Topiramate-Positive Death-Investigation and Impaired-Driving Cases in Washington State

Abstract

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.

Review of topiramate for the treatment of epilepsy in elderly patients

“…One gross effect of TPM on daily life has been evaluated by examining motor vehicle performance and at least two studies have found TPM-related decreases in driving ability 72,78. In one, a subsample of patients with partial seizures taking part in a randomized, double-blind, controlled study comparing the cognitive effects of TPM and LTG, was administered a computerized task measuring scanning, divided attention, and effective field of view (via the Performance On-Line, or POL) 72.…”

A pilot study to test multiple medication usage and driving functioning

“…In forensic toxicology investigations of topiramate-positive drivers reported by Gordon and Logan (2006), psychomotor impairment was evident with blood concentrations within normal therapeutic range. As an example, a 31-year-old female was prescribed topiramate for an eating disorder.…”

“…Topiramate (an anti-epileptic also used in migraine revention and other therapies) Topiramate (Topamax) is a seizure disorder treatment that received additional FDA approval for prevention of migraine headaches in August 2004, and is being prescribed for offlabel uses such as psychiatric disorders (e.g., schizophrenia and bi-polar disorder); eating disorders (e.g., bulimia, binge eating, obesity, and anorexia nervosa); as an adjunct therapy to treat weight gain associated with olanzapine, SSRIs, and other anti-psychotic medications; neuropathic pain; and alcohol and drug dependency (Gordon & Logan, 2006). Its potentially driver impairing side effects include sedation; dizziness; confusion; difficulty concentrating; shaky and unsteady body movements; rapid and repetitious involuntary eye movements; decreased visual acuity; hypoglycemia leading to loss of consciousness; and tingling or numbness in the arms and legs.…”

Topiramate: Safety and Efficacy of its Use in the Prevention and Treatment of Migraine

“…The Washington State Toxicology Laboratory reported data regarding topiramate-positive death investigation and impaired-driving cases 43. Topiramate-positive findings have increased in this area because of the additional prescriptions for offlabel use of topiramate.…”

“…Topiramate-positive findings have increased in this area because of the additional prescriptions for offlabel use of topiramate. From 1998 to 2004, the laboratory reported 63 death investigations, 68 suspected impaired drivers, and one sexual assault case 43. The mean reported serum topiramate concentration is 8.4 mg/L.…”