Thirteen of 14 reported methylene blue CNS reactions met the criteria for serotonin toxicity
A review of reported cases found 13 of 14 CNS reactions to methylene blue met the Hunter Serotonin Toxicity Criteria. An IV dose of only 0.75 mg/kg reached levels that inhibit MAO-A; severe toxicity occurred at 1 mg/kg.
Weak or heavily disputed. Treat as a question, not an answer. how we score evidence
Caveat on this rating: Fourteen selected case reports, IV dosing only; the author also co-wrote the mechanism study, so the two are not independent.
The case review that tied methylene blue reactions to serotonin toxicity, written by a co-author of the enzyme study in this library.
Significant findings
Gillman (Journal of Psychopharmacology, 2011) reviewed the reported cases of central nervous system toxicity after methylene blue, which is given intravenously for methemoglobinemia, vasoplegia and as an aid in parathyroid surgery "at doses of 1-7.5 mg kg(-1)". The review "concludes that 13 of 14 of the reported cases of CNS toxicity were serotonin toxicity that met the Hunter Serotonin Toxicity Criteria." The cause: "Serotonin toxicity is precipitated by the monoamine oxidase inhibitor (MAOI) property of methylene blue interacting with serotonin reuptake inhibitors."
On dose: "Recent human data showed that an intravenous dose of only 0.75 mg kg(-1) of methylene blue produced a peak plasma concentration of 500 ng ml(-1) (1.6 µM), indicating that the concentration in the central nervous system reaches a level that inhibits monoamine oxidase A. That is consonant with the actual occurrence of severe serotonin toxicity in humans at the dose of only 1 mg kg(-1)." Gillman adds that "all proposed uses of methylene blue entail levels that block monoamine oxidase".
The other direction
Fourteen published cases are a small, selected set; case reports show that a reaction can happen, not how often. The dose figures are intravenous, and oral absorption is a separate question. The paper's closing advice, that "cessation of serotonin reuptake inhibitors should be very carefully considered before using methylene blue", is written for clinicians planning a procedure. It is not a signal for a patient to stop an antidepressant alone. Gillman also wrote the enzyme study, so the two rows are not independent confirmations.
What this does not show
It does not give a safe dose by mouth. Methylene blue has no approved psychiatric use. It is not a reason to change any medication without the prescriber.
Worth asking
If I am scheduled for surgery and take an antidepressant, will anyone be using methylene blue?
Source
CNS toxicity involving methylene blue: the exemplar for understanding and predicting drug interactions that precipitate serotonin toxicity — Gillman PK (2011)
Reputable peer-reviewed journal
Read the source: https://doi.org/10.1177/0269881109359098
DOI: 10.1177/0269881109359098
How this was scored
- Study design
- Narrative review
- Funding
- Funding not disclosed
- Published in
- Reputable peer-reviewed journal
- Sample size
- 14
- Preregistered
- not recorded
- Conflicts disclosed
- not recorded
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published October 21, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "contested". Weak or heavily disputed. Treat as a question, not an answer. It scores 30 out of 100 on our published rubric. One caveat travels with that badge: Fourteen selected case reports, IV dosing only; the author also co-wrote the mechanism study, so the two are not independent. 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?
CNS toxicity involving methylene blue: the exemplar for understanding and predicting drug interactions that precipitate serotonin toxicity — Gillman PK (2011). Published in: Reputable peer-reviewed journal. DOI: 10.1177/0269881109359098. 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: Narrative review. 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 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.