Myths vs facts: CYP2D6 and fatigue

The claim that a specific CYP2D6 variant directly causes fatigue is a myth. CYP2D6 is an enzyme primarily involved in metabolizing drugs (e.g., antidepressants, beta-blockers, opioids). Genetic variants determine whether a person is a poor, intermediate, normal, or ultrarapid metabolizer. Fatigue can arise as a side effect of medications whose dosing is not adjusted for the CYP2D6 phenotype – but not from the gene itself. Without drug intake, there is no robust evidence linking CYP2D6 to fatigue. Most consumer DNA tests report only the metabolizer status without clinical guidance. The predictive value is limited because many factors (liver function, drug interactions) matter. Evidence: mechanistic/unclear. Caveat: Do not change medication without consulting a physician.