Ural Federal University, Ekaterinburg, Russia.
Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia.
Eur J Pharmacol. 2018 Jun 15;829:129-140. doi: 10.1016/j.ejphar.2018.04.003. Epub 2018 Apr 5.
Antidepressant drugs are currently one of the most prescribed medications. In addition to treatment resistance and side effects of antidepressants, their clinical use is further complicated by antidepressant discontinuation syndrome (ADS). ADS is a common problem in patients following the interruption, dose reduction, or discontinuation of antidepressant drugs. Clinically, ADS resembles a classical drug withdrawal syndrome, albeit differing from it because antidepressants generally do not induce addiction. The growing clinical importance and prevalence of ADS necessitate novel experimental (animal) models of this disorder. Currently available preclinical models of ADS are mainly rodent-based, and study mostly serotonergic antidepressants and their combinations. Here, we systematically assess clinical ADS symptoms and discuss current trends and challenges in the field of experimental (animal) models of ADS. We also outline basic mechanisms underlying ADS pathobiology, evaluate its genetic, pharmacological and environmental determinants, and emphasize how using animal models may help generate important translational insights into human ADS condition, its prevention and therapy.
抗抑郁药目前是最常被开的药物之一。除了抗抑郁药的治疗抵抗和副作用，它们的临床使用还因抗抑郁药停药综合征（ADS）而进一步复杂化。ADS 是患者在中断、减少剂量或停止使用抗抑郁药后常见的问题。临床上，ADS 类似于经典的药物戒断综合征，尽管与后者不同，因为抗抑郁药通常不会引起成瘾。ADS 的临床重要性和普遍性不断增加，需要对这种疾病进行新的实验（动物）模型研究。目前可用的 ADS 临床前模型主要基于啮齿动物，并且主要研究 5-羟色胺能抗抑郁药及其组合。在这里，我们系统地评估了临床 ADS 症状，并讨论了 ADS 实验（动物）模型领域的当前趋势和挑战。我们还概述了 ADS 病理生物学的基本机制，评估了其遗传、药理学和环境决定因素，并强调了使用动物模型如何有助于为人类 ADS 状况、预防和治疗提供重要的转化见解。
