- 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.
J. Neurol. Sci. 1998; 25: S13-S15