(942) Why So Blue? Serotonin Syndrome in Dapsone-Induced Methemoglobinemia

Introduction: Serotonin syndrome (SS), characterized by enhanced synaptic serotonergic activity, may arise from interactions between selective serotonin reuptake inhibitors (SSRIs) and other medications. Manifestations range from mental status changes, serious autonomic disturbances, and subtle neuromuscular abnormalities. We present a case of SS triggered by the combination of Methylene Blue (MB) and antidepressants.

Description: A 54-year-old woman, with depression (on paroxetine and bupropion), and diffuse large B-cell lymphoma (on rituximab, dexamethasone, cytarabine, and oxaliplatin, last dosed one month before admission) presented to the hospital with shortness of breath, headaches and demonstrated hypoxemia. Critical Care was called for refractory hypoxemia despite 100% FiO2 via high-flow nasal cannula. Methemoglobinemia was suspected based on PaO2-SpO2 differential and recent dapsone use. Co-oximetry showed 11.1% methemoglobin, for which she received 100mg of IV MB. An hour after, she developed acute encephalopathy despite improved oxygenation. CT head and repeat arterial blood gas were normal. Neurological exam was notable for inattention, inability to follow commands, and repetitive speech. Cranial nerves were intact and she moved all extremities without signs of rigidity. She had a temperature of 39.3C despite antipyretics. She was treated with IV crystalloids, IV lorazepam and discontinuation of antidepressants. Her mental status returned to baseline after several hours, and she was discharged home two days later.

Discussion: In the US, 37 million adults use SSRIs. The frequent use of multiple medications in cancer patients raises the risk of polypharmacy-induced SS. Mild SS symptoms can be subtle and easily overlooked, SS may be under-detected. MB, utilized for many indications including methemoglobinemia, inhibits monoamine oxidase (MAO), which impedes serotonin breakdown. This inhibition may amplify serotonergic activity and induce SS in patients using SSRIs concurrently. Early identification and intervention, such as discontinuing offending agents, are vital to prevent life-threatening progression. This case underlines the necessity of heightened vigilance for increased serotonergic activity in patients using SSRIs and MAO inhibitors, and the consideration of alternative treatments.