Serotonin Syndrome Precipitated by Amantadine in a Patient With Persistent Post Concussive Symptoms – A Case Report

Symptoms after mild traumatic brain injury (MTBI) can persist for greater than 1 month in up to 20% of individuals, yet there are no current medications approved by the Food and Drug Administration for treatment of specific concussion related sequelae. Amantadine, a dopamine agonist and N-Methyl-D-aspartate antagonist, is increasingly being used as a treatment option for individuals with traumatic brain injury across the spectrum of injury severity. This case report describes a 22-year-old individual who sustained an MTBI without loss of consciousness or post-traumatic amnesia after striking their head against a metal cabinet. The individual was referred to an interdisciplinary outpatient brain rehabilitation program secondary to persistent symptoms after MTBI, was prescribed amantadine for post-traumatic headache 97 days after injury, and subsequently developed symptoms of serotonin syndrome (SS) within 10 days of medication initiation. While SS caused by amantadine has been described in individuals with renal failure, this case report is the first to describe amantadine precipitating SS - confirmed by a validated diagnostic criterion and successfully treated with lorazepam and cyproheptadine - in a patient with normal renal function already on duloxetine, bupropion, and gabapentin. This case report is important in elucidating potential contributions of amantadine to the development of SS and highlighting the important role clinicians have in assessing for polypharmacy when prescribing amantadine for individuals with traumatic and acquired brain injuries.