Treating the depression side of bipolar disorder is always a challenge. All too often, antidepressants don’t work or they have undesirable side effects. Many of the most popular and effective antidepressants also carry the risk of unmasking the manic side of bipolar disorder, particularly in patients with Bipolar I.

Because of this, researchers are looking for other treatment options. Results from a recent study entitled “N-Acetyl Cysteine for Depressive Symptoms in Bipolar Disorder—A Double-Blind Randomized Placebo-Controlled Trial,” look hopeful.

According to researchers who performed the study, individuals with both depression and bipolar disorder experience a glutathione deficiency. Glutathione is an antioxidant that protects cells from toxins. In the study scheduled for publication in the September 15th issue of Biological Psychiatry, Dr. Michael Berk and colleagues sought to evaluate whether N-acetyl cysteine (NAC), “a safe, orally bioavailable precursor of glutathione,” could help alleviate depressive symptoms.

In a randomized, double-blind, placebo-controlled trial, they evaluated the mood symptoms of individuals with bipolar disorder, half of whom received placebo and half of whom received NAC (1 g twice daily), as an add-on therapy to their usual treatment. Over the 24 weeks of the study, NAC was well tolerated, and induced a marked and significant improvement in depressive symptoms.

Additionally there were no significant side effects reported in the group taking NAC compared to the group taking a sugar pill. The study only looked at results for up to 20 weeks of treatment with NAC. The remaining 4 weeks of the study followed participants through a “wash out period.” The benefits were lost when the NAC was stopped.

From the study, the researches concluded: “NAC appears a safe and effective augmentation strategy for depressive symptoms in bipolar disorder.”

“Brain glutathione metabolism appears to be a valuable new treatment target for psychiatric disorders, and we hope the impressive results of this study open up a new treatment option.”

– Dr. Michael Berk

Ashley Bush, M.D., Ph.D., the article’s corresponding author, further explains: “Glutathione is the brain’s primary antioxidant defense, and there is evidence of increased oxidative stress in bipolar disorder. Therefore, we studied the potential benefit of NAC treatment in bipolar disorder and found that it impressively remedied residual depressive symptoms.”

John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, comments: “The preliminary evidence of efficacy of NAC is very interesting. This study might suggest a number of novel approaches to treating depression. In subsequent efforts to replicate this preliminary finding, it will be important to determine how much NAC reaches the brain after oral administration.”

As noted by both the authors and Dr. Krystal, additional studies will be necessary to further evaluate and replicate these findings.

Caution: As always, we caution against self-medicating, even with over-the-counter medications and supplements. Discuss this option with the doctor in charge of managing your medications before adding it to your treatment regimen.

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