N-Acetylcysteine for the Treatment of Psychiatric Disorders: A Review of Current Evidence

Abstract

N-acetylcysteine, a sulphur-containing amino acid for the treatment of paracetamol overdose and chronic obstructive pulmonary disease, is a widely available off-the-shelf oral antioxidant supplement in many countries. With the potential to modulate several neurological pathways, including glutamate dysregulation, oxidative stress, and inflammation that can be beneficial to the brain functions, N-acetylcysteine is being explored as an adjunctive therapy for many psychiatric conditions. This narrative review synthesises and presents the current evidence from systematic reviews, meta-analyses, and latest clinical trials on N-acetylcysteine for addiction and substance abuse, schizophrenia, obsessive-compulsive and related disorders, and mood disorders. Good evidence exists to support the use of N-acetylcysteine as an adjunct treatment to reduce the total and negative symptoms of schizophrenia. N-acetylcysteine also appears to be effective in reducing craving in substance use disorders, especially for the treatment of cocaine and cannabis use among young people, in addition to preventing relapse in already abstinent individuals. Effects of N-acetylcysteine on obsessive-compulsive and related disorders, as well as on mood disorders, remain unclear with mixed reviews, even though promising evidence does exist. Larger and better-designed studies are required to further investigate the clinical effectiveness of N-acetylcysteine in these areas. Oral N-acetylcysteine is safe and well tolerated without any considerable adverse effects. Current evidence supports its use as an adjunctive therapy clinically for psychiatric conditions, administered concomitantly with existing medications, with a recommended dosage between 2000 and 2400 mg/day.

Sulfane sulfur – new findings on an old topic

“…Echevarria and others (Echevarria et al, 2017) published an extensive review of currently available literature dealing with NAC efficacy in the treatment of cocaine addiction, based on which it can be concluded that NAC may be suitable for reducing the relapse rate in the already abstinent subjects. Similar review about using NAC in the treatment of psychiatric disorders has been recently published by other researchers (Ooi et al, 2018). These authors support the use of NAC as an adjunctive treatment to reduce the total and negative symptoms of schizophrenia, as well as a medication helpful in reducing the cocaine and cannabis use.…”

Antioxidants as a Potential Target against Inflammation and Oxidative Stress in Attention-Deficit/Hyperactivity Disorder

“…N-Acetylcysteine (NAC), a precursor of L-cysteine and the antioxidant glutathione (GSH), is found in plants, especially the onion [96][97][98]. NAC has been used as an adjuvant therapy in many psychiatric disorders (e.g., Alzheimer´s disease, schizophrenia, autism, addiction, substance abuse, obsessive-compulsive and mood disorders [24,[99][100][101][102][103][104]), with promising results and no relevant side effects after its administration against inflammation [97]. The use of NAC in a chronic unpredictable mild-stress animal model inhibited the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in the hippocampus and prefrontal cortex and exhibited antidepressant-like effects [71].…”

“…The NAC molecule scavenges ROS and there has been growing evidence of its role in attenuating psychiatric and neurological disorders and associated pathophysiological processes such as oxidative stress, mitochondrial dysfunction and glutamate and dopamine dysregulation [96,97,141]. In rats, amphetamine produces oxidative stress (by increasing hydroxyl radical formation and MDA) and dopaminergic neurotoxicity, but treatment with NAC protected against amphetamine-induced damage [84].…”

Oxidative-Antioxidant Imbalance and Impaired Glucose Metabolism in Schizophrenia

“…Abbreviations: Progression of schizophrenia is increasingly associated with the treatment-resistant (TRS) form of the disease. The severity of symptoms is the result of sulfuric stress and is positively correlated with high levels of homocysteine and the failure of transsulfuration process, which metabolizes homocysteine in the l-cysteine pathway [143,268]. l-cysteine deficiency and lack of response from the transsulfuration pathway (low activity of cystathionine β-synthase and cystathionine γ-lyase) become the cause of the recorded low levels of glutathione and glutathione pathway enzymes (i.e., GPx) in the brain and blood of patients with schizophrenia [269].…”