在一项旨在达到最低有效剂量的抗精神病药物减量指导试验（GARMED）中，通过血清药物水平验证维持治疗的成功情况。

Verification of successful maintenance by serum drug level during a guided antipsychotic reduction to reach minimum effective dose (GARMED) trial.

作者信息

Liu Chun-I, Liu Chih-Min, Chiu Huai-Hsuan, Chuang Chia-Chi, Hwang Tzung-Jeng, Hsieh Ming H, Chien Yi-Ling, Lin Yi-Ting, Yen Ko, Liu Chen-Chung

机构信息

Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.

Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwan.

出版信息

Psychol Med. 2024 Sep 26;54(14):1-11. doi: 10.1017/S0033291724002356.

DOI:10.1017/S0033291724002356

PMID:39324399

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11578910/

Abstract

BACKGROUND

Inconsistent results regarding the risk of relapse and better subjective outcomes of previous antipsychotic dose reduction trials in patients with remitted psychosis have not been verified using therapeutic drug monitoring (TDM). This study examined plasma drug concentrations of a dose-tapering trial which exhibited the potential of successful maintenance under lower antipsychotic dosages.

METHODS

A 2-year open-label randomized prospective trial recruited remitted patients to undergo guided antipsychotic tapering. Blood samples were collected at baseline, annually, and after each dose reduction. Plasma aripiprazole/dehydroaripiprazole concentrations were determined using LC-MS/MS. The relationship between the dose and serum drug levels was examined using Spearman's correlation. Divided at 120 ng/mL, relapse rate, global function, quality of life, and psychopathology were compared between high- and low- drug level groups.

RESULTS

A total of 126 blood samples were collected, after excluding13 samples due of non-adherence. The correlation coefficients between dosage and drug level were 0.853 (aripiprazole) and 0.864 (dehydroaripiprazole), and the dose and concentration plots were parallel along the tapering trajectories, except patients with non-adherence. The concentration-to-dose ratio of aripiprazole in this cohort, 17.79 ± 7.23 ng/mL/mg, was higher than that in Caucasian populations. No significant differences were observed in the clinical outcomes between the high- and low-level groups. Remarkably, 12 of 15 patients maintained remission at plasma aripiprazole concentrations of <120 ng/mL.

CONCLUSIONS

The lower-than-expected doses reached in our antipsychotic tapering trial were substantiated to provide adequate prophylactic effects by TDM results in a subset of patients treated with aripiprazole, even considering the differences in pharmacogenomics between ethnicities.

摘要

背景

既往针对缓解期精神病患者进行的抗精神病药物减量试验，在复发风险和更好的主观疗效方面结果不一致，尚未通过治疗药物监测（TDM）进行验证。本研究检测了一项剂量递减试验的血浆药物浓度，该试验显示出在较低抗精神病药物剂量下成功维持治疗的潜力。

方法

一项为期2年的开放标签随机前瞻性试验招募了缓解期患者，进行指导性抗精神病药物减量。在基线、每年以及每次减量后采集血样。使用液相色谱-串联质谱法（LC-MS/MS）测定血浆阿立哌唑/去氢阿立哌唑浓度。使用Spearman相关性分析剂量与血清药物水平之间的关系。以120 ng/mL为界进行划分，比较高药物水平组和低药物水平组之间的复发率、整体功能、生活质量和精神病理学情况。

结果

共采集了126份血样，排除13份因未依从导致的样本。剂量与药物水平之间的相关系数分别为阿立哌唑0.853、去氢阿立哌唑0.864，除未依从患者外，剂量-浓度曲线在减量过程中呈平行状态。该队列中阿立哌唑的浓度-剂量比为17.79±7.23 ng/mL/mg，高于白种人群。高低水平组之间的临床结局未观察到显著差异。值得注意的是，15例患者中有12例在血浆阿立哌唑浓度<120 ng/mL时维持缓解状态。