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A wake-up call: Sleep physiology and related translational discrepancies in studies of rapid-acting antidepressants
Progress in Neurobiology ( IF 6.7 ) Pub Date : 2021-08-14 , DOI: 10.1016/j.pneurobio.2021.102140
Okko Alitalo 1 , Roosa Saarreharju 1 , Ioline D Henter 2 , Carlos A Zarate 2 , Samuel Kohtala 3 , Tomi Rantamäki 1
Affiliation  

Depression is frequently associated with sleep problems, and clinical improvement often coincides with the normalization of sleep architecture and realignment of circadian rhythm. The effectiveness of treatments targeting sleep in depressed patients, such as sleep deprivation, further demonstrates the confluence of sleep and mood. Moreover, recent studies showing that the rapid-acting antidepressant ketamine influences processes related to sleep-wake neurobiology have led to novel hypotheses explaining rapid and sustained antidepressant effects. Despite the available evidence, studies addressing ketamine’s antidepressant effects have focused on pharmacology and often overlooked the role of physiology. To explore this discrepancy in research on rapid-acting antidepressants, we examined articles published between 2009–2019. A keyword search algorithm indicated that vast majority of the articles completely ignored sleep. Out of the 100 most frequently cited preclinical and clinical research papers, 89 % and 71 %, respectively, did not mention sleep at all. Furthermore, only a handful of these articles disclosed key experimental variables, such as the times of treatment administration or behavioral testing, let alone considered the potential association between these variables and experimental observations. Notably, in preclinical studies, treatments were preferentially administered during the inactive period, which is the polar opposite of clinical practice and research. We discuss the potential impact of this practice on the results in the field. Our hope is that this perspective will serve as a wake-up call to (re)-examine rapid-acting antidepressant effects with more appreciation for the role of sleep and chronobiology.



中文翻译:

敲响警钟:速效抗抑郁药研究中的睡眠生理学和相关转化差异

抑郁症通常与睡眠问题有关,临床改善通常与睡眠结构的正常化和昼夜节律的重新调整相吻合。针对抑郁症患者睡眠的治疗(例如睡眠剥夺)的有效性进一步证明了睡眠和情绪的融合。此外,最近的研究表明速效抗抑郁药氯胺酮会影响与睡眠-觉醒神经生物学相关的过程,这导致了解释快速和持续抗抑郁作用的新假设。尽管有可用的证据,解决氯胺酮抗抑郁作用的研究都集中在药理学上,而常常忽视生理学的作用。为了探索速效抗抑郁药研究中的这种差异,我们检查了 2009-2019 年间发表的文章。关键字搜索算法表明,绝大多数文章完全忽略了睡眠。在 100 篇最常被引用的临床前和临床研究论文中,分别有 89% 和 71% 根本没有提到睡眠。此外,这些文章中只有少数披露了关键的实验变量,例如治疗管理或行为测试的时间,更不用说考虑这些变量与实验观察之间的潜在关联了。值得注意的是,在临床前研究中,治疗优先在非活动期进行,这与临床实践和研究截然相反。我们讨论了这种做法对该领域结果的潜在影响。

更新日期:2021-09-15
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