Topiramate in clinical practice: long-term experience in patients with refractory epilepsy referred to a tertiary epilepsy center

Abstract

For the treatment of patients with chronic refractory epilepsies, information about the long-term efficacy and safety profile of any new antiepileptic drug is crucial. Topiramate has been proven to be effective in patients with refractory chronic partial epilepsies in short-term controlled clinical trials, but the long-term retention, long-term efficacy, and long-term side-effect profile have not been sufficiently investigated. We analyzed all patients who had been treated with topiramate in the Epilepsy Centre Kempenhaeghe from the introduction of the drug in the spring of 1993 up to a final assessment point in mid-2002. In total, 470 patients were identified. The data show that the clinical dose achieved was about 200mg/day, reached after approximately 6 months of treatment. Further dose escalation in the survivors was slow, with a mean dose of about 300 mg/day after 24 months of treatment. Mean titration dose is 25mg/week, but titration strategy is mostly individual and responds to patient complaints. With respect to seizure frequency, 10-15% of the patients were seizure-free at the 6-month evaluation; 4 patients achieved a 2-year remission. Retention rate was 53% after 1 year, 45% after 2 years, 38% after 3 years, and 30% after 4 years. At 4 years, almost 70% of the patients had discontinued topiramate. The main reason was adverse events, which accounted for about 65% of the discontinuations. Behavioral side effects were dominant, with mental slowing (27.6%), dysphasia (16.0%), and mood problems (agitation: 11.9%) being the most frequently reported side effects. In about 10% of the patients side effects led to discontinuation despite the obvious favorable effects on seizure frequency. Comparisons between the patients who discontinued topiramate treatment and those who continued topiramate showed that discontinuation was associated with comedication (vigabatrin and lamotrigine). Our conclusion is that TPM is associated with a high incidence of side effects in clinical practice, affecting long-term retention. Meaningful prognostic factors that may help us in clinical decision making, i.e., to prevent the side effects or to help us identify those at risk, have not been found.

Cognitive Disorders in Juvenile Myoclonic Epilepsy

“…In general, the cognitive effects of AEDs are less than the sum total of other factors and are usually reversible. [34] R. Thomas et al [35] examined 60 patients with drugrefractory JME and concluded that patients were profoundly impaired across the range of tests evaluating intellectual function, memory, language and naming, executive function, the impact of epilepsy, and AED side effects. Eighty-three percent of patients exhibited frank executive dysfunction, which was moderate to severe in 66%.…”

Subjectively Perceived Side-Effects of Anti-Epileptic Drugs in Chronic Refractory Epilepsy

“…Cognitive complaints, related to confirmed cognitive dysfunction has been reported with almost all the older drugs and especially for phenobarbital (PB), phenytoin (PHT) and vigabatrin (VGB) [4,5]. Some newer AEDs such as topiramate (TPM) and zonisamide (ZNS) are also known to cause significant cognitive side-effects: both have diffuse cognitive effects, as well as specific effects on language and memory [5][6][7][8][9]. This concurs with the patient-reported cognitive side-effects that are more common with TPM, followed by ZNS and phenytoin (PHT) and are least likely to be reported with GBP, valproate (VPA), LTG and carbamazepine (CBZ) [10,11].…”

Cognitive and emotional changes in patients with juvenile myoclonic epilepsy

“…Особого внимания заслуживают препараты группы топирамата (ТПМ), вызывающие дозозависимые речевые нарушения, расстройства памяти и внимания [19], но в то же время ТПМ обладает антидепрессивным действием при условии медленной титрации [20]. Однако удержание на те-рапии через 4 года, по данным H.P.…”

“…Bootsma и соавт. [19], со-ставляет 30%; при этом в половине случаев отказом от лече-ния послужили когнитивные расстройства, снижающие ка-чество жизни пациентов. Препараты группы леветирацета-ма (ЛЕВ), по данным большинства исследователей, не ока-зывают неблагоприятного действия на когнитивные функ-ции [21][22][23], а препараты группы ламотриджина (ЛТД) и вальпроевой кислоты (ВК) улучшают память и оказывают нормотимическое действие как в моно-, так и в политера-пии [5,24].…”