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1.
Antioxidant interventions in autism spectrum disorders: A meta-analysis.
Liu, Y, Yang, Z, Du, Y, Shi, S, Cheng, Y
Progress in neuro-psychopharmacology & biological psychiatry. 2022;:110476
Abstract
BACKGROUND Autism spectrum disorder (ASD) might be associated with oxidative stress, and antioxidants are commonly used in the treatment of young people with ASD. However, the evidence about the effectiveness of these interventions remains debatable. We performed a meta-analysis to evaluate the effect of antioxidants on the symptoms of patients with autism. METHODS Data sources: PubMed and Web of Science databases. STUDY SELECTION We selected placebo-controlled, double-blind, randomized clinical trials published until February 2021 to evaluate the efficacy of antioxidant interventions on ASD. DATA ANALYSIS Aberrant Behavior Checklist (ABC), Repetitive Behavior Scale-Revised (RBS), Social Responsiveness Scale (SRS), Developmental Behavior Checklist (DBC) and Clinical Global Impressions Severity scale (CGIS) were used to evaluate the 22 different symptom outcomes. The Hedges-adjusted g value was used to estimate the effect of each dietary intervention relative to the placebo. RESULTS In this meta-analysis, we examined 13 double-blind randomized clinical trials, comprising a total of 570 patients with ASD: 293 in the intervention group and 277 in the placebo group. Antioxidants (N-acetylcysteine (NAC), other antioxidants) are more effective than placebos in improving the irritability among symptoms in the ABC and communication disturbance symptoms in the DBC. There was a good trend of improvement in the stereotypic behavior symptoms in the ABC. Treatment with NAC antioxidants showed a good trend of improvement in irritability in the ABC and symptoms of hyperactivity. The effect size was small, and there was a low risk of statistical heterogeneity and publication bias. LIMITATIONS The number of studies in this meta-analysis was small and the sample size was small. CONCLUSION This meta-analysis suggests that antioxidant intervention has a potential role in the management of some symptoms in patients with ASD, and indicates the feasibility of using antioxidants to treat autism in the future.
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2.
The effect of N-acetylcysteine on bipolar depression: a systematic review and meta-analysis of randomized controlled trials.
Pittas, S, Theodoridis, X, Haidich, AB, Bozikas, PV, Papazisis, G
Psychopharmacology. 2021;(7):1729-1736
Abstract
RATIONALE The current pharmacotherapy of bipolar depression often presents limited efficacy and increased risk for adverse events. N-acetylcysteine (NAC) has been suggested as potentially effective and well-tolerated adjunctive treatment for bipolar disorder (BD). OBJECTIVES This systematic review and meta-analysis aimed to examine the efficacy of N-acetylcysteine, as an adjunctive therapy, for treating bipolar depression. METHODS PubMed, Cochrane Library, Scopus databases, and grey literature were searched for studies retrieval. Randomized controlled trials including patients with a diagnosed bipolar disorder and a current depressive episode were included in the analysis. The measured variables included symptoms, functioning, and quality of life scales. The mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) was set as the primary outcome. RESULTS A total of five studies were included in the analysis. A significant improvement was not observed from the addition of NAC to standard therapy in symptomatology [MADRS (MD = -3.32; 95% CI = -12.79 to 6.16), Young Mania Rating Scale (MD = -0.7; 95% CI = -2.15 to 0.75), Bipolar Depression Rating Scale (MD = -3.19; 95% CI = -15.48 to 9.1), and Clinical Global Impression for severity (MD = -0.13; 95% CI = -0.33 to 0.08)], functioning, [Global Assessment of Functioning Scale (MD = 3.21; 95% CI = -12.55 to 18.97), Social and Occupational Functioning Assessment Scale (MD = 0.47; 95% CI = -4.60 to 5.53), or quality of life [Quality of Life Enjoyment and Satisfaction Questionnaire (MD = 2.27; 95% CI = -9.13 to 13.67)]. CONCLUSIONS There is no evidence indicating that NAC has beneficial effects as an adjunctive treatment for bipolar depression. Future trials with improved methodological design and efficient sample sizes are required to draw safer conclusions.
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3.
N-acetylcysteine as an adjunctive treatment for bipolar depression and major depressive disorder: a systematic review and meta-analysis of double-blind, randomized placebo-controlled trials.
Kishi, T, Miyake, N, Okuya, M, Sakuma, K, Iwata, N
Psychopharmacology. 2020;(11):3481-3487
Abstract
RATIONALE It remains unclear whether using N-acetylcysteine as an adjunctive treatment has any benefit for bipolar depression and major depressive disorder. OBJECTIVES A systematic review and random-effect meta-analysis of double-blind, randomized placebo-controlled trials was conducted to explore the clinical question. METHODS Outcomes included improvement in depression scale scores (primary), Young Mania Rating Scale score, Hamilton Anxiety Rating Scale score, Clinical Global Impression-Severity Scale (CGI-S) score, Global Assessment of Functioning Scale score, Social and Occupational Functioning Assessment Scale score, Range of Impaired Functioning Tool score, Streamed Longitudinal Interval Clinical Evaluation for the Longitudinal Interview Follow-Up Evaluation score, quality of life scales scores, and the incidence of all-cause discontinuation and individual adverse events. RESULTS Seven studies (n = 728, 8-24 weeks, mean age = 46.81, % female = 58.45%) were included. N-acetylcysteine did not improve depressive symptoms compared with placebo (N = 7, n = 579, standardized mean difference (SMD) = - 0.12, 95% confidence interval (95% CI) = - 0.38, 0.14, p = 0.38, I2 = 52.74%). The meta-regression analysis detected an association between effect size and publication year (coefficient = 0.06, 95% CI = 0.00, 0.11, p = 0.04, I2 = 27.56%). Although N-acetylcysteine was superior to placebo in CGI-S score (N = 6, n = 563, SMD = - 0.28, 95% CI = - 0.47, - 0.10, p < 0.01, I2 = 14.88%), there was no significant difference in the other efficacy outcomes between the treatment groups. Although N-acetylcysteine was associated with a higher incidence of gastrointestinal adverse events compared with placebo (N = 4, n = 537, risk ratio = 1.79, 95% CI = 1.37, 2.32, p < 0.01, I2 = 0.00%, number needed to treat to harm = 7), there was no significant difference in all-cause discontinuation and other safety outcomes between the treatments. CONCLUSIONS Although N-acetylcysteine decreased CGI-S score, no specific improvements in symptoms were identified.
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4.
The effects of N-acetylcysteine on inflammatory and oxidative stress biomarkers: A systematic review and meta-analysis of controlled clinical trials.
Faghfouri, AH, Zarezadeh, M, Tavakoli-Rouzbehani, OM, Radkhah, N, Faghfuri, E, Kord-Varkaneh, H, Tan, SC, Ostadrahimi, A
European journal of pharmacology. 2020;:173368
Abstract
Prolonged inflammation could be considered as the leading cause of chronic diseases such as cardiovascular disorders, type two diabetes, and obesity. N-acetylcysteine (NAC) is considered an antioxidant. The present meta-analysis aims to determine the efficacy of NAC in alleviating inflammation and oxidative stress. PubMed-Medline, SCOPUS, Web of Science and Embase databases and Google Scholar were searched up to Nov 2019. Random effect analysis was used to perform meta-analysis. Subgroup analyses were carried out to find heterogeneity sources. Meta-regression analysis was used to explore linear relationship between effect size and variables. Trim and fill analysis were performed in case of the presence of publication bias. Quality assessment was performed using Cochrane Collaboration's tool. A total of 28 studies were included in meta-analysis. NAC significantly decreased malondialdehyde (MDA) (SMD = -1.44 μmol/L; 95% CI: -2.05, -0.84; P < 0.001), IL-8 (WMD = -2.56 pg/ml; 95% CI: -3.89, -1.23; P < 0.001) and homocysteine (WMD = -1.45 pg/ml; 95% CI: -2.74, -0.17; P = 0.027) levels. There were no significant effects of NAC supplementation on CRP (SMD = -0.1 g/L; 95% CI: -0.52, 0.32; P = 0.647), TNF- α (WMD = -0.2 pg/ml; 95% CI: -0.65, 0.25; P = 0.378) and IL-6 (WMD = -0.41 pg/ml; 95% CI: -1.15, 0.32; P = 0.270) levels. However, NAC effects were significant in ameliorating TNF-α and IL-6 using sensitivity analysis. NAC significantly decreased MDA, IL-8, and homocysteine levels. The effects of NAC on amending TNF-α and IL-6 levels were significant after sensitivity analysis. No significant change was observed on CRP levels.
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5.
Comparison of the efficacy between NAC and metformin in treating PCOS patients: a meta-analysis.
Song, Y, Wang, H, Huang, H, Zhu, Z
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2020;(3):204-210
Abstract
Our aim is to evaluate the clinical effectiveness and safety by comparing N-acetyl-cysteine (NAC) with metformin administrated by polycystic ovary syndrome (PCOS) patients. Systematic review and meta-analysis of randomized clinical trials (RCTs). MEDLINE, EMBASE, Web of Science and China National Knowledge Infrastructure were searched for studies. 10 studies were considered eligible for inclusion. NAC significantly reduced BMI and total testosterone, there was no significant difference in pregnancy rate, serum LH level, fasting insulin, and LH/FSH ratio. In conclusions, NAC may be considered as an alternative supplement to metformin, but large-scale randomized controlled trials are needed to assess the efficacy and safety of NAC in PCOS patients.
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6.
N-acetylcysteine use among patients undergoing cardiac surgery: A systematic review and meta-analysis of randomized trials.
Pereira, JEG, El Dib, R, Braz, LG, Escudero, J, Hayes, J, Johnston, BC
PloS one. 2019;(5):e0213862
Abstract
BACKGROUND Cardiac surgeries are complex procedures aiming to re-establish coronary flow and correct valvular defects. Oxidative stress, caused by inflammation and ischemia-reperfusion injury, is associated with these procedures, increasing the risk of adverse outcomes. N-acetylcysteine (NAC) acts as an antioxidant by replenishing the glutathione stores, and emerging evidence suggests that NAC may reduce the risk of adverse perioperative outcomes. We conducted a systematic review and meta-analysis to investigate the addition of NAC to a standard of care among adult patients undergoing cardiac surgery. METHODS We searched four databases (PubMed, EMBASE, CENTRAL, LILACS) from inception to October 2018 and the grey literaure for randomized controlled trials (RCTs) investigating the effect of NAC on pre-defined outcomes including mortality, acute renal insufficiency (ARI), acute cardiac insufficiency (ACI), hospital length of stay (HLoS), intensive care unit length of stay (ICULoS), arrhythmia and acute myocardial infarction (AMI). Reviewers independently screened potentially eligible articles, extracted data and assessed the risk of bias among eligible articles. We used the GRADE approach to rate the overall certainty of evidence for each outcome. RESULTS Twenty-nine RCTs including 2,486 participants proved eligible. Low to moderate certainty evidence demonstrated that the addition of NAC resulted in a non-statistically significant reduction in mortality (Risk Ratio (RR) 0.71; 95% Confidence Interval (CI) 0.40 to 1.25), ARI (RR 0.92; 95% CI 0.79 to 1.09), ACI (RR 0.77; 95% CI 0.44 to 1.38), HLoS (Mean Difference (MD) 0.21; 95% CI -0.64 to 0.23), ICULoS (MD -0.04; 95% CI -0.29 to 0.20), arrhythmia (RR 0.79; 95% CI 0.52 to 1.20), and AMI (RR 0.84; 95% CI 0.48 to 1.48). LIMITATIONS Among eligible trials, we observed heterogeneity in the population and interventions including patients with and without kidney dysfunction and interventions that differed in route of administration, dosage, and duration of treatment. This observed heterogeneity was not explained by our subgroup analyses. CONCLUSIONS The addition of NAC during cardiac surgery did not result in a statistically significant reduction in clinical outcomes. A large randomized placebo-controlled multi-centre trial is needed to determine whether NAC reduces mortality. REGISTRATION PROSPERO CRD42018091191.
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7.
Comparative efficacy of pharmacological interventions for contrast-induced nephropathy prevention after coronary angiography: a network meta-analysis from randomized trials.
Ma, WQ, Zhao, Y, Wang, Y, Han, XQ, Zhu, Y, Liu, NF
International urology and nephrology. 2018;(6):1085-1095
Abstract
BACKGROUND Contrast-induced nephropathy (CIN) is the major complication related to contrast media administration in patients after coronary angiography (CAG). However, inconsistent results have been published in the literature regarding the effects of pharmacological drugs on CIN prevention. We conducted a network meta-analysis to evaluate the relative efficacy of pharmacological interventions for the prevention of CIN. METHODS We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to July 2017. We included any randomized controlled trials of eleven pharmacological interventions that reported the prevention of CIN. RESULTS We identified 3850 records through database searches, of which 107 studies comprising 21,450 participants were finally identified. Compared with intravenous saline, intravenous saline plus pharmacological drugs including statin [relative risk (RR) 0.57; 95% credibility interval (CrI) 0.39 to 0.83], N-acetylcysteine (NAC) (RR 0.84; 95% CrI, 0.71 to 0.98), vitamin and its analogues (RR 0.66; 95% CrI 0.45 to 0.97), brain natriuretic peptide (BNP) and its analogues (RR 0.46; 95% CrI 0.30 to 0.70), prostaglandin analogues (RR 0.37; 95% CrI 0.18 to 0.76), NAC plus sodium bicarbonate (SB) (RR 0.60; 95% CrI 0.39 to 0.90), and statin plus NAC (RR 0.39; 95% CrI 0.21 to 0.70), have helped to reduce the incidence of CIN in patients after CAG. The top four ranked treatments were statin plus NAC, BNP and its analogues, statin, and vitamin and its analogues, respectively. NAC plus intravenous saline was associated with lower incidence of short-term all-cause mortality than intravenous saline alone (RR 0.62; 95% CI, 0.40 to 0.96; P = 0.03). However, no evidence indicated that any of the pharmacological drugs were associated with a reduced requirement for dialysis and major adverse cardiac and cerebrovascular events (MACCE). CONCLUSIONS Statin plus NAC plus intravenous saline seems to be the most effective treatment for the prevention of CIN in patients after CAG. NAC plus intravenous saline may have a protective role against short-term all-cause mortality. However, none of these drugs has effectively decreased the requirement for dialysis and MACCE.
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8.
N-Acetylcysteine for the Treatment of Psychiatric Disorders: A Review of Current Evidence.
Ooi, SL, Green, R, Pak, SC
BioMed research international. 2018;:2469486
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.
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9.
Efficacy of N-Acetylcysteine in Preventing Acute Kidney Injury After Cardiac Surgery: A Meta-Analysis Study.
Mei, M, Zhao, HW, Pan, QG, Pu, YM, Tang, MZ, Shen, BB
Journal of investigative surgery : the official journal of the Academy of Surgical Research. 2018;(1):14-23
Abstract
PURPOSE To evaluate whether perioperative N-acetylcysteine (NAC) administration reduces the risk of cardiac surgery associated acute kidney injury (CSA-AKI). MATERIALS AND METHODS A systematic literature review (Medline, PubMed, Cochrane, Biomedical central, Google Scholar) identified 10 studies (1391 patients; 695 NAC and 696 placebo) that compared the efficacy and adverse effects of perioperative NAC administration for CSA-AKI prevention in adults undergoing elective cardiac surgery. Meta-analysis was performed using Comprehensive Meta-Analysis statistical software. RESULTS Patients in the NAC-treated and placebo groups had similar rate of CSA-AKI occurrence, change in creatinine levels, as well as the in-hospital mortality rate (RR = 0.841, 95% CI = 0.691 to 1.023, p = 0.083; pooled difference in means = -0.328, 95% CI = -0.712 to 0.056, p = 0.094; RR = 0.741, 95% CI = 0.388 to 1.418, p = 0.366, respectively). CONCLUSIONS Our study does not support perioperative NAC administration as a mean to reduce the risk of CSA-AKI.
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10.
Chinese herbal medicines compared with N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis: Protocol for a systematic review.
Guo, J, Li, B, Li, W, Pan, Y, Wang, Z, Wu, Y, Wang, F
Medicine. 2018;(44):e13077
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Abstract
BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a major public health problem worldwide. There is no curative treatment for IPF except lung transplantation. Chinese herbal medicines (CHMs) are widely used in the treatment of IPF in China. However, their effectiveness and safety are still obscure and deserve further investigation. The aim of the study was to assess the efficacy and safety of CHMs in treating IPF compared with N-acetylcysteine (NAC). METHODS This review summarizes and meta-analyzes randomized controlled trials (RCTs) of CHMs for the treatment of IPF. RCTs compare either CHMs alone or in combination with NAC or conventional medicine treatment (CMT) vs NAC alone or in combination with CMT have been included. The following electronic databases have been searched: PubMed, Cochrane Library, Embase, CNKI, CBM, VIP, and WANFANG DATA. The methodologic quality of RCTs has been assessed using the Cochrane risk assessment tool. All trials included are analyzed according to the criteria of the Cochrane Handbook. Review Manager 5.3, R-3.5.1 software, and GRADE pro GDT web solution are used for data synthesis and analysis. RESULTS This review evaluates the effects of CHMs on acute exacerbation, mortality, the quality of life, 6-minute walking test distance, lung function (total lung capacity, diffusing capacity of the lungs for carbon monoxide, and forced vital capacity), partial pressure of oxygen in blood (PaO2), and safety in patients with IPF. CONCLUSION This review provides clear evidence to assess the effectiveness and safety of CHMs for IPF.