Double-blind, placebo-controlled study of topiramate in patients with refractory partial epilepsy

Sharief, Mohammed; Viteri, C.; Ben‐Menachem, Elinor; Weber, M; Reife, R.; Pledger, Gordon; Karim, Rezaul

doi:10.1016/s0920-1211(96)00029-0

Cited by 155 publications

(118 citation statements)

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“…Twenty-nine patients (17%) responded to 100 mg of TPM or less. These doses were much lower than those used in the clinical trial prograin that studied the addition of 200-1,000 mg of TPM daily (7)(8)(9)(10)(11)(12)20). Combining TPM with phenytoin, lamotrigine, and carbamazepine seemed to be the most successful regimens.…”

Section: Discussionmentioning

confidence: 95%

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Topiramate in Refractory Epilepsy: A Prospective Observational Study

2000

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Summary:Purpose: This prospective observational study explored the efficacy and tolerability of topiramate (TPM) in patients with refractory epilepsy attending a single outpatient clinic.Methods: One hundred seventy patients (82 men, 88 women, aged 18-75 years) with refractory localization-related (n = 134) or idiopathic generalized epilepsy (n = 36) were started on adjunctive TPM using a standard titration schedule. TPM was introduced after a 3-month prospective baseline, and doses were adjusted according to clinical response. End points were seizure freedom for 6 months, 250% seizure reduction for 6 months compared with baseline at the highest tolerated TPM dose (responder), or discontinuation of TPM because of side effects, lack of efficacy, or both.Results: Thirty-nine (23%) patients were seizure-free, and 80 (47%) more patients had a useful therapeutic response. Thirteen seizure-free patients and 16 responders took 100 mg of TPM daily or less. TPM was discontinued in 51 (30%) patients. The most common side effects resulting in withdrawal were fatigue, weight loss, irritability, paresthesia, depression, and headache. Concomitant antiepileptic drugs (AEDs) were stopped in 30 patients. Twelve were established on TPM monotherapy, eight of whom remained seizure-free. Final TPM doses and concentrations varied widely among the three outcome groups.Conclusions: TPM was efficacious as add-on and monotherapy in patients with refractory partial and generalized seizures in everyday clinical use. A good response was obtained in many patients with TPM doses substantially lower than those studied in regulatory clinical trials. The wide variation in doseresponse and dose-toxicity relationships may reflect different neurobiologies causing refractory epilepsy and differential efficacy of AED combinations.

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Section: Discussionmentioning

confidence: 95%

“…Accepted March 15, 2000. TPM has proven efficacy as an add-on therapy for partial-onset, myoclonic, and generalized tonic-clonic seizures in adults and children (7)(8)(9)(10)(11)(12). It may also be useful for Lennox-Gastaut syndrome (13) and infantile spasms (14).…”

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confidence: 99%

Topiramate in Refractory Epilepsy: A Prospective Observational Study

2000

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“…There were eight articles with class I evidence that assessed the efficacy of topiramate for refractory partial seizures as add-on therapy. [17][18][19][20][21][22][23][24] The target doses in these studies ranged between 200 mg/day and 800 mg/day. The 50% responder rate ranged from 27% at doses of 200 mg/day to 50.6% at mean doses of 450 mg/day.…”

mentioning

confidence: 99%

“…The five most common adverse events were dizziness, sedation, nausea, diplopia, and fatigue. In the presurgical study, 42 21.6% of patients developed hyponatremia versus 2% on placebo.…”

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confidence: 99%

Efficacy and tolerability of the new antiepileptic drugs II: Treatment of refractory epilepsy [RETIRED]

et al. 2004

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Abstract-Objective:To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide) in the treatment of children and adults with refractory partial and generalized epilepsies. Methods: A 23-member committee including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until March 2003. Results: All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. Gabapentin can be effective for the treatment of mixed seizure disorders, and gabapentin, lamotrigine, oxcarbazepine, and topiramate for the treatment of refractory partial seizures in children. Limited evidence suggests that lamotrigine and topiramate are also effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox Gastaut syndrome. Conclusions: The choice of AED depends upon seizure and/or syndrome type, patient age, concomitant medications, AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes where more evidence is necessary.

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“…This methodologic approach allowed direct comparisons to be made between all experimental groups with regard to the effectiveness of the drug(s) and their ability to afford neuroprotection or a cessation of seizure activity or both. The results suggest that although TPM is an effective AED in the clinic (26)(27)(28)(29), and despite clinical reports of its use in status epilepticus (30), monoadministration of the drug (20-320 mg/kg, i.p.) does not stop continual seizure activity in perforant path -stimulated rats.…”

Section: Discussionmentioning

confidence: 80%

Synergism between Topiramate and Budipine in Refractory Status Epilepticus in the Rat

et al. 2004

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Summary:Purpose: To evaluate the antiepileptic and neuroprotective properties of topiramate (TPM) alone and with coadministration of the N-methyl-D-aspartate (NMDA)-receptor antagonist budipine in a rat model of refractory status epilepticus.Methods: Male Sprague-Dawley rats had electrodes implanted into the perforant path and dentate granule cell layer of the hippocampus under halothane anesthesia. Approximately 1 week after surgery, the perforant path of each animal was electrically stimulated for 2 h to induce self-sustaining status epilepticus. Successfully stimulated rats were given intraperitoneally vehicle (n = 6), TPM (20-320 mg/kg; n = 28), budipine (10 mg/kg; n = 5), or budipine (10 mg/kg) and TPM (80 mg/kg; n = 6) 10 min after the end of the stimulation and monitored behaviorally and electroencephalographically for a further 3 h.The animals were killed 14 days later, and histopathology was assessed.Results: Neither budipine alone nor TPM at any dose terminated status epilepticus. Despite this, TPM resulted in various degrees of neuroprotection at doses between 40 and 320 mg/kg. Coadministration of budipine with TPM terminated the status epilepticus in all rats. This combination also significantly improved the behavioral profile and prevented status-induced cell death compared with control.Conclusions: Budipine and TPM are an effective drug combination in stopping self-sustained status epilepticus, and TPM alone was neuroprotective, despite the continuation of seizure activity.

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Double-blind, placebo-controlled study of topiramate in patients with refractory partial epilepsy

Cited by 155 publications

References 4 publications

Topiramate in Refractory Epilepsy: A Prospective Observational Study

Topiramate in Refractory Epilepsy: A Prospective Observational Study

Efficacy and tolerability of the new antiepileptic drugs II: Treatment of refractory epilepsy [RETIRED]

Synergism between Topiramate and Budipine in Refractory Status Epilepticus in the Rat

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