The efficacy of adjunctive N-acetylcysteine in major depressive disorder: a double-blind, randomized,…
The largest NAC trial in depression missed its main endpoint — before I try it, what would we agree counts as it working, and when would we stop?
Reasonable evidence with real limitations. how we score evidence
Caveat on this rating: The positive signals appeared at week 16, after treatment had been discontinued at week 12, and in secondary outcomes and a severity subgroup — the classic shape of findings that do not replicate. The trial is from the research group that has published most of the positive NAC literature, and its senior author's disclosures elsewhere record consultancy to Bioadvantex, a NAC commercialiser, hence independent false. No funding or disclosure statement was readable for this paper.
NAC sits in an unusual place.
252 people in a current episode of major depression added NAC or placebo to their usual treatment for 12 weeks. The trial missed its primary endpoint: the group-by-visit interaction on the Montgomery-Asberg Depression Rating Scale was not significant (P=.067) and the groups did not separate at week 12 (P=.265). Some secondary measures favoured NAC — functioning at week 12, and response, remission and symptom scores at week 16, four weeks after treatment stopped — and NAC caused more gastrointestinal and musculoskeletal adverse events. The authors' own summary is that, being negative at the week 12 endpoint, the study "provides only limited support" for NAC in depression.
Worth asking
The largest NAC trial in depression missed its main endpoint — before I try it, what would we agree counts as it working, and when would we stop?
Source
The efficacy of adjunctive N-acetylcysteine in major depressive disorder: a double-blind, randomized, placebo-controlled trial. — Berk M, Dean OM, Cotton SM, Jeavons S, Tanious M, et al. (2014)
Reputable peer-reviewed journal
Read the source: https://doi.org/10.4088/JCP.13m08454
DOI: 10.4088/JCP.13m08454
How this was scored
- Study design
- Randomised controlled trial
- Funding
- Funding not disclosed
- Published in
- Reputable peer-reviewed journal
- Sample size
- 252
- Preregistered
- Yes
- Conflicts disclosed
- No
- 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 60 out of 100 on our published rubric. One caveat travels with that badge: The positive signals appeared at week 16, after treatment had been discontinued at week 12, and in secondary outcomes and a severity subgroup — the classic shape of findings that do not replicate. The trial is from the research group that has published most of the positive NAC literature, and its senior author's disclosures elsewhere record consultancy to Bioadvantex, a NAC commercialiser, hence independent false. No funding or disclosure statement was readable for this paper. 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?
The efficacy of adjunctive N-acetylcysteine in major depressive disorder: a double-blind, randomized, placebo-controlled trial. — Berk M, Dean OM, Cotton SM, Jeavons S, Tanious M, et al. (2014). Published in: Reputable peer-reviewed journal. DOI: 10.4088/JCP.13m08454. 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: Funding not disclosed. 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.