N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action

Abstract

There is an expanding field of research investigating the benefits of alternatives to current pharmacological therapies in psychiatry. N-acetylcysteine (NAC) is emerging as a useful agent in the treatment of psychiatric disorders. Like many therapies, the clinical origins of NAC are far removed from its current use in psychiatry. Whereas the mechanisms of NAC are only beginning to be understood, it is likely that NAC is exerting benefits beyond being a precursor to the antioxidant, glutathione, modulating glutamatergic, neurotropic and inflammatory pathways. This review outlines the current literature regarding the use of NAC in disorders including addiction, compulsive and grooming disorders, schizophrenia and bipolar disorder. N-acetylcysteine has shown promising results in populations with these disorders, including those in whom treatment efficacy has previously been limited. The therapeutic potential of this acetylated amino acid is beginning to emerge in the field of psychiatric research.

Figures

Fig. 1

Mechanisms of action of N-acetylcysteine (NAC). Top to bottom: increased activity of cystine–glutamate antiporter results in increased activation of metabotropic glutamate receptors on inhibitory neurons and facilitates vesicular dopamine release; NAC is associated with reduced levels of inflammatory cytokines and acts as a substrate for glutathione synthesis. These actions are believed to converge upon mechanisms promoting cell survival and growth factor synthesis, leading to increased neurite sprouting. BDNF = brain-derived neurotrophic factor; IL = interleukin; NADP = nicotinamide adenine dinucleotide phosphate; NADPH = reduced form of NADP; TNF = tumour necrosis factor.