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Tuesday, November 29, 2011

kNACk for Bipolar Depression

I enjoyed reading Natasha Tracy's blog post on the use of NAC (N-acetylcysteine) as a low cost add-on for treating bipolar depression.  The post got me thinking.  I decided to take a closer look and see if I should use NAC in my own treatment program.

The fundamental problem is there are few choices of medication for effectively managing bipolar depression.  One article states, "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."  I never knew we were so hosed.


A 2010 comprehensive review of clinical trials and other data was performed to assess NAC effectiveness.  The review's tepid conclusion: "bipolar disorder treatment outcomes may potentially be improved by additional use of [NAC] with conventional [psych meds]."  They also urged caution when interpreting the large effects of several isolated studies, as they have not yet been replicated in larger trials. Okay, so now what.

One article studied NAC efficacy as an add-on for maintenance medication.  The authors studied bipolar individuals with moderate depression.  Results showed a "robust [drop] in depression scores with NAC treatment."  That sounds better.

In another study, NAC was given to 75 depressed bipolar patients at 1 gm twice a day in combination along with their usual bipolar medications.  The results showed a significant improvement in mood, global functioning (whatever that is), and social/occupational functioning.

How it works

NAC is a precursor of glutathione and works to replenish depleted sources of glutathione in the brain.  Low glutathione levels in specific brain areas are linked to mood disorders, particularly schizophrenia and bipolar disorder.

Anything else?

Finally, in regards to risk one journal article concludes:  "While dosages, pharmacological strategies (monotherapy versus augmentation), and long-term risks are not fully evident, NAC appears to be a promising, relatively low-risk intervention."  I can live with that.

Conclusion: Go for it!

The supplement appears safe at the oral doses given in the studies.  And according to Ms. Tracy's blog post NAC is inexpensive at $25 per month and readily available over-the-counter!

Now, how should I go about doing this?  First, I will get buy-in from my mental health team - which consists of my parents, psychiatrist, and a few close friends.

This should be straightforward forward, I hope.

And I need to decide if I'm going to stay at 15 mg/day Abilify (recently reduced from 30 mg/day) or try and get off it completely.  I'm leaning towards just getting off the stuff.  I haven't noticed anything negative since the reduction a couple of weeks ago.

What about the dose?  Well, one study administered a dose of 1 mg of NAC twice per day on moderately depressed bipolar individuals.  I would say I'm mostly moderately depressed so I'll just use that dosage.

So, I'll check-in with my mental health team, dump the Abilify, and start taking NAC. Stay tuned!

Anybody else take supplements for bipolar depression?

DISCLAIMER: I am not a trained mental health professional.  This post is my opinion only.  Do not change or adjust your medications without first consulting your psychiatrist or other mental health professional.


  1. Hi Jeff,

    Thanks for writing about this - I missed Natasha's post on it (and have now read it). I think it sounds like a promising option, especially if you are struggling with depression a lot.

    I take Vitamin D, and Omega 3 supplements. Generally, I eat fish high in omega 3 everyday, so I find if my mood slips, I just pop about 9000mg of fish oil and my mood elevates to normal levels within 1-2 days. I then carry this on for a couple of weeks and reduce it again because I find that high dosage of omega-3 makes my tummy go funny! But it always works for me in lifting depression. Have you tried it?

    Natasha mentioned that there is no long-term data on NAC, which is a major concern for me. If I were suffering from a depression, I would try it for a certain amount of time until the depression lifted, plus eat lots of foods that will naturally boost glutathione, and then reduce the NAC. But that's just me, and I am really cautious!

    Did any of the studies indicate whether it had triggered hypomania or mania??

    If you end up doing it, I would love to know how it goes :)


  2. Hi Sara -

    Good to hear from you. I did not find any long-term data on NAC so you are doing the right thing by being cautious. But then I ask myself how much long-term data do we have for most of the psych meds we take? Not much. I figure if it's something we get naturally from foods then it should be okay.

    None of the studies I read indicated NAC caused hypomania or mania. However, they were relatively short term (e.g., 20 weeks). Since I'm in the valley of depression and have been for over a year so I think the chances of mania with me are low. But later down the road when things get better??

    Sounds like you are doing quite well with the supplements you take. That is very encouraging to hear! Yes, I take a fish oil capsule with 300mg Omega 3 daily. I also take a multivitamin that has 1000mg of vitamin D. I don't really notice if they help or not but I'm sure they do.

    That's great you respond so well to fish oil! In fact, your overall diet sounds really healthy for the brain. My diet is certainly something that needs improving. What sort of foods would you eat to boost glutathione?

    It won't be for sometime (weeks?) until I try NAC, but will report back when I do.

    Take care,


  3. Hi Jeff,

    Glad my article helped!

    A couple of things, there is only one well-designed study on NAC and bipolar. There is an additional meta-study (using the same data) and one that is open-label but with financial ties to the product.

    2. You can eat glutathione but "glutathione taken orally is not well absorbed across the gastrointestinal tract." That's the reason that NAC exists.

    3. There are no known cases (that I'm aware of) of NAC causing switching to hypomania/mania.

    - Natasha Tracy

  4. Natasha -

    Thanks for commenting and clarifying on taking glutathione directly. I will read up on the wiki link you sent. Keep us posted on beneficial supplements as you do your research.


  5. Jeff,

    Will do what I can but I don't consider supplements to be very promising in all honesty. NAC is a rare exception to that.

    - Natasha

  6. Natasha -

    I wonder about that myself. I've tried 5-HTP and St. John's Wort in the past and didn't notice a change. It seems supplements have some benefits for mild depression but little or no positive effects for bipolar. I haven't run across any promising studies about other supplements. I think a lot of it is internet hype or sites selling supplements. Besides my plan to try NAC I think I'll wait for better trials (randomized, blind, placebo) that clearly show benefits before I try other supplements. Also, taking unproven supplements can be harmful. I read a case study about a gal who took hydroxytryptophan while on MAOIs and went manic! Yikes! Thanks for your comment!