N‐acetylcysteine for depression and glutamate changes in the left prefrontal cortex in adolescents and young adults at risk for bipolar disorder: A pilot study

Abstract Aims To investigate the mechanism of action of N ‐acetylcysteine (NAC) in depressive symptoms in young individuals at familial risk for bipolar disorder. Methods We conducted an 8‐week open label clinical trial of NAC 2400 mg/days in 15–24 years old depressed offspring of a bipolar I disorder parent, with baseline and endpoint proton magnetic resonance spectroscopy acquired within the left ventrolateral prefrontal cortex (VLPFC). Results Nine participants were enrolled and finished the study. NAC significantly improved depressive and anxiety symptom scores, and clinical global impression (all p < .001). There was a non‐significant reduction in glutamate levels in the left VLPFC. Reduction in depressive symptom scores was positively associated with reduction in glutamate levels in the left VLPFC ( p = .007). Conclusions This pilot study suggests that NAC might be efficacious for depressive symptoms in at‐risk youth, and that its mechanism of action involves the modulation of glutamate in the left VLPFC.