Case files of the Program in Medical Toxicology at Brown University: Amantadine withdrawal and the neuroleptic malignant syndrome

Abstract

A sixty-one-year old woman with a history of depression and idiopathic dystonia presented to the emergency department (ED) with fever, nausea, muscle rigidity, and redness in her extremities. The patient had seen various specialists for her dystonia during the preceding year and had tried multiple medication regimens, including benztropine and tizanidine. The patient described her home medications as tizanidine 2 mg three times daily, diazepam 2.5 mg daily, escitalopram 100 mg daily, rosuvastatin 10 mg daily and bupropion 300 mg nightly. At ED presentation her vital signs were: temperature 37.5°C (99.5F), blood pressure 157/76 mmHg, heart rate 105 beats per minute, respirations 24 per minute, and oxygen saturation of 100% on room air. Her physical examination was significant for diaphoresis, tachycardia, diffuse flushing, tremors in her upper and lower extremities, muscle rigidity, and hyperreflexia in the upper and lower extremities. The tremors were low amplitude and worse with intention, while the rigidity had cogwheeling features and was more notable in her lower extremities. Initial laboratory evaluation was significant for a creatine phosphokinase (CPK) of 1146 IU/L. Her electrocardiogram showed sinus tachycardia with normal QRS and QT intervals, and no evidence of acute ischemia. Two months earlier, the patient’s neurologist had started her on amantadine 100 mg twice daily for dystonia. Three days prior to ED presentation, the patient abruptly stopped taking her amantadine on the advice of a pharmacist, secondary to bilateral lowerextremity edema. The following day, the patient presented to her primary care physician complaining of nausea, tremors, and diffuse flushing. The physician treated her for an allergic reaction with oral steroids and diphenhydramine. The patient’s symptoms worsened over the next day with increasing tremors and rigidity, low-grade fever, nausea, and flushing, which prompted her presentation to the ED.