Safety and tolerability of topiramate and N-acetyl cysteine combination in individuals with alcohol use disorder: a 12 week, randomized, double-blind, pilot study.

IF 2.1 4区 医学 Q3 SUBSTANCE ABUSE
Nassima A-D Tiouririne, Tevfik Kalelioglu, Chamindi Seneviratne, Xin-Qun Wang
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引用次数: 0

Abstract

Topiramate (TPM), a GABA/glutamate modulator, has shown positive results for treating alcohol use disorder (AUD), but causes significant cognitive adverse effects. TPM causes cognitive side effects by reducing glutathione levels in the frontal lobe. N-acetyl cysteine (NAC) increases level of intracellular glutathione. We hypothesized that combining NAC with TPM may mitigate the possible cognitive side effects of TPM, as well as working synergistically in reducing alcohol consumption more efficaciously than using TPM alone. A 12-week, double-blind randomized trial assessing the effects of combining NAC (1200 mg/day) with TPM (200 mg/day) vs TPM alone (i) cognitive side effects caused by TPM, (ii) percentage of heavy drinking days (PHDD) and percentage of days abstinent (PDA) using weekly calendar, and (iii) craving outcomes using the obsessive-compulsive drinking scale. Seventeen participants were randomized into the study (nine received TPM + NAC and eight matching TPM + Placebo). Cognitive adverse events were not significantly different between the treatment arms (P = 0.581). There was no difference in PHDD (P = 0.536) and in PDA over the entire study period (P = 0.892). However, both treatment groups at study end, compared with the baseline, significantly reduced their PHDD and increased their PDA. As for cravings: TPM + NAC group has shown higher level in automaticity of drinking (P = 0.029) and interference due to drinking (P = 0.014) subscales compared with the TPM + Placebo group. No difference was observed between groups in terms of Drinking Obsessions and Alcohol Consumption subscales. This pilot study indicates that combining NAC with TPM is overall safe, but the addition of NAC has no significant benefit over placebo in the incidence of TPM-related cognitive impairment, and alcohol drinking. Furthermore, craving outcomes may become worse with the addition of NAC.

托吡酯和 N-乙酰半胱氨酸复方制剂对酒精使用障碍患者的安全性和耐受性:一项为期 12 周的随机双盲试验研究。
托吡酯(TPM)是一种 GABA/谷氨酸调节剂,对治疗酒精使用障碍(AUD)有积极的效果,但会对认知产生明显的不良影响。TPM 会降低额叶中的谷胱甘肽水平,从而对认知产生副作用。N- 乙酰半胱氨酸(NAC)能提高细胞内谷胱甘肽的水平。我们假设,将 NAC 与 TPM 结合使用可减轻 TPM 可能对认知产生的副作用,同时在减少酒精消耗方面发挥协同作用,比单独使用 TPM 更有效。一项为期 12 周的双盲随机试验评估了将 NAC(1200 毫克/天)与 TPM(200 毫克/天)结合使用与单独使用 TPM 相比在以下方面的效果:(i) TPM 引起的认知副作用;(ii) 使用周历计算的大量饮酒天数百分比(PHDD)和戒酒天数百分比(PDA);(iii) 使用强迫性饮酒量表计算的渴求结果。17 名参与者被随机纳入研究(9 人接受 TPM + NAC,8 人接受 TPM + 安慰剂)。治疗组之间的认知不良事件无明显差异(P = 0.581)。在整个研究期间,PHDD(P = 0.536)和 PDA(P = 0.892)没有差异。不过,在研究结束时,与基线相比,两个治疗组的 PHDD 都显著降低,PDA 显著增加。至于渴望:与 TPM + 安慰剂组相比,TPM + NAC 组的饮酒自动性(P = 0.029)和饮酒干扰(P = 0.014)分量表水平更高。在 "饮酒强迫症 "和 "酒精消耗量 "分量表方面,各组之间没有差异。这项试点研究表明,将 NAC 与 TPM 结合使用总体上是安全的,但与安慰剂相比,添加 NAC 对 TPM 相关认知障碍和饮酒的发生率并无明显益处。此外,添加 NAC 后,渴求结果可能会变得更糟。
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
Alcohol and alcoholism
Alcohol and alcoholism 医学-药物滥用
CiteScore
4.70
自引率
3.60%
发文量
62
审稿时长
4-8 weeks
期刊介绍: About the Journal Alcohol and Alcoholism publishes papers on the biomedical, psychological, and sociological aspects of alcoholism and alcohol research, provided that they make a new and significant contribution to knowledge in the field. Papers include new results obtained experimentally, descriptions of new experimental (including clinical) methods of importance to the field of alcohol research and treatment, or new interpretations of existing results. Theoretical contributions are considered equally with papers dealing with experimental work provided that such theoretical contributions are not of a largely speculative or philosophical nature.
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