Evidence supporting the use of: N-acetylcysteine
For the health condition: Bipolar Mood Disorder

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Synopsis

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

N-acetylcysteine (NAC) has been investigated as an adjunctive treatment in Bipolar Mood Disorder due to its antioxidant and glutamatergic modulating properties. Several randomized controlled trials (RCTs) and meta-analyses have explored its efficacy, with mixed but generally modest results. The largest and most influential study was a double-blind, placebo-controlled trial published in Biological Psychiatry (2008) by Berk et al., which found that adjunctive NAC (1,000 mg twice daily) led to significant improvements in depressive symptoms in bipolar disorder over 24 weeks, compared to placebo. Follow-up studies and meta-analyses have reported small but statistically significant benefits for depressive symptoms, but not for mania or overall functioning. The proposed mechanisms include NAC's ability to replenish glutathione, reduce oxidative stress, and modulate glutamate neurotransmission, all of which may be dysregulated in bipolar disorder.

However, subsequent trials have not consistently replicated these positive findings, and some have failed to find significant benefit over placebo. Recent meta-analyses (e.g., Fernandes et al., 2016; Treweeke et al., 2022) generally conclude that while NAC is safe and well-tolerated, its efficacy for bipolar depression is limited and the effect size is small. As of 2024, NAC is not included in major clinical guidelines as a standard treatment for bipolar disorder, but it may be considered as an adjunct in select cases. In summary, scientific evidence exists but is modest and not definitive.

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