Hostname: page-component-76fb5796d-vvkck Total loading time: 0 Render date: 2024-04-26T15:02:13.841Z Has data issue: false hasContentIssue false

Drug-related and illness-related factors in the outcome of chlorpromazine treatment: testing a model

Published online by Cambridge University Press:  09 July 2009

T. Kolakowska*
Affiliation:
Department of Psychiatry, Littlemore Hospital, Oxford
M. G. Gelder
Affiliation:
Department of Psychiatry, Littlemore Hospital, Oxford
M. W. Orr
Affiliation:
Department of Psychiatry, Littlemore Hospital, Oxford
*
1Address for correspondence: Dr T. Kolakowska, University of Oxford, Department of Psychiatry, Littlemore Hospital Research Unit, Littlemore Hospital, Oxford 0X4 4XN.

Synopsis

Patients who presented with acute psychoses and were treated with chlorpromazine were first divided into 2 groups with good (23) and poor (13) outcome. These outcome groups differed little in their initial clinical features and showed no difference in 2 indices of dopamine receptor blockade (extrapyramidal symptoms and plasma prolactin concentrations). The group which improved was then subdivided on the basis of evidence of dopaminergic blockade into 15 who had improved and also showed anti-dopamine effects (‘responders’) and 8 who had improved but showed no anti-dopamine effects (‘remitters’) The remainder were eventually classified as ‘resistant’ to the effects of the drug. The group of ‘remitters’ contained no patients with nuclear schizophrenia; the ‘responders’ were mainly nuclear schizophrenics; and the ‘resistant’ patients were schizophrenic or schizo-affective. The 3 groups who were defined in this way also differed in their subsequent clinical course. It is suggested that this scheme for dividing patients may be useful in clinical work and could also assist research workers to identify the patients who can most appropriately be studied to determine mechanisms of drug action.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1980

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

Bergling, R., Mjorndal, T., Oreland, L., Rapp, W. & Wold, S. (1975). Plasma levels and clinical effects of thioridazine and thiothixene. Journal of Clinical Pharmacology 15, 178186.Google Scholar
Beumont, P. J. V., Corker, C. S., Friesen, H. G., Kolakowska, T., Mandelbrote, B. M., Marshall, J., Murray, M. A. F. & Wiles, D. H. (1974). The effects of phenothiazines on endocrine function. II. British Journal of Psychiatry 124, 420430.CrossRefGoogle ScholarPubMed
Clemens, J. A., Smalstig, E. B. & Sawyer, B. D. (1974). Antipsychotic drugs stimulate prolactin release. Psychopharmacologia (Berlin) 40, 123127.Google Scholar
Curry, S. H. (1968). Determination of nanogram quantities of chlorpromazine and some of its metabolites using gas liquid chromatography with an electron capture detector. Analytical Chemistry 40, 12511255.Google Scholar
Gelder, M. G. & Kolakowska, T. (1979). Variability of response to neuroleptics in schizophrenia: clinical, pharmacological and neuroendocrine correlates. Comprehensive Psychiatry 20 (5), 397408.CrossRefGoogle ScholarPubMed
Gruen, P. H., Sachar, E. J., Langer, G., Altman, N., Leifer, M., Frantz, A. & Halpern, F. S. (1978). Prolactin responses to neuroleptics in normal and schizophrenic subjects. Archives of General Psychiatry 35, 108116.Google Scholar
Harrow, M., Tucker, G. J. & Bromet, E. (1969). Short-term prognosis in schizophrenic patients. Archives of General Psychiatry 21, 195202.Google Scholar
Johnstone, E. C., Frith, C. D., Crow, T. J., Carney, M. W. P. & Prise, J. S. (1978). Mechanisms of the antipsychotic effect in the treatment of acute schizophrenia. Lancet i, 848851.Google Scholar
Klein, D. & Rosen, B. (1973). Premorbid asocial adjustment and response to phenothiazine treatment among schizophrenic inpatients. Archives of General Psychiatry 29, 480485.CrossRefGoogle ScholarPubMed
Kolakowska, T., Orr, M. W., Gelder, M. G., Heggie, M., Wiles, D. H. & Franklin, M. (1979). Clinical significance of plasma drug and prolactin levels during acute chlorpromazine treatment: a replication. British Journal of Psychiatry 135, 352359.Google Scholar
Langer, C., Sachar, E. J., Gruen, P. H. & Halpern, F. S. (1977). Human prolactin responses to neuroleptic drugs correlate with anti-schizophrenic potency. Nature 266, 639640.Google Scholar
Lindholm, H., Gullberg, B., Ohman, A. & Sedvall, G. (1978). Effects of perphenazine enanthate injections on prolactin levels in plasma from schizophrenic women and men. Psychopharmacologia 7, 14.Google Scholar
Mackay, A. V. P., Healey, A. F. & Baker, J. (1974). The relationship of plasma chlorpromazine to its 7–hydroxyl and sulphoxide metabolites in a large population of chronic schizophrenics. British Journal of Clinical Pharmacology 1, 425430.Google Scholar
McNeilly, A. S. & Hagen, C. (1974). Prolactin, TSH, LH and FSH responses to a combined LHRH/TRH test at different stages of the menstrual cycle. Clinical Endocrinology 3, 427435.Google Scholar
Mandelbrote, B. M. & Trick, K. L. K. (1970). Social and clinical factors in the outcome of schizophrenia. Acta psychiatrica et neurological scandinavica 40, 2434.Google Scholar
May, P. R. A., Van Putten, T., Yale, C., Potepan, P., Jenden, D. J., Fairchild, M. D., Goldstein, M. J. & Dixon, W. J. (1976). Predicting individual responses to drug treatment in schizophrenia: a test dose model. Journal of Nervous and Mental Disease 162, 177183.Google Scholar
Meltzer, H. Y. & Fang, V. S. (1976). The effect of neuroleptics on serum prolactin in schizophrenic patients. Archives of General Psychiatry 33, 279286.Google Scholar
Meltzer, H. Y., Good, D. J. & Fang, V. S. (1978). The effect of psychotropic drugs on endocrine function. I. Neuroleptics, precursors and agonists. In Psychopharmacology: a Generation of Progress (ed. Lipton, M. A., DiMascio, A. and Killam, M. F.), pp. 499507. Raven Press: New York.Google Scholar
Mielke, D. H., Gallant, D. M. & Kessler, C. (1977). An evaluation of a unique new antipsychotic agent, sulpiride: effects on serum prolactin and growth hormone levels. American Journal of Psychiatry 134, 13711375.Google Scholar
Overall, G. E. & Gorham, D. R. (1962). The brief psychiatric rating scale. Psychological Reports 10, 799.Google Scholar
Sakalis, G., Curry, S. H., Mould, G. P. & Lader, M. H. (1972). Physiologic and clinical effects of chlorpromazine and their relationship to plasma level. Clinical Pharmacology and Therapeutics 13, 931946.Google Scholar
Simpson, G. H. & Angus, J. W. S. (1970). A rating scale for extrapyramidal side-effects. Acta psychiatrica scandinavica Suppl. 212, 1119.Google Scholar
Siris, S. G., Van Kammen, D. P. & De Fraits, E. G. (1978). Serum prolactin and antipsychotic responses to pimozide in schizophrenia. Psychopharmacology Bulletin 14 (1), 1114.Google Scholar
Spitzer, R. L., Endicott, J., Robins, E., Kuriamsky, J. & Gurland, B. (1975). Preliminary report of the reliability of research diagnostic criteria applied to psychiatric case records. In Predictability in Psychopharmacology (ed. Sudilovsky, A., Gershon, S. and Beer, B.), pp. 747. Raven Press: New York.Google Scholar
Taylor, M. A. & Abrams, R. (1975). Manic-depressive illness and good prognosis schizophrenia. American Journal of Psychiatry 132, 741742.Google Scholar
Wiles, D. H., Kolakowska, T., McNeilly, A. S., Mandelbrote, B. M. & Gelder, M. G. (1976). Clinical significance of plasma chlorpromazine levels. I. Plasma levels of the drug, some of its metabolites and prolactin during acute treatment. Psychological Medicinei 6, 407415.Google Scholar
Wing, J. K., Cooper, J. E. & Sartorius, N. (1974). Measurement and Classification of Psychiatric Symptoms. Cambridge University Press: Cambridge.Google Scholar
Wode-Helgodt, B., Borg, S., Fyro, B. & Sedvall, G. (1978). Clinical effects and drug concentrations in plasma and cerebrospinal fluid in psychotic patients treated with fixed doses of chlorpromazine. Acta psychiatrica scandinavica 58, 149173.Google Scholar