Advertisement

Psychotropic Drug Blood Levels: Measurement and Relation to Behavioral Outcome in Mentally Retarded Persons

  • Mark H. Lewis
  • Richard B. Mailman
Part of the Disorders of Human Learning, Behavior, and Communication book series (HUMAN LEARNING)

Abstract

A major factor determining response to pharmacotherapy is the quantity of drug (and sometimes active metabolite) that is available to be taken up into the brain. Drug and metabolite measurements in blood are necessary to determine this bioavailability. This chapter is concerned with issues relevant to the measurement and clinical utility of blood concentrations of psychotropic drugs and their metabolites in mentally retarded persons. Much of the discussion addresses several confounding factors that can adversely affect the relationship between blood levels and behavioral outcome. However, despite technical and theoretical difficulties inherent in blood level measurements, such studies may improve pharmacotherapy by (a) establishing “therapeutic windows” for specific behavioral or psychiatric disorders, (b) preventing behavioral toxicity, (c) identifying non-responders or negative responders, and (d) ascertaining compliance. Relatively little research has been done quantifying drug concentrations with mentally retarded subjects as compared with other clinical populations, and many basic questions remain to be answered. The application of pharmacokinetics to drug treatment of retarded persons (who often cannot relate toxic effects or subjective indices of improvement) can only improve clinical practice and provide rational empirical criteria for treatment decisions in this field.

Keywords

High Performance Liquid Chromatography Blood Level Active Metabolite Antipsychotic Drug Tardive Dyskinesia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Referenecs

  1. Alfredsson, G., & Sedvall, G. (1976). Mass fragmentographic analysis of chlorpromazine in human plasma. In G. Sedvall, B. Uvnas, & Y. Zotterman (Eds.), Antipsychotic drugs: Pharmacokinetics. (pp. 367–372 ) Oxford: Pergamon Press.Google Scholar
  2. Aman, M.G., & Singh, N.N. (1980). The usefulness of thioridazine for treating childhood disorders—fact or folklore? American Journal of Mental Deficiency, 84, 331–338.PubMedGoogle Scholar
  3. Aman, M.G., & Singh, N.N. (1983). Pharmacological intervention. In J.L. Matson & J.A. Mulick (Eds.), Handbook of mental retardation. (pp. 317–337 ). Elmsford, NY: Pergamon.Google Scholar
  4. Aman, M.G., Singh, N.N., Stewart, A.W., & Field, C.J. (1985a). The Aberrant Behavior Checklist: A behavior rating scale for the assessment of treatment effects. American Journal of Mental Deficiency, 89, 485–491.PubMedGoogle Scholar
  5. Aman, M.G., Singh, N.N., Stewart, A.W., & Field, C.J. (1985b). Psychometric characteristics of the Aberrant Behavior Checklist. American Journal of Mental Deficiency, 89, 492–502.PubMedGoogle Scholar
  6. Axelsson, R. (1977). On the serum concentrations and antipsychotic effects of thioridazine, thioridazine side-chain sulfoxide and thioridazine side-chain sulfone in chronic psychotic patients. Current Therapeutic Research, 21, 588–589.Google Scholar
  7. Axelsson, R., & Aspenstrom, G. (1982). Electrocardiographic changes and serum concentrations in thioridazine-treated patients. Journal of Clinical Psychiatry, 43, 332–335.PubMedGoogle Scholar
  8. Axelsson, R., & Martensson, E. (1977). The concentration pattern of nonconjugated thioridazine metabolites in serum by thioridazine treatment and its relationship to physiological and clinical variables. Current Therapeutic Research, 21, 561–586.Google Scholar
  9. Baldessarini, R.J., Cole, J.O., Davis, J.M., Gardos, G., Preskorn, S.H., Simpson, G.M., & Tarsy, D. (1980). Tardive dyskinesia: Task Force Report. Washington DC: American Psychiatric Association.Google Scholar
  10. Bolvig Hansen, L., Elley, J., Christensen, T.R., Larsen, N-E., Naestoft, J., & Hvidberg, E.J. (1979). Plasma levels of perphenazine and its major metabolites during simultaneous treatment with anticholinergic drugs. British Journal of Clinical Pharmacology, 7, 75–80.PubMedGoogle Scholar
  11. Bunney, B.S. (1984). Antipsychotic drug effects on the electrical activity of dopaminergic neurons. Trends in Neurosciences, 7, 212–215.CrossRefGoogle Scholar
  12. Casper, R., Garver, D.L., Dekirmenjian, H., Chang, S., & Davis, J. (1980). Phenothiazine levels in plasma and red blood cells. Archives of General Psychiatry, 37, 301–305.PubMedGoogle Scholar
  13. Cohen, B.M., Lipinski, J.F., Pope, H.G., Harris, P.Q., & Altesman, R.I. (1980). Neuroleptic blood levels and therapeutic effect. Psychopharmacology, 70, 191–193.PubMedCrossRefGoogle Scholar
  14. Cooper, T.B. (1978). Plasma level monitoring of antipsychotic drugs. Clinical Pharmacokinetics, 3, 14–38.PubMedCrossRefGoogle Scholar
  15. Cooper. A.F., & Fowlie, H.C. (1973). Control of gross self-mutilation with lithium carbonate. British Journal of Psychiatry, 122, 370–371.PubMedCrossRefGoogle Scholar
  16. Creese, I., & Snyder, S.H. (1977). A simple and sensitive radioreceptor assay for antischizophrenic drugs in blood. Nature, 270, 180–182.PubMedCrossRefGoogle Scholar
  17. Cseransky, J.G., Kaplan, J., Holman, C.A., & Hollister, L.E. (1983). Serum neuroleptic activity, prolactin, and tardive dyskinesia in schizophrenic outpatients. Psychopharmacology, 81, 115–118.CrossRefGoogle Scholar
  18. Dahl, S.G. (1982). Active metabolites of neuroleptic drugs: Possible contribution to therapeutic and toxic effects. Therapeutic Drug Monitoring, 4, 33–40.PubMedCrossRefGoogle Scholar
  19. Dahl, S.G. (1986). Plasma level monitoring of antipsychotic drugs: Clinical utility. Clinical Pharmacokinetics, 11, 36–61.PubMedCrossRefGoogle Scholar
  20. Dale, P.G. (1980). Lithium therapy in aggressive mentally subnormal patients. British Journal of Psychiatry, 137, 469–474.PubMedCrossRefGoogle Scholar
  21. Davis, J.M., Erickson, S., & Dekirmenjian, H. (1978). Plasma levels of anti-psychotic drugs and clinical response. In M.A. Lipton, A. DiMascio, & K.F. Killam (Eds.), Psychopharmacology: A generation of progress. (pp. 905–916 ). New York: Raven Press.Google Scholar
  22. Davis, J.M., Javaid, J.I., Janicak, P.G., & Mostert, M. (1985). Antipsychotics: Plasma levels and clinical response. In G.D. Burrows, T.R. Norman, & B. Davies (Eds.), Drugs in psychiatry: Vol. 3. Antipsychotics. (pp. 57–70 ). Amsterdam: Elsevier.Google Scholar
  23. Dysken, M.W., Javaid, J.I., Chang, S.S., Schaffer, C., Shahid, A., & Davis, J.M. (1981). Fluphenazine pharmacokinetics and therapeutic response. Psychopharmacology, 73, 205–210.PubMedCrossRefGoogle Scholar
  24. Fairbairn, A.F., Rowell, F.J., Hui, S.M., Hassanyeh, F., Robinson, A.J., & Eccleston, D. (1983). Serum concentrations of depot neuroleptics in tardive dyskinesia. British Journal of Psychiatry, 142, 579–583.PubMedCrossRefGoogle Scholar
  25. Friedel, R.O. (1984). An overview of neuroleptic plasma levels: Pharmacokinetics and assay methodology. Journal of Clinical Psychiatry Monograph, 2, 7–12.Google Scholar
  26. Garver, D.L., Davis, J.M., Dekirmenjian, H., Jones, F.D., Casper, R., & Haraszti, J. (1976). Pharmacokinetics of red blood cell phenothiazine and clinical effects. Archives of General Psychiatry, 33, 862–866.PubMedGoogle Scholar
  27. Garver, D.L., Dekirmenjian, H., Davis, J.M., Casper, R., & Ericksen, S. (1977). Neuroleptic drug levels and therapeutic response: Preliminary observations with red blood cell-bound butaperazine. American Journal of Psychiatry, 134, 304–307.PubMedGoogle Scholar
  28. Gottschalk, L.A., Dinovo, E., Biener, R., & Nandi, B.R. (1978). Plasma concentrations of thioridazine metabolites and ECG abnormalities. Journal of Pharmaceutical Sciences, 67, 155–157.PubMedCrossRefGoogle Scholar
  29. Greenblatt, D.J., Divoll, M., Abernethy, D.R., Ochs, H.R., & Shader, R.I. (1984). Benzodiazepine pharmacokinetics: An overview. In G.D. Burrows, T.R. Norman, & B. Davies (Eds.), Drugs in psychiatry: Vol. 2. Antianxiety agents, (pp. 79–92 ). Amsterdam: Elsevier.Google Scholar
  30. Gualtieri, C.T., Breuning, S.E., Schroeder, S.R., & Quade, D. (1982). Tardive dyskinesia in mentally retarded children, adolescents and young adults: North Carolina and Michigan studies. Psychopharmacology Bulletin, 18, 62–65PubMedGoogle Scholar
  31. Hawes, E.M., Hubbard, J.W., Martin, M., McKay, G., Yeung, P.K.F., & Midha. K.K. (1986). Therapeutic monitoring of chlorpromazine: III. Minimal interconversion between chlorpromazine and metabolites in human blood. Therapeutic Drug Monitoring, 8, 37–41.PubMedCrossRefGoogle Scholar
  32. Hill, B.K., Balow, E.A., & Bruininks, R.H. (1985). A national study of prescribed drugs in institutions and community residential facilities for mentally retarded people. Psychopharmacology Bulletin, 21, 279–284.PubMedGoogle Scholar
  33. Intagliata, J., & Rinck, C. (1985). Psychoactive drug use in public and community residential facilities for mentally retarded persons. Psychopharmacology Bulletin, 21, 268–278.PubMedGoogle Scholar
  34. Itoh, H., Yagi, G., Ohtsuka, N., Iwamura, K., & Ichikawa, K. (1980). Serum level of haloperidol and its clinical significance. Progress in Neuropsychopharmacology and Biological Psychiatry, 4, 171–183.Google Scholar
  35. Itoh, H., Yagi, G., Tateyama, M., Fuji, Y. Iwamura, K., & Ichikawa, K. (1984). Monitoring of haloperidol serum levels and its clinical significance. Progress in Neuropsychopharmacology and Biological Psychiatry, 8, 51–62.CrossRefGoogle Scholar
  36. Jeste, D.V., DeLisi, L.E., Zalcman, S., Wise, C.D., Phelps, B.H., Rosenblatt, J.E., Potkin, S.G., Bridge, T.P., & Wyatt, R.J. (1981). A biochemical study of tardive dyskinesia in young male patients. Psychiatry Research, 4, 327–331.PubMedCrossRefGoogle Scholar
  37. Jeste, D.V., Rosenblatt, J.E., Wagner, R.L., & Wyatt, R.L. (1979). High serum neuroleptic levels in tardive dyskinesia? New England Journal of Medicine, 301, 1184.PubMedGoogle Scholar
  38. Kilts, C.D., Knight, D., Mailman, R.B., Widerlov, E., & Breese, G.R. (1984). Effects of thioridazine and its metabolites on dopaminergic function: Drug metabolism as a determinant of the antidopaminergic actions of thioridazine. Journal of Pharmacology and Experimental Therapeutics, 231, 334–342.PubMedGoogle Scholar
  39. Kilts, C.D., Patrick, K.S., Breese, G.R., & Mailman, R.B. (1982). Simultaneous determination of thioridazine and its S-oxidized and N-demethylated metabolites using HPLC on radially compressed silica. Journal of Chromatography, 232, 377–391.CrossRefGoogle Scholar
  40. Korpi, E.R., Costakos, D.T., & Wyatt, J.R. (1985). Interconversions of haloperidol and reduced haloperidol in guinea pig and rat liver microsomes. Biochemical Pharmacology, 34, 2923–2927.PubMedCrossRefGoogle Scholar
  41. Korpi, E.R., & Wyatt, R.J. (1984). Reduced haloperidol effects on striatal dopamine metabolism and conversion to haloperidol in the rat. Psychopharmacology, 83, 34–337.PubMedCrossRefGoogle Scholar
  42. Lewis, M.H., Baumeister, A.A., McCorkle, D., & Mailman, R.B. (1985). A computer-supported method for analyzing behavioral observations: Studies with stereotypy. Psychopharmacology, 85, 204–209.PubMedCrossRefGoogle Scholar
  43. Lewis, M.H., & MacLean, W.E., Jr. (1982). Issues in treating emotional disorders. In J.L. Matson & R.P. Barrett (Eds.), Psychopathology in the mentally retarded. (pp. 1–36 ). New York: Grune & Stratton.Google Scholar
  44. Lewis, M.H., Staples, L., McCorkle, D., & Mailman, R.B. (1983). Thioridazine pharmacodynamics: In vitro correlations and dependence on drug metabolism. Society for Neuroscience Abstracts, 9: 432.Google Scholar
  45. Lewis, M.H., Steer, R.A., Favell, J.E., McGimsey, J., Clontz, L., Trivette, C., Jodry, W., Schroeder, S., Kanoy, R. & Mailman, R.B. (1986). Thioridazine metabolism and effects on stereotyped behavior in mentally retarded patients. Psychopharmacology Bulletin, 22, 1040–1044.Google Scholar
  46. Lewis, M.H., Widerlov, E., Knight, D.L., Kilts, C.D., & Mailman, R.B. (1983). N-oxides of phenothiazine antipsychotics: Effects on in vivo and in vitro dopaminergic function. Journal of Pharmacology and Experimental Therapeutics, 225, 539–545, 1983.PubMedGoogle Scholar
  47. Linnoila, M., Viukari, M., Vaisanen, K., & Auvinen, J. (1980). Effect of anticonvulsants on plasma haloperidol and thioridazine levels. American Journal of Psychiatry, 137, 819–821.PubMedGoogle Scholar
  48. Linnoila, M., Viukari, M., Vaisanen, K., & Auvinen, J. (1981). Plasma neuroleptic and prolactin levels in mentally retarded patients. Acta Pharmacologica et Toxicologica, 46, 159.CrossRefGoogle Scholar
  49. Lipman, R.S. (1970). The use of psychopharmacological agents in residential facilities for the retarded. In F.J. Menolascino (Ed.), Psychiatric approaches to mental retardation. (pp. 387–398 ). New York: Basic Books.Google Scholar
  50. Lydiard, R.B., & Gelenberg, A.J. (1982). Hazards and adverse effects of lithium. Annual Review of Medicine, 33, 327–344.PubMedCrossRefGoogle Scholar
  51. Mailman, R.B., DeHaven, D.L., Halpern, E., & Lewis, M.H. (1984). Serum effects confound the neuroleptic radioreceptor assay. Life Sciences, 34, 1057–1064.PubMedCrossRefGoogle Scholar
  52. Mailman, R.B., Pierce, J.P., Crofton, K.M., Petitto, J., DeHaven, D.L., & Lewis, M.H. (1984). Thioridazine and the neuroleptic radioreceptor assay. Biological Psychiatry, 19, 833–847.PubMedGoogle Scholar
  53. Mavroidis, M.L., Kanter, D.R., Hirschowitz, J., & Garver, D.L. (1984). Therapeutic blood levels of fluphenazine: Plasma or RBC determinations? Psychopharmacology Bulletin, 20, 168–170.PubMedGoogle Scholar
  54. Neborsky, R.J., Janowsky, D.S., & Perel, J.M. (1982). Red blood cell/plasma haloperidol ratios and antipsychotic efficacy. Psychiatry Research, 6, 123–124.PubMedCrossRefGoogle Scholar
  55. Neborsky, R.J., Janowsky, D.S., Perel, J.M., Munson, E., & Depry, D. (1984). Plasma/RBC haloperidol ratios and improvement in acute psychotic symptoms. Journal of Clinical Psychiatry, 45, 10–13.PubMedGoogle Scholar
  56. Niedzwiecki, D.M., Mailman, R.B., & Cubeddu, L.X. (1984). Greater potency of mesoridazine and sulforidazine than thioridazine on striatal dopamine auto-receptors Journal of Pharmacology and Experimental Therapeutics, 228, 686–689.Google Scholar
  57. Norman, T.R. & Burrows, G.D. (1984). Benzodiazepine plasma concentrations and anxiolytic response. In G.D. Burrows, T.R. Norman, & B. Davies (Eds.), Drugs in psychiatry: Vol. 2. Antianxiety drugs. (pp. 93–106). Amsterdam: Elsevier. Nunnally, J. (1967). Psychometric theory. New York: McGraw-Hill.Google Scholar
  58. Papadopoulos, A.S., Chand, T.G., Crammer, J.L., & Lader, S. (1980). A pilot study of plasma thioridazine and metabolites in chronically treated patients. British Journal of Psychiatry, 136, 591–596.PubMedCrossRefGoogle Scholar
  59. Preskorn, S.H., Weller, E., Hughes, C., & Weller, R. (1986). Plasma monitoring of tricyclic antidepressants: Defining the therapeutic range for imipramine in depressed children. Clinical Neuropharmacology, 9 (suppl. 4), 265–267.PubMedGoogle Scholar
  60. Richardson, M.A., Haugland, G., Pass, R., & Craig, T.J. (1986). The prevalence of tardive dyskinesia in a mentally retarded population. Psychopharmacology Bulletin, 22, 243–249.PubMedGoogle Scholar
  61. Rivera-Calimlim, L., Kerzner, B., & Karch, F.E. (1979). Effect of lithium on plasma chlorpromazine levels. Clinical Pharmacology and Therapeutics, 23, 451–455.Google Scholar
  62. Rivinus, T.M., & Harmatz, J.S. (1979). Diagnosis and lithium treatment of affective disorder in the retarded: Five case studies. American Journal of Psychiatry, 136, 551–554.PubMedGoogle Scholar
  63. Rowell, F.J., Rich, C.G., Hall, G., Fairbairn, A.F., & Hassanyeh, F. (1983). Serum chlorpromazine levels in tardive dyskinesia. British Journal of Clinical Pharmacology, 15, 141–142.Google Scholar
  64. Sakalis, G., Traficante, L.J., Gardos, G., & Gershon, S. (1980). Treatment of drug-resistant schizophrenics with mesoridazine. In E. Usdin, H. Eckert, & I.S. Forrest (Eds.), Phenothiazines and structurally related drugs: Basic and clinical studies. (pp. 207–214 ). New York: Elsevier/North Holland.Google Scholar
  65. Shader, R.I., & Greenblatt, D.J. (1977). Clinical implications of benzodiazepine pharmacokinetics. American Journal of Psychiatry, 134, 652–655.PubMedGoogle Scholar
  66. Shvartsburd, A., Nwokeafor, V., & Smith, R.C. (1984). Red blood cell and plasma levels of thioridazine and mesoridazine in schizophrenic patients. Psychoparmacology, 82, 55–61.CrossRefGoogle Scholar
  67. Smith, R.C., Baumgartner, R., Ravichandran, G.K., Shvartsburd, A., Schoolar, J.C., Allen, P., & Johnson, R. (1984). Plasma and red cell levels of thioridazine and clinical response in schizophrenia. Psychiatry Research, 12, 287–296.PubMedCrossRefGoogle Scholar
  68. Smith, R.C., Vroulis, G., Shvartsburd, A., Allen, R., Lewis N., Schoolar, J.C., Chojnacki, M., & Johnson, R. (1982). RBC and plasma levels of haloperidol and clinical response in schizophrenia. American Journal of Psychiatry, 139, 1054–1056.PubMedGoogle Scholar
  69. Smith, R.C., Vroulis, G., Misra, C.H., Schoolar, J.C., DeJohn, C., Korivi, P., Leelavathi, D.E., & Arzu, D. (1980). Receptor techniques in the study of plasma levels of neuroleptics and antidepressant drugs. Communications in Psychopharmacology, 4, 451–465.PubMedGoogle Scholar
  70. Sprague, R.L. (1977). Overview of psychopharmacology for the retarded in the United States. In P. Mittler (Ed.), Research to practice in mental retardation: Vol. 3. Biomedical aspect. (pp. 199–202 ). Baltimore: University Park Press.Google Scholar
  71. Sprague, R.L., & Werry, J.S. (1971). Methodology of psychopharmacological studies with the retarded. In N.R. Ellis (Ed.), International review of research in mental retardation (Vol. 5, pp. 147–210 ). New York: Academic Press.Google Scholar
  72. Task Force on the Use of Laboratory Tests in Psychiatry. (1985). Tricyclic antidepressants-blood level measurements and clinical outcome: An APA task force report. American Journal of Psychiatry, 142, 155–162.Google Scholar
  73. Tyrer, S.P., Walsh, A., Edwards, D.E., Berney, T.P., & Stephens, D.A. (1984). Factors associated with a good response to lithium in aggressive mentally handicapped subjects. Progress in Neuropsychopharmacology and Biological Psychiatry, 8, 751–755.CrossRefGoogle Scholar
  74. Vaisanen, K., Viukari, M., Rimon R., & Raisanen, P. (1981). Haloperidol, thioridazine and placebo in mentally subnormal patients: Serum levels and clinical effects. Acta Psychiatrica Scandanavica, 63, 262–271.CrossRefGoogle Scholar
  75. Volavka, J., & Cooper, T.B. (1987). Review of haloperidol blood level and clinical response: Looking through the window. Journal of Clinical Psychopharmacology, 7, 25–30.PubMedCrossRefGoogle Scholar
  76. Widerlov, E., Haggstrom, J.-E., Kilts, C.D., Andersson, U., Breese, G., & Mailman, R.B. (1982). Serum concentrations of thioridazine, its major metabolites and serum neuroleptic-like activities in schizophrenics with and without tardive dyskinesia. Acta Psychiatrica Scandanavica, 66, 294–305.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1988

Authors and Affiliations

  • Mark H. Lewis
  • Richard B. Mailman

There are no affiliations available

Personalised recommendations