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Progabide
Published in Stanley R. Resor, Henn Kutt, The Medical Treatment of Epilepsy, 2020
Progabide antiepileptic efficacy was assessed in open and in double-blind trials. In three pilot studies, 36 patients suffering from very frequent seizures, either partial or generalized, received PGB at doses ranging from 12 to 30 mg/kg as add-on therapy. The drug was without effect at doses of 12 to 15 mg/kg. At higher doses (20 to 30 mg/kg) it led to a more than 50% reduction of seizure frequency in 47% of the cases (11). In a series of eight double-blind crossover randomized trials, PGB versus placebo, as add-on therapy, PGB was administered at a daily dose of about 30 mg/kg. In individual studies, PGB has been found superior to placebo in five trials (12–16), whereas in three others (17–19) no significant differences versus placebo could be found. On the whole, the trials have shown that PGB administered as add-on to preexisting therapies may be beneficial in about 30 to 50% of drug-resistant epilepsies, with differences in percentages of responders that vary according to the type of epilepsy and the severity of the syndrome (20). Ttoo comparative studies of PGB versus valproate (VPA) have been conducted. In the first (21) the activity of PGB was comparable to that of VPA, whereas in the second (22) it was inferior.
Anticonvulsant Drugs with New Mechanisms of Action
Published in Carl L. Faingold, Gerhard H. Fromm, Drugs for Control of Epilepsy:, 2019
Highly potent GABA agonists such as muscimol and THIP can facilitate certain epileptic discharges (e.g., the absence-like spike-and-wave discharges in certain Wistar rats and the bilateral spike-and-wave discharges in baboon12,13) and produce diffuse myoclonus in animals and man. Similar effects can be produced by potent GABA uptake inhibitors.14 The clinical usefulness of direct GABA agonists has yet to be established. Progabide is a weak agonist at both GABAA and GABAB receptors and has significant anticonvulsant activity in various animal models.15 Clinically it is of limited efficacy16 and was withdrawn from trial following evidence of hepatotoxicity.
Repeated Measures and Longitudinal Data Analysis
Published in Mohamed M. Shoukri, Analysis of Correlated Data with SAS and R, 2018
This data have been analyzed by Thall and Vail (1990) and Stukel (1993) using several models for longitudinal count data. It is a randomized clinical trial of the antiepileptic drug Progabide, in which 59 patients were seen, and the count of seizures was taken at baseline and at four follow-up visits. The main objective was to estimate the treatment effect and its possible modification by disease severity (seizure count at baseline), and age. The data are given in Table 7.4.
Brain circuits and neurochemical systems in essential tremor: insights into current and future pharmacotherapeutic approaches
Published in Expert Review of Neurotherapeutics, 2018
Sara M Schaefer, Ana Vives Rodriguez, Elan D Louis
Progabide is a GABAA receptor agonist that has shown not to work in ET [62,63]. It is not clear which subunits progabide may or may not act upon, as it has not been explored in ET since the 1980s. Tiagabine is a GABA reuptake inhibitor (rather than a GABA receptor agonist) that is also ineffective for the treatment of ET [64]. Zolpidem has high affinity for α1–3 and γ subunits, like benzodiazepines, but does not act on α5 subunits as benzodiazepines do [20]. It has not been studied in ET. Baclofen, a selective GABAB receptor agonist, has shown an effect in harmaline-induced tremor in rats, but has not been studied in ET patients [65].
Bayesian rank-based hypothesis testing for the rank sum test, the signed rank test, and Spearman's ρ
Published in Journal of Applied Statistics, 2020
J. van Doorn, A. Ly, M. Marsman, E.-J. Wagenmakers
Thall and Vail [57] investigated a data set obtained by D. S. Salsburg concerning the effects of the drug progabide on the occurrence of epileptic seizures. During an initial eight week baseline period, the number of epileptic seizures was recorded in a sample of 31 epileptics. Next, the patients were given progabide, and the number of epileptic seizures was recorded for another eight weeks. In order to accommodate the discreteness and non-normality of the data, Thall and Vail [57] applied a log-transformation on the counts.