Dose-response analysis of aripiprazole in patients with schizophrenia in Taiwan

Abstract

Background: Aripiprazole is a third-generation antipsychotic agent with acceptable efficacy and a good safety profile. Previous studies have indicated the therapeutic serum concentration of aripiprazole to be 100 to 350 ng/ml; however, most of these studies examined a Western population. Patients with schizophrenia from Tungs’ Taichung MetroHarbor Hospital in central Taiwan were recruited to analyze the dose–response relationship of aripiprazole in the Chinese population. Objective: We aimed to investigate whether a serum concentration of aripiprazole higher than the current suggested range leads to higher response rates. Design: A prospective cohort study was designed to investigate the response rates in different studied cohorts grouped by serum concentration of aripiprazole. Data Sources and Methods: Data of 64 patients who presented to a single medical center in central Taiwan and who received therapeutic drug monitoring (TDM) were obtained. Serum concentrations of aripiprazole were correlated with the clinical response of patients by using the Clinical Global Impressions (CGI) scores. Results: The mean concentration of aripiprazole was 432.1 ± 275.1 ng/ml in the study cohort. Among the much-improved patients, the mean serum concentration of aripiprazole was 494 ± 273 ng/ml (25th–75th percentiles 264–666 ng/ml), which was higher than the current recommended therapeutic target of 100–350 ng/ml for aripiprazole. The response rate in the severe group (baseline CGI score of 6 or 7) was significantly higher than in the moderate group (baseline CGI score of 4 or 5; 86.7% versus 55.9%, p = 0.007). Conclusion: A significantly higher response rate was observed in the study cohort with serum aripiprazole concentrations over 300 ng/ml. Therefore, dosing higher than the current recommended range may potentially improve the treatment efficacy in the Chinese population. Because the serum concentration varies among patients due to multiple intrinsic and extrinsic factors, TDM, especially in outpatients, is recommended if the clinical response is limited.

Therapeutic Drug Monitoring in Psychiatry: Enhancing Treatment Precision and Patient Outcomes

“…In regard to "third generation" antipsychotics (TGAs), and in particular aripiprazole (level 2 of recommendation), the established recommended therapeutic range is 120-270 ng/mL (180-380 ng/mL for its active metabolite dehydroaripiprazole), even though the relationship between concentration and efficacy, as well as the correlation between concentration and adverse effects, remains unclear [132]. However, a recent study by Tien and colleagues, based on a Chinese population of patients taking aripiprazole, found a higher response rate in patients with a serum concentration over 300 ng/mL, suggesting that increasing aripiprazole concentrations above the current recommended range could potentially improve patients' response to treatment [133].…”