Current Evidence of Acetyl-L-Carnitine Use in Mood Disorders-: A Systematic Review and Meta-Analysis

Acetyl-l-carnitine (ALC) is increasingly recognized for its potential psychopharmacological mechanism and role in the treatment of mood disorders, particularly major depressive disorder (MDD) and bipolar disorder (BD). Emerging evidence suggests that ALC levels are reduced in individuals with MDD, and this deficiency may contribute to depressive symptoms through disruptions in mitochondrial fatty acid transport, neuroplasticity, and neurotransmission. This review synthesizes findings from randomized controlled trials, open-label studies, and observational research examining ALC use and clinical outcomes in adults treated with ALC in MDD and BD. A systematic review (n=15) and meta-analysis (n=10) studies (14 randomized controlled trials [RCTs] and 1 open label) involving 809 participants (treatment group: 392; comparator group: 417) revealed that ALC significantly reduces depressive symptoms compared to placebo, with comparable efficacy to standard antidepressants and fewer adverse effects. Subgroup analyses suggest enhanced benefits in older adults and those with treatment-resistant depression. These findings support the potential of ALC as both a biomarker and a therapeutic agent in mood disorders. Further large-scale, longitudinal studies are needed to clarify its clinical utility and mechanistic pathways in mood disorders.