Fatal topiramate overdose with antemortem cardiac conduction abnormality and seizures

• Published in: Clinical toxicology (Philadelphia, Pa.) Pa.), 2005-10, Vol.43 (6), p.734-734
• Main Authors: Cumpston, K L, Jones-Lovato, H
• Format: Article
• Language: English
• ISSN: 1556-3650

One fatality has been attributed to topiramate, but the details of the clinical toxicity are not well described. The data provided in the literature insufficiently describes the severe clinical toxicity of topiramate. We present a case of a critically ill topiramate overdose with cardiovascular instability, seizures, coma and death. An 18 year old female, who had been hording her prescription medication with the intent of suicide, was found unresponsive with bottles of topiramate 200 mg, ranitidine 300 mg, bupropion 200 mg XR, near her. When paramedics arrived she had a seizure, agonal respirations, and bradycardia. The seizure was treated with a benzodiazepine and her cardiac rhythm deteriorated to asystole. The trachea was intubated and standard advanced cardiac life support was initiated. The cardiac rhythm converted to atrial fibrillation (140 bpm) and the systolic blood pressure (SBP) improved to 90 mm Hg. A prolonged QRS complex was noted on the cardiac monitor and three ampules of IV sodium bicarbonate was successful in narrowing the QRS width. She was also treated with epinephrine and dopamine to maintain her blood pressure (BP). Her BP eventually stabilized, but her two day hospital course involved an unknown number of possible seizures, pneumonia, and persistant coma. Finally, an EEG confirmed brain death and support was withdrawn. The urine drug screen was positive for only amphetamines and negative for all others including TCAs. The general serum drug screen on antemortem blood was positive for burpropion and topiramate, but confirmatory testing by National Medical Services confirmed that only topiramate had a detectable concentration (29 mcg/mL). The antiepileptic mechanism of action of topiramate involves direct sodium channel blockade and inhibition of the kainate glutamate receptor. With this concept in mind, one would expect to see the clinical manifestations described in our patient. A topiramate overdose may manifest itself with a prolonged QRS complex, seizure, coma, and death.