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

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.