The Anti-inflammatory Effect of the Tricyclic Antidepressant Clomipramine and Its High Penetration in the Brain Might Be Useful to Prevent the Psychiatric Consequences of SARS-CoV-2 Infection

• Published in: Frontiers in pharmacology 2021-03, Vol.12, p.615695-615695
• Main Authors: Nobile, B, Durand, M, Olié, E, Guillaume, S, Molès, J P, Haffen, E, Courtet, P
• Format: Article
• Language: English
• Subjects: antidepressants; clomipramine; COVID-19; Emerging diseases; Human health and pathology; Infectious diseases; inflammation; Life Sciences; Neurobiology; Neurons and Cognition; Pharmaceutical sciences; Pharmacology; psychiatric pathology; SARS-CoV-2
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2021.615695

At the time of writing (December 2020), coronavirus disease 2019 (COVID-19) has already caused more than one million deaths worldwide, and therefore, it is imperative to find effective treatments. The "cytokine storm" induced by Severe Acute Respiratory Syndrome-Coronavirus type 2 (SARS-CoV-2) is a good target to prevent disease worsening, as indicated by the results obtained with tocilizumab and dexamethasone. SARS-CoV-2 can also invade the brain and cause neuro-inflammation with dramatic neurological manifestations, such as viral encephalitis. This could lead to potentially incapacitating long-term consequences, such as the development of psychiatric disorders, as previously observed with SARS-CoV. Several pathways/mechanisms could explain the link between viral infection and development of psychiatric diseases, especially neuro-inflammation induced by SARS-CoV-2. Therefore, it is important to find molecules with anti-inflammatory properties that penetrate easily into the brain. For instance, some antidepressants have anti-inflammatory action and pass easily through the blood brain barrier. Among them, clomipramine has shown very strong anti-inflammatory properties , (animal models) and human studies, especially in the brain. The aim of this review is to discuss the potential application of clomipramine to prevent post-infectious mental complications. Repositioning and testing antidepressants for COVID-19 management could help to reduce peripheral and especially central inflammation and to prevent the acute and particularly the long-term consequences of SARS-CoV-2 infection.