Treating Bipolar Depression with N-Acetyl Cysteine

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.



  1. Great post, i’ve got a friend who is bibolar – she has to take medication daily however sometimes she goes off it. last time she lasted 2 years before she had to get back on it though. she’s getting good at recognizing the signs and seeking medicine before the effects take over.
    I’m sending this to her. Thanks 🙂

  2. You talk about antidepressants “unmasking the manic side of bipolar disorder”

    I know way too many people who figured out that the mania caused by antidepressants was simply an adverse drug reaction…they refused to continue on the med merry go round so many of us get stuck on and NEVER have an episode again…

    this is not unmasking what is there—its a toxic drug reaction. It’s really horrifying to think of all the people labeled bipolar because of an adverse drug reaction who then get stuck on toxic soul killing drugs for no good reason.

  3. Very informative post for glutathione user like me. It give’s us a deep information about the glutathione capsules that we drink. Thanks and keep it up

  4. We’ve been researching Dr. Krystal a fair bit lately. Lots of great studies and information. Were always interested in learning more about manic states, my friend is bi-polar – she’s always finding ways to keep stress levels down and finds she doesn’t need medication so long as she’s not stressed out.

    Great post.

  5. barbara

    Diagnosed 13 months ago bipolar 1. I commend everyone taking all steps possible to help all
    with this debilitating disorder! Keep on Going
    as I keep on praying. Sincerely, Barbara

  6. Brian

    I am trying to find nore success stories about treating depression with N-aceytl-cystine verses going on prescribed antidepressants. I was looking for recommendation of dossage and duration of time required for results. The scientific research in the artical is promising but I would not mind seeing more. Another question I had was do N-acetyl-cystine and glutithoine levels have any relation to SAM e levels?
    Thank You,

  7. Glutathione is a major anti-oxidant,and immunomodulator which has profound effects upon the hormonal system, the nervous system, DNA synthesis,NK cell production, lymphocyte production and many other daily bodily functions.
    Glutathione has been found helpful in bi-polar disease and many other diseases which have a hormonal component.

  8. T

    Hi: I have just finished particpating in a four month study of nac and depression. I have no idea if I was on the placebo or not but I can tell you that I “washed out” considerably in the washout period. The study was for 2 x 500 mg capsules twice a day. I have stared taking the 1000 mg twice a day and I pray that this will work again.

  9. JP

    Proven to help bipolar and depression NATURALLY!

    Oxidative Stress increases from age 20 on and glutathione one of our bodies most important molecules decreases as we age.

    I represent a all natural product that has been scientifically proven to reduce Ox idative stress up to 70% and increase glutathione 300% daily!

    Do some research with glutathione, oxidative stress and bipolar and you will see what I stated.

    PLEASE CONTACT ME IF YOU ARE INTERESTED in how to research clinical trials proving this information, or if you are interested in more information on my product.
    Warm Regards,

  10. WakingPeopleUp

    Yo, where can I get some glutathione? Or are we supposed to look for the N-Acetyl-Cysteine? Thanks.

    • talon

      Buy NAC it crosses the blood barrier

  11. Joe

    I purchased glutathione online at BestVite.

  12. mateo

    Most people diagnosed with Bi-Polar have no disease at all. What they have are substance abuse, behavior, nutrition deficiency, or undiagnosed celiac disorders. When these things are all adressed about 90% of Bi-Polar simply disappears.

    • talon

      Do you have scientific source to back up your statement? R u a dr? Because many of us have genuine bipolar like myself. Denial almost killed me.

  13. jinni

    my dr. has prescribed NAC for OCD. I have very bad anxiety, and I am afraid this will add the the anxiety/mania… should I be worried?

  14. Joe

    Hi, Jinni–

    Nothing in this post or the study suggests that NAC will add to anxiety/mania. In the first paragraph, where Dr. Fink mentions “unmasking” mania, she’s referring to the standard antidepressants, including the SSRI’s like Paxil and Prozac, NOT N-Acetyl Cysteine, which is a supplement — a substance the body can use to produce glutathione. In other words, you need not worry.

  15. John

    My doctor recently had me start using a glutathione support formula topical cream along with vitamin B-12 injections and it’s made a HUGE difference in terms of how I feel everyday. I had been on a glutathione support formula in a pill form but it didn’t seem to do much. If you’re not having much luck with antidepressants you should definitely ask your doctor about giving it a try. The only negative side effect I’ve noticed is that my sleep seems to be a little lighter than it used to.

  16. Susie

    I have had bi-polar 1 as long as i can remember,i have had no relief from medications.I certainly hope this works because more often then not i wish i were dead.I will re-post if i have any success with NAC.

    • Joe

      Hi, Susie–Which medications have you tried for treating bipolar I?

  17. Hi. I need advice. Ok. So lately I have been feeling very stressed and anxious about school and homework. I have been getting headaches everyday for the past two months and I think my anxiety is also causing my asthma to flare up. I think I finally reached my breaking point because I have been crying ALOT lately and I have been feeling less motivated to get my homework done. Usually I have everything done on time and feel prepared for my tests but lately I have just stopped caring as much as I used to and I don’t know why. I think I also feel somewhat depressed. I don’t know. But any way my question is will it be beneficial to talk to my school counselor about this? Or will she think I am just wasting her time? Thank you.

  18. talon

    Bipolar 1 taking 1200mg of NAC daily w meds and having pleasant results. Carefully doing my self checks for mania as i feel a touch hypomanic. For me thats a great exchange from DD. In my opinion its worth a try.

  19. talon

    “N-acetylcysteine (NAC). While it is beyond the scope of this article to offer an intensive review of all agents, we do wish to briefly mention NAC, which affects the glutathione antioxidant system. In patients with BP, a subgroup analysis found that NAC led to remission of manic symptoms.30 Most studies, however, suggest that NAC has more robust effects on depressive symptoms” ~Phyciatric times

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