Skip to main content
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1981 May;11(5):443–456. doi: 10.1111/j.1365-2125.1981.tb01149.x

Methods of assessment of antiepileptic drugs.

N Milligan, A Richens
PMCID: PMC1401602  PMID: 7272157

Abstract

Epilepsy is a symptom with protean manifestations and as such it is a difficult disease in which to carry out a therapeutic trial. The methods available to research workers for the assessment of new antiepileptic drugs are hampered by the fact that epilepsy is a fluctuant condition. Although it is a chronic disorder open to study using cross-over trials and within-patient comparisons, accurate assessment cannot be easily made at any one point in time. Research workers are therefore automatically placed at a time factor disadvantage and this is especially so for those searching for quick methods of evaluating new compounds. The need for a quick and reliable method of assessing a new antiepileptic drug has long been appreciated. This article will discuss the methods currently available and we will begin by considering the most commonly used method of assessment with particular reference to some of the problems involved in conducting a controlled clinical trial in epilepsy.

Full text

PDF
445

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altman D. G. Statistics and ethics in medical research: III How large a sample? Br Med J. 1980 Nov 15;281(6251):1336–1338. doi: 10.1136/bmj.281.6251.1336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bancaud J., Ribet M. F., Chagot D. Proceedings: Comparison between discharges of subclinical spikes and clinical epileptic attacks in patients with epilepsy. Electroencephalogr Clin Neurophysiol. 1975 Nov;39(5):554–554. [PubMed] [Google Scholar]
  3. Birket-Smith E., Lund M., Mikkelsen B., Vestermark S., Olsen P. Z., Holm P. A controlled trial on Ro 5-4023 (clonazepam) in the treatment of psychomotor epilepsy. Acta Neurol Scand Suppl. 1973;53:18–25. doi: 10.1111/j.1600-0404.1973.tb02278.x. [DOI] [PubMed] [Google Scholar]
  4. Browne T. R., Penry J. K. Benzodiazepines in the treatment of epilepsy. A review. Epilepsia. 1973 Sep;14(3):277–310. doi: 10.1111/j.1528-1157.1973.tb03965.x. [DOI] [PubMed] [Google Scholar]
  5. Browne T. R., Penry J. K., Proter R. J., Dreifuss F. E. Responsiveness before, during, and after spike-wave paroxysms. Neurology. 1974 Jul;24(7):659–665. doi: 10.1212/wnl.24.7.659. [DOI] [PubMed] [Google Scholar]
  6. Cereghino J. J., Brock J. T., Van Meter J. C., Penry J. K., Smith L. D., White B. G. Carbamazepine for epilepsy. A controlled prospective evaluation. Neurology. 1974 May;24(5):401–410. doi: 10.1212/wnl.24.5.401. [DOI] [PubMed] [Google Scholar]
  7. Cereghino J. J., Meter J. C., Brock J. T., Penry J. K., Smith L. D., White B. G. Preliminary observations of serum carbamazepine concentration in epileptic patients. Neurology. 1973 Apr;23(4):357–366. doi: 10.1212/wnl.23.4.357. [DOI] [PubMed] [Google Scholar]
  8. Covanis A., Jeavons P. M. Once-daily sodium valproate in the treatment of epilepsy. Dev Med Child Neurol. 1980 Apr;22(2):202–204. doi: 10.1111/j.1469-8749.1980.tb04328.x. [DOI] [PubMed] [Google Scholar]
  9. Goode D. J., Penry J. K., Dreifuss F. E. Effects of paroxysmal spike-wave on continuous visual-motor performance. Epilepsia. 1970 Sep;11(3):241–254. doi: 10.1111/j.1528-1157.1970.tb03888.x. [DOI] [PubMed] [Google Scholar]
  10. Gotman J., Ives J. R., Gloor P. Automatic recognition of inter-ictal epileptic activity in prolonged EEG recordings. Electroencephalogr Clin Neurophysiol. 1979 May;46(5):510–520. doi: 10.1016/0013-4694(79)90004-x. [DOI] [PubMed] [Google Scholar]
  11. Gram L., Flachs H., Würtz-Jørgensen A., Parnas J., Andersen B. Sodium valproate, serum level and clinical effect in epilepsy: a controlled study. Epilepsia. 1979 Jun;20(3):303–311. doi: 10.1111/j.1528-1157.1979.tb04808.x. [DOI] [PubMed] [Google Scholar]
  12. Harding G. F., Herrick C. E., Jeavons P. M. A controlled study of the effect of sodium valproate on photosensitive epilepsy and its prognosis. Epilepsia. 1978 Dec;19(6):555–565. doi: 10.1111/j.1528-1157.1978.tb05036.x. [DOI] [PubMed] [Google Scholar]
  13. Houghton G. W., Richens A. Phenytoin intoxication induced by sulthiame in epileptic patients. J Neurol Neurosurg Psychiatry. 1974 Mar;37(3):275–281. doi: 10.1136/jnnp.37.3.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ives J. R. 4-channel 24 hour cassette recorder for long-term EEG monitoring of ambulatory patients. Electroencephalogr Clin Neurophysiol. 1975 Jul;39(1):88–92. doi: 10.1016/0013-4694(75)90131-5. [DOI] [PubMed] [Google Scholar]
  15. Jeavons P. M., Clark J. E., Maheshwari M. C. Treatment of generalized epilepsies of childhood and adolescence with sodium valproate ("epilim"). Dev Med Child Neurol. 1977 Feb;19(1):9–25. doi: 10.1111/j.1469-8749.1977.tb08015.x. [DOI] [PubMed] [Google Scholar]
  16. Jeavons P. M., Clark J. E. Sodium valproate in treatment of epilepsy. Br Med J. 1974 Jun 15;2(5919):584–586. doi: 10.1136/bmj.2.5919.584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kellaway P., Frost J. D., Jr, Crawley J. W. Time modulation of spike-and-wave activity in generalized epilepsy. Ann Neurol. 1980 Nov;8(5):491–500. doi: 10.1002/ana.410080506. [DOI] [PubMed] [Google Scholar]
  18. Killam K. F., Killam E. K., Naquet R. An animal model of light sensitive epilepsy. Electroencephalogr Clin Neurophysiol. 1967 Jun;22(6):497–513. doi: 10.1016/0013-4694(67)90058-2. [DOI] [PubMed] [Google Scholar]
  19. Lee S. I., Messenheimer J. A., Wilkinson E. C., Brickley J. J., Jr, Johnson R. N. Visual evoked potentials to stimulus trains: normative data and application to photosensitive seizures. Electroencephalogr Clin Neurophysiol. 1980 Apr;48(4):387–394. doi: 10.1016/0013-4694(80)90131-5. [DOI] [PubMed] [Google Scholar]
  20. Levy R. H., Pitlick W. H., Troupin A. S., Green J. R., Neal J. M. Pharmacokinetics of carbamazepine in normal man. Clin Pharmacol Ther. 1975 Jun;17(6):657–668. doi: 10.1002/cpt1975176657. [DOI] [PubMed] [Google Scholar]
  21. Luborsky L., Docherty J. P., Todd T. C., Knapp P. H., Mirsky A. F., Gottschalk L. A. A context analysis of psychological states prior to petit mal EEF paroxysms. J Nerv Ment Dis. 1975 Apr;160(4):282–298. doi: 10.1097/00005053-197504000-00007. [DOI] [PubMed] [Google Scholar]
  22. Lücking C. H., Creutzfeldt O. D., Heinemann U. Visual evoked potentials of patients with epilepsy and of a control group. Electroencephalogr Clin Neurophysiol. 1970 Dec;29(6):557–566. doi: 10.1016/0013-4694(70)90098-2. [DOI] [PubMed] [Google Scholar]
  23. Meldrum B. S., Anlezark G., Balzamo E., Horton R. W., Trimble M. Photically induced epilepsy in Papio papio as a model for drug studies. Adv Neurol. 1975;10:119–132. [PubMed] [Google Scholar]
  24. Patel I. H., Levy R. H., Cutler R. E. Phenobarbital--valporic acid interaction. Clin Pharmacol Ther. 1980 Apr;27(4):515–521. doi: 10.1038/clpt.1980.72. [DOI] [PubMed] [Google Scholar]
  25. Porter R. J., Penry J. K. Responsiveness at the onset of spike-wave bursts. Electroencephalogr Clin Neurophysiol. 1973 Mar;34(3):239–245. doi: 10.1016/0013-4694(73)90251-4. [DOI] [PubMed] [Google Scholar]
  26. Quy R. J., Fitch P., Willison R. G. High-speed automatic analysis of eeg spike and wave activity using an analogue detection and microcomputer plotting system. Electroencephalogr Clin Neurophysiol. 1980 Jul;49(1-2):187–189. doi: 10.1016/0013-4694(80)90367-3. [DOI] [PubMed] [Google Scholar]
  27. Reilly E. L., Peters J. F. Relationship of some varieties of electroencephalographic photosensitivity to clinical convulsive disorders. Neurology. 1973 Oct;23(10):1050–1057. doi: 10.1212/wnl.23.10.1050. [DOI] [PubMed] [Google Scholar]
  28. Richens A., Ahmad S. Controlled trial of sodium valproate in severe epilepsy. Br Med J. 1975 Nov 1;4(5991):255–256. doi: 10.1136/bmj.4.5991.255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rodin E. A., Rim C. S., Rennick P. M. The effects of carbamazepine on patients with psychomotor epilepsy: results of a double-blind study. Epilepsia. 1974 Dec;15(4):547–561. doi: 10.1111/j.1528-1157.1974.tb04028.x. [DOI] [PubMed] [Google Scholar]
  30. Rowan A. J., Binnie C. D., Warfield C. A., Meinardi H., Meijer J. W. The delayed effect of sodium valproate on the photoconvulsive response in man. Epilepsia. 1979 Feb;20(1):61–68. doi: 10.1111/j.1528-1157.1979.tb04776.x. [DOI] [PubMed] [Google Scholar]
  31. Rowan A. J., Pippenger C. E., McGregor P. A., French J. H. Seizure activity and anticonvulsant drug concentration. Arch Neurol. 1975 May;32(5):281–288. doi: 10.1001/archneur.1975.00490470025002. [DOI] [PubMed] [Google Scholar]
  32. Shorvon S. D., Chadwick D., Galbraith A. W., Reynolds E. H. One drug for epilepsy. Br Med J. 1978 Feb 25;1(6111):474–476. doi: 10.1136/bmj.1.6111.474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wada J. A., Terao A., Booker H. E. Longitudinal correlative analysis of epileptic baboon, Papio papio. Neurology. 1972 Dec;22(12):1272–1285. doi: 10.1212/wnl.22.12.1272. [DOI] [PubMed] [Google Scholar]
  34. White P. T., Plott D., Norton J. Relative anticonvulsant potency of primidone; a double blind comparison. Arch Neurol. 1966 Jan;14(1):31–35. doi: 10.1001/archneur.1966.00470070035004. [DOI] [PubMed] [Google Scholar]
  35. Wilkus R. J., Dodrill C. B. Neuropsychological correlates of the electroencephalogram in epileptics: I. Topographic distribution and average rate of epileptiform activity. Epilepsia. 1976 Mar;17(1):89–100. doi: 10.1111/j.1528-1157.1976.tb03387.x. [DOI] [PubMed] [Google Scholar]
  36. Wilkus R. J., Dodrill C. B., Troupin A. S. Carbamazepine and the electroencephalogram of epileptics: a double blind study in comparison to phenytoin. Epilepsia. 1978 Jun;19(3):283–291. doi: 10.1111/j.1528-1157.1978.tb04491.x. [DOI] [PubMed] [Google Scholar]
  37. Yamamoto J., Furuya E., Wakamatsu H., Hishikawa Y. Modification of photosensitivity in epileptics during sleep. Electroencephalogr Clin Neurophysiol. 1971 Nov;31(5):509–513. doi: 10.1016/0013-4694(71)90172-6. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES