Effects of paroxetine on aripiprazole and individualized administration in depressed patients based on model-informed precision dosing

doi:10.5498/wjp.117458

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World Journal of Psychiatry

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2220-3206

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Psychiatry. Jul 19, 2026; 16(7): 117458
Published online Jul 19, 2026. doi: 10.5498/wjp.117458

Effects of paroxetine on aripiprazole and individualized administration in depressed patients based on model-informed precision dosing

Ying-Wei Jin, Yue Zhang, Jie Wang, Lei Jiang, Su-Mei He, Cun Zhang, Dong-Dong Wang

Ying-Wei Jin, Department of Pharmacy, The Suqian Clinical College of Xuzhou Medical University, Suqian 223800, Jiangsu Province, China

Yue Zhang, Jie Wang, Lei Jiang, Dong-Dong Wang, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy and School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China

Su-Mei He, Department of Pharmacy, Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou 215153, Jiangsu Province, China

Cun Zhang, Department of Pharmacy, Xuzhou Oriental Hospital Affiliated to Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China

Co-first authors: Ying-Wei Jin and Yue Zhang.

Co-corresponding authors: Su-Mei He and Dong-Dong Wang.

Author contributions: Jin YW and Zhang Y analyzed the data and wrote the manuscript, they contributed equally to this article and are the co-first authors of this manuscript; Jin YW, Zhang Y, Wang J, Jiang L, He SM, Zhang C, and Wang DD performed the research; He SM and Wang DD designed the study, they contributed equally to this article, they are the co-corresponding authors of this manuscript; and all the authors contributed to the interpretation of the results, manuscript revision, and approved the final version of the manuscript.

Supported by the Science and Technology Program of Xuzhou, No. KC25105; Basic Science (Natural Science) Project of Higher Education Institutions in Jiangsu Province, No. 25KJD310004; Suzhou Applied Basic Research Science and Technology Innovation Project, No. SYWD2024258; Xuzhou Medical University Research Project on Reform of Postgraduate Education and Teaching, No. XYJGKT202506; and Xuzhou Medical University Teaching Academic Research Topics, No. 2024ZDKT02-Y03.

Institutional review board statement: This study was approved by the Medical Ethics Committee of Xuzhou Oriental Hospital Affiliated to Xuzhou Medical University, approval No. 20220725011.

Informed consent statement: The informed consent was waived by the Institutional Review Board.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.

Data sharing statement: Data used in this study can be available from the corresponding author upon request.

Corresponding author: Dong-Dong Wang, PhD, Adjunct Professor, Principal Investigator, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy and School of Pharmacy, Xuzhou Medical University, No. 209 Tongshan Road, Xuzhou 221004, Jiangsu Province, China. 13852029591@163.com

Received: December 8, 2025
Revised: January 19, 2026
Accepted: March 5, 2026
Published online: July 19, 2026
Processing time: 202 Days and 19.8 Hours

Abstract

BACKGROUND

Aripiprazole can be used as an adjunctive treatment for depression, however, the drug-drug interactions (DDI) and initial dosage of aripiprazole in depressed patients remains unclear.

AIM

To explore DDI and optimal initial dosage of aripiprazole in depressed patients.

METHODS

Eighty- seven depressed patients were included and model-informed precision dosing was used to analyze potential DDI and recommend optimal initial dosage regimen of aripiprazole in depressed patients.

RESULTS

In the final aripiprazole model-informed precision dosing model, weight and paroxetine hydrochloride tablet influenced the clearance rate of aripiprazole in depressed patients, and aripiprazole clearance rate decreased 53.3% in depressed patients taking paroxetine hydrochloride tablet. Further, for depressed patients without paroxetine hydrochloride tablet, 0.5 mg/kg and 0.4 mg/kg aripiprazole were recommended to 40-80 kg depressed patients and 80-120 kg depressed patients, respectively. For depressed patients with paroxetine hydrochloride tablet, 0.3 mg/kg aripiprazole was recommended to 40-120 kg depressed patients.

CONCLUSION

Paroxetine hydrochloride reduces the clearance rate of aripiprazole and, when taking paroxetine hydrochloride tablet simultaneously, the dosage of aripiprazole should be reduced in depressed patients.

Keywords: Drug-drug interactions; Individualized administration; Aripiprazole; Depressed patients; Model-informed precision dosing

Core Tip: This study explores drug-drug interactions and optimal initial dosage of aripiprazole in depressed patients based on model-informed precision dosing. When depressed patients take paroxetine hydrochloride tablet at the same time, it will reduce the clearance rate of aripiprazole. Aripiprazole clearance rate decreases 53.3% in depressed patients taking paroxetine hydrochloride tablet. Therefore, when taking paroxetine hydrochloride tablet simultaneously, the dosage of aripiprazole should be reduced in depressed patients.