The Role of Methylene Blue in Serotonin Syndrome: A Systematic Review

Background: A recent series of case reports has demonstrated a significant, previously unrecognized drug interaction between serotonin reuptake inhibitors (SRIs) and methylene blue (MB). Objective: The authors review the case reports and clinical audits relevant to this interaction and consider the diagnosis of serotonin syndrome in these cases. Method: Articles were obtained from a systematic search of MEDLINE and PsychInfo databases, and from the bibliographies of relevant articles. Studies were considered relevant if the patient received MB and developed an acute confusional state, neuropsychiatric complications, or autonomic instability. Results: The review identified nine case reports and two retrospective reviews; 26 patients developed an acute confusional state after MB infusion; 24 of these patients were taking an SRI, and 1 was taking clomipramine. Serotonin syndrome was a possible diagnosis in all 25 of these patients. Conclusion: SRIs can interact with MB, causing a serious adverse reaction consistent with serotonin syndrome. (Psychosomatics 2010; 51: 194-200)