Antidepressants on Multiple Sclerosis: A Review of In Vitro and In Vivo Models

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.ResultsIn 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.

Serotonergic drug repurposing in multiple sclerosis: A new possibility for disease-modifying therapy

“…In addition, there is no data on the effect of treatment with fluoxetine on immune response in patients with MS. Nevertheless, the results of our study correspond to the data from other studies in vivo and in vitro, confirming the anti-inflammatory effect of fluoxetine in autoimmune diseases (3,5). In particular, similar effects of treatment with SSRIs was observed in rheumatoid arthritis and psoriasis (3).…”

“…In this regard, much attention is drawn to the potential ability to inhibit neuroinflammation by treatment with serotonergic drugs. In vitro and in vivo studies have shown that selective serotonin reuptake inhibitors (SSRIs) can reduce EAE and MS severity (5). However, the immune mechanism of the anti-inflammatory effect of SSRIs on MS pathogenesis needs further study.…”

Psychometric Properties of the HADS Measure of Anxiety and Depression Among Multiple Sclerosis Patients in Croatia

“…The results of a study in the United States ( Boeschoten et al, 2017 ) revealed 20.6% of MS patients suffered from depression. A significant factor responsible for MS relapses is stressful life events ( Brown et al, 2005 ; Stamoula et al, 2021 ). From a clinical point of view, it is therefore recommended to monitor psychological constructs such as depression, anxiety, and stress in pwMS ( Glaser et al, 2019 ).…”

The Dual Role of the β2-Adrenoreceptor in the Modulation of IL-17 and IFN-γ Production by T Cells in Multiple Sclerosis

“…Furthermore, the ability of immune cells to produce catecholamines has been demonstrated, suggesting the possible autoregulation by activating dopaminergic and noradrenergic receptors. Finally, biogenic amines’ involvement in MS pathogenesis is confirmed by the influence of serotoninergic and dopaminergic drugs on experimental encephalomyelitis (EAE) and MS course and the impact of disease-modifying therapeutics (DMT) of MS on the production of catecholamines by the immune cells [ 2 , 3 , 4 ]. In line with these data, the repurposing of dopaminergic, noradrenergic, and serotoninergic therapeutics as additional pathogenetic treatments in MS is discussed [ 3 , 4 ].…”