Abstract
Recent studies have shown that most newly diagnosed epileptic patients can be satisfactorily treated with a single antiepileptic drug. We therefore undertook a prospective randomised pragmatic trial of the comparative efficacy and toxicity of four major antiepileptic drugs, utilised as monotherapy in newly diagnosed epileptic patients. Between 1981 and 1987 243 adult patients aged 16 years or over, newly referred to two district general hospitals with a minimum of two previously untreated tonic-clonic or partial with or without secondary generalised seizures were randomly allocated to treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform with standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to enter one year remission. The overall outcome with all of the four drugs was good with 27% remaining seizure free and 75% entering one year of remission by three years of follow up. No significant differences between the four drugs were found for either measure of efficacy at one, two, or three years of follow up. The overall incidence of unacceptable side effects, necessitating withdrawal of the randomised drug, was 10%. For the individual drugs phenobarbitone (22%) was more likely to be withdrawn than phenytoin (3%), carbamazepine (11%), and sodium valproate (5%). In patients with newly diagnosed tonic-clonic or partial with or without secondary generalised seizures, the choice of drug will be more influenced by considerations of toxicity and costs.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Callaghan N., Kenny R. A., O'Neill B., Crowley M., Goggin T. A prospective study between carbamazepine, phenytoin and sodium valproate as monotherapy in previously untreated and recently diagnosed patients with epilepsy. J Neurol Neurosurg Psychiatry. 1985 Jul;48(7):639–644. doi: 10.1136/jnnp.48.7.639. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Elwes R. D., Johnson A. L., Reynolds E. H. The course of untreated epilepsy. BMJ. 1988 Oct 15;297(6654):948–950. doi: 10.1136/bmj.297.6654.948. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Elwes R. D., Johnson A. L., Shorvon S. D., Reynolds E. H. The prognosis for seizure control in newly diagnosed epilepsy. N Engl J Med. 1984 Oct 11;311(15):944–947. doi: 10.1056/NEJM198410113111503. [DOI] [PubMed] [Google Scholar]
- Gram L., Bentsen K. D., Parnas J., Flachs H. Controlled trials in epilepsy: a review. Epilepsia. 1982 Oct;23(5):491–519. doi: 10.1111/j.1528-1157.1982.tb05437.x. [DOI] [PubMed] [Google Scholar]
- Johnson T. Valproate versus carbamazepine for seizures. N Engl J Med. 1993 Jan 21;328(3):208–209. [PubMed] [Google Scholar]
- Mattson R. H., Cramer J. A., Collins J. F. A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. The Department of Veterans Affairs Epilepsy Cooperative Study No. 264 Group. N Engl J Med. 1992 Sep 10;327(11):765–771. doi: 10.1056/NEJM199209103271104. [DOI] [PubMed] [Google Scholar]
- Mattson R. H., Cramer J. A., Collins J. F., Smith D. B., Delgado-Escueta A. V., Browne T. R., Williamson P. D., Treiman D. M., McNamara J. O., McCutchen C. B. Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures. N Engl J Med. 1985 Jul 18;313(3):145–151. doi: 10.1056/NEJM198507183130303. [DOI] [PubMed] [Google Scholar]
- Peto R., Pike M. C., Armitage P., Breslow N. E., Cox D. R., Howard S. V., Mantel N., McPherson K., Peto J., Smith P. G. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design. Br J Cancer. 1976 Dec;34(6):585–612. doi: 10.1038/bjc.1976.220. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ramsay R. E., Wilder B. J., Berger J. R., Bruni J. A double-blind study comparing carbamazepine with phenytoin as initial seizure therapy in adults. Neurology. 1983 Jul;33(7):904–910. doi: 10.1212/wnl.33.7.904. [DOI] [PubMed] [Google Scholar]
- Reynolds E. H. Chronic antiepileptic toxicity: a review. Epilepsia. 1975 Jun;16(2):319–352. doi: 10.1111/j.1528-1157.1975.tb06062.x. [DOI] [PubMed] [Google Scholar]
- Reynolds E. H., Heller A. J., Chadwick D. Valproate versus carbamazepine for seizures. N Engl J Med. 1993 Jan 21;328(3):207–209. doi: 10.1056/NEJM199301213280310. [DOI] [PubMed] [Google Scholar]
- Reynolds E. H., Shorvon S. D. Monotherapy or polytherapy for epilepsy? Epilepsia. 1981 Feb;22(1):1–10. doi: 10.1111/j.1528-1157.1981.tb04327.x. [DOI] [PubMed] [Google Scholar]
- Shorvon S. D., Reynolds E. H. Unnecessary polypharmacy for epilepsy. Br Med J. 1977 Jun 25;1(6077):1635–1637. doi: 10.1136/bmj.1.6077.1635. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shorvon S. D. The temporal aspects of prognosis in epilepsy. J Neurol Neurosurg Psychiatry. 1984 Nov;47(11):1157–1165. doi: 10.1136/jnnp.47.11.1157. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilder B. J., Ramsay R. E., Murphy J. V., Karas B. J., Marquardt K., Hammond E. J. Comparison of valproic acid and phenytoin in newly diagnosed tonic-clonic seizures. Neurology. 1983 Nov;33(11):1474–1476. doi: 10.1212/wnl.33.11.1474. [DOI] [PubMed] [Google Scholar]