Synopsis

Source of validity: Scientific
Rating (out of 5): 2

N-acetyl-cysteine (NAC) is a precursor to the antioxidant glutathione and has been investigated for its potential role in supporting or treating depression. The scientific interest in NAC for depression primarily stems from its ability to modulate oxidative stress, inflammation, and glutamate neurotransmission—mechanisms increasingly recognized as relevant in the pathophysiology of depression. Several small randomized controlled trials and meta-analyses have explored the efficacy of NAC as an adjunctive treatment for major depressive disorder (MDD) and depressive symptoms in psychiatric conditions such as bipolar disorder. A 2016 meta-analysis (Berk et al., 2016, World Journal of Biological Psychiatry) found a modest but statistically significant benefit for NAC supplementation in mood symptoms, particularly as an add-on to standard antidepressant therapy. However, the number of studies is limited, and most have small sample sizes. The largest trials suggest that while NAC may improve depressive symptoms, the effect size is generally small, and results are not always consistent across studies. The safety profile of NAC is favorable, which makes it an attractive candidate for adjunctive therapy, but more robust evidence is needed. Overall, NAC is supported by preliminary scientific evidence for use in depression, but the quality and quantity of the data warrant a cautious interpretation. It is not a first-line treatment, but may be considered as an adjunct under clinical supervision.

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