Clonazepam (Rivotril®) and Carbamazepine (Tegretol®) in Psychomotor Epilepsy: A Randomized Multicenter Trial

Berggreen, Peter; Joensen, Poul; Kristensen, Ole; Köhler, Ole; Mikkelsen, B

doi:10.1111/j.1528-1157.1981.tb06152.x

Cited by 31 publications

(22 citation statements)

References 18 publications

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“…Many reports are double-blind studies comparing the antiepileptic effect of carbamazepine with that of phenytoin, clonazepam or valproate (Callaghan et al 1985;Mikkelsen et al 1981;Ramsay et al 1983;Simonsen et al 1976;Troupin et al 1977). These studies have not been designed with the primary aim of investigating the plasma concentration-effect relationship.…”

Section: Total Plasma Concentration and Clinical Effectsmentioning

confidence: 94%

“…The study of Shorvon et al (1980), like others (Callaghan et al 1985;Mikkelsen et al 1981;Ramsay et al 1983;Sillanpaa et al 1979;Strandjord & Johannessen 1980), comprised newly diagnosed, previously untreated patients. Seizure control at lower plasma concentrations appears to be more common in this patient category.…”

Section: Total Plasma Concentration and Clinical Effectsmentioning

confidence: 95%

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Clinical Pharmacokinetics and Pharmacological Effects of Carbamazepine and Carbamazepine-10,11-Epoxide

Bertilsson

Tomson

1986

Clinical Pharmacokinetics

266

120

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Carbamazepine is a first-line drug in the treatment of most forms of epilepsy and also the drug of first choice in trigeminal neuralgia. Furthermore, it is now frequently used in bipolar depression. Most oral formulations of carbamazepine are well absorbed with high bioavailability. The drug is 75% bound to plasma proteins. The degree of protein binding shows little variation between different subjects, and there is no need to monitor free rather than total plasma concentrations. Carbamazepine is metabolised in the liver by oxidation before excretion in the urine. A major metabolite is carbamazepine-10,11-epoxide which is further metabolised by hydration before excretion. This epoxide-diol pathway is induced during long term treatment with carbamazepine. Co-medication with phenytoin or phenobarbitone further induces this metabolic pathway. Some but not all studies indicate an increased metabolism of carbamazepine during pregnancy. The drug crosses the placenta, and the newborns who are exposed to the drug during fetal life eliminate the drug readily after birth. There seems to be no problem to nurse children during treatment with carbamazepine. Metabolism of carbamazepine is comparable in children and adults. Several studies have tried to establish a relationship between plasma carbamazepine and clinical effect in epilepsy, but very few of these are controlled. The best anticonvulsant effect seems to be obtained at plasma concentrations of 15 to 40 mumol/L and a similar optimal plasma concentration range was found in a controlled study in trigeminal neuralgia. Side effects are more frequent at higher plasma concentrations but are also seen within that range. In some patients, with pronounced fluctuation of plasma concentrations during the dosage interval, side effects may be avoided by more frequent dosing. Carbamazepine-10,11-epoxide is a potent anticonvulsant in animal models. During treatment with carbamazepine the plasma concentrations of this metabolite are usually 10 to 50% of those of the parent drug. It has not been possible to establish the relative contribution of the two compounds to the pharmacological effects. The epoxide has therefore been given to humans with the aim of determining the relative potency of the parent drug and its metabolite. After single oral doses of carbamazepine-10,11-epoxide to healthy subjects, the compound was rapidly absorbed. As a mean of 90% of the given dose was recovered in urine as trans-10,11-dihydroxy-10,11-dihydro-carbamazepine, a complete absorption of unchanged epoxide was shown.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Total Plasma Concentration and Clinical Effectsmentioning

confidence: 94%

Section: Total Plasma Concentration and Clinical Effectsmentioning

confidence: 95%

Clinical Pharmacokinetics and Pharmacological Effects of Carbamazepine and Carbamazepine-10,11-Epoxide

Bertilsson

Tomson

1986

Clinical Pharmacokinetics

266

120

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“…In a study of 36 children and adults with newly diagnosed complex partial seizures, Mikkelsen et al (1981) reported no difference between carbamazepine and clonazepam in the number of patients who became completely seizure free in 6 months (49% versus 46%). Patients in this study were included regardless of age and number of seizures.…”

Section: Complete Seizure Controlmentioning

confidence: 98%

“…In the assessment of the efficacy of antiepileptic drugs, five criteria may be used in this determination: Rodin 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, 1966placebo Gruber et al, 1956 primidone vs. placebo White et al, 1966Phenytoin vs. pheneturide Gibberd et al, 1982Phenobarbital vs. clorazepate Wilensky et al, 1981Valproic acid vs. placebo Richens and Ahmad, 1975Gram et al, 1977Valproic acid vs. valproic acid Gram et al, 1979 Carbamazepine vs. phenobarbital -5. the duration of time patients remain on a drug (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.…”

Section: Efficacy Of Antiepileptic Drugsmentioning

confidence: 99%

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

Treiman

1987

Epilepsia

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Twenty randomized, double-blind, controlled clinical trials of antiepileptic drugs (AEDs) in mostly adult patients with mostly partial onset and/or generalized tonic-clonic seizures have been reported, with a total of 1,336 patients. None of these studies has demonstrated significant differences in antiepileptic efficacy between available antiepileptic drugs, but the results show that there are considerable individual differences between patients' responses to the same drug. While side effects are common with all of the antiepileptic drugs currently available, these are usually mild and reversible. Although some toxic effects may occur more frequently with certain drugs, there is sufficient overlap between the effects of various antiepileptic drugs that most side effects cannot be attributed with certainty to any one drug. Since side effects are generally dose-related, they can frequently be avoided or minimized by careful dosage titration and individualization of therapy.

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“…Oral diazepam became obsolete. Clonazepam began to be used as an adjunct in drug-resistant patients and as a first-line agent in Scandinavian countries (16). Attention also was called to the superiority of clobazam by Gastaut and Low (17).…”

Section: The Drug Choicementioning

confidence: 99%

Clinical Experience with New Antiepileptic Drugs: Antiepileptic Drugs in Europe

Loiseau

1999

Epilepsia

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Summary: The use of antiepileptic drugs (AEDs), singly and in combination, has been marked by variation among European countries and by a slow progress toward a standard of care that is still far from uniform. Phenobarbital, phenytoin, trimethadione, and primidone, given in various combinations, were the predominant agents used in the first half of this century. Prescribing habits differed among the Latin countries, the United Kingdom, and Scandinavia, based on local trends, divergent teaching philosophies of medical schools, and the medical specialty of the prescribing physician. The advent of carbamazepine and valproate, in the early 1960s, changed European prescribing habits. Despite early fears regarding bone marrow toxicity, carbamazepine was found to be superior for treatment of complex partial seizures. Valproate, when the proper therapeutic dosage was belatedly realized, was seen as a superior treatment for generalized and partial epilepsies. Both agents are now considered first‐line treatments for these seizure types. The role of the benzodiazepines as adjunctive anticonvulsant therapy remains controversial because of concerns about neurotoxicity and patient tolerance. The number of AEDs marketed in Europe has grown dramatically in the past decade, with agents such as felbamate, gabapentin, lamotrigine, and tiagabine having been approved as either adjunctive or sole therapy. However, not all new agents are available in each European country, and some variation in prescribing persists.

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Clonazepam (Rivotril®) and Carbamazepine (Tegretol®) in Psychomotor Epilepsy: A Randomized Multicenter Trial

Cited by 31 publications

References 18 publications

Clinical Pharmacokinetics and Pharmacological Effects of Carbamazepine and Carbamazepine-10,11-Epoxide

Clinical Pharmacokinetics and Pharmacological Effects of Carbamazepine and Carbamazepine-10,11-Epoxide

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

Clinical Experience with New Antiepileptic Drugs: Antiepileptic Drugs in Europe

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