Skip to main content
Log in

The importance of dosage in antipsychotic drug administration — A review of dose-response studies

  • Published:
Psychopharmacologia Aims and scope Submit manuscript

Abstract

Methodologically adequate clinical dose-response studies with antipsychotic compounds are reviewed. A number of consistent findings have emerged. Treatment resistant schizophrenics, and schizophrenics under 40, hospitalized less than 10 years often benefit from high or very high doses of antipsychotics. Low dose treatment is to be considered for apathetic or depressed schizophrenics who are not floridly psychotic. Placebo or no medication is optimal for a hitherto not well defined subgroup. The usual clinical dose range appears to be most therapeutic for the remaining schizophrenic populations, probably including most out-patients. Methodological problems encountered in dose-response studies and clinical problems in posology are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Brotman, R. K., Muzekari, L. H., Shanken, Phyllis, M.: Butaperazine in chronic schizophrenic patients: A double-blind study. Curr. ther. Res. 11, 5–8 (1969).

    Google Scholar 

  • Carscallen, H. B., Rockman, H., Lovegrove, T. D.: High dosage trifluoperazine in schizophrenia. Canad. Psychiat. Ass. J. 13, 459–461 (1968).

    Google Scholar 

  • Clark, M. L., Ramsey, H. R., Ragland, R. E., Rahhal, D. K., Serafetinides, E. A., Costiloe, J. P.: Chlorpromazine in chronic schizophrenia: behavioral dose-response relationships. Psychopharmacologia (Berl.) 18, 260–270 (1970).

    Google Scholar 

  • Cole, J. O., Davis, J. M.: Clinical efficacy of the phenothiazines as antipsychotic drugs. In: Psychopharmacology: A review of progress, pp. 1057–1063. Ed. by D. H. Efron. Washington: U.S. Gov. Printing Office 1968.

    Google Scholar 

  • Curry, S. H., Davis, J. M., Jankowsky, D. S., Marshall, J. H. L.: Factors affecting chlorpromazine plasma levels in psychiatric patients. Arch. gen. Psychiat. 22, 209–214 (1970).

    Google Scholar 

  • DeBuck, R. P.: The relative safety and efficacy of high and low dose administration of fluphenazine HCl to psychotic patients. Presented at C.I.N.P. Congress, Copenhagen 1972.

  • Everett, G. M.: Pharmacological aspects of clinical psychotropic drug studies: A critique on the dose-response problem. In: Psychopharmacology. A review of progress, pp. 985–988. Ed. by D. H. Efron. Washington: U.S. Gov. Printing Office 1968.

    Google Scholar 

  • Ezhkov, A. A.: The treatment of schizophrenic patients with Triperidol (Trisedil). Zh. Nervopat. Psikhiat. 68, 1394–1400 (1968) (Rus.).

    Google Scholar 

  • Galbrecht, C. R., Klett, C. J.: Predicting response to phenothiazines: The right drug for the right patient. J. nerv. ment. Dis. 147, 173–183 (1968).

    Google Scholar 

  • Gardos, G., Cole, J. O.: The dual action of Thiothixene. Arch. gen. Psychiat. (in press).

  • Gittleman-Klein, R., Klein, D. F.: Long-term effects of „Antipsychotic” agents: A review. In: Psychopharmacology. A review of progress, pp. 1119–1153. Ed. by D. H. Efron: Washington: U.S. Gov. Printing Office 1968.

    Google Scholar 

  • Goldberg, S. C.: Prediction of response to antipsychotic drugs. In: Psychopharmacology. A Review of Progress, pp. 1101–1117. Ed. by D. H. Efron. U.S. Gov. Printing Office 1968.

  • Hollister, L. E., Overall, J. E., Bennett, J. L., Kimball, I., Shelton, J.: Specific therapeutic actions of acetophenazine, perphenazine and benzquinamide in newly admitted schizophrenic patients. Clin. Pharmacol. Ther. 8, 249–255 (1967).

    Google Scholar 

  • Itil, T. M., Keskiner, A., Heinemann, L., Han, T., Gannon, P., Hsu, W.: Treatment of resistant schizophrenics with extreme high dosage fluphenazine hydrochloride. Psychosomatics 11, 456–463 (1970).

    Google Scholar 

  • Itil, T. M., Saletu, B., Hsu, W., Kiremitci, N., Keskiner, A.: Clinical and quantitative EEG changes at different dosage levels of fluphenazine treatment. Acta psychiat. scand. 47, 440–451 (1971).

    Google Scholar 

  • Klein, D. F., Davis, J. M.: Diagnosis and Drug Treatment of Psychiatric Disorders. Baltimore: The Williams & Wilkins Co. 1969.

    Google Scholar 

  • Overall, J. E., Hollister, L. E., Honigfeld, G., Kimbell, I. H., Meyer, F., Bennett, J. L., Caffey, E.: Comparison of acetophenazine with perphenazine in schizophrenics: Demonstration of differential effects based on computer-derived diagnostic models. Clin. Pharmacol. Ther. 4, 200–208 (1963).

    Google Scholar 

  • Platz, A. R., Klett, C. J., Caffey, E. M., Jr.: Selective drug action related to chronic schizophrenic subtype. Dis. nerv. Syst. 28, 601–605 (1967).

    Google Scholar 

  • Polvan, N., Yagcioglu, V., Itil, T. M., Fink, M.: High and very high dose fluphenazine in the treatment of chronic psychosis. In: Proceedings of the VI International Congress of the C.I.N.P. Tarragona, Excerpta Medica International Congress Series, No. 180, pp. 495–497 (1968).

  • Prien, R. F., Cole, J. O.: High dose chlorpromazine therapy in chronic schizophrenia. Arch. gen. Psychiat. 18, 482–495 (1968).

    Google Scholar 

  • Prien, R. F., Levine, J., Cole, J. O.: High dose trifluoperazine therapy in chronic schizophrenia. Amer. J. Psychiat. 126, 53–61 (1969).

    Google Scholar 

  • Rosati, D.: Prolonged high dosage ataractic medication in chronic schizophrenia. Brit. J. Psychiat. 110, 61–63 (1964).

    Google Scholar 

  • Schiele, B., Mendelson, R. M., Penman, A. S., Schofield, W.: Comparison of low and high dosage procedures in chlorpromazine therapy. Psychiat. Quart. 33, 252–259 (1959).

    Google Scholar 

  • Simpson, G. M., Amin, M., Kurz-Bartholini, E., Watts, P. T. S., Laska, E.: Problems in the evaluation of the optimal dose of a phenothiazine (butaperazine). Dis. nerv. Syst. 29, 478–484 (1968).

    Google Scholar 

  • Voskresenskaya, A. N., Leyzerovich, F. A.: Opyt primeneniya malykh doz stelazina pri lechenii psykhicheskikh zabolevaniy (Use of small doses of Stelazine in the treatment of mental disease). In: Voprosy Psikhofarmakologii (Problems in Psychopharmacology). Moscow: Ministry of Public Health, Scientific Research Institute of Psychiatry, pp. 150–154 (1967).

    Google Scholar 

  • Wilkens, B., Malitz, S.: Some problems of dose variation in the use of tranquilizing drugs. Amer. J. Psychiat. 117, 23–29 (1960).

    Google Scholar 

  • Williams, J. R., Solecki, R. T., Puttkammer, S.: Effects of single, combined and non-drug treatments of chronic mental patients. Dis. nerv. Syst. 30, 696–701 (1969).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Partially supported by the National Institute of Mental Health, Grant No. MH-16128.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gardos, G., Cole, J.O. & Orzack, M.H. The importance of dosage in antipsychotic drug administration — A review of dose-response studies. Psychopharmacologia 29, 221–230 (1973). https://doi.org/10.1007/BF00414036

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00414036

Key words

Navigation