Evidence supporting the use of: N-acetyl-cysteine (NAC)
For the health condition: Bipolar Mood Disorder

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Synopsis

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

N-acetyl-cysteine (NAC) has been investigated as a potential adjunctive treatment for Bipolar Mood Disorder, primarily based on its role in modulating glutamatergic neurotransmission, oxidative stress, and inflammation—all of which are implicated in the pathophysiology of bipolar disorder. Several randomized controlled trials have evaluated the efficacy of NAC in treating bipolar depression, most notably a 2008 double-blind, placebo-controlled study published in Biological Psychiatry, which found a significant improvement in depressive symptoms over six months in patients receiving NAC compared to placebo. Subsequent meta-analyses and systematic reviews, including a 2016 review in Bipolar Disorders, have suggested that NAC may provide modest benefits for depressive symptoms but show inconsistent effects on mania or overall functioning. The effect sizes observed are generally small to moderate, and some recent studies have failed to replicate earlier positive findings, raising questions about consistency and clinical significance. NAC is generally well-tolerated, which adds to its appeal as an adjunctive agent. However, major guidelines do not currently recommend NAC as a first-line or standalone treatment for bipolar disorder, citing insufficient high-quality evidence. In summary, there is some scientific validation for the use of NAC as an adjunct to standard therapy for bipolar depression, but the strength of evidence is moderate at best, and further large-scale studies are needed to clarify its role.

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