A comparison of phenytoin and pheneturide in patients with epilepsy: a double-blind cross-over trial

Abstract

SUMMARY A double-blind cross-over trial between pheneturide and phenytoin in ninety-four outpatients with epilepsy is described. There was no significant difference between the frequency of seizures in the two groups. The difficulties in comparing two anticonvulsants of similar efficacy are discussed particularly in relation to ethical problems, the selection of patients and trial design.Recent research in anticonvulsant drugs has concentrated on their mode of action, their absorption, metabolism and elimination. Thus while the pharmacokinetics of these drugs are well understood, there are few adequate trials to test their efficacy in the management of epilepsy,' 2 possibly because ethical and design difficulties frequently

Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes

“…Combined with the previous 23 RCTs from the last report, CBZ, VPA, and PHT were the most commonly studied AEDs (n = 12 each) (Sommerfeld-Ziskin, 1940;Shakir et al, 1981;Gibberd et al, 1982;Turnbull et al, 1982Turnbull et al, , 1985Ramsay et al, 1983Ramsay et al, , 1992Callaghan et al, 1985;Dam et al, 1989;Feksi et al, 1991;Rastogi et al, 1991;Placencia et al, 1993;Richens et al, 1994;Brodie et al, 1995Brodie et al, , 2002aHeller et al, 1995;Kalviainen et al, 1995;Reunanen et al, 1996;Bill et al, 1997;Christe et al, 1997;Steiner et al, 1999;Privitera et al, 2003;Arroyo et al, 2005;Ramsay et al, 2010). The number of studies for each AED and their distribution by RCT class of evidence is shown in Table S4.…”

“…Among the six RCTs, two were considered class I studies (Brodie et al, 2007;Baulac et al, 2012), whereas the other four met criteria for class III studies because of an open-label design (Steinhoff et al, 2005;Marson et al, 2007a), too brief treatment duration (Steinhoff et al, 2005;Ramsay et al, 2010), or lack of an adequate comparator (Kwan et al, 2011). Combined with the previous 33 RCTs from the last report, carbamazepine (CBZ) remains the most frequently studied (n = 23), followed by phenytoin (PHT) (n = 12) and valproate (VPA) (n = 11) (Sommerfeld-Ziskin, 1940;Mikkelsen et al, 1981;Shakir et al, 1981;Gibberd et al, 1982;Turnbull et al, 1982;Ramsay et al, 1983Ramsay et al, , 2010Loiseau et al, 1984;Callaghan et al, 1985;Mattson et al, 1985;Turnbull et al,1985;Dam et al, 1989;Feksi et al, 1991;Rastogi et al, 1991;Mattson et al, 1992;Placencia et al, 1993;Richens et al, 1994;Brodie et al, 1995;Heller et al, 1995;Kalviainen et al, 1995;Reunanen et al, 1996;Tanganelli & Regesta, 1996;Bill et al, 1997;Christe et al, 1997;Chadwick et al, 1998;Chadwick, 1999;Steiner et al, 1999;Nieto-Barrera et al, 2001;Brodie et al, 2002a,b;Gilliam et al, 2003;…”

Efficacy and Safety of Antiepileptic Drugs: A Review of Controlled Trials

“…Thirty-one patients preferred clorazepate and 12 preferred phenobarbital. Gibberd et al (1982), in a double-blind, randomized, crossover trial, compared the effects of monotherapy with phenytoin and pheneturide on the number of seizure-free days in 94 newly diagnosed patients over the age of 15 years who required anticonvulsant therapy. Each patient was randomly assigned to a regimen of either pheneturide, 200 mg three times a day, or phenytoin, 100 mg three times a day.…”

“…It is the purpose of this review to consider what is known about the efficacy and toxicity of commonly used, currently marketed antiepileptic drugs, as derived from information obtained from Pryse-Phillips et al, 1970Rodin et al, 1974 Carbarnazepine vs. phenytoin Rajotte et al, 1967Sirnonsen et al, 1976Troupin et al, 1977Kosteljanetz et al, 1979Ramsay et al, 1983Majerrison et al, 1968Rodin et al, 1976Mikkelsen et al, 1981 phenobarbital Cereghino et al, 1974 Carbarnazepine vs. phenytoin vs. phenobarbital vs. primidone Mattson et al, 1985 Carbarnazepine vs. phenytoin and/or phenobarbital and/or primidone Bird et al, 1966 placebo Gruber et al, 1956 primidone vs. placebo White et al, 1966 Phenytoin vs. pheneturide Gibberd et al, 1982Phenobarbital vs. clorazepate Wilensky et al, 1981 Valproic acid vs. placebo Richens andAhmad, 1975 Gram et al, 1977 Valproic acid vs. valproic acid Gram et al, 1979 Carbamazepine vs. phenobarbital (i.e., how long the drug remains sufficiently effective with sufficiently few side effects for the patient to continue using that drug rather than switching to another). -This review considers the results from the 20 controlled trials, discussed here in the context of these criteria for the evaluation of the efficacy of antiepileptic drugs.…”

Dr Brian Gibberd (1931–2006): a pioneering clinician in Refsum's disease

“…time to do some basic clinical pharmacology and publish on epilepsy [3,4] and therapeutic drug monitoring while remaining an active service clinician. His interest in Refsum's disease was sparked in 1979 by the presentation of two patients with a constellation of signs including retinitis pigmentosa, anosmia, polyneuropathy and ichythosis [5].…”