Castelnovo Anna, Miano Silvia, Ferri Raffaele, Raggi Alberto, Maestri Michelangelo, Bottasini Valentina, Anelli Matteo, Zucconi Marco, Castronovo Vincenza, Ferini-Strambi Luigi, Manconi Mauro
Sleep Medicine Unit, Neurocenter of Southern Switzerland, Ospedale Civico, Civic Hospital of Lugano, Via Tesserete 46, 6900 Lugano, Switzerland.
Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6900 Lugano, Switzerland.
Brain Sci. 2023 Feb 21;13(3):375. doi: 10.3390/brainsci13030375.
Benzodiazepine (BDZ) misuse is a growing health problem, with 1-2% of patients under BDZ treatment meeting the criteria for use disorder or dependence. Although BDZ addiction potential has been known for decades, much remains unknown its effects on brain functions. The aim of this study was to assess the neuropsychological and neurophysiological profile of a group of chronic insomniacs taking long-term high doses of benzodiazepine. We recruited 17 consecutive patients admitted to our third-level Sleep Medicine Unit for drug discontinuation (7 males, mean age 49.2 ± 11.2 years, mean education 13.7 ± 3.9 years, mean daily diazepam-equivalent BDZ: 238.1 ± 84.5 mg) and 17 gender/age-matched healthy controls (7 males, mean age 46.8 ± 14.1 years, mean education 13.5 ± 4.5 years). We performed a full neuropsychological evaluation of all subjects and recorded their scalp event-related potentials (Mismatch-Passive Oddball-Paradigm and Active Oddball P300 Paradigm). Patients with chronic insomnia and BDZ use disorder showed a profound frontal lobe executive dysfunction with significant impairment in the cognitive flexibility domain, in face of a preserved working, short and long-term memory. In patients, P300 amplitude tended to be smaller, mainly over the frontal regions, compared to controls. BDZ use disorder has a severe cognitive impact on chronic insomnia patients. Long-term high-dose BDZ intake should be carefully evaluated and managed by clinicians in this specific patient population, especially in relation to risky activities.
苯二氮䓬(BDZ)滥用是一个日益严重的健康问题,接受BDZ治疗的患者中有1%-2%符合使用障碍或依赖的标准。尽管BDZ的成瘾潜力在几十年前就已为人所知,但其对脑功能的影响仍有很多未知之处。本研究的目的是评估一组长期高剂量服用苯二氮䓬的慢性失眠症患者的神经心理学和神经生理学特征。我们连续招募了17名因停药而入住我院三级睡眠医学科的患者(7名男性,平均年龄49.2±11.2岁,平均受教育年限13.7±3.9年,平均每日地西泮等效BDZ剂量:238.1±84.5mg)和17名性别/年龄匹配的健康对照者(7名男性,平均年龄46.8±14.1岁,平均受教育年限13.5±4.5年)。我们对所有受试者进行了全面的神经心理学评估,并记录了他们的头皮事件相关电位(失配-被动Oddball范式和主动Oddball P300范式)。患有慢性失眠和BDZ使用障碍的患者表现出严重的额叶执行功能障碍,在认知灵活性领域有显著损害,而工作记忆、短期和长期记忆则保持完好。与对照组相比,患者的P300波幅往往较小,主要出现在额叶区域。BDZ使用障碍对慢性失眠患者有严重的认知影响。临床医生应仔细评估和管理这一特定患者群体长期高剂量服用BDZ的情况,尤其是与危险活动相关的情况。