Tricyclic antidepressant intoxication is one of the most frequently encountered and life-threatening causes of intoxication among referrals to emergency departments due to drug intoxication. There is no known antidote against any of the tricyclic antidepressants. The American Society for Apheresis (ASFA) recommends plasmapheresis to support primary treatment in this type of drug poisoning, which does not respond to certain and traditional treatments. We present a 15-year-old girl who ingested amitriptyline with suicidal intent. On admission, she was in a comatose state (Glasgow Coma Scale score: 5), with no spontaneous respiration and presence of pathological reflexes. Due to the intake history of lethal doses and the severe clinical picture, plasmapheresis was performed. She was discharged on her fifth day of hospitalization.Due to the high plasma protein binding property of amitriptyline, plasma exchange therapy should be considered in cases of severe amitriptyline intoxication as a life-saving therapeutic modality.