Abstract
Using a liquid chromatographic assay, we measured serum neuroleptic concentrations in eight middle-aged or elderly female inpatients with tardive dyskinesia (TD) and eight controls. All 16 patients were receiving either thioridazine or mesoridazine at stable doses. TD patients were found to have a significantly higher ratio of serum concentration to daily dose of neuroleptics compared with controls. A 1-year follow-up revealed that this ratio did not change appreciably in those patients who continued to receive neuroleptics. Differences in serum neuroleptic levels were not related to peripheral inflammatory activity as indicated by serum α-1-acid glycoprotein concentrations. Of the various thioridazine metabolites, sulforidazine (which is reportedly the most potent in terms of affinity for dopaminergic and α-noradrenergic receptors) seemed to be significantly elevated in the serum of TD patients as compared with non-TD patients. Our data suggest a need for further pharmacokinetic investigations to study neuroleptic metabolism in patients with TD.
Similar content being viewed by others
References
Bacher NM Lewis HA (1980) Low-dose propranolol in tardive dyskinesia. Am J Psychiatry 137:495–497
Baldessarini RJ, Cole JO, Davis JM, Gardos G, Preskorn SH, Simpson GM, Tarsy D (1980) Tardive dyskinesia: Task force report. American Psychiatric Association, Washington D.C.
Beyer WH (1966) Handbook of tables of probability and statistics. The Chemical Rubber Co., Cleveland, Ohio
Brandon S, McClelland HA, Protheroe C (1971) A study of facial dyskinesia in a mental hospital population. Br J Psychiatry 118:171–184
Cohen BM, Herschel M, Aoba A (1979) Neuroleptic, antimuscarinic, and antiadrenergic activity of chlorpromazine, thioridazine, and their metabolites. Psychiatr Res 1:199–208
Creese I, Synder SH (1977) A simple and sensitive radioreceptor assay for antischizophrenic drugs in blood. Nature 270:180–182
Freedman R, Kirch D, Bell J, Adler LE, Pecevich M, Pachtman E, Denver P (1982) Clonidine treatment of schizophrenia: Double-blind comparison to placebo and neuroleptic drugs. Acta Psychiat Scand 65:35–45
Jeste DV, Wyatt RJ (1981) Changing epidemiology of tardive dyskinesia: An overview. Am J Psychiatry 138:297–306
Jeste DV, Wyatt RJ (1982) Understanding and treating tardive dyskinesia. Guilford, New York (in press)
Jeste DV, Rosenblatt JE, Wagner RL, Wyatt RJ (1979) High serum neuroleptic levels in tardive dyskinesia? N Engl J Med 301:1184
Jeste DV, De Lisi LE, Zalcman S, Wise CD, Phelps BH, Rosenblatt JE, Potkin SG, Bridge TP, Wyatt RJ (1981) A biochemical study of tardive dyskinesia in young male patients. Psychiatr Res 4:327–331
Jus A, Peneau R, Lachance R, Pelchat G, Jus K, Pires P, Villeneuve R (1976) Epidemiology of tardive dyskinesia. II. Dis Nerv Syst 37:257–261
Kulik FA, Wilbur R (1980) Propranolol for tardive dyskinesia and extrapyramidal side effects (pseudoparkinsonism) from neuroleptics. Psychopharmacol Bull 16:18–19
Mallya A, Jose C, Baig M, Williams R, Cho D, Mehta D, Volavka J (1979) Antiparkinsonics, neuroleptics and tardive dyskinesia. Biol Psychiatry 14:645–649
Moreira MJC, Karnio IG (1979) Improvement of tardive dyskinesia with high doses of propranolol: A case report. Rev Paul Med 93:76–78
Peroutka SJ, Synder SH (1980) Relationship of neuroleptic drug effects at brain dopamine, serotonin, α-adrenergic, and histamine receptors to clinical potency. Am J Psychiatry 137:1518–1522
Piafsky KM, Borga O, Odar-Cederlor I, Johansson C, Sjoqvist F (1978) Increased plasma protein binding of propranolol and chlorpromazine mediated by disease-induced elevations of plasma α-1-acid glycoprotein. N Engl J Med 26:1435–1439
Rosenblatt JE, Pary RJ, Bigelow LB (1980) Measurement of serum neuroleptic concentrations by radioreceptor assay: Concurrent assessment of clinical response and toxicity. Psychopharmacol Bull 16:78–80
Simpson GM, Kline NS (1976) Tardive dyskinesia manifestations, incidence, etiology and treatment. In: Yahr MD (ed) The basal ganglia. Raven, New York
Simpson GM, Varga E, Lee JH, Zoubok B (1978) Tardive dyskinesia and psychotropic drug history. Psychopharmacology 58:117–124
Skinner T, Gochnauer R, Linnoila M (1981) Liquid chromatographic method to measure thioridazine and its active metabolites in biological samples. Acta Pharmacol Toxicol (Copenh) 48:223–226
Smith JM, Oswald WT, Kucharski LT, Waterman LJ (1978) Tardive dyskinesia: Age and sex differences in hospitalized schizophrenics. Psychopharmacology 58:207–211
Viukari M, Linnoila M (1975) Effect of methyldopa on tardive dyskinesia in psychogeriatric patients. Curr Ther Res 18:417–424
Viukari M, Linnoila M (1977) Effect of fusaric acid on tardive dyskinesia and mental state in psychogeriatric patients. Acta Psychiatr Scand 56:57–61
Wyatt RJ (1976) Biochemistry and schizophrenia. IV. The neuroleptics, their mechanism of action: A review of the biochemical literature. Psychopharmacol Bull 12:5–50
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jeste, D.V., Linnoila, M., Wagner, R.L. et al. Serum neuroleptic concentrations and tardive dyskinesia. Psychopharmacology 76, 377–380 (1982). https://doi.org/10.1007/BF00449128
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00449128