The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: An open label trial
Open accessAbstract
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 randomised placebo controlled clinical trial of the efficacy of 1g 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.
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N-acetyl Cysteine for 2 months suppressed BDRS scores in patients with moderate depression.
“An open-label trial revealed a solid suppression of Bipolar Depression Rating Scale (BDRS) scores following 2 months of treatment with N-Acetyl-Cysteine in patients with moderate depression (Berk et al. 2011).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Berk et al. 2011
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- Authors
- Berk, M., Dean, O., Cotton, S. M., Gama, C. S., Kapczinski, F., Fernandes, B. S., Kohlmann, K., Jeavons, S., Hewitt, K., Allwang, C., Cobb, H., Bush, A. I., Schapkaitz, I., Dodd, S., & Malhi, G. S.
- Affiliations
- The University of Melbourne (AU)
- Mental Health Research Institute (AU)
- Universidade Federal do Rio Grande do Sul (BR)
- Deakin University (AU)
- Royal North Shore Hospital (AU)
- ORCID
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 135
- Issue
- 1-3
- Pages
- 389-394
- ISSN
- 0165-0327 (ISSN-L)
- OpenAlex
- W1970774237
- Cited by
- 181
- References
- 52
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 7 · 2022: 7 · 2021: 10 · 2020: 15 · 2019: 12 · 2018: 19 · 2017: 11 · 2016: 17 · 2015: 13 · 2014: 18 · 2013: 25 · 2012: 16
- FWCI
- 13.11
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Licence
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Funders
- Stanley Medical Research Institute (06TGF-996)
- NHMRC Program (510135)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Keywords
- N-acetylcysteine, bipolar depression, adjunctive therapy, glutathione precursor, redox dysregulation, antioxidant therapy, antidepressant efficacy, quality of life, functioning
- MeSH terms
- Acetylcysteine, Adult, Antidepressive Agents, Bipolar Disorder, Depression, Depressive Disorder, Female, Humans, Male, Middle Aged, Quality of Life, Severity of Illness Index, Free Radical Scavengers, Treatment Outcome, Antimanic Agents, Mood Disorders
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