Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON): a randomised, double-blind placebo-controlled trial. N-acetylcysteine add-on treatment in refractory obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled trial. Potential of N-acetylcysteine as treatment for the adult respiratory distress syndrome. N-Acetylcysteine as an Adjunct to Risperidone for Treatment of Negative Symptoms in Patients With Chronic Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study Improvement by N-acetylcysteine of acute respiratory distress syndrome through increasing intracellular glutathione, and extracellular thiol molecules and anti-oxidant power: evidence for underlying toxicological mechanisms N-acetylcysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis Antioxidant treatment with N‐acetylcysteine during adult respiratory distress syndrome: A prospective, randomized, placebo‐controlled study The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: an open label trial. N-Acetyl Cysteine as a Glutathione Precursor for Schizophrenia—A Double-Blind, Randomized, Placebo-Controlled Trial N-acetylcysteine as adjunctive treatment in severe malaria: A randomized, double-blinded placebo-controlled clinical trial* N-acetylcysteine add-on treatment leads to an improvement of fornix white matter integrity in early psychosis: a double-blind randomized placebo-controlled trial Adjunctive sarcosine plus benzoate improved cognitive function in chronic schizophrenia patients with constant clinical symptoms: A randomised, double-blind, placebo-controlled trial Add-on treatment of benzoate for schizophrenia: a randomized, double-blind, placebo-controlled trial of D-amino acid oxidase inhibitor. Omega-3 fatty acids in first-episode schizophrenia - a randomized controlled study of efficacy and relapse prevention (OFFER): rationale, design, and methods Supplementation of Antipsychotic Treatment with the Amino Acid Sarcosine Influences Proton Magnetic Resonance Spectroscopy Parameters in Left Frontal White Matter in Patients with Schizophrenia High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis. Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial
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 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 The adult respiratory distress syndrome ( ARDS ) , often referred to as non-cardiac pulmonary oedema , is now regarded as a very complicated inflammatory process with oedema being only one facet . In recognition of this , pharmacologic therapy with anti-inflammatory corticosteroids was used widely until the completion of r and omized clinical trials . Unfortunately , corticosteroids have not been proved to be useful in preventing ARDS in septic patients nor in patients with established ARDS and this has led to investigations with pharmacologic agents which are safer and more specifically targeted to certain parts of the inflammatory process . We have examined the role of the glutathione anti-oxidant system in the sheep model of ARDS as well as in patients with established ARDS through use of intravenous N-acetylcysteine ( NAC ) . We have found that the response to endotoxin is markedly blunted in sheep treated with NAC . In our controlled clinical trials with NAC we found that patients with ARDS have depressed plasma and red cell glutathione concentrations , that these levels are substantially increased by therapy with intravenous NAC and there are measurable clinical responses to treatment with regard to increased oxygen delivery , improved lung compliance and resolution of pulmonary oedema 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 In acute respiratory distress syndrome ( ARDS ) , there is extensive overproduction of free radicals to the extent that endogenous anti-oxidants are overwhelmed , permitting oxidative cell damage . The present study examined the benefit of the anti-oxidant compound N-acetylcysteine ( NAC ) in the management of ARDS by measuring patient 's intracellular glutathione ( inside red blood cells ) and extracellular ( plasma ) anti-oxidant defense biomarkers and outcome . Twenty-seven ARDS patients were recruited from the intensive care unit of a teaching Hospital and r and omly divided into two groups . Both groups were managed similarly by regular treatments but 17 patients received NAC 150 mg/kg at the first day that followed by 50 mg/kg/day for three days and 10 patients did not receive NAC . Treatment by NAC  increased extracellular total anti-oxidant power and total thiol molecules and also improved intracellular glutathione and the outcome of the patients . In conclusion , patients with ARDS are in a deficient oxidant — anti-oxidant balance that can get a significant benefit if supplemented with NAC . Human & Experimental Toxicology ( 2007 ) 26 , 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 Objective To examine whether the antioxidant N-acetylcysteine could ameliorate the course of the adult respiratory distress syndrome ( ARDS ) in man . Design R and omized , double-blind , placebo-controlled study . Setting Medical and surgical ICU in a regional hospital . Patients Sixty-six ICU patients with ARDS . Interventions Patients with ARDS ( Pao2/FIO2 ratio < 250 torr ) were treated with either the antioxidant N-acetylcysteine 150 mg/kg as a loading dose and then 20 mg/kg/hr , or with placebo for 6 days . Measurements and Main Results No improvement could be demonstrated in the Pao2/FIO2 ratio in the study group as compared with the control group on any day . Pulmonary compliance was higher in the N-acetylcysteine group than in the placebo group on all days , but this difference did not reach the chosen 5 % level of significance . No difference between the two groups could be demonstrated on chest radiograph or on survival rate . We documented that N-acetylcysteine acts as an anticoagulant and perhaps decreases pulmonary fibrin uptake during ARDS . Conclusions N-acetylcysteine might be of benefit in ARDS . Before further clinical studies are started , problems with N-acetylcysteine and coagulation have to be eluci date d in order to find out whether N-acetylcysteine could have a beneficial effect in the treatment of ARDS 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 BACKGROUND Brain glutathione levels are decreased in schizophrenia , a disorder that often is chronic and refractory to treatment . N-acetyl cysteine ( NAC ) increases brain glutathione in rodents . This study was conducted to evaluate the safety and effectiveness of oral NAC ( 1 g orally twice daily [ b.i.d . ] ) as an add-on to maintenance medication for the treatment of chronic schizophrenia over a 24-week period . METHODS A r and omized , multicenter , double-blind , placebo-controlled study . The primary readout was change from baseline on the Positive and Negative Symptoms Scale ( PANSS ) and its components . Secondary readouts included the Clinical Global Impression ( CGI ) Severity and Improvement scales , as well as general functioning and extrapyramidal rating scales . Changes following a 4-week treatment discontinuation were evaluated . One hundred forty people with chronic schizophrenia on maintenance antipsychotic medication were r and omized ; 84 completed treatment . RESULTS Intent-to-treat analysis revealed that subjects treated with NAC improved more than placebo-treated subjects over the study period in PANSS total [ -5.97 ( -10.44 , -1.51 ) , p = .009 ] , PANSS negative [ mean difference -1.83 ( 95 % confidence interval : -3.33 , -.32 ) , p = .018 ] , and PANSS general [ -2.79 ( -5.38 , -.20 ) , p = .035 ] , CGI-Severity ( CGI-S ) [ -.26 ( -.44 , -.08 ) , p = .004 ] , and CGI-Improvement ( CGI-I ) [ -.22 ( -.41 , -.03 ) , p = .025 ] scores . No significant change on the PANSS positive subscale was seen . N-acetyl cysteine treatment also was associated with an improvement in akathisia ( p = .022 ) . Effect sizes at end point were consistent with moderate benefits . CONCLUSIONS These data suggest that adjunctive NAC has potential as a safe and moderately effective augmentation strategy for chronic schizophrenia Objective : Markers of oxidative stress are reported to be increased in severe malaria . It has been suggested that the antioxidant N-acetylcysteine ( NAC ) may be beneficial in treatment . We studied the efficacy and safety of parenteral NAC as an adjunct to artesunate treatment of severe falciparum malaria . Design : A r and omized , double-blind , placebo-controlled trial on the use of high-dose intravenous NAC as adjunctive treatment to artesunate . Setting : A provincial hospital in Western Thail and and a tertiary referral hospital in Chittagong , Bangladesh . Patients : One hundred eight adult patients with severe falciparum malaria . Interventions : Patients were r and omized to receive NAC or placebo as an adjunctive treatment to intravenous artesunate . Measurements and Main Results : A total of 56 patients were treated with NAC and 52 received placebo . NAC had no significant effect on mortality , lactate clearance times ( p = 0.74 ) , or coma recovery times ( p = 0.46 ) . Parasite clearance time was increased from 30 hours ( range , 6–144 hours ) to 36 hours ( range , 6–120 hours ) ( p = 0.03 ) , but this could be explained by differences in admission parasitemia . Urinary F2-isoprostane metabolites , measured as a marker of oxidative stress , were increased in severe malaria compared with patients with uncomplicated malaria and healthy volunteers . Admission red cell rigidity correlated with mortality , but did not improve with NAC . Conclusion : Systemic oxidative stress is increased in severe malaria . Treatment with NAC had no effect on outcome in patients with severe falciparum malaria in this setting Mechanism-based treatments for schizophrenia are needed , and increasing evidence suggests that oxidative stress may be a target . Previous research has shown that N-acetylcysteine ( NAC ) , an antioxidant and glutathione ( GSH ) precursor almost devoid of side effects , improved negative symptoms , decreased the side effects of antipsychotics , and improved mismatch negativity and local neural synchronization in chronic schizophrenia . In a recent double-blind r and omized placebo-controlled trial by Conus et al. , early psychosis patients received NAC add-on therapy ( 2700 mg/day ) for 6 months . Compared with placebo-treated controls , NAC patients showed significant improvements in neurocognition ( processing speed ) and a reduction of positive symptoms among patients with high peripheral oxidative status . NAC also led to a 23 % increase in GSH levels in the medial prefrontal cortex ( GSHmPFC ) as measured by 1H magnetic resonance spectroscopy . A subgroup of the patients in this study were also scanned with multimodal MR imaging ( spectroscopy , diffusion , and structural ) at baseline ( prior to NAC/placebo ) and after 6 months of add-on treatment . Based on prior translational research , we hypothesized that NAC would protect white matter integrity in the fornix . A group × time interaction indicated a difference in the 6-month evolution of white matter integrity ( as measured by generalized fractional anisotropy , gFA ) in favor of the NAC group , which showed an 11 % increase . The increase in gFA correlated with an increase in GSHmPFC over the same 6-month period . In this secondary study , we suggest that NAC add-on treatment may be a safe and effective way to protect white matter integrity in early psychosis patients Abstract Objectives Hypofunction of NMDA receptor is implicated in the pathophysiology , particularly cognitive impairment , of schizophrenia .  Sarcosine , a glycine transporter I ( GlyT-1 ) inhibitor , and sodium benzoate , a d-amino acid oxidase ( DAAO ) inhibitor , can both enhance NMDA receptor-mediated neurotransmission . We proposed simultaneously inhibiting DAAO and GlyT-1 may be more effective than inhibition of either in improving the cognitive and global functioning of schizophrenia patients . Methods This study compared add-on sarcosine ( 2 g/day ) plus benzoate ( 1 g/day ) vs. sarcosine ( 2 g/day ) for the clinical symptoms , as well as the cognitive and global functioning , of chronic schizophrenia patients in a 12-week , double-blind , r and omised , placebo-controlled trial . Participants were measured with the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale every 3 weeks . Seven cognitive domains , recommended by the Measurement and Treatment Research to Improve Cognition in Schizophrenia Committee , were measured at weeks 0 and 12 . Results Adjunctive sarcosine plus benzoate , but not sarcosine alone , improved the cognitive and global functioning of patients with schizophrenia , even when their clinical symptoms had not improved . Conclusions This finding suggests N-methyl-d-aspartate receptor-enhancement therapy can improve the cognitive function of patients with schizophrenia , further indicating this pro-cognitive effect can be primary without improvement in clinical symptoms IMPORTANCE In addition to dopaminergic hyperactivity , hypofunction of the N-methyl-d-aspartate receptor ( NMDAR ) has an important role in the pathophysiology of schizophrenia . Enhancing NMDAR-mediated neurotransmission is considered a novel treatment approach . To date , several trials on adjuvant NMDA-enhancing agents have revealed beneficial , but limited , efficacy for positive and negative symptoms and cognition . Another method to enhance NMDA function is to raise the levels of d-amino acids by blocking their metabolism . Sodium benzoate is a d-amino acid oxidase inhibitor . OBJECTIVE To examine the clinical and cognitive efficacy and safety of add-on treatment of sodium benzoate for schizophrenia . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled trial in 2 major medical centers in Taiwan composed of 52 patients with chronic schizophrenia who had been stabilized with antipsychotic medications for 3 months or longer . INTERVENTIONS Six weeks of add-on treatment of 1 g/d of sodium benzoate or placebo . MAIN OUTCOMES AND MEASURES The primary outcome measure was the Positive and Negative Syndrome Scale ( PANSS ) total score . Clinical efficacy and adverse effects were assessed biweekly . Cognitive functions were measured before and after the add-on treatment . RESULTS Benzoate produced a 21 % improvement in PANSS total score and large effect sizes ( range , 1.16 - 1.69 ) in the PANSS total and subscales , Scales for the Assessment of Negative Symptoms-20 items , Global Assessment of Function , Quality of Life Scale and Clinical Global Impression and improvement in the neurocognition subtests as recommended by the National Institute of Mental Health 's Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative , including the domains of processing speed and visual learning .  Benzoate was well tolerated without significant adverse effects . CONCLUSIONS AND RELEVANCE Benzoate adjunctive therapy significantly improved a variety of symptom domains and neurocognition in patients with chronic schizophrenia . The preliminary results show promise for d-amino acid oxidase inhibition as a novel approach for new drug development for schizophrenia Background Polyunsaturated fatty acid ( PUFA ) metabolism abnormalities have been long implicated in the etiology of schizophrenia . Although several r and omized clinical trials have been carried out to assess the efficacy of omega-3 PUFA as add-on therapy in reducing psychopathology in population s of chronic patients with schizophrenia , only a few concern first-episode schizophrenia . The majority of these studies used a 12-week intervention based on ethyl-eicosapentaenoic acid ( ethyl-EPA ) , however , with conflicting results . An intervention based on docosahexaenoic acid plus EPA has not been used in first-episode schizophrenia studies so far . No add-on supplementation studies have been carried out in medicated first-episode schizophrenia patients to assess the efficacy of omega-3 PUFA in preventing relapses . Methods A r and omized placebo-controlled one-center trial will be used to compare the efficacy of 26-week intervention , composed of either 1320 mg/day of EPA and 880 mg/day of DHA , or olive oil placebo with regard to symptom severity and relapse rate in first-episode schizophrenia patients . Eighty-two patients ( aged 16–35 ) will be recruited for the study . Eligible patients will be r and omly allocated to one of two intervention arms : an active arm or a placebo arm ( olive oil ) . The primary outcome measure of the clinical evaluation is schizophrenia symptom severity measured by the Positive and Negative Syndrome Scale ( PANSS ) . Other outcomes include depressive symptoms , patient functioning and the level of insight . Correlates of change measured during the study will include structural brain changes , oxidative stress and defense , as well as neuroplasticity indicators . Metabolic syndrome components will also be assessed throughout the study . Discussion By comparing 26-week administration of EPA + DHA or ( placebo ) olive oil as add-on therapy in reducing symptom severity and one-year relapse rate in patients with first episode schizophrenia , it is intended to provide new insights into the efficacy of omega-3 PUFA and correlates of change , and contribute to the improvement of mental health care for individuals suffering from schizophrenia . Trial registration This study has been registered at Clinical Trials.gov with the following number : NCT02210962 Dysfunction of the glutamatergic system , the main stimulating system in the brain , has a major role in pathogenesis of schizophrenia . The frontal white matter ( WM ) is partially composed of axons from glutamatergic pyramidal neurons and glia with glutamatergic receptors . The natural amino acid sarcosine , a component of a normal diet , inhibits the glycine type 1 transporter , increasing the glycine level . Thus , it modulates glutamatergic transmission through the glutamatergic ionotropic NMDA ( N-methyl-d-aspartate ) receptor , which requires glycine as a co-agonist . To evaluate the concentrations of brain metabolites ( NAA , N-acetylaspartate ; Glx , complex of glutamate , glutamine , and γ-aminobutyric acid ( GABA ) ; mI , myo-inositol ; Cr , creatine ; Cho , choline ) in the left frontal WM , Proton Nuclear Magnetic Resonance ( 1H-NMR ) spectroscopy was used . Twenty-five patients r and omly chosen from a group of fifty with stable schizophrenia ( DSM-IV-TR ) and dominant negative symptoms , who were receiving antipsychotic therapy , were administered 2 g of sarcosine daily for six months . The remaining 25 patients received placebo . Assignment was double blinded . 1H-NMR spectroscopy ( 1.5 T ) was performed twice : before and after the intervention . NAA , Glx and mI were evaluated as Cr and Cho ratios . All patients were also assessed twice with the Positive and Negative Syndrome Scale ( PANSS ) . Results were compared between groups and in two time points in each group . The sarcosine group demonstrated a significant decrease in WM Glx/Cr and Glx/Cho ratios compared to controls after six months of therapy . In the experimental group , the final NAA/Cr ratio significantly increased and Glx/Cr ratio significantly decreased compared to baseline values . Improvement in the PANSS scores was significant only in the sarcosine group . In patients with schizophrenia , sarcosine augmentation can reverse the negative effect of glutamatergic system overstimulation , with a simultaneous beneficial increase of NAA/Cr ratio in the WM of the left frontal lobe . Our results further support the glutamatergic hypothesis of schizophrenia 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 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
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 .