N-Acetyl Cysteine (NAC) has been investigated as an adjunctive treatment for Bipolar Mood Disorder, particularly for its potential to reduce depressive symptoms. The rationale is based on NAC’s ability to modulate glutamatergic neurotransmission, reduce oxidative stress, and regulate inflammation—mechanisms implicated in mood disorders. Several randomized controlled trials (RCTs) and meta-analyses have assessed NAC’s efficacy in bipolar disorder. Notably, a 2008 double-blind RCT (Berk et al., Biological Psychiatry) found that adding NAC to standard treatment improved depressive symptoms over 24 weeks compared to placebo. However, subsequent studies have produced mixed results—some failing to replicate the initial positive findings, particularly in maintenance or prevention of relapse. Recent meta-analyses suggest that NAC may have a modest benefit for depressive symptoms but is unlikely to impact manic symptoms or overall illness course.

Importantly, guidelines do not recommend NAC as a first-line treatment for bipolar disorder, citing insufficient and inconsistent evidence. While it is generally considered safe and well-tolerated, NAC’s use remains experimental and is typically reserved for adjunctive purposes in refractory cases. Thus, while there is some scientific validation for its use, the strength and consistency of evidence are limited (score: 2/5).