Phosphodiesterase-5 inhibitors: Shedding new light on the darkness of depression?
Depression therapy
Drug repurposing in depression
Major depressive disorder
PDE
Phosphodiesterase-5
Phosphodiesterase-5 inhibitors
Journal
Journal of affective disorders
ISSN: 1573-2517
Titre abrégé: J Affect Disord
Pays: Netherlands
ID NLM: 7906073
Informations de publication
Date de publication:
01 03 2020
01 03 2020
Historique:
received:
24
07
2019
revised:
22
11
2019
accepted:
26
11
2019
entrez:
15
2
2020
pubmed:
15
2
2020
medline:
16
2
2021
Statut:
ppublish
Résumé
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.
Sections du résumé
BACKGROUND
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.
METHODS
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.
RESULTS
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.
LIMITATIONS
The low number of preclinical and absence of clinical studies to support the antidepressant effect of PDE5Is.
CONCLUSIONS
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.
Identifiants
pubmed: 32056743
pii: S0165-0327(19)31954-8
doi: 10.1016/j.jad.2019.11.114
pii:
doi:
Substances chimiques
Phosphodiesterase 5 Inhibitors
0
Cyclic Nucleotide Phosphodiesterases, Type 5
EC 3.1.4.35
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
138-149Informations de copyright
Copyright © 2019. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.