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Methylene Blue, serious CNS reactions possible when given to patients taking serotonergic psychiatric medications

The FDA ( Food and Drug Administration ) has updated healthcare professionals and the public on the potential drug interaction between Methylene Blue and serotonergic psychiatric medications.
Most cases from the Adverse Event Reporting System ( AERS ) of serotonin syndrome in patients given serotonergic psychiatric medications and Methylene Blue occurred in the context of parathyroid surgery, which involved the intravenous administration of Methylene Blue as a visualizing agent.
Methylene Blue doses ranged from 1 to 8 mg/kg.

Limited data exist regarding Methylene Blue use in various settings, it is not known whether there is a risk of serotonin syndrome in patients taking serotonergic psychiatric medications who are given Methylene Blue by other routes ( e.g., orally or by local tissue injection ) or at intravenous doses lower than 1 mg/kg.

In addition, not all serotonergic psychiatric drugs have an equal capacity to cause serotonin syndrome with Methylene Blue. The cases of serotonin syndrome with Methylene Blue occurred in patients taking specific serotonergic psychiatric drugs, namely a selective serotonin reuptake inhibitor ( SSRI ), a serotonin norepinephrine reuptake inhibitor ( SNRI ), or Clomipramine ( Anafranil ).
It is unclear at this time whether intravenous Methylene Blue administration in patients receiving other psychiatric drugs with lesser degrees of serotonergic activity poses a comparable risk.

Methylene Blue is used to treat methemoglobinemia, vasoplegic syndrome, ifosfamide-induced encephalopathy, and cyanide poisoning. It is also used as a dye in therapeutic and diagnostic applications.
Methylene blue is a potent, reversible monoamine oxidase inhibitor ( MAOI ). Although the exact mechanism of this drug interaction is unknown, Methylene blue inhibits the action of monoamine oxidase A, an enzyme responsible for breaking down serotonin in the brain.
It is believed that when Methylene Blue is given to patients taking serotonergic psychiatric medications, high levels of serotonin can build up in the brain, causing toxicity. This is referred to as serotonin syndrome; signs and symptoms include mental changes ( confusion, hyperactivity, memory problems ), muscle twitching, excessive sweating, shivering or shaking, diarrhea, trouble with coordination and/or fever.

Methylene Blue should generally not be given to patients taking serotonergic drugs. However, there are some conditions that may be life-threatening or require urgent treatment with Methylene Blue such as when it is used in the emergency treatment of methemoglobinemia, Ifosfamide-induced encephalopathy, or cyanide poisoning. ( Xagena )

Source: FDA, 2011