A randomised controlled trial of a mitochondrial therapeutic target for bipolar depression: mitochondrial agents,…
NAC did not beat placebo for bipolar depression in a properly sized trial — is there anything about my situation that would make it worth trying anyway?
Reasonable evidence with real limitations. how we score evidence
Caveat on this rating: A clean null on the primary outcome, with post-discontinuation secondary signals that the authors themselves flag as needing explanation. Study medications and placebos were supplied by commercial nutraceutical companies (Nutrition Care, BioCeuticals and Catalent, Australia) alongside public NHMRC and CRC funding, hence MIXED; the senior author's disclosed consultancy to Bioadvantex, a NAC commercialiser, is why independence is marked false. A published erratum (BMC Med 2019;17(1):35) applies.
NAC sits in an unusual place.
181 people with bipolar disorder and current depressive symptoms were randomised for 16 weeks to NAC 2,000 mg/day, NAC plus a combination of other mitochondrial nutraceuticals, or placebo, added to usual treatment. Among the 148 with post-randomisation data there were no between-group differences on any clinical or functioning measure — the primary MADRS outcome included. Some measures favoured the combination arm at a week-20 visit after treatment had been discontinued. Gastrointestinal symptoms were significantly more common on NAC than placebo. The authors describe the results as "overall negative".
Worth asking
NAC did not beat placebo for bipolar depression in a properly sized trial — is there anything about my situation that would make it worth trying anyway?
Source
A randomised controlled trial of a mitochondrial therapeutic target for bipolar depression: mitochondrial agents, N-acetylcysteine, and placebo. — Berk M, Turner A, Malhi GS, Ng CH, Cotton SM, et al. (2019)
Reputable peer-reviewed journal
Read the source: https://doi.org/10.1186/s12916-019-1257-1
DOI: 10.1186/s12916-019-1257-1
How this was scored
- Study design
- Randomised controlled trial
- Funding
- Mixed public and industry funding
- Published in
- Reputable peer-reviewed journal
- Sample size
- 181
- Preregistered
- Yes
- Conflicts disclosed
- Yes
- Independent of proponent
- No
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published August 19, 2026.
Where we put this study in context
Questions
How strong is the evidence behind this?
Resolv rates this source "moderate evidence". Reasonable evidence with real limitations. It scores 66 out of 100 on our published rubric. One caveat travels with that badge: A clean null on the primary outcome, with post-discontinuation secondary signals that the authors themselves flag as needing explanation. Study medications and placebos were supplied by commercial nutraceutical companies (Nutrition Care, BioCeuticals and Catalent, Australia) alongside public NHMRC and CRC funding, hence MIXED; the senior author's disclosed consultancy to Bioadvantex, a NAC commercialiser, is why independence is marked false. A published erratum (BMC Med 2019;17(1):35) applies. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
A randomised controlled trial of a mitochondrial therapeutic target for bipolar depression: mitochondrial agents, N-acetylcysteine, and placebo. — Berk M, Turner A, Malhi GS, Ng CH, Cotton SM, et al. (2019). Published in: Reputable peer-reviewed journal. DOI: 10.1186/s12916-019-1257-1. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Randomised controlled trial. Funding: Mixed public and industry funding. The researchers were not independent of whoever benefits from the result. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is nac, n-acetylcysteine, n-acetyl-l-cysteine, acetylcysteine, acetadote, mucomyst FDA approved for this use?
No. Its current status is: Not FDA-evaluated for this use. NAC sits in an unusual place.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.