Aripiprazole Adjunctive to Antidepressant Therapy

To the Editor: We would like to clarify the dosing for aripiprazole adjunctive to antidepressant therapy in patients with major depressive disorder as suggested in the American Psychiatric Association (APA) Practice Guideline for the Treatment of Patients With Major Depressive Disorder (1), published as a supplement to the October 2010 issue of the Journal. The medication product information states that for adjunctive treatment of major depressive disorder, aripiprazole should be initiated at 2–5 mg per day, with a target dose of 5–10 mg per day and a maximum dose of 15 mg/day. Dose adjustments of up to 5 mg/day should occur gradually, at intervals of no less than 1 week, and no dosage adjustments are needed for the current antidepressant.

The current guidelines state that adjunctive aripiprazole is typically initiated at 2.5–5 mg/day and titrated upward as tolerated to a maximum dose of 30 mg/day. In the study cited for this recommendation (2), adjunctive aripiprazole was initiated at 5 mg/day and, if tolerability permitted, increased to the target dose of 10 mg/day at the start of week 2. The dose could be reduced to 2 mg if necessary for tolerability. The maximal dose in the study was 20 mg/day. There is no recommendation in the product information for a maximum dose of 30 mg/day for aripiprazole adjunctive to antidepressants. When making treatment decisions, it is important to consider the doses that were studied in three large, placebo-controlled, double-blind clinical trials for aripiprazole adjunctive to antidepressants in the treatment of major depressive disorder (2–4), and these data provide the foundation for the recommended doses in the product information.