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Methods of Assessment of Antiepileptic Drugs

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Methods in Clinical Pharmacology—Central Nervous System

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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 assessments 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.

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References

  • AHMAD, S., PERUCCA, E. & RICHENS, A. (1977). The effect of frusemide, mexiletine, (+) propranolol and three benzodiazepine drugs on interictal spike discharges in the electroencephalogram of epileptic patients. Br. J. clin. Pharmac., 4, 683–688.

    Article  CAS  Google Scholar 

  • ALTMAN, D.G. (1980). Statistics and ethics in medical research. Br. med. J., 281, 1336–1338.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • AMBROZ, A., CHALMERS, T.C., SMITH, H., SCHROEDER, B., FRIEMAN, J.A. & SHARECK, E.P. (1978). Deficiencies of randomised controlled trials. Clin. Res., 26, 280 A.

    Google Scholar 

  • BANCOUD, J., RIBET, M.F. & CHAGOT, D. (1975). Comparison between discharges of subclinical spikes and clinical epileptic attacks in patients with epilepsy. Electroencephalogr. clin. Neurophysiol., Soc. Proc. 39, 554.

    Google Scholar 

  • BINNIE, C.D. (1980). The use of the EEG in the diagnosis of the epilepsies. J. Electrophysiol. Technol, 6, 59–74.

    Google Scholar 

  • BIRKET-SMITH, E., LUND, M., MIKKELSEN, B., VESTER-MARK, S., ZANDER-OLSEN, P. & HULM, P. (1973). A controlled trial of Ro 5–4023 (clonazepam) in the treatment of psychomotor epilepsy. Acta neurol. Scand., 49, Suppl. 53, 18–25.

    Google Scholar 

  • BROWNE, T.R. & PENRY, J.K. (1973). Benzodiazepines in the treatment of epilepsy: A review. Epilepsia, 14, 277–310.

    Article  PubMed  CAS  Google Scholar 

  • BROWNE, T.R., PENRY, J.K., PORTER, R.J. & DREIFUSS, F.E. (1974). Responsiveness before, during and after spike-wave paroxysms. Neurology (Minneap.), 7, 659–665.

    Article  Google Scholar 

  • BULPITT, C.J. (1975). The design of clinical trials. Br. J. Hosp. Med., 13,611–620.

    Google Scholar 

  • CARRIE, J.R.G. (1976). Computer assisted EEG sharp-transient detection and quantification during overnight recordings in an epileptic patient. In Quantitative Analytic Studies in Epilepsy, eds Kellerway, P. & Petersen, I. New York: Raven Press.

    Google Scholar 

  • CEREGHINO, J.J., BROCK, J., VAN METER, J., PENRY, J.K., SMITH, L. & WHITE, B. (1974). Carbamazepine for epilepsy. A controlled prospective evaluation. Neurology (Minneap.), 24, 401–410.

    Article  CAS  Google Scholar 

  • CEREGHINO, J.J. & PENRY, J.K. (1972). General principles: testing of anticonvulsants in man. In Anti-epileptic Drugs, eds Woodbury, D.M., Penry, J.K. & Schmidt, R.P., pp. 63–73. New York: Raven Press.

    Google Scholar 

  • CEREGHINO, J.J., VAN METER, J., BROCK, J.T., PENRY, J.K., SMITH, L. & WHITE, B.G. (1973). Preliminary observations of serum carbamazepine concentration in epileptic patients. Neurology (Minneap.), 23, 357–366.

    Article  CAS  Google Scholar 

  • COVANIS, A. & JEAVONS, P.M. (1980). Once-daily sodium valproate in the treatment of epilepsy. Dev. Med. Child Neurol., 22,202–204.

    Article  PubMed  CAS  Google Scholar 

  • GASTAUT, H. (1969). Classification of the epilepsies. Proposal for an international classification. Epilepsia, 10, Suppl. 514–521.

    Google Scholar 

  • GIBBS, F.A., DAVIS, H. & LENNOX, W.G. (1935). The electroencephalogram in epilepsy and in conditions of impaired consciousness. Arch. Neurol. Psychiatr., 34, 1133–1148.

    Article  Google Scholar 

  • GOODE, D.J., PENRY, J.K. & DREIFUSS, F.E. (1970). Effects on paroxysmal spike-wave activity on continuous visual-motor performance. Epilepsia, 11, 241–254.

    Article  PubMed  CAS  Google Scholar 

  • GOTMAN, J., IVES, J.R. & GLOOR, P. (1979). Automatic recognition of inter-ictal epileptic activity in prolonged EEG recordings. Electroencephalogr. clin. Neuro-physiol., 46, 510–520.

    Article  CAS  Google Scholar 

  • GRAM, L., FLACHS, H., WÃœRTZ-JORGENSEN, A., PARNAS, J. & ANDERSEN, B. (1979). Sodium valproate, serum level and clinical effect in epilepsy: a controlled study. Epilepsia, 20, 303–312.

    Article  PubMed  CAS  Google Scholar 

  • GRANT, R.H.E. & BAROT, N.H. (1976). The use of sodium valproate in severely handicapped patients with epilepsy. In Clinical and Pharmacological Aspects of Sodium Valproate (Epilim) in the Treatment of Epilepsy, ed. Legg, N.J. pp. 14–22. Tunbridge Wells: MCS Consultants.

    Google Scholar 

  • GREEN, J.R. & KUPFERBERG, H.J. (1972). Sulthiame. In Antiepileptic Drugs, eds Woodbury, D.M., Penry, J.K. & Schmidt, R.P., pp. 477–485. New York: Raven Press.

    Google Scholar 

  • HALLIDAY, A.M. & MUSHIN, J. (1980). The visual evoked potential in neuro-ophthalmology. International Ophthalmology Clinics, 20, 155–183. Massachusetts: Little, Brown and Company.

    Article  PubMed  CAS  Google Scholar 

  • HARDING, G.F.A., HERRICK, CE. & JEAVONS, P.M. (1978). A controlled study of the effect of sodium valproate on photosensitive epilepsy and its prognosis. Epilepsia, 19, 555–565.

    Article  PubMed  CAS  Google Scholar 

  • HOUGHTON, G.W. & RICHENS, A. (1974a). Inhibition of phenytoin metabolism by sulthiame in epileptic patients. Br. J. clin. Pharmac., 1, 59–66.

    Article  CAS  Google Scholar 

  • HOUGHTON, G.W. & RICHENS, A. (1974b). Phenytoin intoxication induced by sulthiame in epileptic patients. J. Neurol. Neurosurg. Psychiat., 37, 275–281.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • ILAE COMMISSION ON ANTIEPILEPTIC DRUGS (1973). Principles for clinical testing of antiepileptic drugs. Epilepsia, 14,451–458.

    Article  Google Scholar 

  • IVES, J.R. & WOODS, J.F. (1975). 4-channel 24 hour cassette recorder for long term monitoring of ambulatory patients. Electroencephalogr. clin. Neurophysiol. 39, 88–92.

    Article  PubMed  CAS  Google Scholar 

  • JEAVONS, P.M. & CLARK, J.E. (1974). Sodium valproate in treatment of epilepsy. Br. med. J., 2, 584–586.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • JEAVONS, P.M., CLARK, J.E. & MAHESHWARI, P. (1977). Treatment of generalised epilepsies of childhood and adolescence with sodium valproate (Epilim). Dev. Med. Child Neurol., 19,9–25.

    Article  PubMed  CAS  Google Scholar 

  • JEAVONS, P.M. & HARDING, G.F.A. (1975). Photosensitive Epilepsy. A Review of the Literature and a study of 460 Patients. William Heinemann Books.

    Google Scholar 

  • KELLERWAY, P., FROST, J.D. Jr. & CRAWLEY, J.W. (1980). Time modulation of spike and wave activity in generalised epilepsy. Ann. Neurol., 8, 491–500.

    Article  Google Scholar 

  • KILLAM, K.F., KILLAM, E.K. & NAQUET, R. (1967). An animal model of light sensitive epilepsy. Electroencephalogr. clin. Neurophysiol., 22,497–513.

    Article  PubMed  CAS  Google Scholar 

  • KILLAM, E.K., MATSUZAKI, M. & KILLAM, K.F. (1973). Studies of anticonvulsant compounds in the Papiopapio model of epilepsy. In Brain Function, ed. Sebelli, H.C., pp. 161–171. New York: Raven Press.

    Google Scholar 

  • LEE, S.I., MESSENHEIMER, J.A., WILKINSON, E.C., BRICKLEY, J.J. Jr. & JOHNSON, R.N. (1980). Visual evoked potentials to stimulus trains: normative data and application to photosensitive seizures. Electroencephalogr. clin. Neurophysiol., 48, 387–394.

    Article  PubMed  CAS  Google Scholar 

  • LEVY, R., PITLICK, W., TROUPIN, A, GREEN, J. & NEAL, J. (1975). Pharmacokinetics of carbamazepine in normal man. Clin. Pharmac. Ther., 17, 657–668.

    CAS  Google Scholar 

  • LUBORSKY, L., DOCHERTY, J.P., TODD, T.C., KNAPP, P.H., MIRSKY, A.F. & GOTTSCHALK, L.A. (1975). A context of analysis of psychological states prior to petit mal EEG paroxysms. J. Nervous Mental Dis., 160, 282–298.

    Article  CAS  Google Scholar 

  • LÃœCKING, C.H., CREUTZFELDT, O.D. & HEINEMANN, U. (1970). Visual evoked potentials of patients with epilepsy and a control group. Electroencephalogr. clin. Neurophysiol., 29, 557–566.

    Article  PubMed  Google Scholar 

  • MARSDEN, C.D. (1975). Neurology. In A Textbook of Epilepsy, eds Laidlaw, J. & Richens, A. London and Edinburgh: Churchill Livingstone.

    Google Scholar 

  • MELDRUM, B.S., ANLEZARK, G., BALZAMO, E., HORTON, R.W. & TRIMBLE, M. (1975). Photically induced epilepsy in Papio papio as a model for drug studies. In Advances in Neurology, 10, eds Meldrum, B.S. & Marsden, C.D., pp. 119–132. New York: Raven Press.

    Google Scholar 

  • NEWMARK, M.E. & PENRY, J.K. (1979). Photosensitivity and Epilepsy: A Review. New York: Raven Press.

    Google Scholar 

  • PATEL, I.H., LEVY, R.H. & CUTLER, R.E. (1980). Phénobarbital—valproic acid interaction. Clin. Pharmac. Ther., 27, 515.

    Article  CAS  Google Scholar 

  • PENRY, J.K., PORTER, R.J. & DREIFUSS, F.E. (1971). Quantitation of paroxysmal abnormal discharges in the EEGs of patients with absence (petit-mal) seizures for the evaluation of antiepileptic drugs. Epilepsia, 12, 278–279.

    Google Scholar 

  • PORTER, R.J., PENRY, J.K. & DREIFUSS, F.E. (1973). Responsiveness at the onset of spike-wave bursts. Electroencephalogr. clin. Neurophysiol., 34,239–245.

    Article  PubMed  CAS  Google Scholar 

  • PORTER, R.J., WOLF, A.A. Jr. & PENRY, J.K. (1971). Human electroencephalographic telemetry. A review of systems and their applications and a new receiving system. Am. J. EEG. Technoi, 11,145–159.

    Google Scholar 

  • QUY, R.J. (1978). A miniature preamplifier for ambulatory monitoring of the electroencephalogram. J. Physiol. (Lond.), 284,23–24.

    Google Scholar 

  • QUY, R.J., FITCH, P. & WILLISON, R.G. (1980). High speed automatic analysis of EEG spike and wave activity using an analogue detection and microcomputer plotting system. Electroencephalogr. clin. Neurophysiol., 49, 187–189.

    Article  PubMed  CAS  Google Scholar 

  • QUY, R.J., WILLISON, R.G., FITCH, P. & GILLIATT, R.W. (1980). Some developments in ambulatory monitoring of the EEG. In ISAM 1979: Proceedings of the Third International Symposium on Ambulatory Monitoring, eds Stott, F.D., Raftery, E.B., Sleight, P. & Goulding, L. pp. 393–398. London: Academic Press.

    Google Scholar 

  • REILLEY, E.L. & PETERS, J.F. (1973). Relationship of some varieties of electroencephalographic photosensitivity to clinical convulsive disorders. Neurology (Minneap.), 23, 1050–1057.

    Article  Google Scholar 

  • RICHENS, A. (1975). Clinical pharmacology and medical treatment. In A Textbook of Epilepsy, eds Laidlaw, J. & Richens, A. London and Edinburgh: Churchill Livingstone.

    Google Scholar 

  • RICHENS, A. (1976). Drug Treatment of Epilepsy. London: Henry Kimpton.

    Google Scholar 

  • RICHENS, A. & AHMAD, S. (1975). A controlled trial of sodium valproate in severe major epilepsy. Br. med. J., 4, 255–256.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • RODIN, E., RIM, C. & RENNICK, P. (1974). The effects ofcarbamazepine on patients with psychomotor epilepsy: Results of a double-blind study. Epilepsia, 15, 547–561.

    Article  PubMed  CAS  Google Scholar 

  • ROWAN, A.J., BINNIE, C.D., de BEER-PAWLIKOWSKI, N.K.B., GOEDHART, D.M., GUTTER, T.L., VAN PARIJS, J.A.P., MEINARDI, H. & MEIJER, J.W.A. (1978). 24 hour EEG studies with very frequent antiepileptic drug concentration determinations in the study of sodium valproate. In Advances in Epileptology 1977, eds Meinardi, H. & Rowan, A.J. Amsterdam and Lisse: Swets and Zeitlinger.

    Google Scholar 

  • ROWAN, A.J., BINNIE, C.D., WARFIELD, C.A., MEINARDI, H. & MEIJER, J.W.A. (1979). The delayed effect of sodium valproate on the photoconvulsive response in man. Epilepsia, 20, 61–68.

    Article  PubMed  CAS  Google Scholar 

  • ROWAN, A.J., PIPPENGER, C.E., McGREGOR, P.A. & FRENCH, J. (1975). Seizure activity and anticonvulsant drug concentration. Arch. Neurol, 32, 281–288.

    Article  PubMed  CAS  Google Scholar 

  • SATO, S., PENRY, J.K. & DREIFUSS, F.E. (1976). Electro-encephalographic monitoring of generalised spike-wave paroxysms in the hospital and at home. In Quantitative Analytic Studies in Epilepsy, eds Kellerway, P. & Petersen, I., pp. 237–251. New York: Raven Press.

    Google Scholar 

  • SHORVON, S.D., CHADWICK, D., GALBRAITH, A.W. & REYNOLDS, E.H. (1978). One drug for epilepsy. Br. med. J., 1, 474–476.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • WADA, J.A., TERAO, A. & BOOKER, H.E. (1972). Longitudinal correlative analysis of epileptic baboon, Papio papio. Neurology (Minneap.), 22, 1272–1285.

    Article  CAS  Google Scholar 

  • WHITE, P.T., PLOTT, D. & NORTON, J. (1966). Relative anticonvulant potency of primidone. A double-blind comparison. Arch. Neurol. (Chic), 14, 31–35.

    Article  CAS  Google Scholar 

  • WILKUS, R.J. & DODRILL, C.B. (1976). Neuropsychological correlates of the electroencephalogram in epileptics: 1, topographic distribution. Epilepsia, 17, 89–100.

    Article  PubMed  CAS  Google Scholar 

  • WILKUS, R.J., DODRILL, C.B. & TROUPIN, A.S. (1978). Carbamazepine and the electroencephalogram of epileptics: a double-blind study in comparison to Phenytoin. Epilepsia, 19,283–291.

    Article  PubMed  CAS  Google Scholar 

  • YAMAMOTO, J., FURAYA, E., WAKAMATSU, H. & HISHIKAWA, Y. (1971). Modification of photosensitivity in epileptics during sleep. Electroencephalogr. clin. Neurophysiol., 31, 509–513.

    Article  PubMed  CAS  Google Scholar 

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  1. Clinical Pharmacology Unit, Institute of Neurology, Queen Square, London, WC1, UK

    Norman Milligan & Alan Richens

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  1. Norman Milligan
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  2. Alan Richens
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M. H. Lader A. Richens

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© 1981 Palgrave Macmillan, a division of Macmillan Publishers Limited

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Milligan, N., Richens, A. (1981). Methods of Assessment of Antiepileptic Drugs. In: Lader, M.H., Richens, A. (eds) Methods in Clinical Pharmacology—Central Nervous System. Palgrave Macmillan, London. https://doi.org/10.1007/978-1-349-06038-2_11

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