Improvement of cognitive function in schizophrenia with<i>N</i>-acetylcysteine: A theoretical review

Yolland, Caitlin; Phillipou, Andrea; Castle, David; Neill, Erica; Hughes, Matthew; Galletly, Cherrie; Smith, Zoe M.; Francis, Paul S.; Dean, Olivia; Sarris, Jerome; Siskind, Dan; Harris, Anthony; Rossell, Susan L.

doi:10.1080/1028415x.2018.1478766

Cited by 34 publications

(30 citation statements)

References 92 publications

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“…N‐acetylcysteine acts as a precursor to glutathione, the primary endogenous antioxidant, neutralizing cellular reactive oxygen and nitrogen. Glutathione production in astrocytes is rate limited by cysteine.…”

Section: Discussionmentioning

confidence: 99%

The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta‐review of meta‐analyses of randomized controlled trials

et al. 2019

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The role of nutrition in mental health is becoming increasingly acknowledged. Along with dietary intake, nutrition can also be obtained from “nutrient supplements”, such as polyunsaturated fatty acids (PUFAs), vitamins, minerals, antioxidants, amino acids and pre/probiotic supplements. Recently, a large number of meta‐analyses have emerged examining nutrient supplements in the treatment of mental disorders. To produce a meta‐review of this top‐tier evidence, we identified, synthesized and appraised all meta‐analyses of randomized controlled trials (RCTs) reporting on the efficacy and safety of nutrient supplements in common and severe mental disorders. Our systematic search identified 33 meta‐analyses of placebo‐controlled RCTs, with primary analyses including outcome data from 10,951 individuals. The strongest evidence was found for PUFAs (particularly as eicosapentaenoic acid) as an adjunctive treatment for depression. More nascent evidence suggested that PUFAs may also be beneficial for attention‐deficit/hyperactivity disorder, whereas there was no evidence for schizophrenia. Folate‐based supplements were widely researched as adjunctive treatments for depression and schizophrenia, with positive effects from RCTs of high‐dose methylfolate in major depressive disorder. There was emergent evidence for N‐acetylcysteine as a useful adjunctive treatment in mood disorders and schizophrenia. All nutrient supplements had good safety profiles, with no evidence of serious adverse effects or contraindications with psychiatric medications. In conclusion, clinicians should be informed of the nutrient supplements with established efficacy for certain conditions (such as eicosapentaenoic acid in depression), but also made aware of those currently lacking evidentiary support. Future research should aim to determine which individuals may benefit most from evidence‐based supplements, to further elucidate the underlying mechanisms.

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Section: Discussionmentioning

confidence: 99%

The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta‐review of meta‐analyses of randomized controlled trials

et al. 2019

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“…Additionally, Sepehrmanesh et al (2018) [ 69 ] showed that the administration of 1200 mg of NAC had a positive impact on the positive, negative, general, and total psychopathological symptoms analyzed by PANSS, along with an improvement of cognitive performance. A meta-analysis also supported that NAC administered for a period of 24 weeks or more improves the symptoms of schizophrenia, as well as the cognitive domain of working memory, where studies had a daily dose range of 600 mg to 3600 mg [ 70 ].…”

Section: Clinical Indicationsmentioning

confidence: 99%

N-Acetylcysteine (NAC): Impacts on Human Health

et al. 2021

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N-acetylcysteine (NAC) is a medicine widely used to treat paracetamol overdose and as a mucolytic compound. It has a well-established safety profile, and its toxicity is uncommon and dependent on the route of administration and high dosages. Its remarkable antioxidant and anti-inflammatory capacity is the biochemical basis used to treat several diseases related to oxidative stress and inflammation. The primary role of NAC as an antioxidant stems from its ability to increase the intracellular concentration of glutathione (GSH), which is the most crucial biothiol responsible for cellular redox imbalance. As an anti-inflammatory compound, NAC can reduce levels of tumor necrosis factor-alpha (TNF-α) and interleukins (IL-6 and IL-1β) by suppressing the activity of nuclear factor kappa B (NF-κB). Despite NAC’s relevant therapeutic potential, in several experimental studies, its effectiveness in clinical trials, addressing different pathological conditions, is still limited. Thus, the purpose of this chapter is to provide an overview of the medicinal effects and applications of NAC to human health based on current therapeutic evidence.

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“…Whether NAC has a global impact on cognition based on a general reduction of oxidative stress, versus a more specific action (such as the modulation of N -methyl- d -aspartate [NMDA] receptor pathways) is currently unclear (Yolland et al, 2018). There is some evidence that structures relating to memory and learning are more affected by oxidative stress (Skvarc et al, 2017), and some indication of improvements in specific domains of cognition, depending on the disease process (Hajjar et al, 2018); however, much is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Meta-analysis of randomised controlled trials withN-acetylcysteine in the treatment of schizophrenia

Yolland

Hanratty

Neill

et al. 2019

Aust N Z J Psychiatry

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Objective: There is accumulating evidence that adjunctive treatment with N-acetylcysteine may be effective for schizophrenia. This study aimed to conduct a comprehensive meta-analysis examining the efficacy of randomised control trials investigating N-acetylcysteine as an adjunct treatment for schizophrenia and the first to investigate cognition as an outcome. Methods: We systematically reviewed Medline, EmCare, PsycINFO, Embase, CINAHL Complete, China Knowledge Resource Integrated Database and the Cochrane Clinical Trials online registry for randomised control trials of N-acetylcysteine for schizophrenia. We undertook pairwise meta-analyses of N-acetylcysteine vs placebo for psychosis symptoms and cognition. Results: Seven studies, including n = 220 receiving N-acetylcysteine and n = 220 receiving placebo, met inclusion criteria for the pairwise meta-analyses. Positive and Negative Syndrome Scale negative and total scores were significantly improved in the N-acetylcysteine group after 24 weeks of treatment. The cognitive domain of working memory improved with N-acetylcysteine supplementation. Conclusion: Evidence supports the notion that N-acetylcysteine may be a useful adjunct to standard treatment for the improvement of schizophrenia symptoms, as well as the cognitive domain of working memory. Treatment effects were observed at the later time point (⩾24 weeks), suggesting that longer interventions are required for the success of N-acetylcysteine treatment.

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Improvement of cognitive function in schizophrenia withN-acetylcysteine: A theoretical review

Cited by 34 publications

References 92 publications

The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta‐review of meta‐analyses of randomized controlled trials

The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta‐review of meta‐analyses of randomized controlled trials

N-Acetylcysteine (NAC): Impacts on Human Health

Meta-analysis of randomised controlled trials withN-acetylcysteine in the treatment of schizophrenia

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