Topiramate-positive death-investigation and impaired-driving cases in Washington state

Topiramate (Topamax), an effective seizure disorder treatment, received additional FDA approval for prevention of migraine headaches in August 2004 and has gained attention for its off-label uses, including psychiatric and eating disorders, neuropathic pain, and alcohol and drug dependency. Side effects of sedation, dizziness, ataxia, speech difficulty, nystagmus, paresthesia, and metabolic acidosis are described. The manufacturer reports that tolerance to the antiseizure properties does not develop. With its established efficacy for epilepsy treatment and its increased use for other disorders, topiramate-positive findings are more common in death-investigation and human-performance casework. To evaluate the role of topiramate, we reviewed all topiramate-positive cases from our laboratory between 1998 and 2004, which constituted 132 cases (63 death investigations, 68 suspected impaired drivers, and 1 sexual assault case). The subjects were predominantly female (69%) with a mean and median age of 42. Blood topiramate concentrations ranged from 1 to 180 mg/L (median 6.4 mg/L, mean 8.4 mg/L), and 94% were positive for at least one additional drug. There was evidence of psychomotor impairment in some drivers with blood concentrations within the normal therapeutic range, and deaths attributed to topiramate alone occurred at concentrations as low as 50 mg/L.