A controlled trial of methylene blue in severe depressive illness.
A 1987 trial called methylene blue a potent antidepressant and nobody has run a proper trial since — does that absence of follow-up tell us something?
Reasonable evidence with real limitations. how we score evidence
Caveat on this rating: The published abstract gives no sample size, no effect size, and no confidence intervals, so the strength of the result cannot be assessed from the record; sample size is recorded as unknown rather than guessed. The dose it found effective, 15 mg/day, is the same dose the same group's 1986 trial and Alda's 2017 trial both used as the comparator — a direct internal contradiction in this small literature that has never been resolved.
Methylene blue is an FDA-approved drug, but only for one thing: ProvayBlue (methylene blue injection, NDA 204630, Provepharm) is indicated for the treatment of pediatric and adult patients with acquired methemoglobinemia.
A three-week controlled trial compared 15 mg/day of methylene blue with placebo in severe depressive illness and reported significantly greater improvement on methylene blue, concluding it "appears to be a potent antidepressant". Nearly forty years later that call for further clinical evaluation has still not been answered by an adequately powered trial.
Worth asking
A 1987 trial called methylene blue a potent antidepressant and nobody has run a proper trial since — does that absence of follow-up tell us something?
Source
A controlled trial of methylene blue in severe depressive illness. — Naylor GJ, Smith AH, Connelly P. (1987)
Reputable peer-reviewed journal
Read the source: https://doi.org/10.1016/0006-3223(87)90194-6
DOI: 10.1016/0006-3223(87)90194-6
How this was scored
- Study design
- Randomised controlled trial
- Funding
- Funding not disclosed
- Published in
- Reputable peer-reviewed journal
- Sample size
- not recorded
- Preregistered
- No
- Conflicts disclosed
- No
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published August 19, 2026.
Questions
How strong is the evidence behind this?
Resolv rates this source "moderate evidence". Reasonable evidence with real limitations. It scores 58 out of 100 on our published rubric. One caveat travels with that badge: The published abstract gives no sample size, no effect size, and no confidence intervals, so the strength of the result cannot be assessed from the record; sample size is recorded as unknown rather than guessed. The dose it found effective, 15 mg/day, is the same dose the same group's 1986 trial and Alda's 2017 trial both used as the comparator — a direct internal contradiction in this small literature that has never been resolved. 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 controlled trial of methylene blue in severe depressive illness. — Naylor GJ, Smith AH, Connelly P. (1987). Published in: Reputable peer-reviewed journal. DOI: 10.1016/0006-3223(87)90194-6. 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. Independence from the proponent is not recorded. 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 methylene-blue, provayblue, methylthioninium chloride, methylene blue usp, mb FDA approved for this use?
No. Its current status is: Not FDA-evaluated for this use. Methylene blue is an FDA-approved drug, but only for one thing: ProvayBlue (methylene blue injection, NDA 204630, Provepharm) is indicated for the treatment of pediatric and adult patients with acquired methemoglobinemia.
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.