Anticonvulsant Drugs, Behavior, and Cognitive Abilities
Abstract
The literature concerning the relationship of anticonvulsant drugs to disturbances of behavior and cognitive abilities has been reviewed. It is indicated that although completed studies are sparse and although many of the techniques currently used for evaluating the effects of such drugs on patients are inadequate, certain conclusions may be drawn. With regard to the effects on cognitive abilities, the drugs not only impair performance on psychological tests, but some drugs—particularly phenytoin—are associated with a progressive decline of intellectual abilities, which is often insidious and unrecognized. There is little systematic evidence to indicate which anticonvulsant drugs have adverse effects on behavior, but several studies have indicated improvements in behavior associated with carbamazepine and sulthiame.
Keywords
Anticonvulsant Drug Behavior Disorder Epileptic Patient Psychological Test Sodium ValproatePreview
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References
- Al-Kaisi, A.M., and McGuire, R.J. (1974). The effect of sulthiame on disturbed behaviour in mentally subnormal patients. Brit. J. Psychiat. 124: 45–49.PubMedGoogle Scholar
- Ambrosetto, G., Tassinari, C.A., Baruzzi, A., and Laugaresi, E. (1977). Phenytoin encephalopathy as a probable idiosyncratic reaction. Epilepsia. 18: 405–408.PubMedGoogle Scholar
- Barnes, M.., and Fetterman, J.N. (1938). Mentality of dispensary epileptic patients. Arch. Neurol. Psychiat. 40: 903–910.Google Scholar
- Barnes, S.E., and Bower, B.D. (1975). Sodium valproate in the treatment of intractable childhood epilepsy. Devel. Med. Child Neurol. 17: 175–181.Google Scholar
- Bird, C.A.K., Griffin, B.P., Miklascewska, J.M., and Galbraith, A.W. (1966). Tegretol: A controlled trial of a new anticonvulsant. Brit. J. Psychiat. 112: 737–742.Google Scholar
- Bonduelle, M., Bouygues, P., Sallou, C., and Chemal, Y.R. (1964). Clinical trials of an antiepileptic drug G32883. Results of 89 observations. III. Congress of International College of Neuropharmacology. Munich 1962. Elsevier, Amsterdam, pp. 312–316Google Scholar
- Bonneycastle, D.D., Giarman, N.J., and Paasonen, M.K. (1957). Anticonvulsant compounds and 5-hydroxytryptamine in rat brain. Brit. J. Pharmacol. 12: 228–231.Google Scholar
- Booker, H.E. (1972). Primidone: Toxicity, in Antiepileptic Drugs. D.M. Woodbury, J.K. Penry, and R.P. Schmidt, eds. Raven Press, New York.Google Scholar
- Booker, H.E., Matthews, C.G., and Slaby, A. (1967). Effects of diphenylhydantoin on selected physiological-psychological measures in normal adults. Neurol. 17: 949–951.Google Scholar
- Boxer, C.M., Herzberg, J.L., and Scott, D.F. (1976). Has sodium valproate hypnotic effects Epilepsia. 17: 367–370.PubMedGoogle Scholar
- Browne, T.R., Dreifuss, F.E., Dyken, P.R., Goode, D.J., Penry, J.K. Porter, R.J., White, B.J., and White, P.T. (1975). Ethosuximide in the treatment of absence (petit mal) seizures. Neurol. 25: 515–525.Google Scholar
- Cereghino, J.J., Brock, J.T., Van Meter, J.C., Penry, J.R., Smith, L.D., and White, B.G. (1974). Carbamazepine for epilepsy. Neurol. 24: 401–410.Google Scholar
- Chadwick, D., Jenner, P., and Reynolds, E.H. (1975). Amines, anticonvulsants, and epilepsy. Lancet. 1: 473–476.Google Scholar
- Chanarin, I., Elvas, P.C., and Mollin, D.L. (1958). Folic acid studies in megaloblastic anaemia due to primidone. Brit. Med. J. 2: 80–82.Google Scholar
- Chaudhry, M.R., and Pond, D.A. (1961). Mental deterioration in epileptic children. J. Neurol. Neurosurg. Psychiat. 24: 213–219.PubMedGoogle Scholar
- Dalby, M.A. (1975). Behavioural effects of carbamazepine, in Advances in Neurology II. J.K. Penry and D.D. Daly, eds. Raven Press, New York.Google Scholar
- Dalby, M.A. (1971). Antiepileptic and psychotropic effect of carbamazepine in the treatment of psychomotor epilepsy. Epilepsia. 12: 325–334.PubMedGoogle Scholar
- Daneel, A.B. (1967). Tegretol in institutionalised epileptics. S. Afr. Med. J. 41: 772–775.PubMedGoogle Scholar
- de Weis, M.L.M., de Monk, C.G., Chardon, M.C., and Waitz, A.M. (1974). Entoque diagnostico y terapeutico del “nino turbulento.” Sem. Med. 144: 9.Google Scholar
- Dodrill, C.B. (1975a). DPH serum levels, toxicity, and neuropsychological performance in patients with epilepsy. Epilepsia. 16: 593–600.PubMedGoogle Scholar
- Dodrill, C.B. (1975b). Effects of sulthiame upon intellectual, neuropsychological, and social functioning abilities among adult epileptics: Comparison with diphenylhydantoin. Epilepsia. 16: 617–625.PubMedGoogle Scholar
- Finkleman, I., and Arieff, A.J. (1942). Untoward effects of phenytoin sodium in epilepsy. J.A.M.A. 118: 1209–1212.Google Scholar
- Fischer, M., Korskjaer, G., and Pedersen, E. (1965). Psychotic episodes in Zarondan treatment. Epilepsia. 6: 325–334.PubMedGoogle Scholar
- Fox, J.T. (1924). Response of epileptic children to mental and educational tests. Brit. J. Med. Psychol. 4: 235–248.Google Scholar
- Frantzen, E., Hansen, J.M., Hansen, O.E., Kristensen, M. (1967). Phenytoin intoxication. Acta Neuro log. Scand. 43: 440–446.Google Scholar
- Glaser, G.H. (1972). Diphenylhydantoin toxicity, in Antiepileptic Drugs. D.M. Woodbury, J.K. Penry, and R.P. Schmidt, eds. Raven Press, New York.Google Scholar
- Goode, D.J., Penry, J.K., and Dreifuss, F.E. (1970). Effect of paroxysmal spike wave on continuous visual motor performance. Epilepsia. 11: 241–254.PubMedGoogle Scholar
- Gowers, W.R. (1885). Epilepsy and Other Chronic Convulsive Diseases: Their Causes, Symptoms, and Treatment. William Wood, London.Google Scholar
- Grant, R.H.E. (1974). Sulthiame and behaviour. Devel. Med. Child Neurol. 16: 821–824.Google Scholar
- Green, J.R., Troupon, A.S., Halpern, L.M., Friel, P., and Kanarek, P. (1974). Sulthiame: Evaluation as an anticonvulsant. Epilepsia. 15: 329–349.PubMedGoogle Scholar
- Grinker, R.R. (1929). The proper use of phenobarbital in the treatment of the epilepsies. J.A.M.A. 93: 1218–1219.Google Scholar
- Groh, C.L., Rosenmayr, F., and Birnbaumer, N. (1971). Psychotrope Wirkung von Carbamazepine bie nicht epileptischen. Kind. Med. Monats. 25: 329–333.Google Scholar
- Guerrant, J., Anderson, W.W., Fischer, A., Weinstein, M.R., Jarros, R.M., and Deskins, A. (1962). Personality in Epilepsy. Charles C. Thomas, Springfield.Google Scholar
- Guey, J., Charles, C., Coquery, C., Roger, J., and Soulayrol, R. (1967). Study of psychological effect of ethosoximide on 25 children suffering from petit mal epilepsy. Epilepsia. 8: 129–141.Google Scholar
- Haerer, A.F., and Grace, J.B. (1969). Studies of anticonvulsant levels in epileptics. Acta Neurolog. Scand. 45: 18–31.Google Scholar
- Hawkins, C.F., and Meynell, M.J. (1958). Macrocytosis and macrocytic anaemia caused by anticonvulsant drugs. Quart. J. Med. 27: 45–63.PubMedGoogle Scholar
- Holdsworth, L., and Whitmore, K. (1974). A study of children with epilepsy attending ordinary schools. Devel. Med. Child Neurol. 16: 746–758.Google Scholar
- Husby, J. (1963). Delayed toxicity and serum concentrations of phenytoin. Dan. Med. Bull. 10: 236–239.PubMedGoogle Scholar
- Hutt, C., Jackson, P.M., and Level, M. (1966). Behavioural parameters and drug effects. Epilepsia. 7: 250–259.PubMedGoogle Scholar
- Hutt, S.J., Jackson, P.M., Belsham, A., and Higgins, G. (1968). Perceptual motor behaviour in relation to blood phenobarbitone level. A preliminary report. Devel. Med. Child Neurol. 10: 626–632.Google Scholar
- Idestrom, C.M., Schalling, D., Calquist, U., and Sjoquist, F. (1972). Acute effects of diphenyl- hydantoin in relation to plasma levels. Behavioural and psychological studies. Psycholog. Med. 2: 111–120.Google Scholar
- Jacobides, G.M. (1966). New uses and some abuses of carbamyldibenzazepine (Tegretol) as a psychotropic agent. Proceedings of the I V World Cbngress of Psychiatry, Madrid.Google Scholar
- Jeavons, P.M. (1975). The practical management of epilepsy. Hosp. Update. 1: 11–18.Google Scholar
- Kerfriden, P. (1970). Effets psychiques defavorable des medications anticonvitiales. Rev. Neuropsychiat. Infantile. 18: 605–609.Google Scholar
- Klein, O.F., and Greenberg, I.M. (1967). Behavioural effects of DPH in severe psychiatric disorders. Am. J. Psychiat. 124: 847–849.PubMedGoogle Scholar
- Kooiker, J.C., and Sumi, S.M. (1974). Movement disorder as a manifestation of DPH intoxication. Neurol. 24: 68–71.Google Scholar
- Krasovsky, J., Villanueva, R., and Hernandez, O. (1972). La carbamazepine en el tratemiento sintomatico de los trastornos de conducta infantil. Munch. Med. Wochen. 114: 619–622.Google Scholar
- Kutt, H., Winters, W., Kokenge, R., and McDowell, F. (1964). Diphenylhydantoin metabolism, blood levels and toxicity. Arch. Neurol. 11: 642–648.PubMedGoogle Scholar
- Lennox, W.G. (1942). Brain injury, drugs, and environment as a cause of mental decay in epilepsy. Am. J. Psychiat. 99: 174–180.Google Scholar
- Lennox, W.G., and Lennox, M.A. (1960). Epilepsy and Related Disorders. Little, Brown & Co., Boston.Google Scholar
- Liu, M.C. (1966). Clinical experience with sulthiame. Brit. J. Psychiat. 112: 621–628.PubMedGoogle Scholar
- Livingston, S. (1972). Drug Therapy for Epilepsy. Charles C. Thomas, Springfield.Google Scholar
- Logan, W.J., and Freeman, J.M. (1969). Pseudodegenerative disease due to diphenylhydantoin intoxication. Arch. Neurol. 21: 631–637.PubMedGoogle Scholar
- Lorentz de Haas, A.M., and Stoel, L.M.K. (1960). Experiences withoethylamethylsuccinimide in the treatment of epilepsy. Epilepsia. 1: 501–511.Google Scholar
- Loveland, N., Smith, B., and Forster, F. (1957). Mental and emotional changes in epileptic patients on continuous anticonvulsant medication. Neurol, 7: 856–865.Google Scholar
- Mannheimer, E., Packesch, F., Reimer, E.E., and Vetter, H. (1952). Die Haematolgischen Komplikationen der Epilepsiebehandlung mit Hydantoin-korpem. Med. Klinik. 47: 1397–1401.Google Scholar
- Marjerrison, G., Jedlicki, S.M., Keogh, R.P., Hrychuk, W., and Poulakakis, G.M. (1968). Carbamazepine: Behavioural, anticonvulsant, and EEG effects in chronically hospitalised epileptics. Dis. Ner. Syst. 29: 133–136.Google Scholar
- Matthews, C.G., and Harley, J.P. (1975). Differential psychological test performances in toxic and nontoxic adult epileptics. Neurol. 25: 184–188.Google Scholar
- McLellan, D.L., and Swash, M. (1974). Choreoathetosis and encephalopathy induced by Phenytoin. Brit. Med. J. 2: 204–205.PubMedGoogle Scholar
- Melamed, E., Reches, A., and Hershko, C. (1975). Reversible cerebral nervous system dysfunction in folate deficiency. J. Neurolog. Sci. 25: 93–98.Google Scholar
- Merritt, H.H. (1955). A Textbook of Neurology. Lea and Febiger, Philadelphia.Google Scholar
- Millichap, J.G., and Fowler, G.W. (1967). Treatment of “minimal brain dysfunction” syndromes. Paed. Clin. N. Am. 14: 767–777.Google Scholar
- Moffatt, W.R., Siddiqui, A.R., and Mackay, D.N. (1970). The use of sulthiame with disturbed mentally subnormal patients. Brit. J. Psychiat. 117: 673–678.PubMedGoogle Scholar
- Niedermeyer, E., Blumer, D., Holscher, E., and Walker, B.A. (1970). Classical hysterical seizures precipitated by anticonvulsant toxicity. Psychiatrica Clinica. 3: 71.Google Scholar
- Oates, J.A., and Sjoerdsma, A. (1960). Neurological effects of tryptophan in patients receiving a monoamine oxidase inhibitor. Neurol. 10: 1076–1078.Google Scholar
- Ounstead, C. (1955). The hyperkinetic syndrome in epileptic children. Lancet. 2: 303–311.Google Scholar
- Parsonage, M. (1975). Treatment with carbamazepine: Adults, in Advances in Neurology, Vol 11. J.K. Penry and D.D. Daly, eds. Raven Press, New York.Google Scholar
- Patel, H., and Crichton, J.V. (1968). The neurologic hazards of diphenylhydantoin in childhood. J. Paed. 73: 676–684.Google Scholar
- Pereira, J.L.C. (1969). Nossa experiencia com o tegretol nas manifestaçones comiciais näo convulsivas da infancia. O. Hosp. 75: 687–692.Google Scholar
- Perlo, V.P., and Schwab, R.S. (1969). Unrecognized dilantin intoxication, in Modern Neurology,, S Locke, ed. Little, Brown & Co., Boston, pp. 589–597.Google Scholar
- Prensky, A.L., De Vivo, D.C., and Palkes, H. (1971). Severe bradykinesia as a manifestation of toxicity to antiepileptic medication. J. Paed. 78: 700–704.Google Scholar
- Pryse-Phillips, W.E.M., and Jeavons, P.M. (1970). Effect of carbamazepine on the electroen- cephalographic and ward behaviour of patients with chronic epilepsy. Epilepsia. 11: 263–273.PubMedGoogle Scholar
- Puente, R.M. (1975). The use of carbamazepine in the treatment of behavioural disorders in children, In Epileptic Seizures—Behaviour—Pain W. Birkmayer, ed. Hans Huber, Stuttgart.Google Scholar
- Rajotte, P., Jilek, L., Perales, A., Giard, N., Bordeleau, J.M., and Tetreault, L. (1967). Propriétés antiepileptiques et psychotropes de la carbamazepine. Union Med. Canada. 96: 1200–1206.Google Scholar
- Rawson, M.D. (1968). Diphenylhydantoin intoxication and cerebrospinal fluid protein. Neurol. 18: 1009–1011.Google Scholar
- Rett, A. (1976). The so-called psychotropic effect of tegretol in the treatment of convulsions of cerebral origin in children, In Epileptic Seizures—Behaviour—Pain. W. Birkmayer, ed. Hans Huber, Stuttgart.Google Scholar
- Reynolds, E.H. (1967). Schizophrenia-like psychoses of epilepsy and disturbances of folate and B12 metabolism induced by anticonvulsant drugs. Brit. J. Psychiat. 113: 911–919.PubMedGoogle Scholar
- Reynolds, E.H. (1970). Iatrogenic disorders in epilepsy, in Modern Trends in Neurology No. 5. D. Williams, ed. Butterworth, London, pp. 271–286.Google Scholar
- Reynolds, E.H. (1975a). Chronic antiepileptic toxicity: A review. Epilepsia. 16: 319–353.PubMedGoogle Scholar
- Reynolds, E.H. (1975b). In discussion: Behavioural effects of carbamazepine, in Advances in Neurology Vol II. J.K. Penry and D.D. Daly, eds. Raven press, New York. p. 343.Google Scholar
- Reynolds, E.H. (1976). Neurological aspects of folate and B12 metabolism. Clin. Haematol. 5: 661–694.PubMedGoogle Scholar
- Reynolds, E.H., and Travers, R. (1974). Serum anticonvulsant concentrations in epileptic patients with mental symptoms. Brit. J. Psychiat. 124: 440–445.PubMedGoogle Scholar
- Rodin, E.A., Rim, C.S., Kitano, H., Lewis, R., and Rennick, P.M. (1976). A comparison of the effectiveness of primidone versus carbamazepine in epileptic outpatients. J. Nerv. Ment. Dis. 163: 41–46.PubMedGoogle Scholar
- Roger, J., Grangeon, H., Guey, J., and Lob, H. (1968). Psychiatric and psychological effects of ethosuximide treatment in epileptics. Encephale. 57: 407–438.PubMedGoogle Scholar
- Roseman, E. (1961). Dilantin toxicity. Neurol. 11: 912–921.Google Scholar
- Rosen, J.A. (1968). Dilantin dementia. Trans. Am. Neurolog. Assn. 93: 273.Google Scholar
- Royo, D., and Martin, F. (1959). Standardized psychometrical tests applied to the analysis of the effects of anticonvulsant medication on the intellectual proficiency of young epileptics. Epilepsia. 1: 189–207.PubMedGoogle Scholar
- Schain, R.J., Ward, J.W., and Guthrie, D. (1977). Carbamazepine as an anticonvulsant in children. Neurol. 27: 476–480.Google Scholar
- Schlack, H.G. (1974). Ergenyl in the treatment of epilepsy. Therapiewoche. 24: 39.Google Scholar
- Simopoulos, A.M., Pinto, A., Uhlenhuth, E.H., McGee, J.J., and de Rosa, E.R. (1974). D.P.H. effectiveness in the treatment of chronic schizophrenics. Arch. Gen. Psychiat. 30: 106–111.Google Scholar
- Smith, W.L., Philipus, M.J., and Guard, H.L. (1968). Psychometric study of children with learning problems and 14 positive spike EEG patterns, treated with ethosuximide (zarontin) and placebo. Arch. Dis. Childhood. 43: 616–619.Google Scholar
- Smyth, V.O.G. (1964). The use of ospolot in temporal lobe epilepsy. Epilepsia. 5: 293–295.PubMedGoogle Scholar
- Somerfeld-Ziskind, E., and Ziskind, E. (1940). Effect of phenobarbital on the mentality of epileptic patients. Arch. Neurol. Psychiat. 43: 70–79.Google Scholar
- Soulayrol, R., and Rbger, J. (1970). Effets psychiatriques defavourables des medicacions antiepileptiques. Rev. Neuropsychiat. Infantile. 18: 599–603.Google Scholar
- Stores, G. (1975). Behavioural effects of anticonvulsant drugs. Devel. Med. Child Neurol. 17: 647–658.Google Scholar
- Tchicaloff, M., and Gaillard, F. (1970). Quelques effets indesirables des medicaments antiepileptiques sur les rendements intellectuels. Rev. Neuropsychiat. Infantile. 18: 599–603.Google Scholar
- Tempkin, O. (1971). The Falling Sickness. Johns Hopkins, Baltimore.Google Scholar
- Trimble, M.R. and Corbett, J. (1978a): The effects of anticonvulsant drugs on behaviour. (In preparation.)Google Scholar
- Trimble, M.R. and Corbett, J. (1978b). The effects of anticonvulsant drugs on cognitive function. (In preparation.)Google Scholar
- Trimble, M.R., Chadwick, D., Reynolds, E.H., and Marsden, C.D. (1975). L-5- hydroxytryptophan and mood. Lancet. 1: 583.PubMedGoogle Scholar
- Uhlenhuth, E.H., Stephens, J.H., Dim, B.H.,and Covi, L. (1972). D.P.H. and phenobarbital in the relief of psychoneurotic symptoms. Psychopharmacologia. 27: 67.PubMedGoogle Scholar
- Vallarta, J.M., Bell, D.B., and Reichert, A. (1974). Progressive encephalopathy due to chronic hydantoin intoxication. Am. J. Dis. Childhood. 128: 27–34.Google Scholar
- Von Last, G. (1972). Epilepsie—Behandlung mit Mylepsinum. Allemeinmedizin/der Landarzt. 7: 336–341.Google Scholar
- Wapner, L, Thurston, D.L., and Holowach, J. (1962). Phenobarbital: Its effects on learning in epileptic children. J.A.M.A. 182: 937.PubMedGoogle Scholar
- Weiss, C.F., Heffelfinger, J.C., and Buchanan, R.A. (1969). Serial dilantin levels in mentally retarded children. Am. J. Ment. Def 73: 826–830.Google Scholar
- Woodbury, D.M., Penry, J.K., and Schmidt, R.P., eds. 1972. Antiepileptic Drugs. Raven Press, New York.Google Scholar