Recommendation for a Therapeutic Reference Range of Cariprazine-A Short Communication

Background: Therapeutic reference ranges are essential for therapeutic drug monitoring to evaluate results and adjust pharmacotherapy. The measured serum concentrations of cariprazine-treated patients have frequently been found to lie beyond the currently used therapeutic reference range; furthermore, reliable data for establishing evidence-based therapeutic ranges are scarce. The current therapeutic reference ranges have only been estimated; however, real-world data on cariprazine are missing. Individual serum concentrations were analyzed, and the validity of the currently used reference ranges was assessed.

Methods: Serum concentrations of 19 psychiatric patients treated with cariprazine without pharmacokinetic abnormalities were retrospectively analyzed. Only the last measurement per patient was included in the analysis, and patients who underwent a dose adjustment in the subsequent 2 weeks after sampling were excluded (assuming that the target dose and response had been achieved at that time). Serum concentrations were compared with the therapeutic reference range (10-20 ng/mL) of the Arbeitsgemeinschaft für Neuropsychiatrie und Pharmakotherapie consensus guidelines of 2017 and with a recent recommendation for a lower therapeutic reference range (5-15 ng/mL).

Results: The mean serum concentration was 9.1 ± 4.1 SD ng/mL. A total of 47.4% of the values were within the therapeutic reference range of 10-20 ng/mL, and 78.9% fell within the range of 5-15 ng/mL.

Conclusions: These results support previous recommendations for lowering the therapeutic reference range to 5-15 ng/mL. The calculated therapeutic reference range was 5.0-13.2 ng/mL. It may even be potentially lower because clinicians may have tried to titrate the dose to a serum concentration within the current therapeutic reference range of 10-20 ng/mL.