Department of Biomedicine, Pharmacology and Therapeutics Unit, Faculty of Medicine, University of Porto, Porto, Portugal.
Department of Psychiatry and Mental Health, University Hospital Center of São João, Porto, Portugal.
Eur J Clin Pharmacol. 2021 Nov;77(11):1623-1637. doi: 10.1007/s00228-021-03161-6. Epub 2021 Jun 7.
Trazodone is a widely used antidepressant that is also useful in the control of agitation and insomnia in Alzheimer's disease. This drug is now recognized as having a new mechanism of action, an effect on the unfolded protein response (UPR) pathway, restoring protein translation and slowing neurodegenerative progression in mice. This mechanism may have a role in dementia-modifying treatment. To explore the effects of trazodone on human cognition and to search for clinical evidence of its putative benefits in human neurodegenerative diseases, a systematic review was conducted for studies that evaluated the effect of a minimum dose of 25 mg of trazodone daily, for at least 1 week, on cognition in adult humans. The search was run in MEDLINE, Web of Science, and CENTRAL from the Cochrane databases, yielding a total of 16 studies after selection. Overall, seven studies showed no effect of trazodone on cognition, five showed a beneficial effect by improving or reducing cognitive decline, and four evidenced impaired cognitive function. Our analysis highlights the possibility of a dose-independent dual effect of trazodone on human cognition, with acute utilization associated with impaired cognitive function and long-term use with preventing cognitive deterioration. There was no clinical evidence that trazodone could be used as a specific treatment of neurodegenerative diseases. Future studies should explore the role of trazodone in the UPR pathway and the implications in neurodegenerative diseases in humans.
曲唑酮是一种广泛使用的抗抑郁药，在控制阿尔茨海默病的激越和失眠方面也很有用。该药现在被认为具有一种新的作用机制，即对未折叠蛋白反应（UPR）途径的作用，可恢复蛋白质翻译并减缓小鼠的神经退行性进展。这种机制可能在改变痴呆症的治疗中有作用。为了探索曲唑酮对人类认知的影响，并寻找其在人类神经退行性疾病中潜在益处的临床证据，对评估至少每天 25 毫克曲唑酮、至少 1 周对成人认知影响的研究进行了系统评价。检索在 MEDLINE、Web of Science 和 Cochrane 数据库的 CENTRAL 中进行，选择后共获得 16 项研究。总的来说，有 7 项研究表明曲唑酮对认知没有影响，5 项研究表明通过改善或减少认知下降有有益的作用，4 项研究表明认知功能受损。我们的分析强调了曲唑酮对人类认知可能存在剂量无关的双重作用的可能性，急性使用与认知功能受损有关，而长期使用则可预防认知恶化。没有临床证据表明曲唑酮可用于治疗神经退行性疾病。未来的研究应探讨曲唑酮在 UPR 途径中的作用及其对人类神经退行性疾病的影响。
