Glutathione is the brains principal antioxidant. There is evidence of oxidative stress and alterations of free radical defences in bipolar disorder. There is data that established mood stabilisers have a role in ameliorating oxidative stress. N-acetyl cysteine (NAC) is a precursor of glutathione. NAC has been shown to reverse animal models of oxidative stress, and raises peripheral glutathione levels. Preclinical data shows that NAC raised brain glutathione levels and reverses models of glutathione depletion. In a double blind randomised placebo controlled trial, 75 individuals with bipolar disorder received 2g daily of NAC or placebo as add-on therapy to treatment as usual. Outcome measures included measures of mania, depression, global impression, substance use, quality of life, functioning, and tolerability. The duration of the trial was 6 months. NAC treated individuals showed a significant benefit on measures of depression quality of life and functioning at endpoint. Effect sizes were in the moderate to large range. This trial implicates oxidative pathways in the pathophysiology of the disorder, and supports NAC as a novel adjunctive treatment