<i>N</i>‐acetylcysteine for major mental disorders: a systematic review and meta‐analysis of randomized controlled trials

Zheng, Wei; Zhang, Q.-E.; Cai, Dong Bin; Yang, Xin; Qiu, Yuling; Ungvári, Gábor S.; Ng, Chee H.; Berk, Michael; Ning, Yu; Xiang, Yu Tao

doi:10.1111/acps.12862

Cited by 70 publications

(54 citation statements)

References 54 publications

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“…Across all the above disorders, the rates of discontinuation and severe adverse events from N‐acetylcysteine supplementation did not differ significantly from the placebo conditions. There was no significant difference in rates of mild adverse events (particularly with regards to gastrointestinal upset) in people with schizophrenia (N=186, n=2, OR=1.56, 95% CI: 0.87‐2.80, p=0.14, I 2 =0), but N‐acetylcysteine supplementation was associated with higher rates of mild adverse events in mood disorders (N=574, n=5, OR=1.61, 95% CI: 1.01‐2.59, p=0.049).…”

Section: Resultsmentioning

confidence: 94%

“…As an adjunctive treatment for individuals with bipolar disorder (N=224, n=2), 2 g/day N‐acetylcysteine did not differ from placebo in its impact on overall illness severity (Clinical Global Impression ‐ Severity, CGI‐S: SMD=0.11, 95% CI: –0.15 to 0.37, p=0.42, I 2 =90%, and Clinical Global Impression ‐ Improvement, CGI‐I: SMD=0.16, 95% CI: –0.09 to 0.42, p=0.22, I 2 =0%) or mania ratings (N=224, n=2, SMD=0.05, 95% CI: –0.2 to 0.31, p=0.68, I 2 =0.01%). N‐acetylcysteine was also found to be ineffective on depressive symptoms in people with bipolar disorder (N=124, n=2, SMD=0.59, 95% CI: –0.3 to 1.48, p=0.19, I 2 =83%).…”

Section: Resultsmentioning

confidence: 98%

“…No meta‐analyses directly compared nutrient supplementation to psychotropic medications. All studies were placebo‐controlled.…”

Section: Resultsmentioning

confidence: 99%

“…Across three RCTs in people with schizophrenia (N=247), adjunctive treatment with N‐acetylcysteine significantly reduced total symptom scores (SMD=0.74, 95% CI: 0.06‐1.43, p=0.03). Although included trials were rated as high‐quality, the overall strength of evidence was weak due to high risk of publication bias and significant heterogeneity in existing data (I 2 =84%). Regarding symptom subgroups, there was a non‐significant trend indication of beneficial effects on negative symptoms (SMD=0.59, 95% CI: –0.10 to 2.00, p=0.08, I 2 =93%), but no effects beyond placebo for positive symptoms (SMD=0.16, 95% CI: –0.29 to 0.62, p=0.48, I 2 =66%) or general symptomatology (SMD=0.2, 95% CI: –0.21 to 0.62, p=0.34, I 2 =59%).…”

Section: Resultsmentioning

confidence: 99%

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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: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 98%

“…No meta‐analyses directly compared nutrient supplementation to psychotropic medications. All studies were placebo‐controlled.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

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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“…Moreover, a recent RCT demonstrated continuous effects of adjunctive NAC approach in long‐term treatment and effects in early psychosis . A recent meta‐analysis from 6 RCT showed that adjunctive NAC appears to have efficacy for schizophrenia …”

Section: Treatment Based On Glutamate Hypothesismentioning

confidence: 99%

Glutamate hypothesis in schizophrenia

Uno

Coyle

2019

Psychiatry Clin Neurosci

278

172

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Schizophrenia is a chronic and severe psychiatric disorder that has profound impact on an individual’s life and on society. Thus, developing more effective therapeutic interventions is essential. Over the past quarter‐century, an abundance of evidence from pharmacologic challenges, post‐mortem studies, brain imaging, and genetic studies supports the role of glutamatergic dysregulation in the pathophysiology of schizophrenia, and the results of recent randomized clinical trials based on this evidence have yielded promising results. In this article, we review the evidence that alterations in glutamatergic neurotransmission, especially focusing on the N‐methyl‐d‐aspartate receptor (NMDAR) function, may be a critical causative feature of schizophrenia, how this contributes to pathologic circuit function in the brain, and how these insights are revealing whole new avenues for treatment development that could reduce treatment‐resistant symptoms, which account for persistent disability.

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The therapeutic effect of N‐acetylcysteine as an add‐on to methadone maintenance therapy medication in outpatients with substance use disorders: A randomized, double‐blind, placebo‐controlled clinical trial

et al. 2022

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Objective: Patients with substance use disorders (SUD) under methadone maintenance therapy (MMT) are susceptible to a number of complications (psychological and metabolic disorders). Evidence studies have shown the roles of the glutamatergic system in addiction. N-Acetylcysteine (NAC) enhances extracellular glutamate, and is effective in the treatment of neuropsychiatric disorders. We assessed oral NAC as an add-on to MMT medication for the treatment of SUD. Methods:In the current randomized, double-blind, placebo-controlled clinical trial, outpatients with SUD under MMT who were 18-60 years old received 2400 mg/day NAC (n = 30) or placebo (n = 30) for 12 weeks. Psychological status and metabolic biomarkers were assessed at baseline and the end of the trial. Results:Compared with the placebo group, NAC treatment resulted in a significant improvement in depression score (β −2.36; 95% CI, −3.97, −0.76; p = .005), and anxiety score (β −1.82; 95% CI, −3.19, −0.44; p = .01). Furthermore, NAC treatment resultedThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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N‐acetylcysteine for major mental disorders: a systematic review and meta‐analysis of randomized controlled trials

Abstract: Adjunctive NAC appears to be a safe treatment that has efficacy for schizophrenia, but not for bipolar disorder or MDD. Further higher quality RCTs are warranted to determine the role of adjunctive NAC in the treatment of major psychiatric disorders.

Cited by 70 publications

References 54 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

Glutamate hypothesis in schizophrenia

The therapeutic effect of N‐acetylcysteine as an add‐on to methadone maintenance therapy medication in outpatients with substance use disorders: A randomized, double‐blind, placebo‐controlled clinical trial

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