Targeting inflammation in depression: Ketamine as an anti-inflammatory antidepressant in psychiatric emergency

Introduction

Major depressive disorder (MDD) is a common, heterogeneous psychiatric condition with complex, multifactorial aetiology. The Introduction summarises emerging evidence from psychoneuroimmunology that links dysregulated inflammatory processes to MDD and to poorer response to conventional antidepressants. Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, impaired glucocorticoid signalling, peripheral immune activation (for example increased neutrophils, monocytes, cytokines and C‑reactive protein), and inflammatory activation of the kynurenine pathway are described as mechanisms that may drive neuroinflammation, reduce serotonin availability and produce neurotoxic metabolites that contribute to depressive symptoms and suicidality. The resulting picture is of an inflammatory subtype of depression that is over-represented among patients with treatment‑resistant depression (TRD) and active suicidal ideation. This review by Nikkheslat sets out to examine ketamine’s rapid antidepressant properties alongside its effects on peripheral and central inflammation, with the goal of better understanding whether ketamine’s anti‑inflammatory actions contribute to its clinical efficacy in psychiatric emergency settings. The author frames the need for rapid‑acting interventions that can address both severe depressive symptoms and inflammation-driven TRD, emphasising the clinical urgency for alternatives to conventional antidepressants in patients with imminent suicide risk.