N-acetylcysteine add-on treatment in refractory obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled trial. N-Acetyl Cysteine in the Treatment of Obsessive Compulsive and Related Disorders: A Systematic Review The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: an open label trial. High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis. Effect of high-dose N-acetylcysteine on airway geometry, inflammation, and oxidative stress in COPD patients Depression and Chronic Obstructive Pulmonary Disease: Treatment Trials. Randomized, Double-Blind, Placebo-Controlled Trial of N-Acetylcysteine Augmentation for Treatment-Resistant Obsessive-Compulsive Disorder. N-Acetylcysteine in the Treatment of Pediatric Tourette Syndrome: Randomized, Double-Blind, Placebo-Controlled Add-On Trial. The Bronchitis Randomized On NAC Cost-Utility Study (BRONCUS): hypothesis and design. BRONCUS-trial Committee. Efficacy of Ascorbic Acid (Vitamin C) and/N-Acetylcysteine (NAC) Supplementation on Nutritional and Antioxidant Status of Male Chronic Obstructive Pulmonary Disease (COPD) Patients. Omega-3 Polyunsaturated Fatty Acids in Prevention of Mood and Anxiety Disorders Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON): a randomised, double-blind placebo-controlled trial. Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial Antioxidants as a Preventive Treatment for Epileptic Process: A Review of the Current Status N-Acetylcysteine as an Adjunct to Risperidone for Treatment of Negative Symptoms in Patients With Chronic Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study Interferon/antioxidant combination therapy for chronic hepatitis C--a controlled pilot trial. Psychiatric and neurologic risk factors for incident cases of new-onset epilepsy in older adults: data from U.S. Medicare beneficiaries. N-acetylcysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis How effective and safe is medical cannabis as a treatment of mental disorders? A systematic review High-Dose N-Acetylcysteine in the Prevention of COPD Exacerbations: Rationale and Design of the PANTHEON Study Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial. MicroRNA Expression in Response to Controlled Exposure to Diesel Exhaust: Attenuation by the Antioxidant N-Acetylcysteine in a Randomized Crossover Study World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision
OBJECTIVE This study aim ed to evaluate the efficacy and safety of N-acetylcysteine , a glutamate-modulating agent , in patients with treatment-refractory obsessive-compulsive disorder as an adjunct to serotonin reuptake inhibitor treatment . METHODS Forty-eight patients ( 36 women ; mean ± SD age , 30.93 ± 4.99 ) with obsessive-compulsive disorder who failed to respond to a course of serotonin reuptake inhibitor treatment  were r and omized to a 12-week intervention period of N-acetylcysteine ( up to 2400 mg/d ) or placebo . Primary outcome measures were the change in Yale-Brown Obsessive Compulsive Scale ( Y-BOCS ) score from baseline to end point and the rate of full response in each group at the end of trial . Full response was defined as 35 % or greater reduction in Y-BOCS score from baseline . RESULTS Changes of Y-BOCS score were different over time ( P < 0.001 ) and between groups ( P < 0.001 ) . N-acetylcysteine-assigned patients showed significantly improved mean Y-BOCS score ( P = 0.003 ) and Clinical Global Impression-Severity of Illness scale score ( P = 0.01 ) but not Clinical Global Impression-Improvement scale score at study end point . Of the patients in the N-acetylcysteine group , 52.6 % were full responders at the end of the study , which was significantly higher than 15 % of the patients in the placebo group ( P = 0.013 ) . CONCLUSION This trial suggests that N-acetylcysteine may be a safe and effective option to augment st and ard treatment in patients with refractory obsessive-compulsive disorder Objective Obsessive compulsive and related disorders are a collection of debilitating psychiatric disorders in which the role of glutamate dysfunction in the underpinning neurobiology is becoming well established . N-acetyl cysteine ( NAC ) is a glutamate modulator with promising therapeutic effect . This paper presents a systematic review of clinical trials and case reports exploring the use of NAC for these disorders . A further objective was to detail the methodology of current clinical trials being conducted in the area . Methods PubMed , Web of Science and Cochrane Library Data base were search ed for human clinical trials or case reports investigating NAC in the treatment of obsessive compulsive disorder ( OCD ) or obsessive compulsive related disorders . Research ers with known involvement in NAC studies were contacted for any unpublished data . Results Four clinical trials and five case reports/series were identified . Study duration s were commonly 12-weeks , using 2,400–3,000 mg/day of NAC . Overall , NAC demonstrates activity in reducing the severity of symptoms , with a good tolerability profile and minimal adverse effects . Currently there are three ongoing r and omized controlled trials using NAC for OCD ( two adults and one pediatric ) , and one for excoriation . Conclusion Encouraging results have been demonstrated from the few pilot studies that have been conducted . These results are detailed , in addition to a discussion of future potential research BACKGROUND Evidence is accumulating to support the presence of redox dysregulation in a number of psychiatric disorders , including bipolar disorder . This dysregulation may be amenable to therapeutic intervention . Glutathione is the predominant non-enzymatic intracellular free radical scavenger in the brain , and the most generic of all endogenous antioxidants in terms of action . N-acetylcysteine ( NAC ) is a glutathione precursor that effectively replenishes brain glutathione . Given the failure of almost all modern trials of antidepressants in bipolar disorder to demonstrate efficacy , and the limited efficacy of mood stabilisers in the depressive phase of the disorder , this is a major unmet need . METHOD This study reports data on the treatment of 149 individuals with moderate depression during the 2 month open label phase of a r and omised  placebo controlled clinical trial of the efficacy of 1 g BID of NAC that examined the use of NAC as a maintenance treatment for bipolar disorder . RESULTS In this trial , the estimated mean baseline Bipolar Depression Rating Scale ( BDRS ) score was 19.7 ( SE=0.8 ) , and the mean BDRS score at the end of the 8 week open label treatment phase was 11.1 ( SE=0.8 ) . This reduction was statistically significant ( p<0.001 ) . Improvements in functioning and quality of life were similarly evident . CONCLUSION These open label data demonstrate a robust decrement in depression scores with NAC treatment . Large placebo controlled trials of acute bipolar depression are warranted Neutrophilic airway inflammation is a hallmark of cystic fibrosis ( CF ) . As high oxidant producers , airway neutrophils contribute largely to the systemic redox imbalance seen in CF . In turn , this chronic and profound imbalance can impact circulating neutrophils before their migration into airways . Indeed , in 18 CF patients with stable disease , blood neutrophils were readily deficient in the pivotal antioxidant glutathione ( P = 0.003 , compared with 9 healthy controls ) . In a phase 1 study , this deficiency was improved ( P = 0.025 ) by the glutathione prodrug N-acetylcysteine , given orally in high doses ( 0.6 to 1.0 g three times daily , for 4 weeks ) . This treatment was safe and markedly decreased sputum elastase activity ( P = 0.006 ) , the strongest predictor of CF pulmonary function . Consistently , neutrophil burden in CF airways was decreased upon treatment ( P = 0.003 ) , as was the number of airway neutrophils actively releasing elastase-rich granules ( P = 0.005 ) , as measured by flow cytometry . Pulmonary function measures were not improved , as expected with short-term treatment . After excluding data from subjects without baseline airway inflammation , positive treatment effects were more pronounced and included decreased sputum IL-8 levels ( P = 0.032 ) . Thus , high-dose oral N-acetylcysteine has the potential to counter the intertwined redox and inflammatory imbalances in CF Background Previous studies have demonstrated the potential beneficial effect of N-acetylcysteine ( NAC ) in chronic obstructive pulmonary disease ( COPD ) . However , the required dose and responder phenotype remain unclear . The current study investigated the effect of high-dose NAC on airway geometry , inflammation , and oxidative stress in COPD patients . Novel functional respiratory imaging methods combining multislice computed tomography images and computer-based flow simulations were used with high sensitivity for detecting changes induced by the therapy . Methods Twelve patients with Global Initiative for Chronic Obstructive Lung Disease stage II COPD were r and omized to receive NAC 1800 mg or placebo daily for 3 months and were then crossed over to the alternative treatment for a further 3 months . Results Significant correlations were found between image-based resistance values and glutathione levels after treatment with NAC ( P = 0.011 ) and glutathione peroxidase at baseline ( P = 0.036 ) . Image-based resistance values appeared to be a good predictor for glutathione peroxidase levels after NAC ( P = 0.02 ) , changes in glutathione peroxidase levels ( P = 0.035 ) , and reduction in lobar functional residual capacity levels ( P = 0.00084 ) . In the limited set of responders to NAC therapy , the changes in airway resistance were in the same order as changes induced by budesonide/formoterol . Conclusion A combination of glutathione , glutathione peroxidase , and imaging parameters could potentially be used to phenotype COPD patients who would benefit from addition of NAC to their current therapy . The findings of this small pilot study need to be confirmed in a larger pivotal trial Chronic obstructive pulmonary disease ( COPD ) affects over 16 million people in the United States and is a major cause of disability and death worldwide . Its prevalence and mortality are increasing disproportionately among the elderly , women , African-Americans , persons of lower socioeconomic status , and the population s of developing countries in which tobacco is aggressively marketed . In contrast to other major chronic diseases such as heart disease and cancer , medical treatments for COPD have not made decisive inroads into its morbidity or death rates over the last 20 years , result ing in continuing efforts to reduce disability in patients with established disease . Depression is a source of increased disability in COPD , and , as in other chronically ill patient population s , is often unrecognized and untreated in the primary and specialty care sectors . Nearly half of all patients experience some depressive symptoms and at least one-fifth have had one or more major depressive episodes , frequently of long duration . Evidence from r and omized controlled trials supports the thesis that patients with mild depression improve with multidisciplinary rehabilitation , whereas patients with major depression may require specific pharmacotherapy to achieve significant improvement in mood disorder and day-to-day function . In addition to its impact on disability , depression may contribute indirectly to the etiology and progression of COPD through its relationship to addictive smoking . Mood disorder in adolescence and early adulthood contributes to early smoking and failure to quit , even after the onset of respiratory disease in later life . Patients with a history of major depression are more likely to fail in smoking cessation programs and to develop a major depressive episode when they do stop . This relationship calls for psychiatrically informed intervention models to improve long-term abstinence rates . The functional impairments associated with COPD are themselves potential promoters of depressive morbidity and chronicity , acting through complex causal pathways . Progressive hypoxia due to respiratory insufficiency leads to structural brain changes and neurocognitive deficits that impair day-to-day function and reduce adaptive potential ;  and oxygen therapy , as now practice d , offers minimal neurocognitive and mood benefits to most patients . Limited data from studies of experimental hypoxia in animals suggest that relatively mild lack of oxygen impairs the function and plasticity of critical neurotransmitter systems implicated in both cognition and mood , although current practice st and ards withhold oxygen therapy until late in the course of disease when the damaging effects of hypoxia on the brain have become well established . Neuropsychiatric approaches to the prevention , delay , and treatment of brain dysfunction should be a primary objective of research to improve patient outcomes . A comprehensive relational model that links pulmonary disease , hypoxia , neurocognitive impairment , and structural brain disease with depression provides a useful framework for the design of such studies . The near-term research agenda should include three components : ( 1 ) practical methods for improving physician and patient recognition of depression and neurocognitive impairment as targets for intervention ; ( 2 ) additional trials of st and ard antidepressant treatment approaches for both major and minor depression ; and ( 3 ) tests of the hypothesis that late-onset depression in patients with COPD is a marker for the presence of neurocognitive deficits and structural brain changes . The long-range research agenda must aim at preventive interventions design ed to forestall brain deterioration . Controlled clinical trials of supplemental oxygen in patients with mild hypoxia and minimal cognitive deficits are needed to determine whether early treatment can reverse or moderate decline , reduce the incidence and chronicity of depression , and improve response to antidepressant treatment . Novel neuroprotective therapies such as antioxidant supplementation and modulation of monoaminergic neurotransmission , coupled with overall improvements in long-term respiratory disease management that minimize episodes of increased systemic oxidative stress , should be considered for multisite trials design ed to define optimal treatment and prevention OBJECTIVE To evaluate the efficacy of serotonin reuptake inhibitor ( SRI ) augmentation with N-acetylcysteine ( NAC ) , a glutamate modulator and antioxidant medication , for treatment-resistant obsessive-compulsive disorder ( OCD ) . METHODS We conducted a r and omized , double-blind , placebo-controlled , 16-week trial of NAC ( 3,000 mg daily ) in adults ( aged 18 - 65 years ) with treatment-resistant OCD , established according to DSM-IV criteria . Forty subjects were recruited at an OCD-specialized outpatient clinic at a tertiary hospital ( May 2012-October 2014 ) . The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale ( Y-BOCS ) scores . To evaluate the variables group , time , and interaction effects for Y-BOCS scores at all time points , we used nonparametric analysis of variance with repeated measures . Secondary outcomes were the severity scores for anxiety , depression , specific OCD symptom dimensions , and insight . RESULTS Both groups showed a significant reduction of baseline Y-BOCS scores at week 16 : the NAC group had a reduction of 4.3 points ( 25.6 to 21.3 ) , compared with 3.0 points ( 24.8 to 21.8 ) for the placebo group . However , there were no significant differences between groups ( P = .92 ) . Adding NAC was superior to placebo in reducing anxiety symptoms ( P = .02 ) , but not depression severity or specific OCD symptom dimensions . In general , NAC was well tolerated , despite abdominal pain being more frequently reported in the NAC group ( n [ % ] : NAC = 9 [ 60.0 ] , placebo = 2 [ 13.3 ] ; P < .01 ) . CONCLUSIONS Our trial did not demonstrate a significant benefit of NAC in reducing OCD severity in treatment-resistant OCD adults . Secondary analysis suggested that NAC might have some benefit in reducing anxiety symptoms in treatment-resistant OCD patients . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01555970 BACKGROUND Current pharmacological treatments for Tourette Syndrome ( TS ) , such as antipsychotic agents and α-2 agonists , are moderately effective in the treatment of tics , but have substantial side effects that limit their use . N-acetylcysteine ( NAC ) modulates glutamatergic systems , and has been used safely as an antioxidant agent with minimal side effects for decades . NAC has been increasingly studied for the treatment of other obsessive-compulsive spectrum disorders . We aim to examine the efficacy of NAC for the treatment of pediatric TS in a double-blind , placebo-controlled , add-on study . METHODS Thirty-one children and adolescents 8 - 17 years of age with TS were r and omly assigned to receive NAC or matching placebo for 12 weeks . Our primary outcome was change in severity of tics as measured by the Yale Global Tic Severity Scale ( YGTSS ) , Total tic score . Secondary measures assessed comorbid obsessive-compulsive disorder ( OCD ) , depression , anxiety , and attention-deficit/hyperactivity disorder ( ADHD ) . Linear mixed models in SAS were used to examine differences between NAC and placebo . RESULTS Of 31 r and omized subjects , 14 were assigned to placebo ( two females ; 11.5 + 2.8 years ) and 17 to active NAC ( five females ; 12.4 + 1.4 years ) treatment . No significant difference between NAC and placebo was found in reducing tic severity or any secondary outcomes . CONCLUSIONS We found no evidence for efficacy of NAC in treating tic symptoms . Our findings st and in contrast to studies suggesting benefits of NAC in the treatment of other obsessive-compulsive spectrum disorders in adults , including OCD and trichotillomania , but are similar to a recent placebo-controlled trial of pediatric trichotillomania that found no benefit of NAC Chronic obstructive pulmonary disease ( COPD ) is an irreversible disorder characterized by airflow obstruction and a progressive decline in forced expiratory volume in one second ( FEV1 ) . At present , no treatment except quitting smoking appears to affect the progression of the disease . Oxidative stress has been implicated in its pathogenesis . The Bronchitis R and omized on NAC Cost-Utility Study ( BRONCUS ) is a phase III , r and omized , double-blind , placebo-controlled , parallel group , multicentre study design ed to assess the effectiveness of the antioxidant agent N-acetylcysteine ( NAC ) in altering the decline in FEV1 , exacerbation rate , and quality of life in patients with moderate to severe COPD . In addition , cost-utility of the treatment will be estimated . Patients will be followed for 3 yrs and evaluated every 3 months . The necessary sample size to demonstrate an effect on the decline in FEV1 of 20 mL x yr(-1 ) was estimated to be 478 patients . Five hundred and twenty-three patients with moderate to severe COPD were recruited from 10 European countries from June 1 , 1997-December 31 , 1999 . They were 63+/-8 yrs old and consisted of 243 ( 46 % ) current smokers and 280 ( 54 % ) exsmokers . Patients had on the average 4.9+/-1.6 exacerbations during the last 2 yrs . Postbronchodilator FEVI averaged 57+/-9 % and the reversibility after 400 microg of Salbutamol averaged 4+/-4 % predicted . The final results of the trial will be available in about 2 yrs . The study will provide objective data on the effects of N-acetylcysteine on outcome variables in chronic obstructive pulmonary disease Antioxidant therapy has a potential to be introduced as therapeutic modality for chronic obstructive pulmonary disease ( COPD ) patients . This study aim ed to determine the effect of antioxidant supplementation [ ascorbic acid and N-Acetylcysteine ( NAC ) ] on nutritional and antioxidant status in male COPD patients . A parallel and single blind r and omised controlled clinical trial ( RCT ) was conducted at two medical centers in Kuala Lumpur , Malaysia . Seventy-nine subjects were recruited and r and omly divided into four trial arms ( i.e. , NAC , vitamin C , NAC+vitamin C and control groups ) for six mo . The primary outcome was changes in body mass index by estimating power of 90 % and significance level of p<0.05 . Repeated Measure ANOVA showed that there was a significant interaction effect on BMI ( p=0.046 ) and carbohydrate intake ( p=0.030 ) , especially in the NAC group . Plasma glutathione ( GSH ) increased significantly in all intervention groups , especially in vitamin C ( p=0.005 ) . A single supplementation of NAC or vitamin C improved nutritional and antioxidant status of subjects Psychiatric disorders in general , and major depression and anxiety disorders in particular , account for a large burden of disability , morbidity and premature mortality worldwide . Omega-3 polyunsaturated fatty acids ( PUFAs ) have a range of neurobiological activities in modulation of neurotransmitters , anti-inflammation , anti-oxidation and neuroplasticity , which could contribute to psychotropic effects . Here we review ed recent research on the benefits of omega-3 PUFA supplements in prevention against  major depression , bipolar disorders , interferon-α-induced depression patients with chronic hepatitis C viral infection , and posttraumatic stress disorder . The biological mechanisms underlying omega-3 PUFAs ’ psychotropic effects are proposed and review ed . Nutrition is a modifiable environmental factor that might be important in prevention medicine , which have been applied for many years in the secondary prevention of heart disease with omega-3 PUFAs . This review extends the notion that nutrition in psychiatry is a modifiable environmental factor and calls for more research es on prospect i ve clinical studies to justify the preventive application of omega-3 PUFAs in daily practice BACKGROUND Increased oxidative stress and inflammation has a role in the pathogenesis of chronic obstructive pulmonary disease ( COPD ) . Drugs with antioxidant and anti-inflammatory properties , such as N-acetylcysteine , might provide a useful therapeutic approach for COPD . We aim ed to assess whether N-acetylcysteine could reduce the rate of exacerbations in patients with COPD . METHODS In our prospect i ve , r and omised , double-blind , placebo-controlled , parallel-group study , we enrolled patients aged 40 - 80 years with moderate-to-severe COPD ( post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity < 0·7 and FEV1 of 30 - 70 % of predicted ) at 34 hospitals in China . We stratified patients according to use of inhaled corticosteroids ( regular use or not ) at baseline and r and omly allocated them to receive N-acetylcysteine ( one 600 mg tablet , twice daily ) or matched placebo for 1 year . The primary endpoint was the annual exacerbation rate in patients who received at least one dose of study drug and had at least one assessment visit after r and omisation . This study is registered with the Chinese Clinical Trials Registry , ChiCTR-TRC-09000460 . FINDINGS Between June 25 , 2009 , and Dec 29 , 2010 , we screened 1297 patients , of whom 1006 were eligible for r and omisation ( 504 to N-acetylcysteine  and 502  to placebo )  . After 1 year , we noted 497 acute exacerbations in 482 patients in the N-acetylcysteine group who received at least one dose and had at least one assessment visit ( 1·16 exacerbations per patient-year ) and 641 acute exacerbations in 482 patients in the placebo group ( 1·49 exacerbations per patient-year ; risk ratio 0·78 , 95 % CI 0·67 - 0·90 ; p=0·0011 ) . N-acetylcysteine  was well tolerated : 146 ( 29 % ) of 495 patients who received at least one dose of N-acetylcysteine  had adverse events ( 48 serious ) , as did 130 ( 26 % ) of 495 patients who received at least one dose of placebo ( 46 serious ) . The most common serious adverse event was acute exacerbation of COPD , occurring in 32 ( 6 % ) of 495 patients in the N-acetylcysteine group and 36 ( 7 % ) of 495 patients in the placebo group . INTERPRETATION Our findings show that in Chinese patients with moderate-to-severe COPD , long-term use of N-acetylcysteine 600 mg twice daily can prevent exacerbations , especially in disease of moderate severity . Future studies are needed to explore efficacy in patients with mild COPD ( GOLD I ) . FUNDING Hainan Zambon Pharmaceutical BACKGROUND Increased oxidative stress is important in the pathogenesis of chronic obstructive pulmonary disease ( COPD ) . We postulated that treatment with the antioxidant N-acetylcysteine would reduce the rate of lung-function decline , reduce yearly exacerbation rate , and improve outcomes . METHODS In a r and omised  placebo-controlled study in 50 centres , 523 patients with COPD were r and omly assigned to 600 mg daily N-acetylcysteine or placebo . Patients were followed for 3 years . Primary outcomes were yearly reduction in forced expiratory volume in 1 s ( FEV1 ) and the number of exacerbations per year . Analysis was by intention to treat . FINDINGS The yearly rate of decline in FEV1 did not differ between patients assigned N-acetylcysteine and those assigned placebo ( 54 mL [ SE 6 ] vs 47 mL [ 6 ] ; difference in slope between groups 8 mL [ 9 ] ; 95 % CI -25 to 10 ) . The number of exacerbations per year did not differ between groups ( 1.25 [ SD 1.35 ] vs 1.29 [ SD 1.46 ] ; hazard ratio 0.99 [ 95 % CI 0.89 - 1.10 , p=0.85 ] ) . Subgroup analysis suggested that the exacerbation rate might be reduced with N acetylcysteine in patients not treated with inhaled corticosteroids and secondary analysis was suggestive of an effect on hyperinflation . INTERPRETATION N-acetylcysteine is ineffective at prevention of deterioration in lung function and prevention of exacerbations in patients with COPD Epilepsy is known as one of the most frequent neurological diseases , characterized by an enduring predisposition to generate epileptic seizures . Oxidative stress is believed to directly participate in pathways leading to neurodegeneration , which serves as the most important propagating factor , leading to the epileptic condition and cognitive decline . Moreover , there is also a growing body of evidence showing the disturbance of antioxidant system balance and consequently increased production of reactive species in patients with epilepsy . A meta- analysis , conducted in the present review confirms an association between epilepsy and increased lipid peroxidation . Furthermore , it was also shown that some of the antiepileptic drugs could potentially be responsible for additionally increased lipid peroxidation . Therefore , it is reasonable to propose that during the epileptic process neuroprotective treatment with antioxidants could lead to less sever structural damages , reduced epileptogenesis and milder cognitive deterioration . To evaluate this hypothesis studies investigating the neuroprotective therapeutic potential of various antioxidants in cells , animal seizure models and patients with epilepsy have been review ed . Numerous beneficial effects of  antioxidants on oxidative stress markers and in some cases also neuroprotective effects were observed in animal seizure models . However , despite these encouraging results , till now only a few antioxidants have been further applied to patients with epilepsy as an add-on therapy . Based on the several positive findings in animal models , a strong need for more carefully planned , r and omized , double-blind , cross-over , placebo-controlled clinical trials for the evaluation of  antioxidants efficacy in patients with epilepsy is warranted Objectives Despite the burden of negative symptoms on quality of life in schizophrenic patients , no completely effective treatment has been developed to address such symptoms yet . Abnormalities in oxidative stress pathways have been recently demonstrated to be involved in the pathophysiology of schizophrenia , and a growing interest in antioxidant agents is emerging for targeting negative symptoms of schizophrenia . N-Acetylcysteine ( NAC ) is a potent antioxidant with neuroprotective properties . This study aim ed to evaluate the possible effects of NAC as an adjunct to risperidone in treating negative symptoms of schizophrenia . Material s and Methods In this r and omized , double-blind , placebo-controlled , parallel-group study , 42 patients with chronic schizophrenia and a score of 20 or greater on the negative subscale of positive and negative syndrome scale ( PANSS ) were enrolled in the active phase of their illness . The participants were equally r and omized to receive NAC ( up to 2 g/d ) or placebo , in addition to risperidone ( up to 6 mg/d ) for 8 weeks . The participants were rated using PANSS every 2 weeks , and the decrease of PANSS negative subscale score was considered as our primary outcome . Results By the study end point , NAC-treated patients showed significantly greater improvement in the PANSS total ( P = 0.006 ) and negative subscale ( P < 0.001 ) scores than that in the placebo group , but this difference was not significant for positive and general psychopathology subscales . There was no significant difference between the 2 groups in the frequency of adverse effects .  Conclusions NAC add-on therapy showed to be a safe and effective augmentative strategy for alleviating negative symptoms of schizophrenia The effects of two forms of antioxidative co-therapy were analyzed in 24 interferon-alpha (IFN)-naive patients with chronic hepatitis C who were r and omized to either receive IFN monotherapy ( 3 x 4.5 million units IFN-alpha 2a per week ) , ( group A ) , or IFN and N-acetylcysteine ( N-acetylcysteine ( NAC ) 1.800 mg/day ) plus sodium selenite ( 400 microg/day ) supplementation ( group B ) , or treatment as in group B plus vitamin E ( 544 IU/day ) ( group C ) , over 24 weeks . Changes in histology , normalization of ALT , reduction of viral RNA , serum levels of glutathione , selenium , vitamin E , erythrocyte glutathione peroxidase , trolox equivalent antioxidative capacity ( TEAC ) , thiobarbituric acid reactive substances ( TBARS ) and protein carbonyl groups were measured . Low baseline TEAC and elevated TBARS indicated increased oxidative stress before therapy , which was not affected by antioxidant supplementation . At the end of treatment complete responses were found in 3/8 , 2/8 and 6/8 patients in groups A , B and C , respectively , but liver histology had not significantly improved . Vitamin E treated patients had a 2.4 greater chance ( 95 % CI : 1.05 - 5.5 ) of obtaining a complete response and had significantly greater reduction in viral load ( P = 0.028 ) than patients without vitamin E.  Relapses , i.e. re-appearance of detectable hepatitis C virus ( HCV ) RNA and /or re-elevation of ALT-activity occurred in 7 out of the 11 responders within 6 months after termination of therapy ( group A : 2/3 , group B : 1/2 and group C : 4/6 ) . Thus , no overall beneficial effect of antioxidant/IFN therapy was detected . However , the apparent trend towards a more favorable outcome with vitamin E supplementation warrants to further study this substance as an adjuvant to IFN therapy in chronic hepatitis OBJECTIVE Neurologic diseases such as stroke are risk factors for new-onset epilepsy in older adults . Recent evidence suggests that psychiatric disorders independently predict epilepsy in older male veterans . Our aim was to examine the relationship between these disorders in a population -based study of older adults that also included women and minorities . METHODS We used a national 5 % r and om sample of 2005 Medicare beneficiaries including all 50 US states and Washington , DC . Beneficiaries were 65 years of age or older , with continuous Medicare Part A and Part B coverage and not in managed care plans . Epilepsy cases were identified from cl aims for physician visits , hospitalizations , and outpatient procedures . We used logistic regressions for the overall sample and stratified by gender to determine whether risk of new-onset epilepsy was associated with prior history of psychiatric ( i.e. , depression , psychosis , bipolar disorder , schizophrenia , posttraumatic stress disorder ( PTSD ) , adjustment disorder , and substance abuse/dependence ) and neurologic conditions ( i.e. , cerebrovascular disease , dementia , traumatic brain injury , brain tumor , metastatic cancer ) . RESULTS Preexisting psychiatric disorders were significantly associated with new-onset epilepsy in the study population as were the neurologic conditions evaluated . Five of the seven psychiatric disorders examined were independently associated with new-onset epilepsy ; substance abuse , psychosis , bipolar disorder , schizophrenia , and depression . Gender interaction effects were found for substance abuse/dependence and brain tumors . SIGNIFICANCE Both neurologic and psychiatric factors significantly predicted new-onset epilepsy in a population -based sample of male and female older adults . These results support earlier findings and extend the underst and ing of risk models for new-onset epilepsy in broader older adult population Abstract Biomarker-guided treatments are needed in psychiatry , and previous data suggest oxidative stress may be a target in schizophrenia . A previous add-on trial with the antioxidant N-acetylcysteine ( NAC ) led to negative symptom reductions in chronic patients . We aim to study NAC ’s impact on symptoms and neurocognition in early psychosis ( EP ) and to explore whether glutathione (GSH)/redox markers could represent valid biomarkers to guide treatment . In a double-blind , r and omized , placebo-controlled trial in 63 EP patients , we assessed the effect of NAC supplementation ( 2700 mg/day , 6 months ) on PANSS , neurocognition , and redox markers ( brain GSH [ GSHmPFC ] , blood cells GSH levels [ GSHBC ] , GSH peroxidase activity [ GPxBC ] ) . No changes in negative or positive symptoms or functional outcome were observed with NAC , but significant improvements were found in favor of NAC on neurocognition ( processing speed ) . NAC also led to increases of GSHmPFC by 23 % ( P = .005 ) and GSHBC by 19 % ( P = .05 ) . In patients with high-baseline GPxBC compared to low-baseline GPxBC , subgroup explorations revealed a link between changes of positive symptoms and changes of redox status with NAC . In conclusion , NAC supplementation in a limited sample of EP patients did not improve negative symptoms , which were at modest baseline levels . However , NAC led to some neurocognitive improvements and an increase in brain GSH levels , indicating good target engagement . Blood GPx activity , a redox peripheral index associated with brain GSH levels , could help identify a subgroup of patients who improve their positive symptoms with NAC . Thus , future trials with antioxidants in EP should consider biomarker-guided treatment We conducted a review of systematic review s ( SRs ) and r and omized-controlled trials ( RCTs ) to analyze efficacy and safety of cannabis-based medication in patients with mental disorders . Five data bases were systematic ally search ed ( 2006—August 2018 ) ; 4 SRs ( of 11 RCTs ) and 14 RCTs ( 1629 participants ) were included . Diagnoses were : dementia , cannabis and opioid dependence , psychoses/schizophrenia , general social anxiety , posttraumatic stress disorder , anorexia nervosa , attention-deficit hyperactivity disorder , and Tourette`s disorder . Outcome variables were too heterogeneous to conduct a meta- analysis . A narrative synthesis method was applied . The study quality was assessed using the risk-of-bias tool and SIGN-checklists . THC- and CBD-based medicines , given as adjunct to pharmaco- and psychotherapy , were associated with improvements of several symptoms of mental disorders , but not with remission . Side effects occurred , but severe adverse effects were mentioned in single cases only . In order to provide reliable treatment recommendations , more and larger RCTs with follow-up assessment s , consistent outcome measures and active comparisons are needed Abstract Chronic obstructive pulmonary disease ( COPD ) is characterized by persistent airflow limitation ; from a pathophysiological point of view it involves many components , including mucus hypersecretion , oxidative stress and inflammation . N-acetylcysteine ( NAC ) is a mucolytic agent with antioxidant and anti-inflammatory properties . Long-term efficacy of NAC 600mg/d in COPD is controversial ; a dose-effect relationship has been demonstrated , but at present it is not known whether a higher dose provides clinical benefits . The PANTHEON Study is a prospect i ve , ICS stratified , r and omized , double-blind , placebo-controlled , parallel-group , multi-center trial design ed to assess the efficacy and safety of high-dose ( 1200 mg/daily ) NAC treatment for one year in moderate-to-severe COPD patients . The primary endpoint is the annual exacerbation rate . Secondary endpoints include recurrent exacerbations hazard ratio , time to first exacerbation , as well as quality of life and pulmonary function . The hypothesis , design and methodology are described and baseline characteristics of recruited patients are presented . 1006 COPD patients ( 444 treated with maintenance ICS , 562 ICS naive , aged 66.27±8.76 yrs , average post-bronchodilator FEV1 48.95±11.80 of predicted ) have been r and omized at 34 hospitals in China . Final results of this study will provide objective data on the effects of high-dose ( 1200 mg/daily ) long-term NAC treatment in the prevention of COPD exacerbations and other outcome variables OBJECTIVE --To see whether intravenous acetylcysteine would improve outcome in patients with fulminant hepatic failure after paracetamol overdose . DESIGN --A prospect i ve r and omised controlled study . SETTING --The Institute of Liver Studies , King 's College Hospital , London . PATIENTS --50 consecutive patients ( 21 male ) aged 16 - 60 with fulminant hepatic failure after paracetamol overdose who had not previously received acetylcysteine . INTERVENTIONS --Conventional intensive liver care plus either acetylcysteine ( 25 patients ) in the same dose regimen as used early after a paracetamol overdose , except that the infusion was continued until recovery from encephalopathy or death , or an equivalent volume of 5 % dextrose ( 25 patients ) . MAIN OUTCOME MEASURES --Survival ; incidence of cerebral oedema , renal failure , and hypotension requiring inotropic support ; liver function as assessed by prolongation of the prothrombin time ; and degree of encephalopathy . RESULTS --The rate of survival was significantly higher in the acetylcysteine treated group than in the controls ( 48 % ( 12/25 patients ) v 20 % ( 5/25 ) ; p = 0.037 , 95 % confidence interval for difference in proportions surviving 3 % to 53 % ) . Acetylcysteine treated patients had a lower incidence of cerebral oedema ( 40 % ( 10/25 ) v 68 % ( 17/25 ) ; p = 0.047 , 95 % confidence interval for difference in incidence 2 % to 54 % ) , and fewer developed hypotension requiring inotropic support ( 48 % ( 12/25 ) v 80 % ( 20/25 ) ; p = 0.018 , 95 % confidence interval 7 % to 57 % ) . Rates of deterioration and recovery of liver function , however , were similar in the two groups . No adverse reactions to acetylcysteine were seen . CONCLUSIONS --Acetylcysteine is safe and effective in fulminant hepatic failure after paracetamol overdose Background : Adverse health effects associated with diesel exhaust ( DE ) are thought to be mediated in part by oxidative stress , but the detailed mechanisms are largely unknown . MicroRNAs ( miRNAs ) regulate gene expression post-transcriptionally and may respond to exposures such as DE . Objectives : We profiled peripheral blood cellular miRNAs in participants with mild asthma who were exposed to controlled DE with and without antioxidant supplementation .  Methods : Thirteen participants with asthma underwent controlled inhalation of filtered air and DE in a double-blinded , r and omized crossover study of three conditions : a ) DE plus placebo ( DEP ) , b ) filtered air plus placebo ( FAP ) , or c ) DE with N-acetylcysteine supplementation ( DEN ) . Total cellular RNA was extracted from blood drawn before exposure and 6 hr after exposure for miRNA profiling by the NanoString nCounter assay . MiRNAs significantly associated with DEP exposure and a predicted target [ nuclear factor ( erythroid-derived 2)-like 2 ( NRF2 ) ] as well as antioxidant enzyme genes were assessed by reverse transcription – quantitative polymerase chain reaction ( RT-qPCR ) for validation , and we also assessed the ability of N-acetylcysteine supplementation to block the effect of DE on these specific miRNAs . 8-hydroxy-2´-deoxyguanosine ( 8-OHdG ) was measured in plasma as a systemic oxidative stress marker . Results : Expression of miR-21 , miR-30e , miR-215 , and miR-144 was significantly associated with DEP . The change in miR-144 was vali date d by RT-qPCR . NRF2 and its downstream antioxidant genes [ glutamate cysteine ligase catalytic subunit ( GCLC ) and NAD(P)H : quinone oxidoreductase 1 ( NQO1 ) ] were negatively associated with miR-144 levels . Increases in miR-144 and miR-21 were associated with plasma 8-hydroxydeoxyguanosine 8-OHdG level and were blunted by antioxidant ( i.e , DEN ) . Conclusions : Systemic miRNAs with plausible biological function are altered by acute moderate-dose DE exposure . Oxidative stress appears to mediate DE-associated changes in miR-144 In this report , which is an up date of a guideline published in 2002 ( B and elow et al. 2002 , World J Biol Psychiatry 3:171 ) , recommendations for the pharmacological treatment of anxiety disorder , obsessive-compulsive disorder ( OCD ) and post-traumatic stress disorder ( PTSD ) are presented . Since the publication of the first version of this guideline , a substantial number of new r and omized controlled studies of anxiolytics have been published . In particular , more relapse prevention studies are now available that show sustained efficacy of anxiolytic drugs . The recommendations , developed by the World Federation of Societies of Biological Psychiatry ( WFSBP ) Task Force for the Pharmacological Treatment of Anxiety , Obsessive-Compulsive and Post-traumatic Stress Disorders , a consensus panel of 30 international experts , are now based on 510 published r and omized , placebo- or comparator-controlled clinical studies ( RCTs ) and 130 open studies and case reports . First-line treatments for these disorders are selective serotonin reuptake inhibitors ( SSRIs ) , serotonin-noradrenaline reuptake inhibitors ( SNRIs ) and the calcium channel modulator pregabalin . Tricyclic antidepressants ( TCAs ) are equally effective for some disorders , but many are less well tolerated than the SSRIs/SNRIs . In treatment-resistant cases , benzodiazepines may be used when the patient does not have a history of substance abuse disorders . Potential treatment options for patients unresponsive to st and ard treatments are described in this overview . Although these guidelines focus on medications , non-pharmacological were also considered . Cognitive behavioural therapy ( CBT ) and other variants of behaviour therapy have been sufficiently investigated in controlled studies in patients with anxiety disorders , OCD , and PTSD to support them being recommended either alone or in combination with the above medicines
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 .
Oral N-acetylcysteine is safe and well tolerated without any considerable adverse effects .
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 synthesis es and presents the current evidence from systematic review s , meta-analyses , and latest clinical trials on N-acetylcysteine for addiction and substance abuse , schizophrenia , obsessive-compulsive and related disorders , and mood disorders .