Pharmacokinetic aspects of neuroleptics and prediction of outcome

  • S. R. Marder
Conference paper


A number of characteristics of antipsychotic medications have inspired a search for early predictors of drug response. Unless a clinician has a well-documented history that a patient will respond to a particular drug or drug dose, treatment decisions will usually be made on a trial and error basis. After a decision is made to begin a trial of a particular regimen, the clinician and patient will often have to wait for weeks or even months before it is established that the treatment is successful. Moreover, if the patient fails to respond to an adequate trial of a particular drug, the clinician may be unsure if the drug was an effective one that was administered at too high or too low a dose. For these reasons, researchers have searched for pharmacokinetic indicators which can guide pharmacotherapy.


Antipsychotic Activity Plasma Level Measurement Fluphenazine Decanoate Pharmacokinetic Aspect Dopamine Receptor Occupancy 
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  1. Bigelow LB, Kirch DG, Braun T, Korpi BT (1985) Absence of relationship of serum haloperidol concentration and clinical response in chronic schizophrenia: a fixed-dose study. Psychopharmacol Bull 21:66–68.PubMedGoogle Scholar
  2. Bleeker JAC, Dingemans PM, Frohn-De Winder ML (1984) Plasma level and effect of low-dose haloperidol in acute psychosis. Psychopharmacol Bull 20:317–319.PubMedGoogle Scholar
  3. Cohen BM, Waternaux C (1993) Neuroleptic plasma levels: limitations and values. In: Marder SR, Davis JM, Janicak PG (eds) Clinical use of neuroleptic plasma levels. American Psychiatric Press, Washington DC London, pp 1–15.Google Scholar
  4. Cohen BM, Zubenko GS (1985) Relevance of genetic variability to clinical psychopharmacology. Psychopharmacol Bull 21:641–650.PubMedGoogle Scholar
  5. Creese I, Burt DR, Snyder SH (1976) Dopamine receptor binding predicts clinical and pharmacologic potencies of antischizophrenic drugs. Science 192:481–483.PubMedCrossRefGoogle Scholar
  6. Dysken MW, Javaid JI, Chang SS et al. (1981) Fluphenazine pharmacokinetics and therapeutic response. Psychopharmacol (Berl) 73:205–210.CrossRefGoogle Scholar
  7. Farde L, Nordstrom A-L, Wiesel FA et al. (1992) Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Arch Gen Psychiatry 49:538–544.PubMedCrossRefGoogle Scholar
  8. Hitzemann RJ, Garver DL, Mavroidis M et al. (1986) Fluphenazine activity and antipsychotic response. Psychopharmacol (Berl) 90:270–273.CrossRefGoogle Scholar
  9. Itoh H, Yagi G, Fuji Y et al. (1984) The relationship between haloperidol blood levels and clinical responses. Prog Neuropsychopharmacol Biol Psychiatry 8:285–292.PubMedCrossRefGoogle Scholar
  10. Jorgensen A (1986) Metabolism and pharmacokinetics of antipsychotic drugs. In: Bridges JW, Chasseaud LF (eds) Progress in drug metabolism. Taylor and Francis, London Philadelphia, pp 111–174.Google Scholar
  11. Levinson DF, Simpson GM, Lo ES, Cooper TB (1993) Fluphenazine plasma levels, dosage and acute treatment response In: Marder SR, Davis JM, Janicak PG (eds) Clinical use of neuroleptic plasma levels. American Psychiatric Press, Washington DC London, pp 45–61.Google Scholar
  12. Linkowski P, Hubain P, von Frenckell R et al. (1984) Haloperidol plasma levels and clinical response in paranoid schizophrenics. Eur Arch Psychiatry Neurol Sci 234:231–236.PubMedCrossRefGoogle Scholar
  13. Marder SR, Midha KK, Van Putten T, Aravagiri M, Hawes EM, Hubbard JW, McKay G, Mintz J (1991) Plasma levels of fluphenazine in patients receiving fluphenazine decanoate: relationship to clinical response. Br J Psychiatry 158:658–665.PubMedCrossRefGoogle Scholar
  14. Marder SR, Van Putten T, Mintz J, Lebell M, McKenzie J, May PRA (1987) Low and conventional dose maintenance therapy with fluphenazine decanoate: two year outcome. Arch Gen Psychiatry 44:518–521.PubMedCrossRefGoogle Scholar
  15. Mavroidis ML, Kanter DR, Hirschozitz J et al. (1983) Clinical response and plasma haloperidol levels in schizophrenia. Psychopharmacology 81:354–356.PubMedCrossRefGoogle Scholar
  16. Mavroidis ML, Kanter DR, Hirschozitz J et al. (1984) Fluphenazine plasma levels and clinical response. J Clin Psychiatry 45:370–373.PubMedGoogle Scholar
  17. May PRA, Van Putten T (1978) Plasma levels of chlorpromazine in schizophrenia: a critical review of the literature. Arch Gen Psychiatry 35:1081–1087.PubMedCrossRefGoogle Scholar
  18. Midha KK, Hawes EM, Hubbard JW, Korchinski ED, McKay G (1989) Intersubject variation in the pharmacokinetics of chlorpromazine in healthy men. J Clin Psychopharmacol 9:48.Google Scholar
  19. Potkin SG, Shen Y, Zhou D et al. (1985) Does a therapeutic window for plasma haloperidol exist? — Preliminary Chinese data. Psychopharmacol Bull 21:59–61.PubMedGoogle Scholar
  20. Rimon R, Averbuch I, Rozick P et al. (1981) Serum and CSF levels of haloperidol by radioimmunoassay and radioreceptor assay during high-dose therapy of resistant schizophrenic patients. Psychopharmacology 73:197–199.PubMedCrossRefGoogle Scholar
  21. Santos JL, Cabranes JA, Almoguere I (1989) Clinical implications of determination of plasma haloperidol levels. Acta Psychiatr Scand 79:348–354.PubMedCrossRefGoogle Scholar
  22. Seeman P, Lee T, Chau-Wong M, Wong K (1976) Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature 261:717–719.PubMedCrossRefGoogle Scholar
  23. Smith RC, Baumgartner R, Misra CH (1984) Haloperidol plasma levels and prolactin response as predictors of clinical improvement in schizophrenia: chemical vs radioreceptor plasma level assay. Arch Gen Psychiatry 41:1044–1049.PubMedCrossRefGoogle Scholar
  24. Van Putten T, Aravagiri M, Marder SR, Wirshing WC, Mintz J, Chabert N (1991a) Plasma fluphenazine levels and clinical response in newly admitted schizophrenic patients. Psy-chopharmacol Bull 27:91–96.Google Scholar
  25. Van Putten T, Marder SR, Mintz J, Poland RE (1992) Haloperidol plasma levels and clinical response: a therapeutic window relationship. Am J Psychiatry 149:500–505.PubMedGoogle Scholar
  26. Van Putten T, Marder SR, Wirshing WC, Aravagiri M, Chabert N (1991b) Neuroleptic plasma levels. Schizophr Bull 17:197–216.PubMedGoogle Scholar
  27. Volavka J, Cooper T, Czobor P et al. (1992) Haloperidol blood levels and clinical effects. Arch Gen Psychiatry 49:354–361.PubMedCrossRefGoogle Scholar
  28. Wistedt B, Johanidesz G, Omerhodzic M et al. (1984) Plasma haloperidol levels and clinical response in acut schizophrenia. Nordisk Psychiatrik Tidsskrift 1:9–13.CrossRefGoogle Scholar
  29. Wolkin A, Brodie JD, Barouche F et al. (1989) Dopamine receptor occupancy and plasma haloperidol levels. Arch Gen Psychiatry 46:482–483.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1994

Authors and Affiliations

  • S. R. Marder
    • 1
    • 2
  1. 1.Brentwood Division, and the Department of Psychiatry and Biobehavioral Sciences, UCLA School of MedicineWest Los Angeles Veterans Affairs Medical CenterLos AngelesUSA
  2. 2.Psychiatry Service (116A) West Los Angeles Veterans Affairs Medical CenterLos AngelesUSA

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