N-acetylcysteine in the treatment of psychiatric disorders: current status and future prospects

ABSTRACT

Introduction: N-acetylcysteine (NAC) is widely known for its role as a mucolytic and as an antidote to paracetamol overdose. There is increasing interest in the use of NAC in the treatment of several psychiatric disorders. The rationale for the administration of NAC in psychiatric conditions is based on its role as a precursor to the antioxidant glutathione, and its action as a modulating agent of glutamatergic, dopaminergic, neurotropic and inflammatory pathways.

Areas covered: This study reviews the available data regarding the use of NAC in different psychiatric disorders including substance use disorders, autism, obsessive-compulsive spectrum disorders, schizophrenia, depression, bipolar disorder. Promising results were found in trials testing the use of NAC, mainly as an add-on treatment, in cannabis use disorder in young people, depression in bipolar disorder, negative symptoms in schizophrenia, and excoriation (skin-picking) disorder. Despite initial optimism, recent findings regarding NAC efficacy in autism have been disappointing.

Expert opinion: These preliminary positive results require further confirmation in larger samples and with longer follow-ups. Given its high tolerability and wide availability, NAC represents an important target to investigate in the field of new adjunctive treatments for psychiatric conditions.

KEYWORDS:

• N-acetylcysteine
• NAC
• psychiatry
• mechanism of action

Article highlights

• N-acetyl cysteine (NAC) is a precursor of the aminoacid cysteine and glutathione, commonly used in various clinical settings with a growing interest in its possible use in psychiatry

• Clinical reports have documented the outcome of treatment with NAC in a variety of psychiatric disorders, mainly as an add-on agent, with generally negligible side effects

• NAC various clinical applications suggest that the drug targets downstream pathways that are common across disorders

• Data is still only preliminary for most of its psychiatric utilization. A significant fraction of the positive evidence is provided by analysis of secondary outcomes or subanalysis of samples

• Most promising areas for NAC utilization are substance use disorders, especially cannabis, depression in bipolar disorder, excoriation (skin-picking) disorder, and schizophrenia, especially to target negative symptoms

• Larger studies are needed to confirm efficacy, optimal doses, long term tolerability and side effects

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.