N-Acetyl Cysteine as a Glutathione Precursor for Schizophrenia—A Double-Blind, Randomized, Placebo-Controlled Trial

Berk, Michael; Copolov, David L.; Dean, Olivia; Lu, Kristy; Jeavons, Sue; Schapkaitz, Ian; Anderson-Hunt, Murray; Judd, Fiona; Katz, Fiona; Katz, P. Gary; Ording-Jespersen, Sean; Little, John; Conus, Philippe; Cuénod, Michel; Q., Kim; Bush, Ashley I.

doi:10.1016/j.biopsych.2008.03.004

Cited by 491 publications

(406 citation statements)

References 38 publications

Supporting

Mentioning

387

Contrasting

Unclassified

Order By: Relevance

“…N-acetylcysteine was supplied by Zambon (Milan, Italy), and encapsulated by DFC-Pharmamed Pty Ltd (Sydney, Australia) in accordance with Good Manufacturing Practice guidelines. The choice of dose was based on that used in our previous trials of adjunctive N-acetylcysteine in schizophrenia 14 and bipolar disorder, 10,15 which have appeared to be efficacious and well tolerated in both trials, and is also distanced by a fair margin from the maximum dose of 5,000 mg/d used in published trials. 16 To facilitate double-blinding, the trial medications (both N-acetylcysteine and placebo) were dispensed in identical numbers and capsule formulations in sealed containers by the trial pharmacist.…”

Section: Participant Recruitment and Allocationmentioning

confidence: 99%

The Efficacy of AdjunctiveN-Acetylcysteine in Major Depressive Disorder

Berk

Dean²,

Cotton³

et al. 2014

J. Clin. Psychiatry

Self Cite

151

138

View full text Add to dashboard Cite

Objective: Major depressive disorder (MDD) is one of the most common psychiatric disorders, conferring considerable individual, family, and community burden. To date, treatments for MDD have been derived from the monoamine hypothesis, and there is a paucity of emerging antidepressants, especially with novel mechanisms of action and treatment targets. N-acetylcysteine (NAC) is a redox-active glutathione precursor that decreases inflammatory cytokines, modulates glutamate, promotes neurogenesis, and decreases apoptosis, all of which contribute to the neurobiology of depression.Method: Participants with a current episode of MDD diagnosed according to DSM-IV-TR criteria (N = 252) were treated with NAC or placebo in addition to treatment as usual for 12 weeks and were followed to 16 weeks. Data were collected between 2007 and 2011. Results:The omnibus interaction between group and visit for the Montgomery-Asberg Depression Rating Scale (MADRS), the primary outcome measure, was not significant (F 1,520.9 = 1.98, P = .067), and the groups did not separate at week 12 (t 360.3 = −1.12, P = .265). However, at week 12, the scores on the Longitudinal Interval Follow-Up Evaluation-Range of Impaired Functioning Tool (LIFE-RIFT) differed from placebo (P = .03). Among participants with a MADRS score ≥ 25, NAC separated from placebo at weeks 6, 8, 12, and 16 (P < .05). Additionally, the rate of change between baseline and week 16 was significant (t 221.03 = −2.11, P = .036). NAC treatment was superior to placebo at week 16 for secondary readouts of function and clinical impression. Remission and response were greater in the NAC group at week 16, but not at week 12. The NAC group had a greater rate of gastrointestinal and musculoskeletal adverse events. Conclusions:Being negative at the week 12 end point, and with some positive secondary signals, the study provides only limited support for the role of NAC as a novel adjunctive therapy for MDD. These data implicate the pathways influenced by NAC in depression pathogenesis, principally oxidative and inflammatory stress and glutamate, although definitive confirmation remains necessary.Trial Registration: www.anzctr.org.au Identifier: ACTRN12607000134426 Clin Psychiatry 2014;75(6):628-636 J

show abstract

Section: Participant Recruitment and Allocationmentioning

confidence: 99%

The Efficacy of AdjunctiveN-Acetylcysteine in Major Depressive Disorder

Berk

Dean²,

Cotton³

et al. 2014

J. Clin. Psychiatry

Self Cite

151

138

View full text Add to dashboard Cite

show abstract

“…However, it seems to be ineffective in prevention of cancer recurrence, acute hepatic failure and in intensive care [94]. NAC has also been suggested for treatment of cystic fibrosis [106], idiopathic pulmonary fibrosis (IFIGENIA study) [100] and recently for psychiatric disorders such as depressive symptoms in bipolar disorder [107] and schizophrenia [108]. All these new implications seem very promising, however, further studies are needed before NAC can be routinely used for clinical purposes.…”

Section: Treatment Beneficialmentioning

confidence: 99%

Clinical and pharmacological aspects of bath salt use: A review of the literature and case reports

Miotto¹,

Striebel²,

Cho

et al. 2013

Drug and Alcohol Dependence

121

View full text Add to dashboard Cite

Abstract:Reactive oxygen species (ROS) are widely believed to cause or aggravate several human pathologies such as neurodegenerative diseases, cancer, stroke and many other ailments. Antioxidants are assumed to counteract the harmful effects of ROS and therefore prevent or treat oxidative stress-related diseases. In this report, recent human studies exploring the efficiency of antioxidants in prevention and treatment of various diseases are reviewed. Few antioxidants including edaravone (for ischemic stroke in Japan), Nacetylcysteine (for acetaminophen toxicity), alfa-lipoic acid (for diabetic neuropathy) and some flavonoids (polyphenolic compounds present in dietary plants), such as micronized purified flavonoid fraction (diosmin and hesperidin) and oxerutins (for chronic venous insufficiency) as well as baicalein and catechins (for osteoarthritis) have found accepted clinical use. However, despite much enthusiasm in the 1980s and 1990s, many well-known agents such as antioxidant vitamins and also more recently developed compounds such as nitrones have not successfully passed the scrutiny of clinical trials for prevention and treatment of various diseases. This has given rise to a pessimistic view of antioxidant therapy, however, the evidence from human epidemiological studies about the beneficial effects of dietary antioxidants and preclinical in vitro and animal data are compelling. We have probably wasted too much time on agents like antioxidant vitamins instead of focusing on more disease specific, target-directed, highly bioavailable antioxidants. We here discuss possible reasons for the lack of success in some clinical trials and seek to provide some suggestions to be considered if antioxidant therapy is to succeed as an effective therapeutic strategy.

show abstract

“…In this context, it is also important to note that activation of mGluRs reduces the loss of cellular GSH (Sagara and Schubert, 1998). Interestingly, antioxidants including omega-3 fatty acids (Sivrioglu et al, 2007) and NAC have already demonstrated clinical efficacy in the treatment of schizophrenia symptoms (Berk et al, 2008a;Lavoie et al, 2008), obsessive-compulsive disease (Grant et al, 2009;Odlaug and Grant, 2007), and bipolar disorder (Berk et al, 2008b). Our findings provide a rationale for this treatment effect and suggest a therapeutic option for the therapy of G72-associated psychiatric disorders.…”

Section: Discussionmentioning

confidence: 63%

N-acetyl Cysteine Treatment Rescues Cognitive Deficits Induced by Mitochondrial Dysfunction in G72/G30 Transgenic Mice

Otte

Sommersberg

Kudin

et al. 2011

Neuropsychopharmacol

View full text Add to dashboard Cite

Genetic studies have implicated the evolutionary novel, anthropoid primate-specific gene locus G72/G30 in psychiatric diseases. This gene encodes the protein LG72 that has been discussed to function as a putative activator of the peroxisomal enzyme D-aminoacid-oxidase (DAO) and as a mitochondrial protein. We recently generated 'humanized' bacterial artificial chromosome transgenic mice (G72Tg) expressing G72 transcripts in cells throughout the brain. These mice exhibit several behavioral phenotypes related to psychiatric diseases. Here we show that G72Tg mice have a reduced activity of mitochondrial complex I, with a concomitantly increased production of reactive oxygen species. Affected neurons display deficits in short-term plasticity and an impaired capability to sustain synaptic activity. These deficits lead to an impairment in spatial memory, which can be rescued by pharmacological treatment with the glutathione precursor N-acetyl cysteine. Our results implicate LG72-induced mitochondrial and synaptic defects as a possible pathomechanism of psychiatric disorders.

show abstract

N-Acetyl Cysteine as a Glutathione Precursor for Schizophrenia—A Double-Blind, Randomized, Placebo-Controlled Trial

Cited by 491 publications

References 38 publications

The Efficacy of AdjunctiveN-Acetylcysteine in Major Depressive Disorder

The Efficacy of AdjunctiveN-Acetylcysteine in Major Depressive Disorder

Clinical and pharmacological aspects of bath salt use: A review of the literature and case reports

N-acetyl Cysteine Treatment Rescues Cognitive Deficits Induced by Mitochondrial Dysfunction in G72/G30 Transgenic Mice

Contact Info

Product

Resources

About