Adjunctive N-Acetyl Cysteine Effective for Bipolar Depression

Deborah Brauser

June 10, 2011

June 10, 2011 (Pittsburgh, Pennsylvania) — Adjunctive N-acetyl cysteine (NAC) may be efficacious in treating the depressive phase of bipolar disorder, new research suggests.

In an open-label study from Australian researchers presented here at the Ninth International Conference on Bipolar Disorder (ICBD), patients diagnosed with bipolar disorder and given 2000 mg of NAC in addition to their "treatment as usual" showed significantly lower symptom severity scores and increased functioning and quality-of-life scores.

"One of the biggest things I like is not only does [NAC] work symptomatically but it works functionally, which is just really helpful," lead author Olivia Dean, PhD, from the Mental Health Research Institute and Deakin University School of Medicine in Victoria, Australia, told Medscape Medical News.

Dr. Olivia Dean

The investigators note that "this study encompasses a completely novel approach to the treatment of bipolar depression, focusing on established biomarkers to define novel therapeutic targets."

"Given that it has a mild side effect profile and there are such limited treatments for bipolar depression, I think it's really worth including this [agent], especially because it's on top of usual treatment. There's no reason to stop anything — just add this on," said Dr. Dean.

This study has recently been accepted by the Journal of Affective Disorders, with plans to publish soon.

Significant Benefits

According to the study, recent research has found that oxidative stress and inflammation play a role in the pathophysiology of bipolar disorder.

"NAC is a cysteine analogue shown to effectively raise plasma levels of the primary antioxidant, glutathione. NAC also modulates cytokines, glutamates neurotransmission, and enhances neurogenesis," write the investigators.

In this study, 149 patients (67.8% female; mean age at baseline, 45.8 years) with bipolar disorder I, II, or not otherwise specified (mean age at diagnosis, 35.9 years) were given 2000 mg of NAC a day, along with their usual treatment, for 8 weeks.

At baseline, all participants were currently in the depressive phase of the disorder, as shown by a Montgomery Asberg Depression Rating Scale (MADRS) score of 12 or greater.

The primary outcome measure was change in the Bipolar Depression Rating Scale (BDRS). Secondary measurements included the MADRS, Clinical Global Impressions (CGI), the Global Assessment of Functioning (GAF) scale, Social and Occupational Functioning Assessment (SOFA) scale, the Streamlined Longitudinal Interview Clinical Evaluation from the Longitudinal Interval Follow-up Evaluation (SLICE/LIFE), the Range of Impaired Functioning Tool (LIFE/RIFT), the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and the Young Mania Rating Scale (YMRS).

Results showed that significant differences (P < .001) were found between baseline and week 8 for all study measures. Minimal side effects occurred.

"Anecdotally, patients reported that their side effects eased when they drank Diet Coke or orange juice. But there's no science to back that up," laughed Dr. Dean.

Research Continuing

"This study is terribly exciting," Kenneth Jobson, MD, in private practice in Knoxville, Tennessee, and on the clinical faculty at the University of Tennessee, told Medscape Medical News.

"[NAC] is actually used by patients a lot. We don't have a whole lot of data on it but in my clinical experience, there are some people who have responded. And I'm pleased that people in this study did too," said Dr. Jobson, who was not involved in the research.

Dr. Dean reported that after this open-label phase, all participants participated in a 6-month randomized, placebo-controlled trial. Those results will be released soon.

The investigative team is also further investigating markers of inflammation, oxidative biology, and neurogenesis to further understand the effects of NAC.

In addition, they're conducting a new study looking at NAC treatment in children with recently diagnosed autism.

"Autism has been reported to have similar changes in oxidative factors that a lot of psychiatric conditions do. So we're basically following the oxidative pathway to autism," concluded Dr. Dean.

The study was funded by the Stanley Medical Research Institute. The study authors and Dr. Jobson have disclosed no relevant financial relationships.

Ninth International Conference on Bipolar Disorder (ICBD): Poster P35. Presented June 9, 2011.

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