Hostname: page-component-848d4c4894-jbqgn Total loading time: 0 Render date: 2024-06-21T00:12:12.353Z Has data issue: false hasContentIssue false

Adverse effects of anticholinergic medication on positive schizophrenic symptoms

Published online by Cambridge University Press:  09 July 2009

Eve C. Johnstone*
Affiliation:
Division of Psychiatry, Clinical Research Centre, Northwick Park Hospital, Harrow, Middlesex
Timothy J. Crow
Affiliation:
Division of Psychiatry, Clinical Research Centre, Northwick Park Hospital, Harrow, Middlesex
I. Nicol Ferrier
Affiliation:
Division of Psychiatry, Clinical Research Centre, Northwick Park Hospital, Harrow, Middlesex
Christopher D. Frith
Affiliation:
Division of Psychiatry, Clinical Research Centre, Northwick Park Hospital, Harrow, Middlesex
David G. C. Owens
Affiliation:
Division of Psychiatry, Clinical Research Centre, Northwick Park Hospital, Harrow, Middlesex
Rachel C. Bourne
Affiliation:
Division of Psychiatry, Clinical Research Centre, Northwick Park Hospital, Harrow, Middlesex
Stephen J. Gamble
Affiliation:
Division of Psychiatry, Clinical Research Centre, Northwick Park Hospital, Harrow, Middlesex
*
1Address for correspondence: Dr E. C. Johnstone, Division of Psychiatry, Clinical Research Centre, Northwick Park Hospital, Harrow, Middlesex HA1 3UJ.

Synopsis

In a series of 36 patients with acute schizophrenia flupenthixol dosage was blindly adjusted to give a fixed level of sedation. Patients were then randomly allocated to procyclidine or placebo. The patients receiving procyclidine experienced more positive schizophrenic symptoms and less severe extrapyramidal features by comparison with placebo patients. Blood levels of prolactin and flupenthixol estimated by radloimmunoassay were not significantly changed by the addition of procyclidine. Flupenthixol dosage and levels and prolactin levels were significantly related. There was no significant association between clinical and laboratory measures, with the exception that a curvilinear (inverted U) relationship was demonstrated between flupenthixol levels and antipsychotic and extrapyramidal effects. This relationship may be due to the fact that, in a study of this design, patients resistant to the effects of neuroleptic medication are likely to be given the highest doses. The findings support earlier claims that anticholinergic medication has adverse effects on schizophrenic symptoms.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1983

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

Andén, N.-E. (1972). Dopamine turnover in the corpus striatum and the limbic system after treatment with neuroleptic and antiacetylcholine drugs. Journal of Pharmacy and Pharmacology 24, 905906.CrossRefGoogle Scholar
Bishop, M. P., Gallant, D. M. & Sykes, T. F. (1965). Extrapyramidal side effects and therapeutic response. Archives of General Psychiatry 13, 155162.CrossRefGoogle ScholarPubMed
Chien, C. P. & Di Mascio, A. (1967). Drug induced extrapyramidal symptoms and their relations to clinical efficacy. American Journal of Psychiatry 123, 14901498.CrossRefGoogle ScholarPubMed
Chouinard, G., Annable, L. & Cooper, S. (1977). Antiparkinsonian drug administration and plasma levels of penfluridol – a new long acting neuroleptic. Communicable Psychopharmacology 1, 325331.Google ScholarPubMed
Cole, J. O. & Clyde, O. (1961). Extrapyramidal side effects and clinical response to the phenothiazines. Review Canadienne Biologie 20, 565574.Google Scholar
Corbin, K. B. (1949). Trihexyphenidyl, evaluation of the new agent in the treatment of Parkinsonism. Journal of the American Medical Association 141, 377381.CrossRefGoogle ScholarPubMed
Cotes, P. M., Crow, T. J., Johnstone, E. C., Bartlett, W. & Bourne, R. C. (1978). Neuroendocrine changes in acute schizophrenia as a function of clinical state and neuroleptic medication. Psychological Medicine 8, 657665.CrossRefGoogle ScholarPubMed
Crow, T. J., Deakin, J. F. W. & Longden, A. (1977). The nucleus accumbens – possible site of antipsychotic action of neuroleptic drugs. Psychological Medicine 7, 213221.CrossRefGoogle ScholarPubMed
Crow, T. J., Johnstone, E. C. & Owen, F. (1979). Research on schizophrenia. In Recent Advances in Clinical Psychiatry, No. 3 (ed. Granville-Grossman, K.), pp. 136. Churchill Livingstone: London.Google Scholar
Curry, S. H., Marshall, J. H. L., Davis, J. M. & Janowsky, D. S. (1970). Chlorpromazine plasma levels and effects. Archives of General Psychiatry 22, 289295.CrossRefGoogle ScholarPubMed
Davis, J. M. & Janowsky, D. (1975). Cholinergic and adrenergic balance in mania and schizophrenia. In Neurolransmitter Balances Regulating Behaviour (ed. Domino, E. F. and Davis, J. M.), pp. 135148. NPP: Ann Arbor.Google Scholar
Davis, K. L. & Berger, P. A. (1978). Pharmacological investigations of the cholinergic imbalance hypotheses of movement disorders and psychosis. Biological Psychiatry 13, 2349.Google ScholarPubMed
de Belleroche, J. S. & Neal, M. J. (1981). Contrasting effects of both acute and chronic neuroleptic administration on A.Ch release from corpus striatum and nucleus accumbens of rat. Journal of Physiology 312, 1516.Google Scholar
Delay, J., Deniker, P. & Harl, J. M. (1952). Utilisation en thérapeutique psychiatrique d'une phénothiazine d'action central élective (4560 UP). Annales Médico-Psychologiques (Paris) 110, 112117.Google Scholar
Deniker, P. (1960). Experimental neurological syndromes and the new drug therapies in psychiatry. Comprehensive Psychiatry 1, 92102.CrossRefGoogle ScholarPubMed
De Rivera, J. L., Lal, S., Ettigi, P., Mantella, S., Miller, H. F. & Friesen, H. G. (1976). Effect of acute and chronic neuroleptic therapy on serum prolactin levels in men and women of different age groups. Clinical Endocrinology 5, 273282.CrossRefGoogle Scholar
Donlon, P. T. & Tupin, J. P. (1974). Rapid ‘digitalisation’ of decompensated schizophrenic patients with antipsychotic agents. American Journal of Psychiatry 131, 310312.CrossRefGoogle ScholarPubMed
Doshay, L. J., Constable, K. & Zier, A. (1954). Five-year follow up of treatment with trihexyphenidyl (Artane) outcome in four hundred and eleven cases of paralysis agitans. Journal of the American Medical Association 154, 13341336.CrossRefGoogle ScholarPubMed
Dysken, M. W., Javaid, J. I., Chang, S. S., Schaffer, C., Shahid, A. & Davis, J. M. (1981). Fluphenazine pharmacokinetics and therapeutic response. Psychopharmacology 73, 205210.CrossRefGoogle ScholarPubMed
El-Yousef, M. K. & Manier, D. H. (1974). The effect of benztropine mesylate on plasma levels of butaperazine maleate. American Journal of Psychiatry 131, 471472.CrossRefGoogle ScholarPubMed
El-Yousef, M. K., Janowsky, D. S., Davis, J. M. & Seherke, H. J. (1972). Reversal of benztropine toxicity by physostigmine. Journal of the American Medical Association 220, 125.CrossRefGoogle Scholar
Flugel, F. (1953). Thérapeutique par medication neuroleptique obtenue en realisant systematiquement des états Parkinsoniformes. L'Encéphale 45, 10901092.Google Scholar
Forsman, A. & Ohman, R. (1977). Applied pharmacokinetics of haloperidol in man. Current Therapeutic Research 21, 396408.Google Scholar
Friedhoff, A. J. & Alpert, M. (1973). A dopaminergic–cholinergic mechanism in production of psychotic symptoms. Biological Psychiatry 6, 165169.Google ScholarPubMed
Gautier, J., Jus, A., Villeneuve, A., Jus, K., Pires, P. & Villeneuve, R. (1977). Influence of the antiparkinsonian drug on the plasma level of neuroleptics. Biological Psychiatry 12, 389399.Google ScholarPubMed
Godwin-Austen, R. B., Tomlinson, E. B., Frears, C. C. & Kok, H. W. L. (1969). Effects of l-dopa in Parkinson's disease, Lancet ii, 165168.CrossRefGoogle Scholar
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.CrossRefGoogle ScholarPubMed
Haase, H. (1962). Intensity and equivalence of neuroleptic effect and its therapeutic importance. Nervenarzt 33, 213220.Google ScholarPubMed
Halbreich, U., Sachar, E. J., Nathan, R. S., Asnis, G. M. & Halpern, F. S. (1980). The effect of benztropine mesylate on the prolactin response to haloperidol. Psychopharmacology 72, 6165.CrossRefGoogle ScholarPubMed
Howard, J. S. (1974). Haloperidol for chronically hospitalized psychotics: a double blind comparison with thiothixene and placebo: a follow up open evaluation. Diseases of the Nervous System 35, 458463.Google ScholarPubMed
Janowsky, D. S., El-Yousef, M. K., Davis, J. M. & Scherke, H. J. (1973). Antagonistic effects of physostigmine and methylphenidate in man. American Journal of Psychiatry 130, 13701376.CrossRefGoogle ScholarPubMed
Johnson, C. B. (1967). Mystical force of the nightshade. International Journal of Neuropsychiatry 3, 268275.Google ScholarPubMed
Johnstone, E. C., Bourne, R. C., Cotes, P. M., Crow, T. J., Ferrier, I. N., Owen, F. & Robinson, J. D. (1980). Blood levels of flupenthixol in patients with acute and chronic schizophrenia. In Drug Concentrations in Neuropsychiatry, Ciba Foundation Symposium 74 (new series), pp. 99111. Excerpta Medica: Oxford.Google Scholar
Jorgensen, A. (1978). A sensitive and specific radioimmunoassay for cis-fiupenthixol in human serum. Ljfe Sciences 23, 15331542.CrossRefGoogle ScholarPubMed
Kolakowska, T., Wiles, D. H., McNeilly, A. S. & Gelder, M. G. (1975). Correlation between plasma levels of prolactin and chlorpromazine in psychiatric patients. Psychological Medicine 5, 214216.CrossRefGoogle ScholarPubMed
Kolakowska, T., Wiles, D. H., Gelder, M. G. & McNeilly, A. S. (1976). Clinical significance of plasma chlorpromazine levels. II: Plasma levels of the drugs: some of its metabolites and prolactin in patients receiving long term phenothiazine treatment. Psychopharmacology 49, 101107.CrossRefGoogle Scholar
Kolakowska, T., Orr, M., Gelder, M., Heggie, M., Wiles, D. & Franklin, M. (1979). Clinical significance of plasma drug and prolactin levels during acute chlorpromazine treatment: a replication study. British Journal of Psychiatry 135, 352359.CrossRefGoogle ScholarPubMed
Kornetsky, C. & Mirsky, A. F. (1966). On certain psychopharmacological and physiological differences between schizophrenic and normal persons. Psychopharmacologia (Berlin) 8, 309318.CrossRefGoogle ScholarPubMed
Kornetsky, C., Vates, T. S. & Kessler, E. K. (1959). A comparison of hypnotic and residual psychological effects of single doses of chlorpromazine and secoborbital in man. Journal of Pharmacology and Experimental Therapeutics 127, 5154.Google ScholarPubMed
Krawiecka, M., Goldberg, D. & Vaughan, M. (1977). A standardised psychiatric assessment for rating chronic patients. Acta Psychiatrica Scandinavica 55, 299308.CrossRefGoogle Scholar
Ladinsky, H., Consolo, S., Bianchi, S., Ghezzi, D. & Samanin, R. (1978). Link between dopaminergic and cholinergic neurons in the striatum as evidenced by pharmacological, biochemical and lesion studies. In Interactions between Putative Neurotransmitters in the Brain (ed. Garattini, S.), pp. 321. Raven Press: New York.Google Scholar
Lal, S., Mendis, T., Cervantes, P., Guyda, H. & de Rivera, J. L. (1979). Effect of benztropine on haloperidol induced prolactin secretion. Neuropsychobiology 5(6), 327331.CrossRefGoogle ScholarPubMed
Langer, G., Sachar, E. J., Gruen, P. H. & Halpern, F. S. (1977). Human prolactin responses to neuroleptic drugs correlate with antischizophrenic potency. Nature 266, 639640.CrossRefGoogle ScholarPubMed
Lindholm, H., Gullberg, B., Ohman, A. & Sedvall, G. (1978). Effects of perfenazine enanthate injections on prolactin levels in plasma from schizophrenic women and men. Psychopharmacology 57, 14.CrossRefGoogle ScholarPubMed
Loga, S., Curry, S. & Lader, M. (1975). Interaction of orphanadine and phenobarbitone chlorpromazine: plasma concentrations and effects in man. British Journal of Clinical Pharmacology 2, 197208.CrossRefGoogle ScholarPubMed
Macvicar, K. (1977). Abuse of antiparkinsonian drugs by psychiatric patients. American Journal of Psychiatry 134, 809811.Google ScholarPubMed
McCreadie, R. G. & McDonald, I. M. (1977). High dosage haloperidol in chronic schizophrenia. British Journal of Psychiatry 131, 310316.CrossRefGoogle ScholarPubMed
Meddis, R. (1980). Unified analysis of variance by ranks. British Journal of Mathematical and Statistical Psychology 33, 8498.CrossRefGoogle Scholar
Meltzer, H. Y. & Fang, V. S. (1976). The effects of neuroleptics on serum prolactin in schizophrenic patients. Archives of General Psychiatry 33, 279284.CrossRefGoogle ScholarPubMed
Miller, R. J. & Hiley, C. R. (1974). Antimuscarinic properties of neuroleptics and drug induced Parkinsonism. Nature 248, 596597.CrossRefGoogle ScholarPubMed
Miller, R. J., Horn, A. S. & Iversen, L. L. (1974). The action of neuroleptic drugs on dopamine-stimulated adenosine cyclic 3', 5'-monophosphate production in rat neostriatum and limbic forebrain. Molecular Pharmacology 10, 759766.Google Scholar
Mindham, R. H. S., Gaind, R., Anstee, B. H. & Rimmer, L. (1972). Comparison of amantadine, orphenadrine and placebo in the control of phenothiazine induced Parkinsonism. Psychological Medicine 2, 406413.CrossRefGoogle ScholarPubMed
National Institute of Mental Health Psychopharmacology Service Centre Collaborative Study Group (1964). Phenothiazine treatment in acute schizophrenia. Archives of General Psychiatry 10, 246261.CrossRefGoogle Scholar
Owen, F., Crow, T. J., Poulter, M., Cross, A. J., Longden, A. & Riley, G. J. (1978). Increased dopamine-receptor sensitivity in schizophrenia. Lancet ii, 223226.CrossRefGoogle Scholar
Parkes, J. D., Zilkha, K. J., Calver, D. M. & Knill-Jones, R. P. (1970). Controlled trial of amantadine hydrochloride in Parkinson's disease. Lancet i, 259262.CrossRefGoogle Scholar
Pfeiffer, C. C. & Jenney, E. H. (1957). The inhibition of the conditioned response and the counteraction of schizophrenia by muscarinic stimulation of the brain. Annals of the New York Academy of Sciences 66, 753764.CrossRefGoogle ScholarPubMed
Porteus, H. B. & Ross, D. N. (1956). Mental symptoms in Parkinsonism following benzhexol hydrocholoride therapy. British Medical Journal ii, 138140.CrossRefGoogle Scholar
Prien, R. F. & Cole, J. O. (1968). High dose chlorpromazine therapy in chronic schizophrenia. Archives of General Psychiatry 18, 482495.CrossRefGoogle Scholar
Rao, V. A. Rama, Bishop, M. & Coppen, A. (1980). Clinical state, plasma levels of haloperidol and prolactin: a correlation study in chronic schizophrenia. British Journal of Psychiatry 137, 518521.CrossRefGoogle ScholarPubMed
Rivera-Calimlim, L., Nasrallah, H., Strauss, J. & Lasagna, L. (1976). Effect of dose, dosage schedules and drug interactions on plasma chlorpromazine levels. American Journal of Psychiatry 133, 646652.Google ScholarPubMed
Robinson, J. D. & Risby, D. (1977). Radioimmunoassay for flupenshixol in plasma. Clinical Chemistry 23, 20852088.CrossRefGoogle ScholarPubMed
Rosenthal, R. & Bigelow, L. G. (1973). The effects of physostigmine inphenothizine resistantchronic schizophrenicpatients: preliminary observations. Comprehensive Psychiatry 14, 489494.CrossRefGoogle Scholar
Rowntree, D. W., Nevin, S. & Wilson, A. (1950). The effects of diisopropylfluorophosphonase in schizophrenia and manic depressive psychosis. Journal of Neurology, Neurosurgery and Psychiatry 13, 4759.CrossRefGoogle ScholarPubMed
Sangiovanni, F., Taylor, M. A., Abrams, R. & Gaztanaga, P. (1973). Rapid control of psychotic excitement states with intramuscular haloperidol. American Journal of Psychiatry 130, 11551156.CrossRefGoogle ScholarPubMed
Seeman, P., Lee, T., Chau-Wong, M. & Wong, K. (1976). Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature (London) 261, 717719.CrossRefGoogle ScholarPubMed
Shader, R. I. & Greenblatt, D. J. (1971). Uses and toxicity of Belladonna alkaloids and synthetic anticholinergics. Seminars in Psychiatry 3, 449476.Google ScholarPubMed
Simpson, G. M., Varga, E. & Haher, G. J. (1976). Psychotic exacerbations produced by neuroleptics. Diseases of the Nervous System 37, 367369.Google ScholarPubMed
Simpson, G. M., Cooper, T. B., Bark, N., Sud, I. & Lee, J. H. (1980). Effect of antiparkinsonian medication on plasma levels of chlorpromazine. Archives of General Psychiatry 37, 205208.CrossRefGoogle ScholarPubMed
Singh, M. M. & Kay, S. R. (1975). Therapeutic reversal with benztropine in schizophrenics. Journal of Nervous and Mental Disease 160, 258266.CrossRefGoogle ScholarPubMed
Singh, M. M. & Kay, S. R. (1979). Therapeutic antagonism between anticholinergic antiparkinsonian agents and neuroleptics in schizophrenia. Implications for a neuropharmacological model. Neuropsychobiology 5, 7486.CrossRefGoogle ScholarPubMed
Singh, M. M. & Smith, J. M. (1973). Sleeplessness in acute and chronic schizophrenia – response to haloperidol and antiparkinsonian agents. Psychopharmacologia 29, 2132.CrossRefGoogle Scholar
Siris, S. S., van Kamman, D. P. & de Fraites, E. G. (1978). Serum prolactin and antipsychotic responses to pimozide in schizophrenia. Psychopharmacology Bulletin 14, 89.Google ScholarPubMed
Snyder, S. H., Greenberg, D. & Yamamura, H. I. (1974). Antischizophrenic drugs and brain cholinergic receptors. Archives of General Psychiatry 31, 5861.CrossRefGoogle ScholarPubMed
Stephens, D. A. (1967). Psychotoxic effects ofbenzhexol hydrochloride (Artane). British Journal of Psychiatry 113, 213218.CrossRefGoogle ScholarPubMed
van Putten, T., Mutalipassi, L. R. & Malkin, M. D. (1974). Phenothiazine induced decompensation. Archives of General Psychiatry 30, 102105.CrossRefGoogle Scholar
Webster, D. D. (1968). Clinical analysis of the disability in Parkinson's disease. Modern Treatment 5, 257282.Google Scholar
Weintraub, S. (1960). Stramonium poisoning. Postgraduate Medical Journal 28, 364.CrossRefGoogle ScholarPubMed
Wiles, D. H., Kolakowska, T., McNeilly, A. S., Mandelbrote, B. M. & Gelder, M. G. (1976). Clinical significance of plasma chlorpromazine levels. 1. Plasma levels of the drugs, some of its metabolites and prolactin during acute treatment. Psychological Medicine 6, 407415.CrossRefGoogle ScholarPubMed
Wing, J. K., Cooper, J. E. & Sartorius, N. (1974). Measurement and Classification of Psychiatric Symptoms. Cambridge University Press: Cambridge.Google Scholar