A two-year double-blind crossover trial of the prophylactic effect of methylene blue in manic-depressive psychosis

Biol Psychiatry. 1986 Aug;21(10):915-20. doi: 10.1016/0006-3223(86)90265-9.


A 2-year prophylactic trial was carried out in 31 bipolar manic-depressive subjects, comparing 300 mg/day methylene blue on a double-blind crossover basis with 15 mg/day. All patients were also maintained on lithium. Seventeen patients completed the 2-year trial. During the year the patients were treated with methylene blue at 300 mg/day, they were significantly less depressed than during the year on 15 mg/day. No significant difference in the severity of manic symptoms was shown. The trial had obvious limitations, e.g., a small number of subjects, a relatively large number of dropouts, relatively simple rating scales, doubts about blindness, and uncertainty as to whether or not 15 mg methylene blue per day could be considered a placebo. However, the results suggest that methylene blue may be a useful addition to lithium in the long-term treatment of manic-depressive psychosis and warrants further investigation.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bipolar Disorder / prevention & control*
  • Bipolar Disorder / psychology
  • Clinical Trials as Topic
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Humans
  • Long-Term Care
  • Methylene Blue / therapeutic use*
  • Psychiatric Status Rating Scales
  • Random Allocation


  • Methylene Blue