Topiramate--safety and tolerability.

Topiramate is a new novel drug for the treatment of intractable seizures that is to be used in an adjunctive fashion. A review of the seven double-blind controlled studies was undertaken with special attention paid to safety and tolerability data. The studies were similar in design but used varying doses of the drug. To date there has been no evidence of serious systemic side effects such as rash, hepatotoxicity, cardiotoxicity, serious gastrointestinal toxicity or aplastic anemia. Renal stones were reported in 1.5% of patients with over 80% choosing to remain on the drug because of an improved quality of life. The unique observation of "abnormal thinking" was seen that seemed to be related to high doses and introducing the drug too rapidly. Patients, rather than describing psychomotor slowing, described a phenomenon of slow thoughts, decreased cognition, intermittent difficulty calculating, dulled thinking, blunted mental reactions. Lastly, weight loss appears in approximately 10-20% of patients and is probably related to dulling of appetite. Although increasing doses gave increasing degrees of seizure freedom, it appeared that doses beyond 600 mg/day are often not well tolerated.