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

IF 5.9 2区 医学 Q1 PSYCHIATRY
Chun-I Liu, Chih-Min Liu, Huai-Hsuan Chiu, Chia-Chi Chuang, Tzung-Jeng Hwang, Ming H Hsieh, Yi-Ling Chien, Yi-Ting Lin, Ko Yen, Chen-Chung Liu
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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.

在减少抗精神病药剂量以达到最低有效剂量(GARMED)的试验中,通过血清药物水平验证成功的维持治疗。
背景:以往针对缓解型精神病患者进行的抗精神病药物剂量递减试验中,关于复发风险和更好的主观疗效的不一致结果尚未通过治疗药物监测(TDM)得到验证。本研究对一项剂量递减试验的血浆药物浓度进行了检测,该试验显示了在较低抗精神病药物剂量下成功维持治疗的可能性:一项为期两年的开放标签随机前瞻性试验招募了缓解期患者,在指导下进行抗精神病药物减量。在基线、每年和每次减量后采集血液样本。使用LC-MS/MS测定血浆中阿立哌唑/脱氢阿立哌唑的浓度。使用斯皮尔曼相关性检验剂量与血清药物水平之间的关系。以 120 纳克/毫升为标准,比较了高药物水平组和低药物水平组的复发率、整体功能、生活质量和精神病理学:共采集了 126 份血样,排除了 13 份因未坚持服药而采集的血样。剂量与药物浓度之间的相关系数分别为 0.853(阿立哌唑)和 0.864(脱氢阿立哌唑),且除非依从性患者外,剂量与浓度曲线图沿渐减轨迹平行。阿立哌唑的浓度剂量比(17.79 ± 7.23 纳克/毫升/毫克)高于白种人。高剂量组和低剂量组的临床结果没有明显差异。值得注意的是,15 名患者中有 12 名在血浆阿立哌唑浓度达到结论水平时保持了病情缓解:即使考虑到不同种族间药物基因组学的差异,我们的抗精神病药物减量试验中达到的低于预期的剂量也被TDM结果所证实,能够为阿立哌唑治疗的部分患者提供足够的预防效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Psychological Medicine
Psychological Medicine 医学-精神病学
CiteScore
11.30
自引率
4.30%
发文量
711
审稿时长
3-6 weeks
期刊介绍: Now in its fifth decade of publication, Psychological Medicine is a leading international journal in the fields of psychiatry, related aspects of psychology and basic sciences. From 2014, there are 16 issues a year, each featuring original articles reporting key research being undertaken worldwide, together with shorter editorials by distinguished scholars and an important book review section. The journal''s success is clearly demonstrated by a consistently high impact factor.
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