Synopsis

Source of validity: Scientific
Rating (out of 5): 3

N-acetyl-cysteine (NAC) has been investigated as an adjunctive treatment in schizophrenia based on its biological actions and evidence from clinical trials. NAC is a precursor to glutathione, a major antioxidant in the brain, and is thought to modulate glutamatergic and dopaminergic neurotransmission, both of which are implicated in the pathophysiology of schizophrenia. Several randomized controlled trials have examined NAC as an add-on to standard antipsychotic medications. Some of these studies have reported modest benefits on negative symptoms (such as social withdrawal and apathy), cognitive function, and overall functioning, though effects on positive symptoms (such as hallucinations and delusions) are less clear.

The most cited study is Berk et al. (2008, Biological Psychiatry), which found that 2 grams of NAC daily for 24 weeks led to significant improvements in negative symptoms compared to placebo. Meta-analyses and systematic reviews (e.g., Yolland et al., 2020, Psychol Med) generally report small but statistically significant improvements in negative symptoms. The mechanism is hypothesized to involve reduction of oxidative stress, anti-inflammatory effects, and modulation of glutamatergic neurotransmission.

However, not all studies have found consistent benefits, and the effect sizes are generally small. NAC is considered safe and well-tolerated, which supports its investigation as an adjunctive therapy. Overall, there is moderate scientific evidence (rating 3/5) supporting its use as an adjunct for negative symptoms in schizophrenia, but more research is needed for definitive recommendations.

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