Adjunctive <i>N</i>-acetylcysteine in depression: exploration of interleukin-6, C-reactive protein and brain-derived neurotrophic factor

Hasebe, Kyoko; Gray, Laura J.; Bortolasci, Chiara C.; Panizzutti, Bruna; Mohebbi, Mohammadreza; Kidnapillai, Srisaiyini; Spolding, Briana; Walder, Ken; Berk, Michael; Malhi, Gin S; Dodd, Seetal; Dean, Olivia

doi:10.1017/neu.2017.2

Cited by 25 publications

(18 citation statements)

References 37 publications

(56 reference statements)

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“…Table 1C additionally shows that there are also two out of three studies (57, 58) that showed that in the case of add-on n -acetyl cysteine, it was of no use to stratify the patients in low- or high-grade inflammation prior to therapy. Two of the studies of add-on n -acetyl cysteine (one showing and one not showing an effect of prior determination of the inflammatory state) involved both unipolar and bipolar depressed patients.…”

Section: Resultsmentioning

confidence: 99%

Low-Grade Inflammation as a Predictor of Antidepressant and Anti-Inflammatory Therapy Response in MDD Patients: A Systematic Review of the Literature in Combination With an Analysis of Experimental Data Collected in the EU-MOODINFLAME Consortium

Arteaga-Henríquez

Simon

Burger³

et al. 2019

Front. Psychiatry

117

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Low-grade inflammation plays a role not only in the pathogenesis of major depressive disorder (MDD) but probably also in the poor responsiveness to regular antidepressants. There are also indications that anti-inflammatory agents improve the outcomes of antidepressants. Aim: To study whether the presence of low-grade inflammation predicts the outcome of antidepressants, anti-inflammatory agents, or combinations thereof. Methods: We carried out a systematic review of the literature on the prediction capability of the serum levels of inflammatory compounds and/or the inflammatory state of circulating leukocytes for the outcome of antidepressant/anti-inflammatory treatment in MDD. We compared outcomes of the review with original data (collected in two limited trials carried out in the EU project MOODINFLAME) on the prediction capability of the inflammatory state of monocytes (as measured by inflammatory gene expression) for the outcome of venlafaxine, imipramine, or sertraline treatment, the latter with and without celecoxib added. Results: Collectively, the literature and original data showed that: 1) raised serum levels of pro-inflammatory compounds (in particular of CRP/IL-6) characterize an inflammatory form of MDD with poor responsiveness to predominately serotonergic agents, but a better responsiveness to antidepressant regimens with a) (add-on) noradrenergic, dopaminergic, or glutamatergic action or b) (add-on) anti-inflammatory agents such as infliximab, minocycline, or eicosapentaenoic acid, showing—next to anti-inflammatory—dopaminergic or lipid corrective action; 2) these successful anti-inflammatory (add-on) agents, when used in patients with low serum levels of CRP/IL-6, decreased response rates in comparison to placebo. Add-on aspirin, in contrast, improved responsiveness in such “non-inflammatory” patients; 3) patients with increased inflammatory gene expression in circulating leukocytes had a poor responsiveness to serotonergic/noradrenergic agents. Conclusions: The presence of inflammation in patients with MDD heralds a poor outcome of first-line antidepressant therapies. Immediate step-ups to dopaminergic or glutamatergic regimens or to (add-on) anti-inflammatory agents are most likely indicated. However, at present, insufficient data exist to design protocols with reliable inflammation parameter cutoff points to guide such therapies, the more since detrimental outcomes are possible of anti-inflammatory agents in “non-inflamed” patients.

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Section: Resultsmentioning

confidence: 99%

Low-Grade Inflammation as a Predictor of Antidepressant and Anti-Inflammatory Therapy Response in MDD Patients: A Systematic Review of the Literature in Combination With an Analysis of Experimental Data Collected in the EU-MOODINFLAME Consortium

Arteaga-Henríquez

Simon

Burger³

et al. 2019

Front. Psychiatry

117

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“…Forty-two studies were able to provide data of response to exclusively pharmacological treatment and two studies provided the cytokine values by combining both pharmacological and non-pharmacological treatments 24,31 . Three studies pre-selected treatment-resistant patients to study the effect of augmentation treatments [32][33][34] .…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

Peripheral cytokine levels and response to antidepressant treatment in depression: a systematic review and meta-analysis

et al. 2019

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“…A newer trial which explores effects of adjunctive N-acetylcysteine treatment on inflammatory and neurogenesis markers in the unipolar depression provided additional supporting evidence. [ 48 ] In this double-blind, placebo-controlled trials with 252 participants, N-acetylcysteine treatment of 2000 mg/day significantly improved depressive symptoms over the 16 weeks trial period compared to placebo. [ 48 ] However, the study failed to find any relevant inflammatory and neurogenesis marker that directly involved in the therapeutic mechanism of N-acetylcysteine in depression.…”

Section: Clinical Evidencementioning

confidence: 99%

“…[ 48 ] In this double-blind, placebo-controlled trials with 252 participants, N-acetylcysteine treatment of 2000 mg/day significantly improved depressive symptoms over the 16 weeks trial period compared to placebo. [ 48 ] However, the study failed to find any relevant inflammatory and neurogenesis marker that directly involved in the therapeutic mechanism of N-acetylcysteine in depression. [ 48 ] An upcoming 16-week trial which investigates N-acetylcysteine and a combination of other mitochondrial agents compared with placebo was described in the literature.…”

Section: Clinical Evidencementioning

confidence: 99%

“…[ 48 ] However, the study failed to find any relevant inflammatory and neurogenesis marker that directly involved in the therapeutic mechanism of N-acetylcysteine in depression. [ 48 ] An upcoming 16-week trial which investigates N-acetylcysteine and a combination of other mitochondrial agents compared with placebo was described in the literature. The results from this trial are expected to be published soon.…”

Section: Clinical Evidencementioning

confidence: 99%

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N-Acetylcysteine for the Treatment of Psychiatric Disorders: A Review of Current Evidence

Ooi¹,

Green

Pak

2018

BioMed Research International

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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 synthesises and presents the current evidence from systematic reviews, meta-analyses, and latest clinical trials on N-acetylcysteine for addiction and substance abuse, schizophrenia, obsessive-compulsive and related disorders, and mood disorders. 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. Effects of N-acetylcysteine on obsessive-compulsive and related disorders, as well as on mood disorders, remain unclear with mixed reviews, even though promising evidence does exist. Larger and better-designed studies are required to further investigate the clinical effectiveness of N-acetylcysteine in these areas. Oral N-acetylcysteine is safe and well tolerated without any considerable adverse effects. Current evidence supports its use as an adjunctive therapy clinically for psychiatric conditions, administered concomitantly with existing medications, with a recommended dosage between 2000 and 2400 mg/day.

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Adjunctive N-acetylcysteine in depression: exploration of interleukin-6, C-reactive protein and brain-derived neurotrophic factor

Abstract: Overall, this suggests that our results failed to support the hypothesis that IL6, CRP and BDNF are directly involved in the therapeutic mechanism of NAC in depression. IL6 may be a useful marker for future exploration of treatment response.

Cited by 25 publications

References 37 publications

Low-Grade Inflammation as a Predictor of Antidepressant and Anti-Inflammatory Therapy Response in MDD Patients: A Systematic Review of the Literature in Combination With an Analysis of Experimental Data Collected in the EU-MOODINFLAME Consortium

Low-Grade Inflammation as a Predictor of Antidepressant and Anti-Inflammatory Therapy Response in MDD Patients: A Systematic Review of the Literature in Combination With an Analysis of Experimental Data Collected in the EU-MOODINFLAME Consortium

Peripheral cytokine levels and response to antidepressant treatment in depression: a systematic review and meta-analysis

N-Acetylcysteine for the Treatment of Psychiatric Disorders: A Review of Current Evidence

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