Movement Disorders Induced by Psychotherapeutic Agents

Clinical Features, Pathophysiology, and Management
  • Daniel Tarsy
  • Ross J. Baldessarini


The antipsychotic drugs (APD) are a group of compounds that are effective in a wide variety of psychotic disorders, produce characteristic extrapyramidal syndromes in man, and profoundly affect muscle tone, posture, and movement of laboratory animals. Their effect on motor behavior led to their designation as “neuroleptic” drugs and distinguishes them from the sedative-hypnotics, anxiolytics, and other centrally active agents. Several classes of antipsychotic drugs have been developed, including phenothiazines, butyrophenones, diphenylbutylpiperidines, indolones, and dibenzoxazepines, as well as reserpine and its congeners. All produce similar, distinctive extrapyramidal syndromes, although reserpine has been associated with a more limited variety of neurological effects, and clozapine, a dibenzodiazepine, has a particularly low incidence of such effects. Early extrapyramidal effects (occurring within several hours or days to weeks) include acute dyskinesias (acute dystonias), parkinsonism, and akathisia (motor restlessness) and are quickly reversible with reduction or discontinuation of APD drug treatment. Tardive dyskinesia (TD) refers to involuntary movements which appear later (typically after at least 3 months) and are sometimes irreversible.


Tardive Dyskinesia Tourette Syndrome Neuroleptic Malignant Syndrome Malignant Hyperthermia Anticholinergic Drug 


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  1. Ambani, L. H., Van Woert, M. H., and Bowers, M. B. Jr., 1973, Physostigmine effects on phenothiazine-induced extrapyramidal reactions, Arch. Neurol. 29: 444–446.PubMedCrossRefGoogle Scholar
  2. Ayd, R. F. Jr., 1961, A survey of drug-induced extrapyramidal reactions, DAMA 175:102–108.Google Scholar
  3. Baldessarini, R. J., 1985, Clinical and epidemiological aspects of tardive dyskinesia, J. Clin. Psychiatry 46 (4, Sect. 2): 8–13.PubMedGoogle Scholar
  4. Baldessarini, R. J., Cole, J. O., Davis, J. M., Gardos, G., Preskorn, S. H., Simpson, G., and Tarsy, D., 1980, Tardive dyskinesia: Summary of a task force report of the American Psychiatric Association, Am. J. Psychiatry 137: 1163–1172.Google Scholar
  5. Baldessarini, R. J., Cohen, B. M., and Teicher, M. H., 1986, Pharmacologic treatment of psychoses with receptive agents, in: Treatment of Acute Psychosis: Current Concepts and Controversies ( S. T. Levy and P. T. Ninan, eds.), Jason Aronson, New York.Google Scholar
  6. Barany, S., Ingvast, A., and Gunne, L. M., 1979, Development of acute dystonia and tardive dyskinesia in Cebus monkeys, Res. Commun. Chem. Pathol. Pharmacol. 25: 269–279.Google Scholar
  7. Bobruff, A., Gardos, G., Tarsy, D., Rapkin, R. M., Cole, J. O., and Moore, P., 1981, Clonazepam and phenobarbital in tardive dyskinesia, Am. J., Psychiatry 138: 189–193.Google Scholar
  8. Borison, R. L., 1983, Amantadine in the management of extrapyramidal side effects, Clin. Neuropharmacol. 6 (Suppl. 1): S57 - S63.PubMedCrossRefGoogle Scholar
  9. Bruno, A., and Bruno, S. C., 1966, Effects of L-dopa on pharmacological parkinsonism, Acta Psychiatr. Scand. 42: 264.PubMedCrossRefGoogle Scholar
  10. Burke, R. E., Fahn, S., Mayeux, R., et al., 1981, Neuroleptic malignant syndrome caused by dopamine-depleting drugs, in a patient with Huntington’s disease, Neurology 31: 1022–1026.PubMedGoogle Scholar
  11. Burke, R. E., Fahn, S., Jankovic, J., Marsden, C. D., Lang, A. E., Gollomp, S., Ilson, J., 1982, Tardive dystonia: Late onset and persistent dystonia caused by antipsychotic drugs, Neurology 32: 1335–1346.PubMedGoogle Scholar
  12. Carman, J. S., 1972, Methylphenidate in akathisia, Lancet 2: 1093.PubMedCrossRefGoogle Scholar
  13. Caroff, S. N., 1980, The neuroleptic malignant syndrome, J. Clin. Psychiatry 41: 70–83.Google Scholar
  14. Caroff, S., Rosenberg, H., and Gerber, J. C., 1983, Neuroleptic malignant syndrome and malignant hyperthermia, J. Clin. Psychopharmacol. 3: 120–121.PubMedCrossRefGoogle Scholar
  15. Carter, C. J., and Pycock, C. J., 1978, Studies on the role of catecholamines in the frontal cortex, Br. J. Pharmacol. 42: 402 P.Google Scholar
  16. Casey, D., 1985, Clinical and laboratory studies of tardive dyskinesia, J. Clin. Psychiatry 46 (4, Sect. 2): 42–47.PubMedGoogle Scholar
  17. Chase, T. N., Schur, J. A., and Gordon, E. K., 1970, Cerebrospinal fluid monoamine catabolites in drug-induced extrapyramidal disorders, Neuropharmacology 9: 265–275.PubMedCrossRefGoogle Scholar
  18. Clow, A., Jenner, P., and Marsden, C. D., 1979, Changes in dopamine mediated behavior during one year’s neuroleptic administration, Eur. J. Pharmacol. 57: 365–375.PubMedCrossRefGoogle Scholar
  19. Cohen, B. M., Baldessarini, R. J., Pope, H. J., Jr., and Lipinski, J. F., Jr., 1985, Neuroleptic malignant syndrome, N. Engl. J. Med. 313: 1293.CrossRefGoogle Scholar
  20. Coons, D. J., Hillman, F. J., and Marshall, R. W., 1982, Treatment of neuroleptic malignant syndrome with dantrolene sodium: A case report, Am. J. Psychiatry 139: 944–945.PubMedGoogle Scholar
  21. Crane, G. E., 1973, Persistent dyskinesia, Br. J. Psychiatr. 122: 395–405.CrossRefGoogle Scholar
  22. Crow, T. J., Cross, A. J., Johnstone, E. C., Owen, F., Owens, D. G. C., and Waddington, J. L., 1982, Abnormal involuntary movements in schizophrenia: Are they related to the disease process or its treatment? Are they associated with changes in dopamine receptors? J. Clin. Psychopharmacol. 2: 336–340.PubMedCrossRefGoogle Scholar
  23. Delay, J., and Deniker, P., 1968, Drug-induced extrapyramidal syndromes, in: Diseases of the Basal Ganglia ( P. J. Vinken and G. W. Bruyn, eds.), pp. 248–266, North Holland, Amsterdam.Google Scholar
  24. DiMascio, A., and Demirgian, E., 1970, Antiparkinson drug overuse, Psychosomatics 11: 596–601.PubMedGoogle Scholar
  25. Faurbye, A., Rasch, P. J., Bender Petersen, P., Brandborg, G., and Pakkenberg, H., 1964, Neurological symptoms in pharmacotherapy of psychoses, Acta Psychiatr. Scand. 40: 10–27.PubMedCrossRefGoogle Scholar
  26. Gagrat, D., Hamilton, J., and Belmaker, R. H., 1978, Intravenous diazepam in the treatment of neuroleptic-induced acute dystonia and akathisia, Am. J. Psychiatry 135: 1232–1233.PubMedGoogle Scholar
  27. Gardos, G., Cole, J. O., and Tarsy, D., 1978, Withdrawal syndromes associated with antipsychotic drugs, Am. J. Psychiatry 135: 1321–1324.PubMedGoogle Scholar
  28. Garver, D. L., Davis, J. M., and Dekirmenjian, H., 1976, Pharmacokinetics of red blood cell phenothiazine and clinical effects, Arch. Gen. Psychiatry 33: 862–866.PubMedCrossRefGoogle Scholar
  29. Gelenberg, A. J., 1978, Amantadine in the treatment of benztropine-refractory extrapyramidal disorders induced by antipsychotic drugs, Curr. Ther. Res. 23: 375–380.Google Scholar
  30. Gelenberg, A., 1982, A proper role for antiparkinson drugs, Biol. Ther. Psychiatry 5: 10–11.Google Scholar
  31. Gelenberg, A. J., and Mandel, M. R., 1977, Catatonic reactions to high-potency neuroleptic drugs, Arch. Gen. Psychiatry 34: 947–950.PubMedCrossRefGoogle Scholar
  32. Gerlach, J., Reisby, N., and Randrup, A., 1974, Dopaminergic hypersensitivity and cholinergic hypofunction in the pathophysiology of tardive dyskinesia, Psychopharmacologia 34: 21–35.PubMedCrossRefGoogle Scholar
  33. Gessa, R., Tagliamonte, A., and Gessa, G. K., 1972, Blockade by apomorphine of haloperidolinduced dyskinesia in schizophrenic patients, Lancet 2: 981–982.PubMedCrossRefGoogle Scholar
  34. Granato, J. E., Stern, B. J., Ringel, A., et al., 1983, Neuroleptic malignant syndrome: Successful treatment with dantrolene and bromocriptine, Ann. Neurol. 14: 89–90.PubMedCrossRefGoogle Scholar
  35. Growdon, J. H., Hirsch, M. J., Wurtman, R. J., et al., 1977, Oral choline administration to patients with tardive dyskinesia, N. Eng. J. Med. 297: 524–527.CrossRefGoogle Scholar
  36. Henderson, V. W., and Wooten, G. F., 1981, Neuroleptic malignant syndrome: A pathogenetic role for dopamine receptor blockade? Neurology 31: 132–137.PubMedGoogle Scholar
  37. Homykiewicz, O., 1973, Parkinson’s disease: From brain homogenate to treatment, Fed. Proc. 32: 183–190.Google Scholar
  38. Jacobson, G., Baldessarini, R. J., and Manschreck, T., 1974, Tardive and withdrawal dyskinesia associated with haloperidol, Am. J. Psychiatry 131: 910–913.PubMedGoogle Scholar
  39. Jeste, D. V., and Wyatt, R. J., 1982, Understanding and Treating Tardive Dyskinesia, Guilford Press, New York.Google Scholar
  40. Kane, J. M., and Smith, J. M., 1982, Tardive dyskinesia. Prevalence and risk factors, 1959–1979, Arch. Gen. Psychiatry 39: 473–481.PubMedCrossRefGoogle Scholar
  41. Keepers, G. A., Clappison, V. J., and Casey, D. E., 1983, Initial anticholinergic prophylaxis for neuroleptic-induced extrapyramidal syndromes, Arch. Gen. Psychiatry 40: 1113–1117.PubMedCrossRefGoogle Scholar
  42. Klawans, H. L., Bergen, D., and Bruyn, G. W., 1973, Prolonged drug-induced parkinsonism, Confin. Neurol. 35: 368–377.PubMedCrossRefGoogle Scholar
  43. Klawans, H. K., Falk, D. K., Nausieda, P. A., and Weiner, W. J., 1978, Gilles de la Tourette syndrome after long-term chlorpromazine therapy, Neurology 28: 1064–1068.PubMedGoogle Scholar
  44. Kolbe, H., Clow, A., Jenner, P., and Marsden, C. D., 1981, Neuroleptic-induced acute dystonic reactions may be due to enhanced dopamine release on to supersensitive postsynaptic receptors, Neurology 31: 434–439.PubMedGoogle Scholar
  45. Korczyn, A. D., and Goldberg, G. J., 1972, Intravenous diazepam in drug-induced dystonic reactions, Br. J. Psychiatry 121: 75–77.PubMedCrossRefGoogle Scholar
  46. Korczyn, A. D., and Goldberg, G. J., 1976, Extrapyramidal effects of neuroleptics, J. Neurol. Neurosurg. Psychiatry 39: 866–869.PubMedCrossRefGoogle Scholar
  47. Liebman, J., and Meale, R., 1980, Neuroleptic-induced acute dyskinesias in squirrel monkeys: Correlation with propensity to cause extrapyramidal side effects, Psychopharmacology 68: 2529.CrossRefGoogle Scholar
  48. Lipinski, J. F., Zubenko, G. S., Barreira, P., and Cohen, B. M., 1983, Propranolol in the treatment of neuroleptic-induced akathisia, Lancet 2: 685–686.PubMedCrossRefGoogle Scholar
  49. Lipinski, J. F., Zubenko, G., Cohen, B. M., and Barreira, P., 1984, Propranolol in the treatment of neuroleptic-induced akathisia, Am. J. Psychiatry 141: 412–415.PubMedGoogle Scholar
  50. Lotstra, F., Linkowski, P., and Mendlewicz, J., 1983, General anesthesia after neuroleptic malignant syndrome, Biol. Psychiatry 18: 243–247.PubMedGoogle Scholar
  51. Manos, N., Gziouzepas, J., and Logothetis, J., 1981, The need for continuous use of antiparkinsonian medication with chronic schizophrenic patients receiving long-term neuroleptic therapy, Am. J. Psychiatry 138: 184–188.PubMedGoogle Scholar
  52. Marsden, C.D., and Jenner, P., 1980, The pathophysiology of extrapyramidal side-effects of neu-roleptic drugs, Psychol. Med. 10: 55–72.PubMedCrossRefGoogle Scholar
  53. Marsden, C. D., Tarsy, D., and Baldessarini, R. J., 1975, Spontaneous and drug-induced movement disorders in psychotic patients, in: Psychiatric Aspects of Neurologic Disease ( D. F. Benson and D. Blumer, eds.), pp. 219–266, Grune & Stratton, New York.Google Scholar
  54. Matthysse, S., 1973, Antipsychotic drug actions: A clue to the neuropathology of schizophrenia? Fed. Proc. 32: 200–205.PubMedGoogle Scholar
  55. McGeer, P. L., and McGeer, E. G., 1977, Aging and extrapyramidal function, Arch. Neurol. 34: 33–35.PubMedCrossRefGoogle Scholar
  56. Meldrum, B. S., Anlezark, G. M., and Marsden, C. D., 1977, Acute dystonia as an idiosyncratic response to neuroleptics in baboons, Brain 100: 313–336.PubMedCrossRefGoogle Scholar
  57. Meltzer, H. Y., 1973, Rigidity, hyperpyrexia and coma following fluphenazine enanthate, Psychopharmacologia 29: 337–346.PubMedCrossRefGoogle Scholar
  58. Mizrahi, E. M., Holtzman, D., and Tharp, B., 1980, Haloperidol-induced tardive dyskinesia in a child with Gilles de la Tourette’s disease, Arch. Neurol. 37: 780.PubMedCrossRefGoogle Scholar
  59. Nybäck, H., Schubert, J., and Sedvall, G., 1970, Effect of apomorphine and pimozide on synthesis and turnover of labelled catecholamines in mouse brain, J. Pharm. Pharmacol. 10: 622–624.CrossRefGoogle Scholar
  60. Owens, D. G. C., Johnstone, E. C., and Frith, C. D., 1982, Spontaneous involuntary disorders of movement, Arch. Gen. Psychiatry 39: 452–461.PubMedCrossRefGoogle Scholar
  61. Polizos, P., Engelhardt, D. M., Hoffman, S. P., and Waizer, K., 1973, Neurological consequences of psychotropic drug withdrawal in schizophrenic children, J. Autism Child. Schizophrenia 3: 247–253.CrossRefGoogle Scholar
  62. Reches, A., Burke, R. E., Kuhn, C., Hassan, M., Jackson, V., and Fahn, S., 1982, Tetrabenazine blocks dopaminergic receptors in rat brain, Ann. Neurol. 12: 94.CrossRefGoogle Scholar
  63. Regestein, Q. R., Alpert, J. S., and Reich, P., 1977, Sudden catatonic stupor with disastrous outcome, JAMA 238: 618–620.PubMedCrossRefGoogle Scholar
  64. Rifkin, A., Quitkin, F., and Klein, D. F., 1975, Akinesia: A poorly recognized drug-induced extrapyramidal behavioral disorder, Arch. Gen. Psychiatry 32: 672–674.CrossRefGoogle Scholar
  65. Sarwer-Foner, G. J., 1960, Recognition and management of drug-induced extrapyramidal reactions and “paradoxical” behavioral reactions in psychiatry, Can. Med. Assoc. J. 83: 312–318.PubMedGoogle Scholar
  66. Schooler, N. R., and Kane, J. M., 1982, Research diagnoses for tardive dyskinesia, Arch. Gen. Psychiatry 39: 486–487.Google Scholar
  67. Sigwald, J., Bouttier, D., Raymondeaud, C., and Piot, C., 1959, Quatre cas de dyskinésie faciobucco-linguo-masticatrice à evolution prolongée secondaire à un traitement par les neuroleptiques, Rev. Neurol. 100: 751–755.PubMedGoogle Scholar
  68. Simpson, G. M., and Kunz-Bartholini, E., 1968, Relationship of individual tolerance, behavior, and phenothiazine produced extrapyramidal system disturbance, Dis. Nerv. Syst. 29: 269–274.PubMedGoogle Scholar
  69. Skirboll, L. R., Grace, A. A., and Bunney, B. S., 1979, Dopamine auto and postsynaptic receptors: Electro-physiological evidence for differential sensitivity to dopamine agonists, Science 206: 80–82.PubMedCrossRefGoogle Scholar
  70. Smego, R. A., and Durack, D. T., 1982, The neuroleptic malignant syndrome, Arch. Intern. Med. 142: 1183–1185.PubMedCrossRefGoogle Scholar
  71. Smith, J. M., and Baldessarini, R. J., 1980, Changes in prevalence, severity, and recovery in tardive dyskinesia with age, Arch. Gen. Psychiatry 37: 1368–1373.PubMedCrossRefGoogle Scholar
  72. Tamminga, C. A., Crayton, J. W., and Chase, T. N., 1979, Improvement in tardive dyskinesia after muscimol therapy, Arch. Gen. Psychiatry 36: 595–598.PubMedCrossRefGoogle Scholar
  73. Tarsy, D., 1983, History and definition of tardive dyskinesia, Clin. Neuropharmacol. 6: 91–100.CrossRefGoogle Scholar
  74. Tarsy, D., and Baldessarini, R. J., 1974, Behavioral supersensitivity to apomorphine following chronic treatment with drugs which interfere with the synaptic function of catecholamines, Neuropharmacology 13: 927–940.PubMedCrossRefGoogle Scholar
  75. Tarsy, D., and Baldessarini, R. J., 1984, Tardive dyskinesia, Ann. Rev. Med. 35: 605–623.PubMedCrossRefGoogle Scholar
  76. Tarsy, D., and Bralower, N., 1977, Tardive dyskinesia in young adults, Am. J. Psychiatry 134: 1032–1034.PubMedGoogle Scholar
  77. Tolosa, E. S., 1981, Clinical features of Meige’s disease (idiopathic orofacial dystonia), Arch. Neurol. 38: 147–151.PubMedCrossRefGoogle Scholar
  78. Toni, N., Matsuda, O., Makiguch, K., et al., 1981. Neuroleptic malignant syndromelike state following a withdrawal of antiparkinsonian drugs, J. Nerv. Ment. Dis. 169: 324–327.CrossRefGoogle Scholar
  79. Van Praag, H. M., and Korf, J., 1976, Importance of dopamine metabolism for clinical effects and side effects of neuroleptics, Am. J. Psychiatry 133: 1171–1176.PubMedGoogle Scholar
  80. Van Putten, T., 1975, The many faces of akathisia, Compr. Psychiatry 16: 43–47.PubMedCrossRefGoogle Scholar
  81. Willner, H., and Nagakawa, M., 1983, Controversies in malignant hyperthermia, Semin. Neurol. 3: 275–282.CrossRefGoogle Scholar
  82. Wolf, M. E., and Koller, W. C., 1984, Tardive dystonia: Controlled study of trihexyphenidyl treatment, Neurology 34 (Suppl. 1): 129.Google Scholar
  83. Zubenko, G. S., Lipinski, J. F., Cohen, B. M., and Barreira, P. J., 1984, Comparison of metoprolol and propranolol in the treatment of akathisia, Psychiatry Res. 11: 143–149.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1986

Authors and Affiliations

  • Daniel Tarsy
    • 1
  • Ross J. Baldessarini
    • 2
  1. 1.Department of Neurology, Boston University and Harvard Medical School, Neurology SectionNew England Deaconess HospitalBostonUSA
  2. 2.Department of Psychiatry and Neuroscience Program, Harvard Medical School and Massachusetts General Hospital, Mailman Research CenterMcLean HospitalBelmontUSA

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