N-Acetylcysteine (NAC) – Inexpensive Treatment for Bipolar Depression

N-acetylcysteine, also known as N-acetyl-L-cysteine or just acetylcysteine is a supplement that shows promise in the treatment of bipolar depression. This is really big news because there are very few drugs, supplements or anything else that show promise in the area of bipolar depression. But N-acetylcysteine (NAC) is even better than most because:

  • N-acetylcysteine is an over-the-counter supplement
  • N-acetylcysteine is cheap
  • N-acetylcysteine has very few known  side effects

What is N-Acetylcysteine (NAC)?

Don’t be scared by the fancy name, just think of NAC as a supplement like omega-3 or vitamin D.

N-acetylcysteine is the N-acetyl derivative of the amino acid cysteine, and cysteine is an amino acid required for you to live. Your body uses it in your brain, for digestion and many other things.

And more interesting for people with bipolar disorder, cysteine is a precursor to glutathione, which is a precursor to glutamate – a neurotransmitter in the brain. Like the neurotransmitter serotonin is made more effective by using selective-serotonin reuptake inhibitor (SSRI) antidepressants, glutamate is increased by taking NAC.

The Research on N-Acetylcysteine (NAC) and Bipolar Disorder

I have been watching the research on NAC and bipolar depression for a while and it looks very promising.

Note that NAC is always used as an add-on medication for bipolar depression and is not used alone.

  • A recent open-label trial found statistically significant reductions in bipolar depression scores over the course of eight weeks. Improvements in functioning and quality of life were also seen.
  • A randomized double-blind placebo-controlled study found significant reductions in bipolar depression scores. Reduction in depression was seen by week eight but further (“medium to high”) benefits were seen by week 20.

N-acetylcysteine has also been used to treat compulsive behavior (like hair-pulling, trichotillomania and gambling), cocaine craving and cigarette smoking.

How is N-Acetylcysteine (NAC) Dosed? What is the Cost of NAC?

Bipolar Depression and NAC

This is always a call for your doctor but the double-blind placebo-controlled study mentioned above dosed at 1000 mg twice daily. Some studies have gone higher than this.

I pay about $25.00 per month for NAC and I get it from a vitamin shop.

What are the Side Effects of N-Acetylcysteine (NAC)?

This depends on who you ask. In the double-blind placebo-controlled study no side effects were noted as statistically significant but side effects are, of course, possible with any medication. Long-term data is not available on NAC’s safety.

It’s worth noting that in very high doses (much higher than is used in humans) mice were found to develop damage to the heart and lungs.

Natasha Tracy’s Opinion on N-Acetylcysteine (NAC)

In my non-medical opinion, this medication is worth a try for people who have unresolved bipolar depression. Again in my opinion, it is a low-risk option for treatment that really appears to have no downsides.

And on a personal note, I, personally, have found it effective.

Learning More About N-Acetylcysteine

If you’re interested in NAC I encourage you to click on the studies I have linked to and read Dr. Phelps’ write-up on NAC as it contains more detail than I have provided. You may need to provide this information to your doctor as many doctors don’t know about NAC and bipolar depression.

Important Note

This is an informational article and nothing is intended as medical advice. All medications, including supplements should be taken under the care of a doctor only. Please and thank you.

Leave a Reply

  1. I started taking NAC sustained release from Jarrow .. I have chronic sinus problems with post nasal drip , I hoped it would thin the mucous and help .. I was taking one a day but after a couple of days I was getting very bad headaches ..I stopped it had a break for a week and tried it again by day two the headaches were again severe and so have stopped it. I wonder if I would get the same reaction with a different brand and not sustained release .

  2. I’ve been taking NAC for about 18 months now, I have had no side effects, the depressions have not been as bad and I think possibly the highs are less too. I do get psychosis and I haven’t noticed any effect on this. Although my doctor is sceptical I will continue to take it. Hopefully if the trials are successful doctors will be more likely to suggest this treatment. This same doctor recommended glucosamine for my arthritis so it’s not that he is against supplements.

  3. Hi Natasha I just wanted to ask that does NAC really work for bi polar. Also can you email me or give me your email address so I can contact you regarding this.
    Kind regards

    • Hi Jungbaz,

      As I said in the article, there is some evidence that NAC works adjunctively for bipolar depression. If you’re interested in this, I recommend talking with your doctor.

      – Natasha Tracy

  4. Hi Natasha

    I started taking it about 6 months ago after reading your blog about it. I have had no side effects and have had no depressive episodes either. I have had a mixed episode but the depressive symptoms were much less than they would normally be. I’m still cautious about saying it has helped and still monitoring but so far so good. Thank you for mentioning it in the first place. We are all different and some people may have negative effects, that’s the same with anything. I would say give it a go.

  5. You ask for research papers to back up what I stated and you delete them??
    EVERY one of those research papers is valid information that can help people.

    • Hello Wilson,

      Several things:

      1. I did not “hide” anything. Your comment was caught in my spam filter. That happens when a comment has many links.
      2. I didn’t research NAC in its entirety as I’m interested in it with regards to mental illness – bipolar disorder specifically.
      3. It’s interesting research that you’ve pointed out.
      4. In Canada, none of those uses are approved and thus are experimental. So, saying that it _does_ something is, somewhat, disingenuous. Saying the research suggests that it may work is more accurate.

      – Natasha Tracy

  6. N-Acetylcysteine is being widely research and trials are being run more and more often in regards to it’s help in mental illnesses. IT DOES NOT CAUSE DEPRESSION.

    It REDUCES glutamate, it does NOT increase it (glutathione and glutamate are two completely different things), that’s why it is being found very helpful, especially for relief of Schizophrenia symptoms. Also for controlling blood-sugar levels and other bad side-effects of psychotherapeutic medications.

    • It did cause quite nasty depression in my case. Although as I said last year, I don’t always react to medication as expected so it could be an indiosyncratic response.

  7. For 18 months I have been taking 1200mg of N-Acetylcysteine (NAC) a day, with 2.5 grams (2500mg.) of Niacinamide (the active form of Vit. B-3 – Niacin, non-flushing, and has been used in Orthomolecular Therapy for mental disorders since the 1950s). NOT ONE side-effect. For the first four months (to help my liver) I was taking 3600mg of NAC. No side-effects from that dosage either.

    For the first time in 20 years I was able to completely stop taking Lithium (for bi-polar disorder). I was on Lithium ofr 4 times the “allowed duration” and suffered liver, thyroid, and kidney damage. N-Acetylcysteine has also restored my liver (it is used widely to protect the liver after acetaminophen overdose, protect the kidneys from contrast-dye used in flouroscopic x-ray/imaging, reducing creatinine levels when kidneys are failing, used in respiratory diseases in hospitals, and many other things).

  8. Hi Natasha, I gave N-acetylcysteine a go. After about 2 and half weeks I stopped taking it. Slowly over time I had become increasingly depressed, til I found myself in bed one morning thinking I do not want to live. I can only put the depression down to the NAC. It crept up on me slowly and I almost lost awareness. A few days after stopping and my mood is stable. I have to add that I do not act in the way expected to a lot of drugs so it may be down to my particular genetic makeup. SSRIs either don’t work for me at all or make me more depressed and I cannot have any anti psychotics as my psychiatrist recommends I have nothing that affects
    the histamine system as I had severe sleeping, drowsiness and memory problems on an anti psychotic that took about 3 months to recover from. Tricyclics push me into mania or mixed states, but I think that’s quite a common problem. So I think it’s likely the NAC failure/causing depression is a rare problem. I’d love to find something that helps with the depressive side of things though. I’m on Lithium which is great and has put a stop to a lot of distressing symptoms, but the depression still remains.

  9. NAC doesn’t increase glutamate, as you say it does; it DECREASES it. And anti-depressants, like SSRIsor SNRIs, don’t increase serotonin or norepinepherine either. They inhibit the reuptake of these neurotransmitters back into presynaptic neurons, leaving more of them in the synapse for transmission to post-synaptic neurons.

  10. Great information thanks for the help. My pdoc is not so receptive to otc vitamins; simply says that there is no research on the effects so it is not something he will suggest. I think with it might be something he would consider. I was wondering what information you may know about the alternative of Ketamine infusion? It seems like there is little information out there on what the suggested regimen is once you start the treatments.

  11. Hi,

    I was finally diagnosed with bipolar 1 at 50 years of age. SSRI s have not been very helpful also take 6 other meds
    in my med cocktail. I self medicated my symptoms till I was to sick and crashed at 50. I readily hope this helps some’

    this is the first time for me online about my bipolar its been hard to accept at my age but so many things make sence now.

    what other sites or forums do you recommend I am always researching. Being proactive trying to survive.

    Thanks for the info started on 1000mg this evening will keep my fingers and toes crossed Thanks Mitch

  12. Thanks for the info.
    I had a bad cough and read that NAC would clear it up and that NAC has resolved many persistent lung problems.
    I have been trying to lose weight for about the las 3 years. I would start off with great motivation, but after about 3 days just fall back on my old habits. I am not severely overweight , gained about 10 kilos in the past 5 years. I am menopausal. As usual I embarked on my diet on the Monday morning and after a week on NAC (for my nasty cough) I had lost 2 . 5 kilos and my phlegm was gone as well. I feel centered and in control, and I know this time the 10 kilos will not be my boss, and Im sticking to my NAC , I take 1000mg morning and evening. Im even clearing out cupboards, something I haven’t felt like doing in years. I am truly grateful for this new turn in my life and mind.

  13. I get amino acids and glutotathione infusions via IV. With all of my meds, exercise, good nutrition, consistent sleep times (early to bed, must sleep during hrs of darkness only), and therapy I manage quite well. Great to know all alternatives that can lend support to good balanced self care.

    • Hi Amelia,

      That is very interesting. Who gives you the IV infusion? Who recommended you get it? I’ve never heard of anyone having that before.

      – Natasha Tracy

  14. Hi Natasha,
    Another well done article by you. Thank you for pulling it all together for us. Before I was medicated I did quite a few amino acids hoping they would help. I could feel the effects for a while, they there was no hope. That’s when I succumbed to meds. You are a rapid cycler, right? Me too. So I am curious as to how it does affect the manic aspect. I’m glad Cat is able to keep her mania in check but it was definitely my question as to whether anything treating just the depression would bring up more manic feelings. Curious as to your thoughts. Also, since the brain chemistry theory of mental illness went out the window in 1998, I guess we’re just changing more receptors.

    • Hi Meredith,

      Well, I would be the first one to say that this is an adjunct to medication and not a replacement for it. People don’t get that but these types of “natural” treatments are terribly ineffective when compared with medication but can still be helpful when combined.

      In the case of NAC, there is no indication that mania is a side effect so I wouldn’t worry about that. I’m not saying it’s not possible, but it’s not indicated.

      With NAC you’re not really treating the _depression_ as much as you’re treating the brain and that in turns affects the depression so that’s not particularly likely to induce the kind of mood swings like an antidepressant can. And then there’s that bit about them not working to the degree that medications do. That too gives you a bit of a layer of protection.

      It’s not so much that the “brain chemistry” idea went out the window it’s more like we understand that it’s far more than that. Brain chemistry matters, it’s very important and it’s part of what the meds affect, but there is much more at play as well.

      – Natasha Tracy

  15. Hello –

    Thank you for posting this as you reminded me to get another bottle.

    I’ve been in a major bout of seasonal bipolar depression that usually starts around the end of January and does not lift until about mid-June. This year has been particularly horrendous and disabling.

    My psychiatrist has told me that he thinks I needed more Cymbalta, but I’ve been so afraid of the stuff that I didn’t want to try a higher dose. Then he told me to try adding 600 mg of NAC twice a day to 20 mg of cymbalta and 30 mg daily of Adderall. I agreed to increase the Cymbalta to 30 mg and took the NAC with it. After about only five days, i started to feel manic and assumed it was the Cymbalta. So I cut back to 20 mg and then ran out of NAC and didn’t feel it helped so I never bought another bottle.

    I figured I was depressed because of the holidays and a bad relationship breakup, but when it got into that consistently bad feeling like I’d been up all night doing party stimulants (which I have only done a few times in my life when younger) – that next day after feeling where the brain feels totally drained- I knew I was in serious in trouble.

    I was in such bad shape that I went from 20 mg again to 60 mg of Cymbalta and was put on 300 mg of Lithium Carbonate. I just felt tired and the depression was not lifting. Then I found your site and this article and got myself a bottle of NAC again.

    Low and behold, it is working and I am back down to just 30 mg of Cymbalta and the low amount of lithium and the yoga I have practicing almost daily seems to keep me from getting manic. I feel like my brain is once again energized. I am sure it’s the NAC and I am surprised at how fast it seems to work for me.

    I was really suffering and didn’t feel like I could rub two brain cells together no matter what.
    Thank you!

    I will report back in a couple of week or so or a month and let you know how it goes.

    • Hi Cat,

      I’m so happy I could help. I hope it is the NAC and I hope it keeps working for you. Like I said, I did notice a difference but for me it took a really long time to kick in.

      Do let me know how you’re doing. Oh, and kudos to you for having a doctor that embraces non-mainstream treatments :)

      – Natasha Tracy

  16. This is a wonderful post, I have been struggled with bipolar I depression for 25 years, and have been taking NAC for the last 2 years. I have been prescribed many meds for bipolar in the past, and although several medications have helped my mania and cycling, nothing pharmaceutical or natural has ever successfully treated my depression [without causing severe mania and a crash] until NAC.
    I started out with 500 mg per day, which gave me very slight improvement, then just last fall my neurologist suggested decreasing my B vitamins to help with migraines, so I increased my NAC to make up for the lower B vitamins. (B vitamins used to be the only thing I had tried that could ward off extreme depression for me.)
    Just 2-3 weeks after I increased my NAC to 1000 mg per day things got better relatively quickly. In the past I was afraid to take more than 500 mg because I have a very sensitive stomach and knew NAC could cause stomach upset, but I am tolerating the 1000 mg suprisingly well. I think if necessary I will be able to increase to 1500 or 2000 mg total per day and still tolerate it well. Even on the days I take it on an empty stomach I only slightly queasy, which is nothing compared to the extreme side effects (constant nausea and even vomiting) I had with almost every single bipolar medication I was ever presrcibed.
    Thank you for your post, I think this will help many people.

    • AN,

      Good to hear it’s working for you. From what I’ve read, what you’ve had is a pretty unusually positive reaction – but, of course, that doesn’t matter, it’s great if it’s working that well for you.

      I hope the article will help people. I hadn’t heard too much about NAC before (and neither had my doctors) but it does look promising.

      – Natasha Tracy

  17. Just want to say your article is as astounding.The clearness in your post is just spectacular and i could assume you’re an expert on this subject.Well with your permission allow me to grab your feed to keep up to date with forthcoming post.Thanks a million and please keep up the enjoyable work

  18. I have been taking NAC for about 4 weeks. Started out with 2 pills a day but plan to increase dosis. On some sites it is suggested to take it between meals, but this way of taking it seems to upset my stomach somewhat, so I am planning on taking it before meals like you do with most other medications. I have not experienced other sideeffects yet.

    • Hi Claus,

      I’m not sure who would be telling you to take it in between meals, but as you pointed out, it can upset stomachs (from what I understand, that’s pretty common.)

      – Natasha Tracy

  19. Hi Natasha,

    It is an interesting way of looking at possibilities for less invasive (regarding side-effects) methods to control mood swings. I do hope research will continue in the direction of balancing diets, rather than finding additives. (See below.)

    I had already thought of a similar approach, but with Glutamic Acid. As Acetylcysteine is the precursor, I can see the advantages of it.
    (Glutamate also serves as the precursor for the synthesis of the inhibitory GABA, which is what Valporic Acid (which I’m using at current) tries to do as well.)

    Although there is much more research needed to establish the amounts needed for regulating mood swings, a dietary change can also help.
    All meats, poultry, fish, eggs, dairy products, and kombu are excellent sources of glutamic acid. Some protein-rich plant foods also serve as sources. Thirty to 35% of the protein in wheat is glutamic acid. Ninety-five percent of the dietary glutamate is metabolized by intestinal cells in a first pass. (Source wikipedia: Glutamic Acid)
    (Note: kombu was originally used to make MSG (MonoSodium Glutamate), which is a commonly used flavour enhancer. I can’t find references on how it’s broken down in the intestinal tract. The notion that some people experience a variety of discomforting effects -including headaches- might hint on an easier passing of the broken down acid to Glutamate by the blood-brain barrier.)

    There should also be more research on the excitotoxicity, long term use of Valporic Acid might lead to memory loss (and other problems) as reported in a few researches.
    I suspect we’re only at the very beginning of understanding the role of adding glutamate or have a higher than normal intake to our systems.

    In all food for thought… (Pun intended)


    • Hi Perturbee,

      Just to be clear, cysteine in your gut isn’t the same thing has having cysteine in your brain and when you ingest cysteine it goes into your gut, not so much your brain. That is why the cysteine is acetylized.

      – Natasha Tracy

  20. Good information. I have never heard of it. I am in a bipolar depression and like you I’ll take relief any way I can get it. How many mg/day do you take?

  21. Interesting stuff. When I was on quetiapine it’d curb the highs but lows were bad, didn’t use SSRIs as they had bad side effects for me so this sounds like a very cool option

    • Hi Null,

      And you’re in a group with so many people. That’s why I’m so thankful for this med. I can’t say it will work for you, of course, and even if it does, it’s only an incremental benefit (likely) but for me, I’ll take it any way I can get it.

      – Natasha Tracy