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An investigation into the neurobiological properties of tianeptine (McEwen et al, 2010) concludes : “Converging lines of evidences demonstrate actions of tianeptine on the glutamatergic system, and therefore offer new insights into how tianeptine may be useful in the treatment of depressive disorders.” Intriguingly the antidepressant and anxiolytic effects (plus protection against cognitive defects) appear to be due to its ability to protect the brain (particularly in the amygdala and hippocampus) against stress induced glutamate excitotoxicity : “A modification of glutamatergic mechanisms by tianeptine may therefore be implicated in its ability to oppose the negative influence of chronic stress upon hippocampal neurogenesis, cell proliferation, and dendritic remodeling , processes profoundly disrupted in depressive states” Similarly ketamine has a rapid and sustained antidepressant effect through modulation of glutamate neurotransmission as does the novel compound GLYX-13 which has the same beneficial effects without inducing dissociative symptoms usually associated with schizophrenia (Burgdorf et al, 2012) Mental Fatigue Wrapped up within the vague notion of ‘fatigue’ in ME/CFS is the rather more specific description contained in the Canadian Consensus Criteria of a “Low threshold of physical and mental fatigability (lack of stamina)”

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