CYP2D6 and Atomoxetine

Atomoxetine (brand name Strattera) is a drug used to treat children and adults with attention deficit hyperactivity disorder (ADHD). Many drugs for ADHD are stimulants. Atomoxetine is different because it treats both attention and hyperactivity symptoms without being a stimulant.

As with most drugs, the amount of atomoxetine needed for symptom relief and the risk for side effects varies from person to person. Atomoxetine is metabolized mostly by the CYP2D6 drug metabolism enzyme. Variations in the CYP2D6 enzyme may partly explain why people respond to the drug differently.  

Signs of Abnormal Atomoxetine Metabolism

• A CYP2D6 Poor Metabolizer
• May have symptoms that improve more than expected based on the dose. A poor metabolizer is actually being exposed to higher levels of the drug for longer because the drug isn’t broken down as quickly as usual.
• May have a higher heart rate and blood pressure than extensive metabolizers taking the same dose.
• Has a slightly higher risk for certain side effects, especially tremor, but most are relatively mild and don’t cause a person to stop taking the drug.  
• A CYP2D6 Ultrarapid Metabolizer
• May need atomoxetine doses closer to the high end of the normal range, but a difference between ultrarapid and extensive (normal) metabolizers isn’t clear.

Testing for Atomoxetine Response

CYP2D6 testing isn’t routinely recommended for everyone taking (or planning to take) atomoxetine. Although CYP2D6 is clearly important in metabolizing the drug, there aren’t any professional guidelines to help doctors decide when to test patients for CYP2D6 variants to predict atomoxetine response at this time. However, the  Food and Drug Administration (FDA) has special prescribing information for poor metabolizers who take atomoxetine. The FDA highlights that laboratory tests are available to identify CYP2D6 poor metabolizers.  The FDA has also included CYP2D6 testing for atomoxetine on its list of FDA approved biomarkers for drug response. Doctors must weigh all available information and decide if testing is likely to be useful given a patient’s specific medical history.

For more information about ADHD drugs, see National Institute of Mental Health: What medications are used to treat ADHD?