From the Guidelines
Methylene blue should not be used as a first-line treatment for depression due to its potential risks and lack of strong evidence supporting its efficacy. It works as a monoamine oxidase inhibitor (MAOI), increasing levels of neurotransmitters like serotonin, norepinephrine, and dopamine in the brain. Typical dosages range from 15-60 mg per day for depression, though protocols vary. If considering methylene blue, it's crucial to consult with a psychiatrist first as it carries significant risks, particularly serotonin syndrome when combined with other antidepressants, especially SSRIs and SNRIs 1. You must wait at least 2 weeks after stopping these medications before starting methylene blue. Common side effects include blue discoloration of urine and skin, headache, nausea, and dizziness. It may also interfere with certain medical tests and procedures. While some research shows promise for treatment-resistant depression, methylene blue remains an off-label, experimental option that should only be used under close medical supervision when conventional treatments have failed.
Key Considerations
- Methylene blue is not a first-line treatment for depression due to its potential risks and lack of strong evidence supporting its efficacy.
- It should only be considered for treatment-resistant depression under close medical supervision.
- Patients should be aware of the potential risks, including serotonin syndrome, and common side effects.
- The most recent and highest quality study on the topic is from 2023, which highlights the importance of considering alternative options to second-generation antidepressants for major depressive disorder 1.
Recommendations
- Consult with a psychiatrist before considering methylene blue for depression.
- Wait at least 2 weeks after stopping other antidepressants before starting methylene blue.
- Monitor for potential side effects and risks, including serotonin syndrome.
- Consider alternative treatments, such as cognitive behavioral therapy or second-generation antidepressants, as first-line options for depression 1.
From the Research
Methylene Blue for Depression
- Methylene blue has been found to have antidepressant, anxiolytic, and neuroprotective properties in both animal and human studies 2.
- It has been used for over a century in psychiatry, with successful treatment of psychotic and mood disorders, as well as a memory enhancer in fear-extinction training 2.
- A controlled trial found that methylene blue, 15 mg/day, was significantly more effective than placebo in treating severe depressive illness 3.
- Another study found that 14 out of 19 manic depressives who received oral methylene blue showed definite improvement, with 3 patients showing no beneficial response 4.
Mechanism of Action
- Methylene blue's antidepressant effect may be due to its modulation of the nitric oxide cyclic guanosine monophosphate (NO-cGMP) cascade, enhancement of mitochondrial respiration, and antioxidant effects 5.
- It is also a high potency inhibitor of monoamine oxidase (MAO) A, which may contribute to its antidepressant effect, but also to its adverse effects profile 5.
Clinical Trials
- A randomised crossover study found that methylene blue significantly improved symptoms of depression and anxiety in patients with bipolar disorder, with no significant effects on cognitive symptoms 6.
- The study also found that methylene blue was well tolerated, with transient and mild side-effects 6.
- Another study found that methylene blue analogues with marginal monoamine oxidase inhibition retained antidepressant-like activity, suggesting a potential novel group of antidepressant compounds 5.