should be exercised due to the risk of serotonin syndrome 1

• Serotonin syndrome symptoms can develop within 24-48 hours after combining medications and include:

  • Mental status changes (confusion, agitation, anxiety)
  • Neuromuscular hyperactivity (tremors, clonus, hyperreflexia, muscle rigidity)
  • Autonomic hyperactivity (hypertension, tachycardia, arrhythmias, tachypnea, diaphoresis, shivering, vomiting, diarrhea) 1

• Advanced symptoms of serotonin syndrome can include fever, seizures, arrhythmias, and unconsciousness, which can be potentially fatal 1

Safety Considerations for Combined Use

• While there is a theoretical risk of interaction, atomoxetine is primarily noradrenergic rather than serotonergic, making the risk of serotonin syndrome lower than with combinations of two primarily serotonergic medications 2

• Research has shown that atomoxetine can be combined with fluoxetine (another SSRI similar to sertraline) with acceptable safety, suggesting that the atomoxetine-sertraline combination may also be tolerable with proper monitoring 3

• Sertraline may interact with drugs metabolized by CYP2D6, and atomoxetine is metabolized primarily by CYP2D6, which could potentially lead to increased atomoxetine levels 1

Recommendations for Combined Use

• If the combination is clinically necessary:

  • Start the second medication at a low dose
  • Increase the dose slowly
  • Monitor closely for symptoms of serotonin syndrome, especially in the first 24-48 hours after dosage changes 1

• Be particularly vigilant about monitoring:

  • Vital signs (blood pressure and pulse may increase with atomoxetine) 2
  • Mental status changes
  • Neuromuscular symptoms
  • Autonomic nervous system function 1

• The combination should be avoided in patients with:

  • History of seizures (both medications can lower seizure threshold) 1
  • Cardiovascular disease (both can affect heart rate and blood pressure) 2, 4
  • Hepatic insufficiency (may increase atomoxetine exposure) 2

Common Pitfalls and Caveats

• Never combine either medication with monoamine oxidase inhibitors (MAOIs), as this significantly increases the risk of serotonin syndrome 1, 5

• Be aware that poor CYP2D6 metabolizers (approximately 7% of the population) may have greater exposure to atomoxetine and slower elimination, potentially increasing the risk of adverse effects when combined with sertraline 2

• Monitor for potential discontinuation syndrome if sertraline is stopped abruptly 1

• Both medications can cause initial anxiety or agitation, which may be misinterpreted as worsening of the underlying condition rather than a medication side effect 1