The efficacy of adjunctive N-acetylcysteine in acute bipolar depression: A randomized placebo-controlled study

Ellegaard, Pernille Kempel; Licht, Rasmus W; Nielsen, René Ernst; Dean, Olivia; Berk, Michael; Poulsen, Henrik Enghusen; Mohebbi, Mohammadreza; Nielsen, C.

doi:10.1016/j.jad.2018.10.083

Cited by 39 publications

(32 citation statements)

References 41 publications

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“…Duration of treatment as a critical issue is reflected in the data from bipolar studies. A trial with a 6-month duration separated from placebo (Berk et al, 2008b; Magalhães et al, 2011), but failed to separate earlier, and replication studies with shorter time frames have been negative (Berk et al, 2019; Ellegaard et al, 2019). It is likely that a neuroprotective agent like NAC may be working on neuroregenerative pathways in neuroprogressive disorders including neurogenesis, which is likely to be a very slow-moving process.…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis of randomised controlled trials with N-acetylcysteine in the treatment of schizophrenia

Yolland

Hanratty

Neill

et al. 2019

Aust N Z J Psychiatry

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Objective: There is accumulating evidence that adjunctive treatment with N-acetylcysteine may be effective for schizophrenia. This study aimed to conduct a comprehensive meta-analysis examining the efficacy of randomised control trials investigating N-acetylcysteine as an adjunct treatment for schizophrenia and the first to investigate cognition as an outcome. Methods: We systematically reviewed Medline, EmCare, PsycINFO, Embase, CINAHL Complete, China Knowledge Resource Integrated Database and the Cochrane Clinical Trials online registry for randomised control trials of N-acetylcysteine for schizophrenia. We undertook pairwise meta-analyses of N-acetylcysteine vs placebo for psychosis symptoms and cognition. Results: Seven studies, including n = 220 receiving N-acetylcysteine and n = 220 receiving placebo, met inclusion criteria for the pairwise meta-analyses. Positive and Negative Syndrome Scale negative and total scores were significantly improved in the N-acetylcysteine group after 24 weeks of treatment. The cognitive domain of working memory improved with N-acetylcysteine supplementation. Conclusion: Evidence supports the notion that N-acetylcysteine may be a useful adjunct to standard treatment for the improvement of schizophrenia symptoms, as well as the cognitive domain of working memory. Treatment effects were observed at the later time point (⩾24 weeks), suggesting that longer interventions are required for the success of N-acetylcysteine treatment.

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Section: Discussionmentioning

confidence: 99%

Meta-analysis of randomised controlled trials with N-acetylcysteine in the treatment of schizophrenia

Yolland

Hanratty

Neill

et al. 2019

Aust N Z J Psychiatry

Self Cite

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“…Although NAC is promising as a supplement to both boost glutathione levels and potentially mitigate some of the issues related to oxidative stress [57,58], the research is not conclusive [59,60,61,62], and some of the findings are disease specific. There have also been studies with no significant impact by taking NAC.…”

Section: N-acetylcysteine (Nac)mentioning

confidence: 99%

A Review of Dietary (Phyto)Nutrients for Glutathione Support

Minich

Brown²

2019

Nutrients

157

118

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Glutathione is a tripeptide that plays a pivotal role in critical physiological processes resulting in effects relevant to diverse disease pathophysiology such as maintenance of redox balance, reduction of oxidative stress, enhancement of metabolic detoxification, and regulation of immune system function. The diverse roles of glutathione in physiology are relevant to a considerable body of evidence suggesting that glutathione status may be an important biomarker and treatment target in various chronic, age-related diseases. Yet, proper personalized balance in the individual is key as well as a better understanding of antioxidants and redox balance. Optimizing glutathione levels has been proposed as a strategy for health promotion and disease prevention, although clear, causal relationships between glutathione status and disease risk or treatment remain to be clarified. Nonetheless, human clinical research suggests that nutritional interventions, including amino acids, vitamins, minerals, phytochemicals, and foods can have important effects on circulating glutathione which may translate to clinical benefit. Importantly, genetic variation is a modifier of glutathione status and influences response to nutritional factors that impact glutathione levels. This narrative review explores clinical evidence for nutritional strategies that could be used to improve glutathione status.

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“…86 In another study of the efficacy of adjunctive NAC in 80 patients with bipolar disorder acute depression, NAC was not superior to placebo. 87…”

Section: Resultsmentioning

confidence: 99%

“…86 In another study of the efficacy of adjunctive NAC in 80 patients with bipolar disorder acute depression, NAC was not superior to placebo. 87 However, in a recent study comparing NAC, aspirin, NAC plus aspirin and placebo, at 16 weeks, NAC plus aspirin was associated with a higher rate of response (67%), than NAC alone (57%), placebo (55%) or aspirin (33%) alone. 88 To our knowledge only one RCT has prospectively stratified patients based on evidence of inflammation.…”

Section: Use Of Immunomodulatory Agents For the Treatment Of Mddmentioning

confidence: 95%

Inflammation as a treatment target in mood disorders: review

et al. 2020

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Background Mood disorders, i.e. major depressive disorder (MDD) and bipolar disorders, are leading sources of disability worldwide. Currently available treatments do not yield remission in approximately a third of patients with a mood disorder. This is in part because these treatments do not target a specific core pathology underlying these heterogeneous disorders. In recent years, abnormal inflammatory processes have been identified as putative pathophysiological mechanisms and treatment targets in mood disorders, particularly among individuals with treatment-resistant conditions. Aims In this selective review, we aimed to summarise recent advances in the field of immunopsychiatry, including emerging pathophysiological models and findings from treatment ttrials of immunomodulatory agents for both MDD and bipolar disorders. Method We performed a literature review by searching Medline for clinical trials of immunomodulating agents as monotherapy or adjunctive treatments in MDD and bipolar disorders. Included studies are randomised controlled trials (RCTs), cluster RCTs or cross-over trials of immunomodulating agents that had an active comparator or a placebo-arm. Results Current evidence shows an association between inflammation and mood symptoms. However, there is conflicting evidence on whether this link is causal. Conclusions Future studies should focus on identifying specific neurobiological underpinnings for the putative causal association between an activated inflammatory response and mood disorders. Results of these studies are needed before further treatment trials of immunomodulatory agents can be justified.

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The efficacy of adjunctive N-acetylcysteine in acute bipolar depression: A randomized placebo-controlled study

Cited by 39 publications

References 41 publications

Meta-analysis of randomised controlled trials with N-acetylcysteine in the treatment of schizophrenia

Meta-analysis of randomised controlled trials with N-acetylcysteine in the treatment of schizophrenia

A Review of Dietary (Phyto)Nutrients for Glutathione Support

Inflammation as a treatment target in mood disorders: review

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