Abstract
In a double-blind, cross-over study, the comparative therapeutic effects of 6-week courses of two prototypic neuroleptics — haloperidol and chlorpromazine — and the reversal of those effects with benztropine were investigated in a group of 18 schizophrenics. Periodic measurements were made for 32 dimensions of psychopathology, social participation, span of attention, sleeplessness, pulse rate and neurological side effects. The results showed that haloperidol was generally a more effective drug over the period studied. This was particularly apparent in terms of social and emotional responsiveness, communicativeness and cognitive processes. The only superiority of chlorpromazine seemed to be that patients felt less dysphoric on it than they did on haloperidol. Haloperidol also proved to be more rapid in its action. The data failed to support the clinical validity of the distinction often made between “sedative” and “activating” neuroleptics. Consistent with previous reports, benztropine had the effect of diminishing therapeutic response to both neuroleptics. However, haloperidol again proved less susceptible to this effect. The slowness and lesser therapeutic efficiency of chlorpromazine and its greater susceptibility to benztropine reversal were all considered to be due to its built-in anticholinergic properties acting in opposition to its antipsychotic activity. The low potency of chlorpromazine-like drugs was attributed to their inherent anticholinergic characteristics. It was suggested that one of the factors determining potency differences among neuroleptics may be the degree of built-in anticholinergic activity.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ban, T. A.: Treatment of acute and chronic psychoses with haloperidol: Review of clinical results. Curr. ther. Res. 11, 284–288 (1969)
Ban, T. A.: Drug treatment in schizophrenia. Canad. Psychiat. Ass. J. 16, 473–485 (1971)
Bueno, J. R., Himwich, H. E.: Psychotropic drugs used in management of schizophrenia. Int. J. Neurol. 6, 77–93 (1967)
Crane, G. E.: A review of clinical literature on haloperidol. Int. J. Neuropsychiat. 3 (Suppl. 1), S110–S123 (1967)
Davis, J. M.: Efficacy of tranquilizing and antidepressant drugs. Arch. gen. Psychiat. 13, 552–572 (1965)
Delay, J., Deniker, P.: Dix ans de psycho-pharmacologie. In: Neuropsychopharmacology. P. B. Bradley, F. Flügel, and P. H. Hoch, eds., Vol. 3, pp. 529–533. Amsterdam: Elsevier 1964
El-Yousef, M. K., Janowsky, D. S., Davis, J. M., Sekerke, H. J.: Reversal of antiparkinson drug toxicity by physostigmine: A controlled study. Amer. J. Psychiat. 130, 141–145 (1973)
Fox, W., Gobble, I. F., Clos, M., Denison, E.: A clinical comparison of trifluoperidol, haloperidol and chlorpromazine. Curr. ther. Res. 6, 409–415 (1964)
Goldstein, B. J., Clyde, D. J., Caldwell, J. M.: Clinical efficacy of the butyrophenones as antipsychotic drugs. In: Psychopharmacology: A review of progress 1957–1967. D. H. Efron, J. O. Cole, J. Levine, and J. R. Wittenborn, eds., pp. 1085–1091. Washington, D.C.: U.S. Government Printing Office 1968
Hanson, H. M., Stone, C. A., Witoslawski, J. J.: Antagonism of the antiavoidance effects of various agents by anticholinergic drugs. J. Pharmacol. exp. Ther. 173, 117–124 (1970)
Howard, L. R. C.: Hidden factors in drug therapy. Clin Tr. J. 2, 135–139 (1965)
Kay, S. R., Singh, M. M.: A temporal measure of attention in schizophrenia and its clinical significance. Brit. J. Psychiat. 125, 146–151 (1974)
Langfeldt, G.: Schizophreniform states: A katamnestic study based on individual re-examinations. London: Humphrey Milford 1939
Lehmann, H. E., Ban, T. A., Mathews, V., Garcia-Rill, T.: The effects of haloperidol on acute patients: A comparative study of haloperidol, chlorpromazine and chlorprothixene. In: The butyrophenones in psychiatry. H. E. Lehmann and T. A. Ban, eds. Montreal, Quebec: Psychopharmacological Research Association 1964
NIMH Psychopharmacology Center Collaborative Group: Phenothiazine treatment in acute schizophrenia. Arch. gen. Psychiat. 10, 246–261 (1964)
Papeschi, R., Munkvad, I.: Relation of the effect of neuroleptics in animals to pharmacological parkinsonism and antipsychotic action in man. Paper presented in the VIII Congress of Collegium Internationale Neuropsychopharmacologicum, Copenhagen, Aug. 1972
Pfeiffer, C. C., Jenney, E. H.: The inhibition of the conditioned response and counteraction of schizophrenia by muscarinic stimulation of the brain. Ann. N.Y. Acad. Sci. 66, 753–764 (1957)
Pratt, J. P., Bishop, M. P., Gallant, D. M.: Comparison of haloperidol, trifluperidol and chlorpromazine in acute schizophrenic patients. Curr. ther. Res. 6, 562–571 (1964)
Rivera-Calimlim, L., Castañeda, L., Lasagna, L.: Effects of mode of management on plasma chlorpromazine in psychiatric patients. Clin. Pharmacol. Ther. 14, 978–986 (1973)
Shopsin, B., Hekimian, L. J., Gershon, S., Floyd, A.: A controlled evaluation of haloperidol, chlorpromazine, and sodium amobarbital: Intramuscular short-term use in acute psychotic patients. Curr. ther. Res. 11, 561–573 (1969)
Singh, M. M.: Psychopharmacological study of schizophrenia.—Some ways out of an impasse. Int. Pharmacopsychiat. 8, 80–98 (1973)
Singh, M. M., Kay, S. R.: Therapeutic reversal with benztropine in schizophrenics.—Practical and theoretical significance. J. nerv. ment. Dis. 169, 258–266 (1975)
Singh, M. M., Smith, J. M.: Kinetics and dynamics of response to haloperidol in acute schizophrenia.—A longitudinal study of the therapeutic process. Comp. Psychiat. 14, 393–414 (1973a)
Singh, M. M., Smith, J. M.: Reversal of some therapeutic effects of an antipsychotic agent by an anti-Parkinsonism agent. J. nerv. ment. Dis. 157, 50–58 (1973b)
Singh, M. M., Smith, J. M.: Sleeplessness in acute and chronic schizophrenia.—Response to haloperidol and anti-Parkinsonism agents. Psychopharmacologia (Berl.) 29, 21–32 (1973c)
Slater, F., Roth, M.: Mayer-Gross clinical psychiatry, 3rd ed. Baltimore: Williams and Wilkins 1969
Snyder, S., Greenberg, D., Yamamura, H. I.: Antischizophrenic drugs and brain cholinergic receptors. Affinity for muscarinic sites predicts extrapyramidal effects. Arch. gen. Psychiat. 31, 58–61 (1974)
Stein, L.: Chemistry of reward and punishment. In: Psychopharmacology: A review of progress, 1957–1967. D. H. Efron, J. O. Cole, J. Levine, and J. E. Wittenborn, eds., pp. 105–123. Washington, D.C.: U.S. Government Printing Office 1968
Valzelli, L.: Psychopharmacology. An introduction to experimental and clinical principles, pp. 119, 139, 150. New York: Spectrum 1972
Warnes, H.: Toxic psychosis due to anti-Parkinsonism drugs. Canad. Psychiat. Ass. J. 2, 323–326 (1967)
Wauquier, A., Niemegeers, C. J. E., Lal, H.: Differential antagonism by dexetimide of inhibitory effects of haloperidol and fentanyl on brain self-stimulation. Psychopharmacologia (Berl.) 41, 229–235 (1975)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Singh, M.M., Kay, S.R. A comparative study of haloperidol and chlorpromazine in terms of clinical effects and therapeutic reversal with benztropine in schizophrenia. Theoretical implications for potency differences among neuroleptics. Psychopharmacologia 43, 103–113 (1975). https://doi.org/10.1007/BF00421012
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00421012