Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (FIOCRUZ-PE), Recife, PE, Brazil; Graduate Program in Biosciences and Biotechnology for Health (PPGBBS), Aggeu Magalhães Institute (IAM), Recife, PE, Brazil.
Neuropsychopharmacology Laboratory, Drug Research and Development Center, Faculty of Medicine, Universidade Federal do Ceará, Fortaleza, CE, Brazil.
J Affect Disord. 2020 Mar 1;264:138-149. doi: 10.1016/j.jad.2019.11.114. Epub 2019 Nov 30.
Phosphodiesterase-5 inhibitors (PDE5Is) are used to treat erectile dysfunction (ED). Recently, the antidepressant-like effect of PDE5Is was demonstrated in animal models of depression. In clinical settings, PDE5Is were studied only for ED associated depression. Hence, there are no studies evaluating the effects of PDE5Is for the treatment of major depressive disorder (MDD) without ED. In this review article, we aimed to discuss the use of PDE5Is in the context of MDD, highlighting the roles of PDE genes in the development of MDD, the potential mechanisms by which PDE5Is can be beneficial for MDD and the potentials and limitations of PDE5Is repurposing to treat MDD.
We used PubMed (MEDLINE) database to collect the studies cited in this review. Papers written in English language regardless the year of publication were selected.
A few preclinical studies support the antidepressant-like activity of PDE5Is. Clinical studies in men with ED and depression suggest that PDE5Is improve depressive symptoms. No clinical studies were conducted in subjects suffering from depression without ED. Antidepressant effect of PDE5Is may be explained by multiple mechanisms including inhibition of brain inflammation and modulation of neuroplasticity.
The low number of preclinical and absence of clinical studies to support the antidepressant effect of PDE5Is.
No clinical trial was conducted to date evaluating PDE5Is in depressed patients without ED. PDE5Is' anti-inflammatory and neuroplasticity mechanisms may justify the potential antidepressant effect of these drugs. Despite this, clinical trials evaluating their efficacy in depressed patients need to be conducted.
磷酸二酯酶 5 抑制剂（PDE5Is）被用于治疗勃起功能障碍（ED）。最近，PDE5Is 在抑郁动物模型中表现出抗抑郁作用。在临床环境中，仅研究了 PDE5Is 治疗与 ED 相关的抑郁症。因此，尚无研究评估 PDE5Is 治疗无 ED 的重度抑郁症（MDD）的效果。在这篇综述文章中，我们旨在讨论 PDE5Is 在 MDD 背景下的应用，强调 PDE 基因在 MDD 发展中的作用，PDE5Is 可能对 MDD 有益的潜在机制以及 PDE5Is 重新用于治疗 MDD 的潜力和局限性。
我们使用 PubMed（MEDLINE）数据库收集了本综述中引用的研究。选择了不论出版年份均以英文书写的论文。
一些临床前研究支持 PDE5Is 的抗抑郁样活性。患有 ED 和抑郁症的男性的临床研究表明，PDE5Is 可改善抑郁症状。没有针对无 ED 的抑郁患者进行临床研究。PDE5Is 的抗抑郁作用可能通过多种机制来解释，包括抑制脑炎症和调节神经可塑性。
支持 PDE5Is 抗抑郁作用的临床前和临床研究数量较少。
迄今为止，尚无临床试验评估 PDE5Is 在无 ED 的抑郁患者中的作用。PDE5Is 的抗炎和神经可塑性机制可能证明这些药物具有潜在的抗抑郁作用。尽管如此，仍需要进行评估其在抑郁患者中的疗效的临床试验。
