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.