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The gene most commonly associated with variations in drug metabolism for antidepressants and antipsychotics is CYP2D6. This gene is part of the cytochrome P450 enzyme system, which is responsible for metabolizing a significant portion of all clinically used drugs.
Why is CYP2D6 so important?
The CYP2D6 gene is highly polymorphic, meaning it has many different variations (alleles) in the human population. These genetic variations can lead to different levels of enzyme activity, classifying individuals into different metabolizer phenotypes:
• Poor Metabolizers (PMs): These individuals have little to no functional CYP2D6 enzyme. They can experience high drug concentrations, leading to an increased risk of side effects.
• Intermediate Metabolizers (IMs): They have reduced enzyme activity.
• Extensive Metabolizers (EMs): This is the most common phenotype with normal enzyme activity.
• Ultrarapid Metabolizers (UMs): These individuals have multiple copies of the gene, leading to significantly increased enzyme activity. They may break down drugs so quickly that the medication has little or no therapeutic effect.
Because many common antidepressants (like fluoxetine and amitriptyline) and antipsychotics (like risperidone and aripiprazole) are metabolized primarily by the CYP2D6 enzyme, these genetic differences can have a major impact on a patient's response to the medication. Pharmacogenomic testing for the CYP2D6 gene can help clinicians determine the appropriate drug and dose to improve treatment efficacy and reduce the risk of adverse reactions. 💊

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