Aripiprazole Therapy and CYP2D6 Genotype

In: Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012.
[updated ].


Aripiprazole (brand names Abilify or Aristada) is an atypical antipsychotic used to manage schizophrenia, bipolar disorder, major depressive disorder, irritability associated with autistic disorder, and in the treatment of Tourette syndrome. (1)

The metabolism and elimination of aripiprazole is mainly mediated through 2 enzymes, CYP2D6 and CYP3A4. Approximately 8% of Caucasians, 3–8% of Black/African Americans and up to 2% of Asians cannot metabolize CYP2D6 substrates and are classified as “poor metabolizers.” (2)

The FDA-approved drug label for aripiprazole states that in CYP2D6 poor metabolizers, half of the usual dose should be administered. In CYP2D6 poor metabolizers who are taking concomitant strong CYP3A4 inhibitors (for example, itraconazole, clarithromycin), a quarter of the usual dose should be used (Table 1) (1). The dosage reduction is the same regardless of the administration route (oral or long-acting injectable). (3)

The Dutch Pharmacogenetics Working group (DPWG) also recommends a reduced dosage for CYP2D6 poor metabolizers, “no more than 10 mg/day or 300 mg/month” (Table 2). No action is recommended for intermediate or ultrarapid metabolizers. While both of these metabolic variations alter the plasma concentrations of aripiprazole, there is no evidence that this increases the risk of reduced effectiveness or risk of side effects. (4)

In contrast to the recommendations by the FDA and DPWG, some recent studies have suggested CYP2D6 intermediate metabolizers may also require a dose decrease, but this was only based on aripiprazole clearance. (5, 6, 7, 8)

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