Methylene blue treatment for residual symptoms of bipolar disorder: randomised crossover study

Br J Psychiatry. 2017 Jan;210(1):54-60. doi: 10.1192/bjp.bp.115.173930. Epub 2016 Jun 9.

Abstract

Background: Residual symptoms and cognitive impairment are among important sources of disability in patients with bipolar disorder. Methylene blue could improve such symptoms because of its potential neuroprotective effects.

Aims: We conducted a double-blind crossover study of a low dose (15 mg, 'placebo') and an active dose (195 mg) of methylene blue in patients with bipolar disorder treated with lamotrigine.

Method: Thirty-seven participants were enrolled in a 6-month trial (trial registration: NCT00214877). The outcome measures included severity of depression, mania and anxiety, and cognitive functioning.

Results: The active dose of methylene blue significantly improved symptoms of depression both on the Montgomery-Åsberg Depression Rating Scale and Hamilton Rating Scale for Depression (P = 0.02 and 0.05 in last-observation-carried-forward analysis). It also reduced the symptoms of anxiety measured by the Hamilton Rating Scale for Anxiety (P = 0.02). The symptoms of mania remained low and stable throughout the study. The effects of methylene blue on cognitive symptoms were not significant. The medication was well tolerated with transient and mild side-effects.

Conclusions: Methylene blue used as an adjunctive medication improved residual symptoms of depression and anxiety in patients with bipolar disorder.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anxiety / drug therapy*
  • Anxiety / etiology
  • Bipolar Disorder / complications
  • Bipolar Disorder / drug therapy*
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / etiology
  • Cross-Over Studies
  • Depression / drug therapy*
  • Depression / etiology
  • Double-Blind Method
  • Drug Therapy, Combination
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / pharmacology*
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • Humans
  • Lamotrigine
  • Male
  • Methylene Blue / administration & dosage
  • Methylene Blue / adverse effects
  • Methylene Blue / pharmacology*
  • Middle Aged
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / adverse effects
  • Neuroprotective Agents / pharmacology*
  • Outcome Assessment, Health Care*
  • Triazines / administration & dosage
  • Triazines / pharmacology
  • Young Adult

Substances

  • Enzyme Inhibitors
  • Excitatory Amino Acid Antagonists
  • Neuroprotective Agents
  • Triazines
  • Methylene Blue
  • Lamotrigine

Associated data

  • ClinicalTrials.gov/NCT00214877