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.
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
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 .