Topiramate is a structurally novel anti-epileptic drug with at least 3 postulated mechanisms of action including: 1) potentiation of GABA responses, 2) impairment of AMPA/kainate glutamate receptors and 3) suppression of high frequency action potential firing. It has a favourable pharmacokinetic profile with rapid absorption, good bio-availability, linear pharmacokinetics, relatively long half-life and limited pharmacokinetic drug interactions. However, topiramate can reduce the estrogen component of oral contraceptive medications. Women may require birth control preparations containing 50 (Xg of estrogen. Topiramate clearance is reduced in severe renal failure and increased by enzyme-inducing antiepileptic drugs. The dose of topiramate may have to be reduced in renal failure or when withdrawing enzyme inducers.

In controlled clinical trials, topiramate (TopamaxR) has demonstrated efficacy in refractory patients with complex partial seizures and secondarily generalized tonic-clonic seizures. Approximately 45 percent of 534 patients had a ≥ 50 percent reduction in seizure frequency. Limited open label trials have shown that topiramate has broad spectrum activity and may be effective in patients with primary generalized epilepsies. The efficacy of topiramate compares very favourably with the efficacy of other new antiepileptic drugs recently introduced.

Topiramate (TPM), a new antiepileptic medication, is efficacious as adjunctive therapy in adults with partial onset seizures. Its efficacy as adjunctive therapy in children was evaluated in two randomized double-blind placebo-controlled trials involving childhood epileptic encephalopathy (the Lennox-Gastaut syndrome) and partial onset seizures. In these studies, topiramate adjunctive therapy resulted in a significant reduction in drop attacks (tonic or atonic seizures) in patients with the Lennox Gastaut syndrome and a significant reduction in partial onset seizures in children with refractory partial epilepsy. In both trials, TPM's efficacy improved as the dose escalated from the double-blind phase to the open-label portion. The minimally effective topiramate dose for adjunctive therapy in children with refractory epilepsy appears to be 6 mg/kg/day. Topiramate was well tolerated with mild or moderate side effects, predominantly related to the central nervous system. Practical tips are provided that may increase the chance that topiramate will be effective and well tolerated. The most important advice is a “start low, go slow” approach. An initial TPM dose of 0.5 - 1 mg/kg/day followed by weekly increments of 0.5 - 1 mg/kg is usually well tolerated. Based on these studies, topiramate appears to be an important addition to our pediatric AED armamentarium.

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.

Clinical trials are important in determining the relative efficacy and safety of a new antiepileptic drug (AED); however, experience acquired in clinical practice will eventually determine its position in the antiepileptic armamentarium. Topiramate (TPM), a new AED has been available in the United Kingdom since mid-1995 and a considerable number of patients have being treated. As a result of this experience, a number of changes have being made in the way TPM is used, particularly in the starting doses and titration rates. This seems to have improved patients' tolerability of treatment, an important consideration if a drug is to be used to its optimum level. In this article, practical tips for the use of TPM are given and these include starting doses, titration rates, options for managing side effects occurring early in treatment, advice concerning the withdrawal of concomitant AEDs and indications for discontinuation of TPM. The need for adequate patient counseling regarding potential side effects and expectations of treatment is also reviewed.