N-Acetylcysteine (NAC) in Schizophrenia and Bipolar Disorder- Prof Michael Berk

Posted on: December 15, 2016
Last Updated: October 17, 2020

Professor Michael Berk is currently an NHMRC Senior Principal Research Fellow and is Alfred Deakin Chair of Psychiatry at Deakin University and Barwon Health, where he heads the IMPACT Strategic Research Centre. He also is an Honorary Professorial Research Fellow in the Department of Psychiatry, the Florey Institute for Neuroscience and Mental Health and Orygen Youth Health at Melbourne University, as well as in the School of Public Health and Preventive Medicine at Monash University. His major interests are in the discovery and implementation of novel therapies, and risk factors and prevention of psychiatric disorders.

Author Quotes 

The Holy Grail in bipolar disorder is maintenance. You want a treatment that not only is going to get you well – but keeps you well.

In our study we simply did not have enough relapses to detect a statistical signal, so the question in my mind as to whether NAC has any efficacy in maintenance remains open.

I think the evidence at this stage is at best suggestive that higher doses might be better, but we just don’t have enough evidence to be clear about that.

Summary and slides 

Professor Berk presents findings of his research study where NAC showed a statistically significant reduction of negative symptoms in schizophrenia, but no effect on positive symptoms. N-acetyl cysteine treatment also was associated with an improvement in akathisia and explains how these results prompted the team to start looking at mood disorders.

He moves on to how NAC demonstrated large effect sizes across the range of bipolar symptoms; from depression, to functioning, to quality of life etc., and provides an overview of the bipolar maintenance study. A meta-analysis of randomised controlled trials with N-acetylcysteine in the treatment of schizophrenia showed:

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. [Yolland C et al., 2019]

There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. 

In another study, it was revealed that NAC was suggestive of producing higher rates of remission for Mania, compared to a placebo. 

Professor Berk concludes with a presentation of data suggestive of efficacy of NAC for major depression in bipolar disorder.

Take-home Points

  1. NAC showed a statistically significant reduction of negative symptoms in Schizophrenia but no effect on positive symptoms. N-acetyl cysteine treatment also was associated with an improvement in akathisia.
  2. NAC demonstrated large effect sizes across the range of Bipolar symptoms; from depression to functioning, to quality of life, etc.
  3. In the maintenance study, There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations.
  4. In another study, it was revealed that NAC was suggestive of producing higher rates of remission for Mania, compared to a placebo.
  5. NAC may be useful as an adjunctive treatment in Major Depression in Bipolar Disorder.

Quiz


Learn more

  1. Applications of N-Acetylcysteine (NAC) – From Addiction to Autism By Prof Berk
  2. Glutathione, Oxidative Stress and N-Acetylcysteine (NAC) in Psychiatric Disorders – Prof Michael Berk
  3. Oxidative and Inflammatory Biomarkers as Targets for Novel Therapies – Prof Michael Berk
  4. Effect of the Mediterranean Diet On Depression By Prof Michael Berk
  5. Early Life Nutrition and Neurodevelopment by Prof Michael Berk
  6. The Role of the Microbiome and Diet in Depression by Prof Michael Berk
  7. Healthy Diet vs Nutraceuticals in Depression by Prof Michael Berk
  8. Effect of Diet and Lifestyle Changes in Depression by Prof Michael Berk
References:
  1. Berk, M., Copolov, D., Dean, O., Lu, K., Jeavons, S., Schapkaitz, I., … & Ording-Jespersen, S. (2008). N-acetyl cysteine as a glutathione precursor for schizophrenia—a double-blind, randomized, placebo-controlled trial. Biological psychiatry, 64(5), 361-368.