Progabide Treatment in Severe Epilepsy: A Double‐Blind Cross‐over Trial Versus Placebo

Martínez‐Lage, J. M.; Bossi, Laura; Morales, George A.; Vilà, E.; Orofiamma, B.; Viteri, C.

doi:10.1111/j.1528-1157.1984.tb03466.x

Cited by 18 publications

(12 citation statements)

References 22 publications

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“…The efficacy of PGB in the treatment of seizures has been variable. In some studies (Van der Linden et al, 1981;Loiseau et al, 1983;Weber et al, 1983;Martinez-Lage et al, 1984), PGB was clearly more effective than placebo or other standard treatment. Some of these studies formed the basis for recognition of PGB as a drug with sufficient safety and efficacy to warrant approval €or marketing in France.…”

Section: Discussionmentioning

confidence: 98%

“…Some of the European clinical trials have shown it to be effective (Van der Linden et al, 1981;Loi-seau et al, 1983;Weber et a]., 1983;Martinez-Lage et al, 1984), while results of other studies have been less favorable (Dam et al, 1983;Schmidt, 1984). PGB was the first drug to be tested by the Epilepsy Branch of the National Institutes of Health (NIH) under the Antiepileptic Drug Development Program (Leppik et al, 1985).…”

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confidence: 99%

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Double‐Blind Withdrawal of Phenytoin and Carbamazepine in Patients Treated with Progabide for Partial Seizures

Leppik

Brundage

Krall³

et al. 1986

Epilepsia

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Of 30 patients who completed a study of progabide (PGB) as an add-on to both phenytoin (PHT) and carbamazepine (CBZ), 11 volunteered for a double-blind withdrawal protocol in which the PHT and CBZ were to be withdrawn. All patients were receiving 24-32 mg/kg/day PGB in combination with PHT and CBZ. Each patient was randomly assigned to withdrawal of either CBZ or PHT in the first block, and then withdrawal from the other in the second block in an attempt to achieve PGB monotherapy. Seizure occurrence was monitored by sequential analysis, and if a significant increase over baseline seizure frequency occurred, the dose of PGB was increased to a maximum of 45 mg/kg/day. If seizure frequency remained above baseline, the drug being withdrawn was added back and an attempt made to withdraw the other. The study was terminated if these adjustments were not successful in decreasing seizure frequency to baseline. At the conclusion of the study, three patients were being treated with PGB and PHT, two with CBZ and PGB, and six with all three. This study demonstrated the applicability of sequential analysis to antiepileptic drug trials.

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Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

Double‐Blind Withdrawal of Phenytoin and Carbamazepine in Patients Treated with Progabide for Partial Seizures

Leppik

Brundage

Krall³

et al. 1986

Epilepsia

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“…In animal studies, PGB has a wide spectrum of anticonvulsant actions, but little evidence exists for a mechanistic relationship to GABA systems. Several open-label uncontrolled studies suggested efficacy and safety of PGB in a variety of seizure types (Martinez-Lage et al, 1984;Benassi et al, 1988), but other studies in partial (Dam et al, 1983) and absence (Stefan et al, 1988) seizures failed to show benefit. The usual dosage range in clinical trials has been about 15-60 mg/kg/day (Schmidt and Utech, 1986).…”

Section: Progabide (Pgb)mentioning

confidence: 99%

“…The usual dosage range in clinical trials has been about 15-60 mg/kg/day (Schmidt and Utech, 1986). Several open-label uncontrolled studies suggested efficacy and safety of PGB in a variety of seizure types (Martinez-Lage et al, 1984;Benassi et al, 1988), but other studies in partial (Dam et al, 1983) and absence (Stefan et al, 1988) seizures failed to show benefit. Two controlled studies of PGB as an add-on demonstrated unimpressive efficacy (Schmidt and Utech, 1986;Leppik et al, 1987).…”

Section: Progabide (Pgb)mentioning

confidence: 99%

Clobazam, Oxcarbazepine, Tiagabine, Topiramate, and Other New Antiepileptic Drugs

Fisher

Blum

1995

Epilepsia

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Clinical investigators recently have studied at least 21 new antiepileptic drugs (AEDs) in people with epilepsy. This review briefly examines 15 of these new AEDs: clobazam (CLB), dezinamide, flunarizine (FNR), loreclezole, milacemide (MLM), MK-801, nafimidone, ORG-6370, oxcarbazepine (OCBZ), progabide (PGB), ralitoline, stiripentol, tiagabine (TGB), topiramate (TPM), and zonisamide (ZNS). CLB, PGB, and TGB represent agents that act on the GABA system, and MLM acts on the glycine system. MK-801 and ZNS (in part) are excitatory amino acid antagonists, and FNR is a calcium-channel antagonist. OCBZ is a keto analogue of carbamazepine, which is not metabolized to the epoxide and may have fewer side effects. The remaining agents are novel compounds with a variety of suspected mechanisms. TPM appears especially effective for intractable partial seizures but has a high incidence of cognitive side effects. None of these new AEDs is useful for all patients with inadequate seizure control or ongoing toxicity. The role of each will require further clinical study and experience.

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“…In both open pilot studies and placebocontrolled studies, progabide appeared to be an effective antiepileptic drug with a broad spectrum of action [1][2][3][4]7].…”

Section: Introductionmentioning

confidence: 99%

Long-Term Treatment of Epilepsy: Open Multicenter Trial with Progabide in Epileptic Patients

et al. 1987

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A long-term open multicenter trial was carried out in 15 European centers with therapy-resistant epileptics to evaluate the efficacy and safety of progabide, a new antiepileptic GABA receptor agonist; 187 patients, suffering from partial epilepsy (57%), primary generalized epilepsy (20%), secondary generalized epilepsy (21 %), and unclassified generalized epilepsy (2 %), participated in the study. All patients had a total seizure frequency higher than one per month in spite of standard antiepileptic medication; 46 % had a mean partial seizure frequency from daily to weekly. Progabide was administered at a mean daily dose of 30.5 mg/kg/day as an add-on to the standard antiepileptic drugs up to one year in 115 patients; 37 patients (19.8%) dropped out because of reasons which were not drug-related (bad compliance, lost to follow-up); in 12 patients (6.5%) progabide was withdrawn for side effects and in 20 (10.7%) for lack of efficacy. 71.3% of patients treated for one year (62% considering the ‘cumulative’ number of patients) experienced more than a 50% reduction in seizure frequency. This reduction was equally present in patients with partial epilepsy (63.9%) and with generalized epilepsy (62.2% of patients with primary and 57.1% with secondary generalized epilepsy). No signs of tolerance phenomena to the antiepileptic effect of progabide were observed. No side effects were reported in 56.7% of the patients. Clinical side effects were mild and transient, leading to progabide discontinuation in 6.5% of the patients only; an increase in SGPT was observed in 5.7% of the patients, these increases were transient and without any clinical symptom. The results of this long-term study confirm the results from several open and controlled trials and show that progabide is a valuable antiepileptic also in long-term therapy.

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Progabide Treatment in Severe Epilepsy: A Double‐Blind Cross‐over Trial Versus Placebo

Cited by 18 publications

References 22 publications

Double‐Blind Withdrawal of Phenytoin and Carbamazepine in Patients Treated with Progabide for Partial Seizures

Double‐Blind Withdrawal of Phenytoin and Carbamazepine in Patients Treated with Progabide for Partial Seizures

Clobazam, Oxcarbazepine, Tiagabine, Topiramate, and Other New Antiepileptic Drugs

Long-Term Treatment of Epilepsy: Open Multicenter Trial with Progabide in Epileptic Patients

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