Abstract
In a cross-over trial 16 elderly psychiatric patients with tardive dyskinesia were treated with thioridazine (median dose, 267.5 mg/day) for three months, followed by haloperidol (5.25 mg/day), haloperidol (5.25 mg/day) + biperiden (6 mg/day), thioridazine (267.5 mg/day), and clozapine (62.5 mg/day, only 7 patients), all for periods of 4 weeks with 4-week drug-free intervals. The tardive dyskinesia syndrome and the parkinsonism were evaluated blind according to a self-constructed rating scale and a modified Webster scale from weekly video-tape recordings. At the end of the treatment periods the hyperkinesia score was lower during haloperidol than during either thioridazine for 3 months (total score, 2.2 vs. 3.2, P<0.05), thioridazine for 4 weeks (total score, 2.2 vs. 4.8, P<0.02), or haloperidol + biperiden (score, 2.2 vs. 6.2, P<0.01). Clozapine had no significant antihyperkinetic effect, but in one patient it exerted a clear antiparkinsonian effect. After withdrawal of the initial thioridazine treatment, the hyperkinesia score was lower than after the subsequent haloperidol treatment (6.5 vs. 9.0, P<0.01), but after the second thioridazine period the hyperkinesia was of the same magnitude as after the preceding haloperidol periods. Biperiden increased the tardive dyskinesia syndrome during treatment, but did not significantly influence the syndrome after withdrawal of the treatment.
It is concluded that (1) haloperidol (a strong antidopaminergic neuroleptic) has a more pronounced antihyperkinetic effect than thioridazine and clozapine (weaker antidopaminergic neuroleptics); (2) haloperidol might have a greater tendency to induce tardive dyskinesia than thioridazine; (3) administration of anticholinergics concomitant with neuroleptic drugs antagonizes the antihyperkinetic effect of haloperidol, but may not influence the intensity of tardive dyskinesia after withdrawal of the treatment.
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American College of Neuropharmacology — Food and Drug Administration Task Force: Neurological syndromes associated with antipsychotic drug use. Arch. Gen. Psychiatry 28, 463–467 (1973)
Ayd, F. J., Jr.: Persistent dyskinesia: a neurologic complication of major tranquillers. Med. Sci. 18, 32–40 (1967)
Barany, S., Gunne, L.-M.: Studies in tardive dyskinesia and acute dystonia. Presented at the VI World Congress of Psychiatry, Honolulu, Hawaii, August 28 – September 3, 1977
Bartholini, G.: Differential effect of neuroleptic drugs on dopamine turnover in the extrapyramidal and limbic system. J. Pharm. Pharmacol. 28, 429–433 (1976)
Bartholini, G., Haefely, W., Jalfre, M., Keller, H. H., Pletscher, A.: Effects of clozapine on cerebral catecholaminergic neurone systems. Br. J. Pharmacol. 46, 736–740 (1972)
Bunney, N. S., Aghajanian, G. K.: The effect of antipsychotic drugs on the firing of dopaminergic neurons: a reappraisal. In: Antipsychotic drugs: pharmacodynamics and pharmacokinetics (G. Sedvall, B. Uvnäs, Y. Zotterman, eds.), pp. 305–318 New York: Pergamon 1976
Christensen, A. V., Fjalland, B., Møller Nielsen, I.: On the supersensivity of dopamine receptors, induced by neuroleptics. Psychopharmacology 48, 1–6 (1976)
Claveria, L. E., Teychenne, P. F., Calne, D. B., Haskayne, L., Petrie, A., Pallis, C. A., Lodge-Patch, I. C.: Tardive dyskinesia treated with pimozide. J. Neurol. Sci. 24, 393–401 (1975)
Crane, G. E.: Tardive dyskinesia in patients treated with major neuroleptics: a review of the literature. Am. J. Psychiatry 124, 40–48 (1968)
Crane, G. E.: Persistent dyskinesia. Br. J. Psychiatry 122, 395–405 (1973)
Crane, G. E.: Factors predisposing to drug-induced neurologic effects. In: The phenotiazines and structurally related drugs (I. S. Forrest, C. J. Carr, E. Usdin, eds.), pp. 269–279. New York: Raven 1974
Doep, S., Buddeberg, C.: Extrapyramidale Symptome unter Clozapin. Nervenarzt 46, 589–590 (1975)
Fog, R., Pakkenberg, H.: Combined nitoman-pimozide treatment of Huntington's chorea and other hyperkinetic syndromes. Acta Neurol. Scand. 46, 249–251 (1970)
Gardos, G., Cole, J. P., La Brie, R. A.: Drug variables in the etiology of tardive dyskinesia application of discriminant function analysis. Prog. Neuro-Psychopharmacol. 1, 147–154 (1977)
Gautier, J., Jus, A., Villeneuve, A., Jus, K., Pires, P., Villeneuve, R.: Influence of the antiparkinsonian drugs on the plasma level of neuroleptics. Biol. Psychiatry 12, 389–399 (1977)
Gerlach, J.: Relationship between tardive dyskinesia, L-dopa-induced hyperkinesia and parkinsonism. Psychopharmacology 51, 259–263 (1977)
Gerlach, J.: Tardive dyskinesia (thesis). Dan. Med. Bull. (in press, 1978)
Gerlach, J., Reisby, N., Randrup, A.: Dopaminergic hypersensitivity and cholinergic hypofunction in the pathophysiology of tardive dyskinesia. Psychopharmacologia (Berl.) 34, 21–35 (1974)
Gerlach, J., Rye, T., Kristjansen, P.: Effect of baclofen on tardive dyskinesia. Psychopharmacology 56, 145–151 (1978)
Gerlach, J., Thorsen, K.: The movement pattern of oral tardive dyskinesia in relation to anticholinergic and antidopaminergic treatment. Int. Pharmacopsychiatry 11, 1–7 (1976)
Gerlach, J., Thorsen, K., Fog, R.: Extrapyramidal reactions and amine metabolites in cerebrospinal fluid during haloperidol and clozapine treatment of schizophrenic patients. Psychopharmacologia (Berl.) 40, 341–350 (1975)
Gunne, L.-M., Barany, S.: Haloperidol-induced tardive dyskinesia in monkeys. Psychopharmacology 50, 237–240 (1976)
Hyttel, J.: Changes in dopamine synthesis rate in the supersensitivity phase after treatment with a single dose of neuroleptics. Psychopharmacology 51, 205–207 (1977)
Kazamatsuri, H., Chien, C., Cole, J. O.: Treatment of tardive dyskinesia. II. Short-term efficacy of dopamine-blocking agents haloperidol and thiopropazate. Arch. Gen. Psychiatry 27, 100–103 (1972)
Klawans, H. L., Rubovits, R.: Effect of cholinergic and anticholinergic agents on tardive dyskinesia. J. Neurol. Neurosurg. Psychiatry 27, 941–947 (1974)
Overall, J., Gorham, D.: The brief psychiatric rating scale. Psychol. Rep. 10, 799–812 (1962)
Sayers, A., Bürki, H., Ruch, W., Asper, H.: Neuroleptic-induced hypersensitivity of striatal dopamine receptors in the rat as a model of tardive dyskinesias. Effects of clozapine, haloperidol, loxapine and chlorpromazine. Psychopharmacologia (Berl.) 41, 97–104 (1975)
Sayers, A., Bürki, H., Ruch, W., Asper, H.: Anticholinergic properties of antipsychotic drugs and their relation to extrapyramidal side-effects. Psychopharmacology 51, 15–22 (1976)
Sayers, A., Bürki, H., Ruch, W., Asper, H.: Animal models for tardive dyskinesia: effects of thioridazine. Pharmakopsychiatry 10, 201–295 (1977)
Simpson, G. M., Varga, E.: Clozapine — a new antipsychotic agent. Curr. Ther. Res. 16, 679–686 (1974)
Smith, R. C., Davis, J. M.: Behavioral supersensitivity to apomorphine and amphetamine after chronic high dose haloperidol treatment. Psychopharmacol. Commun. 1, 285–293 (1975)
Stille, G., Lauener, H., Eichenberger, E.: The pharmacology of 8-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e] [1,4]diazepine (clozapine). Farmaco, Ed. prat. 26, 603–625 (1971)
Tamminga, C. A., Smith, R. C., Ericksen, S. E., Chang, S., Davis, J. M.: Cholinergic influences in tardive dyskinesia. Am. J. Psychiatry 134, 769–774 (1977)
Tarsy, D., Baldessarini, R. J.: Behavioural supersensitivity to apomorphine following chronic treatment with drugs which interfere with the synaptic function of catecholamines. Neuropharmacology 13, 927–940 (1974)
Tarsy, D., Baldessarini, R. J.: The tardive dyskinesia syndrome. In: Clinical neuropharmacology, vol. 1, (H. L. Klawans, ed.), pp. 29–61. New York: Raven 1976
Tarsy, D., Baldessarini, R. J.: The pathophysiologic basis of tardive dyskinesia. Biol. Psychiatry 12, 431–450 (1977)
Turek, I., Kurland, A. A., Hanlon, T. E., Bohm, M.: Tardive dyskinesia: its relation to neuroleptic and antiparkinson drugs. Br. J. Psychiatry 121, 605–612 (1972)
Webster, D. D.: Critical analysis of the disability in Parkinson's disease. Modern Treatment 5, 257–282 (1968)
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Gerlach, J., Simmelsgaard, H. Tardive dyskinesia during and following treatment with haloperidol, haloperidol + biperiden, thioridazine, and clozapine. Psychopharmacology 59, 105–112 (1978). https://doi.org/10.1007/BF00427742
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DOI: https://doi.org/10.1007/BF00427742