Ketamine is a new, potent and rapid-acting antidepressant approved for therapy of treatment-resistant depression, which has a different mechanism of action than currently-available antidepressant therapies. It owes its uniquely potent antidepressant properties to a complex mechanism of action, which currently remains unclear. However, it is thought that it acts by modulating the functioning of the glutamatergic system, which plays an important role in the process of neuroplasticity associated with depression. However, preclinical and clinical studies have also found ketamine to reduce inflammation, either directly or indirectly (by activating neuroprotective branches of the kynurenine pathway), among patients exhibiting higher levels of inflammation. Inflammation and immune system activation are believed to play key roles in the development and course of depression. Therefore, the present work examines the role of the antidepressant effect of ketamine and its anti-inflammatory properties in the treatment of depression. SIGNIFICANCE STATEMENT: The present work examines the relationship between the antidepressant effect of ketamine and its anti-inflammatory properties, and the resulting benefits in treatment-resistant depression (TRD). The antidepressant mechanism of ketamine remains unclear, and there is an urgent need to develop new therapeutic strategies for treatment of depression, particularly TRD.
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