, Volume 82, Issue 3, pp 194–198 | Cite as

Serum neuroleptic concentrations and clinical response: A radioreceptor assay investigation of acutely psychotic patients

  • L. T. Kucharski
  • P. Alexander
  • L. Tune
  • J. Coyle
Original Investigations


Twenty-two acutely psychotic patients were rigorously assessed for psychopathology at baseline and after 14 days of neuroleptic treatment. The neuroleptic radioreceptor assay (NRRA) was used to determine serum neuroleptic concentrations. Serum neuroleptic concentration was significantly, nonlinearly related to changes in BPRS Total Score, and BPRS Factor Scores for Thought Disturbance and Anxiety-Depression. Clinical improvement was associated with intermediate (11–50, 51–126 ng/ml haloperidol equivalents) while poor clinical outcome was related to both low (less than or equal to 10 ng/ml) or high (greater than 125 ng/ml) serum levels. The results are discussed in terms of a possible “therapeutic window” for the neuroleptics and the implications this might have for clinical practice.

Key words

Neuroleptics Radioreceptor assay Serum levels Psychosis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Calil HM, Avery DH, Hollister LE, Creese I, Snyder SH (1979) Serum levels of neuroleptics measured by dopamine radioreceptor assay and some clinical observations. Psychiatr Res 1:39–44Google Scholar
  2. Cohen BM, Lipinski JR, Pope HG, Harris PO, Altesman RI (1980) Neuroleptic blood levels and clinical effect. Psychopharmacology 70:191–193Google Scholar
  3. Creese I, Snyder SH (1977) A simple and sensitive radioreceptor assay for antischizophrenic drugs in blood. Nature 270:180–182Google Scholar
  4. Garver DL, Dekirmenjian H, Davis JM (1978) Phenothiazine red cell levels and clinical response. Psychopharmacol Bull 14:27–29Google Scholar
  5. Garver DL, Dekirmenjian H, Davis JM, Casper R, Ericksen S (1977) Neuroleptic blood levels and therapeutic response: preliminary observations with red blood cell bound butaperazine. Am J Psychiatry 134:304–307Google Scholar
  6. Guilford JP (1950) Fundamental statistics for psychology and education. McGraw-Hill, New York, NYGoogle Scholar
  7. Guy W (1976) NCDEU Assessment Manual for Psychopharmacology. US Dept. of Health, Education and Welfare, Washington DCGoogle Scholar
  8. Jeste DV, Rosenblatt JR, Wagner RL, Wyatt RJ (1979) High serum levels in tardive dyskinesia. New Engl J Med 301:1184Google Scholar
  9. Kucharski LT, Smith JM, Dunn DD (1980) Tardive dyskinesia and hospital discharge. J Nerv Ment Dis 168:215–218Google Scholar
  10. MacKay AVP, Healey AF, Baker J (1974) The relationship of plasma chlorpromazine to its 7-hydroxy and sulphoxide metabolites in a large population of chronic schizophrenics. Brit J Clin Pharmacol 1:425–430Google Scholar
  11. Magliozzi JR, Hollister LE, Arnold KV, Earle GM (1981) The relationship of serum haloperidol levels to clinical response in schizophrenic patients. Am J Psychiatry 138:365–367Google Scholar
  12. May PRA, Van Putten T (1978) Plasma levels of chlorpromazine in schizophrenia. Arch Gen Psychiatry 35:1081–1087Google Scholar
  13. Overall JE, Gorham DR (1962) The brief psychiatric rating scale. Psychol Rep 10:799–812Google Scholar
  14. Phillipson IT, McKeown JM, Baker J, Healey AF (1977) Correlation between plasma chlorpromazine and its metabolites and clinical rating in patients with actual relapse of schizophrenic and paranoid psychosis. Br J Psychiatry 131:172–185Google Scholar
  15. Rimon R, Averbuch I, Roxick P, Fijman-Danilovich L, Kara T, Dasberg H, Ebstein RP, Belmaker RH (1981) Serum and CSF levels of haloperidol by radioimmunoassay and radioreceptor assay during high dose therapy of resistant schizophrenic patients. Pscychopharmacology 73:191–199Google Scholar
  16. Rivera-Calimlim L, Nassralah H, Strauss J, Lasagna L (1976) Clinical response and plasma levels: effects of dose, dosage schedule and drug interaction on plasma chlorpromazine levels. Am J Psychiatry 133:646–652Google Scholar
  17. Rosenblatt JE, Pary RJ, Bigelow LB (1980) Measurement of serum neuroleptic concentration by radioreceptor assay: concurrent assessment of clinical response and toxicity. Psychopharmacol Bull 16:78–80Google Scholar
  18. Rosenblatt JE, Pert CB, Colison J, van Kammen DP, Scott R, Bunney WE (1979) Measurement of serum neuroleptic concentration by radioreceptor assay: concurrent assessment of clinical psychosis ratings. Commun Psychopharmacol 3:153–158Google Scholar
  19. Sakalis G, Chan TL, Gershon S, Park S (1973) The possible role of metabolites in the therapeutic response to chlorpromazine treatment. Psychopharmacologia 32:279–284Google Scholar
  20. Sakalis G, Chan TL, Sathananthan G, Schooler N, Goldberg S, Gershon S (1977) Relationships among clinical response, extrapyramidal syndrome and plasma chlorpromazine and metabolic ratios. Commun Psychopharmacol 1:157–166Google Scholar
  21. Sakalis G, Curry SH, Mould GP, Lader MH (1972) Physiologic and clinical effects of chlorpromazine and their relationship to plasma level. Clin Pharmacol Ther 13:931–946Google Scholar
  22. Smith RC, Crayton J, Dekirmenjian H, Klass D, Davis JM (1979) Blood levels of neuroleptic drugs in non-responding chronic schizophrenic patients. Arch Gen Psychiatry 36:579–584Google Scholar
  23. Tune LE, Creese I, DePaulo JR, Slavney PR, Coyle JT, Snyder SH (1980) Clinical state and serum neuroleptic levels measured by radioreceptor assay in schizophrenia. Am J Psychiatry 137:187–190Google Scholar
  24. Tune LE, Creese I, DePaulo JR, Slavney PR, Coyle JT, Snyder SH (1981) Neuroleptic serum levels measured by radioreceptor assay and clinical response in schizopherenic patients. J Nerv Ment Dis 169:60–63Google Scholar
  25. Wiles DH, Kolakowski T, McNeilly AS, Mandelbrote BM, Gelder MG (1976) Clinical significance of plasma chlorpromazine levels. I. Plasma levels of drug, some of its metabolites and prolactin during acute treatment. Psychol Med 6:407–415Google Scholar
  26. Wyatt RJ (1976) Biochemistry of schizophrenia, part IV, The neuroleptics, their mechanism of action. Psychopharm Bull 12:5–50Google Scholar

Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • L. T. Kucharski
    • 1
  • P. Alexander
    • 2
  • L. Tune
    • 3
  • J. Coyle
    • 3
  1. 1.Child Psychiatry M-806Boston University School of MedicineBostonUSA
  2. 2.Department of PsychiatryBrown UniversityProvidenceUSA
  3. 3.Department of Neuroscience, Pharmacology and Experimental Therapeutics and PsychiatryJohns Hopkins University School of MedicineBaltimoreUSA

Personalised recommendations