, Volume 56, Issue 2, pp 145–151

Effect of baclofen on tardive dyskinesia

  • J. Gerlach
  • T. Rye
  • P. Kristjansen


Eighteen chronic psychiatric patients with neuroleptic-induced tardive dyskinesia of 1/2–9 years duration participated in a double-blind crossover study on the effect and side effects of baclofen and placebo in the treatment of tardive dyskinesia. Each treatment phase lasted 3 weeks. Evaluation of the results included an assessment of video-tape recording. Baclofen (20–120 mg daily) reduced the hyperkinesias (median score from 5 to 3, P<0.05) and increased the parkinsonism (median score from 5 to 7, P<0.01). The effect on the oral movement pattern of tardive dyskinesia was characterized by a reduced frequency, an unchanged or slightly reduced amplitude, and an increased duration of each separate mouth opening and tongue protrusion, a response pattern very similar to the response pattern of α-methyl-p-tyrosine, an inhibitor of the catecholamine synthesis. Sedation, muscular weakness, and confusion were observed in 50% of the patients. These side effects, appearing mainly in elderly patients, sometimes set in before the anti-hyperkinetic effect, thus limiting the practical usefulness of baclofen in the treatment of tardive dyskinesia.

Key words

Tardive dyskinesia Parkinsonism Baclofen GABA 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. American College of Neuropsychopharmacology-Food and Drug Administration Task Force: Neurological syndromes associated with antipsychotic drug use. Arch. Gen. Psychiatry 28, 463–467 (1973)Google Scholar
  2. Andén, N. E., Dalén, P., Johansson, B.: Baclofen and lithium in Huntington's chorea. Lancet 1973II, 93Google Scholar
  3. Andén, N. E., Stock, G.: Inhibitory effect of gammahydroxybutyric acid and gammaaminobutyric acid on the dopamine cells in the substantia nigra. Naunyn Schmiedebergs Arch. Pharmacol. 297, 89–92 (1973)Google Scholar
  4. Andén, N. E., Wachtel, H.: Biochemical effects of baclofen (β-parachlorophenyl-GABA) on the dopamine and the noradrenaline in the rat brain. Acta Pharmacol. Toxicol. (Kbh.) 40, 310–320 (1977)Google Scholar
  5. Ayd, F. J., Jr.: Persistent dyskinesia: a neurologic complication of major tranquilizers. Med. Sci. 18, 32–40 (1967)Google Scholar
  6. Chase, T. N., Walters, J. R.: Pharmacologic approach to the manipulation of GABA mediated synaptic function man. In: GABA in nervous system function. E. Roberts and T. N. Chase, eds., pp. 497–513. New York: Raven Press 1976Google Scholar
  7. 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)Google Scholar
  8. Costall, B., Naylor, R. J., Pinder, R. M.: Mechanisms of dyskinesia in induction by 1-(3,4-dihydroxyphenyl) piperazine in the rat. Neuropharmacology 15, 203–210 (1976)Google Scholar
  9. Crane, G. E.: Tardive dyskinesia in patients treated with major neuroleptics: a review of the literature. Am. J. Psychiatry 124, 40–48 (1968)Google Scholar
  10. Crane, G. E.: Persistent dyskinesia. Br. J. Psychiatry 122, 395–405 (1973)Google Scholar
  11. Davis, K. L., Hollister, L. E., Berger, P. A.: Baclofen in schizophrenia. Lancet 1976I, 1245Google Scholar
  12. Fuxe, K., Hökfelt, T., Ljungdahl, Å, Agnati, L., Johansson, O., de la Mora, M.: Evidence for an inhibitory gabergic control of the meso-limbic dopamine neurons: possibility of improving treatment of schizophrenia by combined treatment with neuroleptics and gabergic drugs. Med. Biol. 53, 177–183 (1975)Google Scholar
  13. Gerlach, J., Reisby, N., Randrup, A.: Dopaminergic hypersensitivity and cholinergic hypofunction in the pathophysiology of tardive dyskinesia. Psychopharmacologia (Berl.) 34, 21–35 (1974)Google Scholar
  14. Gerlach, J., Thorsen, K.: The movement pattern of oral tardive dyskinesia in relation to anticholinergic and antidopaminergic treatment. Int. Pharmacopsychiatry 11, 1–7 (1976)Google Scholar
  15. Gulman, N. C., Bahr, B., Andersen, B., Eliassen, H. M.: A doubleblind trial of baclofen against placebo in the treatment of schizophrenia. Acta Psychiatr. Scand 54, 287–293 (1976)Google Scholar
  16. Hattori, T., McGeer, P. L., Fibiger, H. H., McGeer, E. G.: On the source of GABA-containing terminals in the substantia nigra. Electron microscopic autoradiographic and biochemical studies. Brain Res. 54, 103–114 (1973)Google Scholar
  17. Honigfeld, G., Klett, C. J.: The nurses' observation scale for inpatient evaluation. A new scale for measuring improvement in chronic schizophrenia. J. Clin. Psychol. 21, 65–71 (1965)Google Scholar
  18. Kazamatsuri, H., Chien, C-p., Cole, J. O.: Treatment of tardive dyskinesia. I. Clinical efficacy of a dopamine-depleting agent, tetrabenazine. Arch. Gen. Psychiatry 27, 95–99 (1972a)Google Scholar
  19. Kazamatsuri, H., Chien, C-p., Cole, J. O.: Treatment of tardive dyskinesia. II. Short-term efficacy of dopamine-blocking agents haloperidol and thiopropazate. Arch. Gen. Psychiatry 27, 100–103 (1972b)Google Scholar
  20. Korsgaard, S.: Baclofen (Lioresal®) in the treatment of neurolepticinduced tardive dyskinesia. Acta Psychiatr. Scand. 54, 17–24 (1976)Google Scholar
  21. Lahti, R. A., Losey, E. G.: Antagonism of the effects of chlorpromazine and morphine on dopamine metabolism by GABA. Res. Commun. Chem. Pathol. Pharmacol. 7, 31–40 (1974)Google Scholar
  22. Linnoila, M., Viukari, M., Hietala, O.: Effects of sodium valproate on tardive dyskinesia. Br. J. Psychiatry 129, 114–119 (1976)Google Scholar
  23. McKenzie, G. M., Viik, K.: Chemically induced choreiform activity: antagonism by GABA and EEG patterns. Exp. Neurol. 46, 229–243 (1975)Google Scholar
  24. Naik, S. R., Guidotto, A., Costa, E.: Central GABA receptor agonists: comparison of muscimol and baclofen. Neuropharmacology 15, 479–484 (1976)Google Scholar
  25. Overall, J. E., Gorham, D. R.: The brief psychiatric rating scale. Psychol. Rep. 10, 799–812 (1962)Google Scholar
  26. Perry, T. L., Hansen, S., Kloster, M.: Huntington's chorea: deficiency of γ-aminobutyric acid in brain. N. Engl. J. Med. 228, 337–342 (1973)Google Scholar
  27. Simpson, G. M., Branchey, M. H., Shrivastava, R. K.: Baclofen in schizophrenia. Lancet 1976I, 967–968Google Scholar
  28. Villeneuve, A., Böszörményi, Z: Treatment of drug-induced dyskinesias. Lancet 1970I, 353–354Google Scholar
  29. Walters, J. R., Roth, R. H., Aghajanian, G. K.: Dopaminergic neurons: similar biochemical and histochemical effects of gamma-hydroxybutyrate and acute lesions of the nigroneostriatal pathways. J. Pharmacol. Exp. Ther. 186, 630–639 (1973)Google Scholar
  30. Webster, D. D.: Critical analysis of the disability in Parkinson's disease. Mod. Treatment 5, 257–282 (1968)Google Scholar
  31. Wålinder, J., Skott, A., Carlsson, A., Roos, B.-E.: Potentiation by metyrosine of thioridazine effects in chronic schizophrenics. Arch. Gen. Psychiatry 33, 501–505 (1976)Google Scholar

Copyright information

© Springer-Verlag 1978

Authors and Affiliations

  • J. Gerlach
    • 1
  • T. Rye
    • 1
  • P. Kristjansen
    • 1
  1. 1.Dept. HSct. Hans HospitalRoskildeDenmark
  2. 2.Psychopharmacological Research LaboratorySct. Hans HospitalRoskildeDenmark

Personalised recommendations