Zonisamide, topiramate, and levetiracetam: efficacy and neuropsychological effects in alcohol use disorders.
Zonisamide, topiramate, and levetiracetam: efficacy and neuropsychological effects in alcohol use disorders.
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DOI：
10.1097/jcp.0000000000000246
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发表时间：
2015-02
影响因子：
2.9
通讯作者：
Richambault C
中科院分区：
文献类型：
--
作者：
Knapp CM;Ciraulo DA;Sarid-Segal O;Richardson MA;Devine E;Streeter CC;Oscar-Berman M;Surprise C;Colaneri L;Putnam M;Waters M;Richambault C
文本中提供了补充数字内容。抗惊厥药托吡酯不仅可以减少酒精依赖（AD）患者的乙醇消耗，还可能产生多种不良事件，包括认知障碍。唑尼沙胺是一种结构相关的抗惊厥药，是治疗 AD 的有前途的药物，并且可能比托吡酯具有更高的耐受性。本研究评估了唑尼沙胺（400 毫克/天）对 AD 受试者饮酒的影响及其神经毒性作用。使用两种比较抗惊厥药物托吡酯（300 mg/d）和左乙拉西坦（2000 mg/d）进行了双盲安慰剂对照临床试验，该药物不会损害认知。研究药物治疗持续 14 周，包括 2 周的减量期。使用简短的行为依从性增强治疗可以促进药物依从性。使用神经心理学测试和 AB 神经毒性量表评估研究药物的神经毒性。与安慰剂相比，唑尼沙胺和托吡酯均显着减少了每日饮酒量、饮酒天数百分比和重度饮酒天数百分比。左乙拉西坦组仅重度饮酒天数百分比显着降低。在研究第 11 周和第 12 周，托吡酯细胞是唯一在神经毒性量表的精神减慢子量表上与安慰剂相比显着增加的组。托吡酯和唑尼沙胺均导致语言流畅性和工作记忆略有下降。这些发现表明唑尼沙胺可能对治疗 AD 有效，其效果大小与托吡酯相似。这两种药物都会产生类似的认知障碍模式，尽管只有托吡酯组报告精神减慢显着增加。
Supplemental digital content is available in the text. The anticonvulsant topiramate not only decreases ethanol consumption in alcohol dependence (AD) but also may produce several adverse events including cognitive impairment. Zonisamide is a structurally related anticonvulsant that is a promising agent for the treatment of AD and may have greater tolerability than topiramate. This study evaluated the effects of zonisamide (400 mg/d) on alcohol consumption and its neurotoxic effects in subjects with AD. A double-blind placebo-controlled clinical trial was conducted using 2 comparator anticonvulsant drugs, topiramate (300 mg/d) and levetiracetam (2000 mg/d), which does not impair cognition. Study medications were administered for 14 weeks, including a 2-week taper period. Medication adherence was facilitated using Brief Behavioral Compliance Enhancement Treatment. The neurotoxicity of the study drugs was assessed using neuropsychological tests and the AB-Neurotoxicity Scale. Compared with placebo, both zonisamide and topiramate produced significant reductions in the drinks consumed per day, percent days drinking, and percent days heavy drinking. Only the percent days heavy drinking was significantly decreased in the levetiracetam group. The topiramate cell was the only group that had a significant increase on the mental slowing subscale of the Neurotoxicity Scale compared with placebo at study weeks 11 and 12. Topiramate and zonisamide both produced modest reductions in verbal fluency and working memory. These findings indicate that zonisamide may have efficacy in the treatment of AD, with effect sizes similar to topiramate. Both of these drugs produced similar patterns of cognitive impairment, although only the topiramate group reported significant increases in mental slowing.