Impact of CYP2D6 genotype on fluoxetine exposure

Fluoxetine, like other selective serotonin reuptake inhibitors (SSRIs), is commonly prescribed for patients with depression, anxiety, and obsessive‐compulsive disorder. Cytochrome P‐450 2D6 (CYP2D6) is the primary isoenzyme responsible for the metabolism of fluoxetine to the active metabolite norfluoxetine. As a result of genetic inheritance of normal versus abnormal variants of the gene that controls activity of the CYP2D6 isoenzyme, CYP2D6 activity is significantly different among four phenotypes of individuals: ultra‐rapid metabolizers (UM) with high enzyme activity, normal metabolizers (NM) with normal enzyme activity, intermediate metabolizers (IM) with below‐normal enzyme activity, and poor metabolizers (PM) with very low or complete absence of enzyme activity.