Abstract

BackgroundIncreased prevalence of depression has been observed among patients with multiple sclerosis (MS) and correlated with the elevated levels of proinflammatory cytokines and the overall deregulation of monoaminergic neurotransmitters that these patients exhibit. Antidepressants have proved effective not only in treating depression comorbid to MS, but also in alleviating numerous MS symptoms and even minimizing stress-related relapses. Therefore, these agents could prospectively prove beneficial as a complementary MS therapy.ObjectiveThis review aims at illustrating the underlying mechanisms involved in the beneficial clinical effects of antidepressants observed in MS patients.MethodsThrough a literature search we screened and comparatively assessed papers on the effects of antidepressant use both in vitro and in vivo MS models, taking into account a number of inclusion and exclusion criteria.Results In vitro studies indicated that antidepressants promote neural and glial cell viability and differentiation, reduce proinflammatory cytokines and exert neuroprotective activity by eliminating axonal loss. In vivo studies confirmed that antidepressants delayed disease onset and alleviated symptoms in Experimental Autoimmune Encephalomyelitis (EAE), the most prevalent animal model of MS. Further, antidepressant agents suppressed inflammation and restrained demyelination by decreasing immune cell infiltration of the CNS.ConclusionAntidepressants were efficient in tackling numerous aspects of disease pathophysiology both in vitro and in vivo models. Given that several antidepressants have already proved effective in clinical trials on MS patients, the inclusion of such agents in the therapeutic arsenal of MS should be seriously considered, following an individualized approach to minimize the adverse events of antidepressants in MS patients.

Highlights

  • Multiple Sclerosis and DepressionMultiple sclerosis (MS) is the most common demyelinating disease of the central nervous system (CNS), involving inflammatory, neurodegenerative and autoimmune patterns in its pathogenesis [1, 2]

  • Along with disease modifying therapies (DMTs), antidepressants are often prescribed to multiple sclerosis (MS) patients,as they are quite prone to manifest symptoms of depression and anxiety [6,7,8]

  • An electronic database literature search was conducted in PubMed, Cochrane and Scopus from inception through 17 April 2021 to provide us with results from in vivo and in vitro studies

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Summary

Introduction

Multiple Sclerosis and DepressionMultiple sclerosis (MS) is the most common demyelinating disease of the central nervous system (CNS), involving inflammatory, neurodegenerative and autoimmune patterns in its pathogenesis [1, 2]. The onset of MS is characterized by a clinical course of relapses and remissions (RRMS) present in almost 90% of MS patients [3] Current therapeutic means such as disease modifying therapies (DMTs) are mostly efficient during this stage, as CNS inflammation is still highly prominent and directly implied in the emergence of relapses [4, 5]. Antidepressants have proved effective in treating depression comorbid to MS, and in alleviating numerous MS symptoms and even minimizing stress-related relapses. These agents could prospectively prove beneficial as a complementary MS therapy

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