Exposure–Response Analysis for Aripiprazole Once‐Monthly in Patients Diagnosed With Bipolar I Disorder

Aripiprazole once‐monthly (AOM) is approved for the maintenance monotherapy treatment of bipolar I disorder (BP‐I) in adults. A previously developed population pharmacokinetic model was validated by applying it to data from patients diagnosed with BP‐I. The model was then used to generate aripiprazole exposures for an exposure‐response model intended to describe the relationship between aripiprazole exposure and time to recurrence of any mood episode in patients with BP‐I. The BP‐I data were best described by a continuous model in which higher aripiprazole exposure was associated with a lower risk of recurrence. For each 1 ng/mL increase in aripiprazole plasma concentration, the predicted hazard for recurrence decreased by 0.34%. An aripiprazole plasma concentration of 95 ng/mL (clinically relevant in schizophrenia) was tested in a separate categorical model and was a significant predictor of time to recurrence ( P = .0270), with a 36% (1.55‐fold) decrease in the predicted risk of recurrence with an aripiprazole concentration of ≥95 versus <95 ng/mL. Plasma aripiprazole concentration was identified as an important predictor of recurrence in patients diagnosed with BP‐I treated with AOM, highlighting the importance of maintenance therapy. A 95 ng/mL threshold is relevant in BP‐I, but with a smaller effect size compared with that in schizophrenia.