Hostname: page-component-586b7cd67f-t7fkt Total loading time: 0 Render date: 2024-11-22T07:58:23.581Z Has data issue: false hasContentIssue false
  • English
  • Français

Schizophrenia-like Psychoses of Epilepsy and Disturbances of Folate and Vitamin B12 Metabolism Induced by Anticonvulsant Drugs

Published online by Cambridge University Press:  29 January 2018

E. H. Reynolds
E. H. Reynolds*
Affiliation:
National Hospital for Nervous Diseases, Queen Square, London, W.C.1
Get access Rights & Permissions [Opens in a new window]

Extract

Since it was first described by Mannheimer, Pakesch, Reimer and Vetter in 1952 megaloblastic anaemia has come to be recognized as an occasional complication of anticonvulsant drug therapy. More recently a disturbance in folic acid and vitamin B12 metabolism has been observed in many non-anaemic drug-treated epileptic patients (Hawkins and Meynell, 1958; Klipstein, 1964; Malpas, Spray and Witts, 1966; Reynolds, Milner, Matthews and Chanarin, 1966a). Reynolds et al. (1966a) found megaloblastic haemopoiesis in 38 per cent. and subnormal serum folates in over 75 per cent. of a series of 54 out-patient epileptics. In addition, serum vitamin B12 levels, though still within the normal range, were significantly lower in the megaloblastic group of patients than in controls. They suggested (1) that the anti-folate effects of phenobarbitone, phenytoin and primidone may be related to their therapeutic actions, and (2) that prolonged drug-induced disturbances of folate and vitamin B12 metabolism may be responsible for certain side-effects, particularly mental symptoms. The latter possibility is supported by the increasing recognition of psychiatric illness due to vitamin B12 deficiency in the absence of anaemia or subacute combined degeneration of the cord. (Langdon, 1905; McAlpine, 1929; Holmes, 1956; Smith, 1960; Edwin, Holten, Norum, Schrumpf and Skaug, 1965; Strachan and Henderson, 1965).

Type
Research Article
Information
The British Journal of Psychiatry , Volume 113 , Issue 501 , August 1967 , pp. 911 - 919
Copyright
Copyright © Royal College of Psychiatrists, 1967 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bourdillon, R. E., Clarke, G. A., Ridges, A. P., Sheppard, P. M., Harper, P., and Leslie, S. A. (1965). “‘Pink spot’ in the urine of schizophrenics.” Nature, Lond., 208, 453–455.Google Scholar
Brune, G. G., and Himwich, H. E. (1963). “Biogenic amines and behaviour in schizophrenic patients.” In: Recent Advance in Biochemical Psychiatry (Ed. Wortis, J.) Vol. 5. New York: Plenum Press. 144–160.Google Scholar
Buchanan, J. M. (1964). “The function of vitamin B12and folic acid coenzymes in mammalian cells.” Medicine, 43, 697–709.Google Scholar
Carson, N. A. J., Cusworth, D. C., Dent, C. E., Field, C. M. B., Neill, D. W., and Westall, R. G. (1963). “Homocystinuria, a new inborn error of metabolism associated with mental deficiency.” Arch. Dis. Child., 38, 425–436.CrossRefGoogle ScholarPubMed
Chanarin, I., Matthews, D. M., and Reynolds, E. H. (1967). In preparation.Google Scholar
Davis, , Beresford, E. (1965). “Schizo-affective disease and periodic schizophreniform psychoses and their relation to schizophrenia.” Acta psychiat. Scand., 41, 313–327.Google Scholar
Dongier, G. (1959). “Statistical study of clinical and electroencephalographic manifestations of 536 psychotic episodes occurring in 516 epileptics between clinical seizures.” Epilepsia, 4th series, 1, 117–142.Google ScholarPubMed
Edwin, E. Holten, K., Norum, K. R., Schrumpf, A., and Skaug, O. E. (1965). “Vitamin B12 hypovita-minosis in mental diseases.” Acta med. Scand., 177, 689–699.CrossRefGoogle Scholar
Friedhoff, A. J., and van Winkle, E. (1962). “Isolation and characterization of a compound from the urine of schizophrenics.” Nature, Land., 194, 897–898.Google Scholar
Gibbs, F. A. (1951). “Ictal and non-ictal psychiatric disorders in temporal lobe epilepsy.” J. nerv. ment. Dis., 113, 522–528.Google Scholar
Hawkins, C. F., and Meynell, M. J. (1958). “Macro-cytosis and macrocytic anaemia caused by anticonvulsant drugs.” Quart. J. Med., 27, 45–63.Google Scholar
Heath, R. G. (1962). “Common characteristics of epilepsy and schizophrenia: clinical observations and depth electrode studies.” Amer. J. Psychiat., 118, 1013–1026.CrossRefGoogle ScholarPubMed
Heath, R. G. (1963). “Closing remarks, with commentary on depth electro encephalography in epilepsy and schizophrenia.” In: EEG and Behaviour (ed. Glaser, G. H.), New York: Basic Books, Inc., 377–393.Google Scholar
Heath, R. G., Nesselhof, W., and Timmons, E. (1966). “D, L-methionine-d, 1-sulfoximine effects in schizophrenic patients.” Arch. gen. Psychiat., 14, 213–217.Google Scholar
Herbert, V., and Zalusky, R. (1961). “Selective concentration of folic acid activity in cerebrospinal fluid.” Fed. Proc., 20, 453.Google Scholar
Hill, D., Pond, D. A., Mitchell, W., and Falconer, M. A. (1957). “Personality changes following temporal lobectomy for epilepsy.” J. ment. Sci., 103, 18–27.Google Scholar
Holmes, J. M. (1956). “Cerebral manifestations of vitamin B12 deficiency.” Brit. med. J., ii, 1394–1398.CrossRefGoogle Scholar
Karagulla, S., and Robertson, E. E. (1955). “Psychical phenomena in temporal lobe epilepsy and the psychoses.” Ibid., i, 748–752.Google Scholar
Klipstein, F. A. (1964). “Subnormal serum folate and macrocytosis associated with anti-convulsant drug therapy.” Blood, 23, 68–86.Google Scholar
Korzeniowski, L. (1965). “Les problèmes diagnostiques concernant les psychoses parano∗iques schizophréni-formes en epilepsie.” Arm. méd.-psychol., 123, 35–42.Google Scholar
Lancet (1965). “The pink spot.” Editorial, ii, 1169–1170.Google Scholar
Landolt, H. (1953). “Einige klinisch-elektroencephalo-graphische Korrelationen bei epileptischen Dämmer-zuständen.” Nervenartz, 24, 479.Google Scholar
Landolt, H. (1958). “Serial electroencephalographic investigations during psychotic episodes in epileptic patients and during schizophrenic attacks.” In: Lectures on Epilepsy (ed. Lorentz De Haas, ). Amsterdam: Elsevier Publishing Company. 91–133.Google Scholar
Langdon, F. W. (1905). “Nervous and mental manifestations of pre-pernicious anaemia.” J. Amer. med. Ass., 45, 1634–1638.Google Scholar
Lees, F. (1961). “Radioactive vitamin B12 absorption in the megaloblastic anaemia caused by anticonvulsant drugs.” Quart. J. Med., 30, 231–248.Google Scholar
McAlpine, D. (1929). “Review of nervous and mental aspects of pernicious anaemia.” Lancet, ii, 643–647.Google Scholar
Malpas, J. S., Spray, G. H., and Witts, L. J. (1966). “Serum folic acid and vitamin B12 levels in anticonvulsant therapy.” Brit. med. J., i, 955–957.CrossRefGoogle Scholar
Mannheimer, R. Pakesch, F., Reimer, E. F., and Vetter, R. (1952). “Die hämatologischen Komplikationen der Epilepsiebehandlung mit Hydantoinkörpern.” Med. Klin., 47, 1397–1401.Google Scholar
Mollin, D. L., and Hoffbrand, A. V. (1965). Series Haematologica, 3, 1.Google Scholar
Osmond, H., Smythies, J., and Harley-Mason, J. (1952). “Schizophrenia: a new approach.” J. ment. Sci., 98, 309–315.Google Scholar
Park, L. C., Baldessarini, R. J., and Kety, S. S. (1965). “Methionine effects on chronic schizophrenics.” Arch. gen. Psychiat., 12, 346–351.CrossRefGoogle ScholarPubMed
Pollin, W., Cardon, P. V., and Kety, S. S. (1961). “Effects of amino acid feedings in schizophrenic patients treated with iproniazid.” Science, 133, 104–105.Google Scholar
Pond, D. A. (1957). “Psychiatric aspects of epilepsy.” J. Ind. med. Prof., 3, 1441–1451.Google Scholar
Reynolds, E. H., Hallpike, J. F., Phillips, B. M., and Matthews, D. M. (1965). “Reversible absorptive defects in anti-convulsant megaloblastic anaemia.” J. clin. Path., 18, 593–598.Google Scholar
Reynolds, E. H., Hallpike, J. F., Phillips, B. M., Milner, G., Matthews, D. M., and Chanarin, I. (1966a). “Anticonvulsant therapy, megaloblastic haemopoiesis and folic acid metabolism.” Qyart. J. Med., 35, 521–537.Google Scholar
Reynolds, E. H., Hallpike, J. F., Phillips, B. M., Chanarin, I., Milner, G., and Matthews, D. M. (1966b). “Anticonvulsant therapy, folic acid and vitamin B12 metabolism and mental symptoms.” Epilepsia, 7, 261–270.CrossRefGoogle Scholar
Slater, E., and Beard, A. W. (1963). “The schizophrenia-like psychoses of epilepsy.” Brit. J. Psychiat., 109, 95–150.Google Scholar
Smith, A. D. M. (1960). “Megaloblastic madness.” Brit. med. J., ii, 1840–1844.Google Scholar
Smythies, J. (1967). “Recent advances in the biochemistry of schizophrenia.” In: Recent Developments in Schizophrenia. Brit. J. Psychiat. Monograph (Ed. Coppen, A. J.).Google Scholar
Spiro, H. R., Schimke, R. N., and Welch, J. P. (1965). “Schizophrenia in a patient with a defect in methionine metabolism.” J. nerv. ment. Dis., 141, 285–290.Google Scholar
Störring, F. K. (1937). “Psychotische Insulinreaktion und Erbgut.” Dtsch. med. Wschr., 63, 10–12.Google Scholar
Strachan, R. W., and Henderson, J. G. (1965). “Psychiatric syndromes due to avitaminosis B12 with normal blood and marrow.” Quart. J. Med., 34, 303–317.Google Scholar
Symonds, Sir C. (1962). “The schizophrenic-like psychoses of epilepsy.” Proc. roy. Soc. Med., 55, 311–316.Google Scholar
Tellenbach, H. (1965). “Epilepsie als Anfallsleiden und als Psychose. Über alternative Psychosen paranoider Prägung bei ‘forcierter Normalisierung’ (Landolt) des Elektroencephalogramms Epileptischer.” Nervenarzt, 36, 190–202.Google Scholar
Todd, E. D. M. (1966). Personal communication.Google Scholar
Wells, D. G., and Casey, H. (1967). Brit. med. J. In press.Google Scholar
Williams, , Denis, (1966). “Temporal lobe epilepsy.” Brit. med. J., i, 1439–1442.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.