Low-dose colchicine: a potential augmenting agent in the treatment of refractory mood disorders.

Treatment-resistant mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD), remain a significant clinical challenge. A confluence of emerging evidence implicates chronic low-grade inflammation in the pathophysiology of at least a subset of mood disorders, potentially mediating their poor response to traditional therapies. Colchicine, a well-established anti-inflammatory agent used in gout and more recently (at low dose) cardiovascular disease, inhibits microtubule polymerisation and suppresses NLRP3 inflammasome activation. Recent advances in immunopsychiatry suggest NLRP3-mediated pathways are key mediators of mood pathology. This hypothesis-generating paper explores how low-dose colchicine may plausibly serve as a novel augmenting agent in refractory mood disorders by targeting these neuroinflammatory pathways. We present mechanistic rationale, integrate preclinical and translational evidence, review long-term safety data and outline biomarker-guided clinical trial proposals.