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

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.

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).

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.

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.