Amisulpride versus bromocriptine in infantile autism: A controlled crossover comparative study of two drugs with opposite effects on dopaminergic function

  • Sonia Dollfus
  • Michel Petit
  • Jean F. Menard
  • Philippe Lesieur
Article

Abstract

An alteration of dopaminergic (DA) function much more complex than simple hyperactivity has been evoked in infantile autism. We therefore compared the clinical efficacy of a DA antagonist (amisulpride) and a DA agonist (bromocriptine) in a randomized, double-blind, crossover trial in 9 children with autism, likely severely mentally retarded. Amisulpride acts preferentially on specific autistic symptoms whereas bromocriptine acts more on motor hyperactivity and attention symptoms. These findings raise the specificity of these two drugs which appear to act preferentially on some target symptoms and are consistent with some clinical and pharmacological observations showing a sedative effect with low doses of DA agonists and a stimulant effect with low doses of DA antagonists such as the benzamides.

Keywords

Opposite Effect Clinical Efficacy Bromocriptine Crossover Trial Benzamides 
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.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. American Psychiatric Association. (1980).Diagnostic and statistical manual of mental disorders (3rd ed.). Washington, DC: Author.Google Scholar
  2. Anderson, L. T., Campbell, M., Grega, D. M., Perry, R., Small, A. M., & Green, W. H. (1984). Haloperidol in the treatment of infantile autism. Effects on learning and behavioral symptoms.American Journal of Psychiatry, 141, 1195–1202.Google Scholar
  3. Barkley, R. A. (1977). A review of stimulant drug research with hyperactive children.Journal of Child Psychology and Psychiatry, 18, 137–165.Google Scholar
  4. Barthélémy, C., Adrien, J. L., Boiron, M., Colombel, P., Langella, B., & Dansart, P. (1986). Behavioral, psychological and biological evaluations in child psychiatry, methodological problems, therapeutic applications.Psychologie Médicale, 18(5), 1–695.Google Scholar
  5. Barthélémy, C., Adrien, J. L., Tanguay, P., Garreau, B., Fermanian, J., Roux, S., Sauvage, D., & Lelord, G. (1990). The behavioral summarized evaluation validity and reliability of a scale for the assessment of autistic behaviors.Journal of Autism and Developmental Disorders, 20, 189–204.Google Scholar
  6. Boyer, P., Puech, A. J., & Lecrubier, Y. (1988). Double blind trial versus placebo of low dose amisulpride (Solian 50) in schizophrenia with exclusively negative symptoms. Preliminary analysis of results.Annals of Psychiatry, 3(3 bis), 321–325.Google Scholar
  7. Burki, H. R., Asper, H., Ruch, W., & Züger, P. (1978). Bromocriptine dihydroergotoxine, methysergide, D-LSD, CF-25-397 and 29-712: Effects on the metabolism of the biogenic amines in the brain of the rat.Psychopharmacology, Vol., 57, 227–237.Google Scholar
  8. Campbell, M., Anderson, L. T., & Cohen, I. L. (1982). Haloperidol in autistic children, effects on learning behavior, and abnormal involuntary movements.Psychopharmacology Bulletin, 18, 110–112.Google Scholar
  9. Campbell, M. Anderson, L. T., Meir, M., Cohen, I. L., Small, A. M., Samit, C., & Sachar, E. J. (1978). A comparison of haloperidol and behavior therapy and their interaction in autistic children.Journal of the American Academy of Child Psychiatry, 17, 640–645.Google Scholar
  10. Campbell, M., Fish, B., Shapiro, T., & Floyd, A. (1972). Acute responses of schizophrenic children to a sedative and a “stimulating” neuroleptic. A pharmacologic yardstick.Current Therapeutic Research, 14, 759–766.Google Scholar
  11. Campbell, M., & Palij, M. (1985). Measurement of side effects including tardive dyskinesia.Psychopharmacology Bulletion, 21, 1063–1082.Google Scholar
  12. Campbell, M., Small, A. M., Collins, P. J., Friedman, E., David, R., & Genieser, N. (1976). Levodopa and levoamphetamine, a crossover study in young schizophrenic children.Current Therapeutic Research, 19, 70–86.Google Scholar
  13. Campbell, M., Small, A. M., Hollander, C. S., Korein, J., Cohen, I. L., Kalmijn, M., & Ferris, S. J. (1978). A controlled crossover study of triiodothyronine in autistic children.Journal of Autism and Childhood Schizophrenia, 8, 371–381.Google Scholar
  14. Clerc, G. (1989). Double blind study of amisulpride (Solian 50) in various dosages in patients with negative schizophrenic symptoms.Semaine des Hôpitaux de Paris, 65, 1079–1082.Google Scholar
  15. Cohen, D. J., Caparulo, B. K., Shaywitz, B. A., & Bowers, M. B. (1977). Dopamine and serotonin metabolism in neuropsychiatrically disturbed children.Archives of General Psychiatry, 34, 545–550.Google Scholar
  16. Cohen, I. L., Campbell, M., Posner, D., Small, A. M., Triebel, D., & Anderson, L. T. (1980). Behavioral effects of haloperidol in young autistic children.Journal of the American Academy of Child Psychiatry, 19, 665–677.Google Scholar
  17. Conners, C. K. (1973). Rating scales for use in drug studies with children.Psychopharmacology Bulletin (Special issue: Pharmacotherapy of children), 24–29.Google Scholar
  18. Colonna, L., Petit, M., & Lepine, J. P. (1979). Bromocriptine in affective disorders.Journal of Affective Disorders, 1, 173–177.Google Scholar
  19. Costentin, J., Dubuc, I., & Protais, P. (1973). Behavioral data suggesting the plurality of central dopamine receptors. In P. Mandel & F. DeFeudis, (Eds.),CNS receptors: From molecular pharmacology to behavior (p. 289). New York: Raven.Google Scholar
  20. Costentin, J., Petit, M., & Dollfus, S. (1987)Les neuroleptiques. PARIS: Ed. Ellipses.Google Scholar
  21. Damasio, A. R., & Maurer, R. G. (1978). A neurological model for childhood autism.Archives of Neurology, 35, 777–786.Google Scholar
  22. Di Chiara, G., Porceddu, M., Vargui, L., Steffanini, E., & Gessa, G. L. (1977). Evidence for selective and long-lasting stimulation of “regulatory” dopamine-receptors by bromocriptine (CB154).Naunyn Schmiedebergs Archivs fur Pharmacologie, 300, 239–245.Google Scholar
  23. Dollfus, S., & Petit, M. (1988).Efficacité et tolérance des psychotropes chez l'enfant. Paris: Ed. Expansion Scientifique Française.Google Scholar
  24. Faretra, G., Dooher, L. & Dowling, J. (1970). Comparison of haloperidol and fluphenazine in disturbed children.American Journal of Psychiatry, 126, 1670–1673.Google Scholar
  25. Gillberg, C., Svennerholm, L., & Hamilton-Hellberg, C. (1983). Childhood psychosis and monoamine metabolites in spinal fluid.Journal of Autism and Developmental Disorders, 13, 383–396.Google Scholar
  26. Jackson, D. M., Jenkins, O. F., & Ross, S. B. (1988). The motor effects of bromocriptine — A review.Psychopharmacology, 95, 433–446.Google Scholar
  27. Josserand, F., & Weber, F. (1988). Amsulpride (Solian 50): an energizing neuroleptic with prompt effectiveness against negative symptoms.Annals of Psychiatry, 3(3 bis), 306–311.Google Scholar
  28. Justin-Besancon, L., Thominet, M., Franceschini, J., Laville, C., Margarit, J., & Borenstein, P. (1978). Propriétés biologiques d'orthonisamides substitués à fonction 4 amine 5 alkyl sulfonc.Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences (Paris), 286, 1169–1170.Google Scholar
  29. Kavale, K. (1982). The efficacy of stimulant drug treatment for hyperactivity: A meta analysis.Journal of Learning Disabilities, 15, 280–289.Google Scholar
  30. Lecrubier, Y., & Douillet, P. (1983). Neuroleptics and the bipolar dopaminergic hypothesis of schizophrenia. In M. Ackenheil & N. Matussek (Eds.),Special aspects of psychopharmacology (pp. 375–385). Paris: Expansion Scientifique Française.Google Scholar
  31. Lelord, G., Callaway, E., Muh, J. P., Arlot, J. C., Sauvage, D., Garreau, B., & Domenech, J. (1978). L'acide homovanillique urinaire et ses modifications par injection de vit B6: Explorations fonctionnelles dans l'autisme de l'enfant.Revue Neurologique (Paris), 134, 797–801.Google Scholar
  32. Ludin, H. P., Ringwald, E., & Lorincz, P. (1978). Bromocriptine in Parkinson's disease.Lancet, 2, 578–579.Google Scholar
  33. Meltzer, H. Y., Kolakowska, T., Robertson, A., & Tricou, B. J. (1983). Effects of low dose bromocriptine in treatment of psychosis: the dopamine autoreceptor stimulation strategy.Psychopharmacology, 81, 37–49.Google Scholar
  34. Mikkelsen, E. J. (1982). Efficacity of neuroleptic medication in pervasive developmental disorders of childhood.Schizophrenia Bulletin, 8, 320–332.Google Scholar
  35. Minderaa, R. B., Anderson, G. M., Volkmar, F. R., Akkerhuis, G. W., & Cohen, D. J. (1989). Neurochemical study of dopamine functioning in autistic and normal subjects.Journal of the American Academy of Child and Adolescent Psychiatry, 28(12), 190–194.Google Scholar
  36. Petit, M., Zann, M., & Colonna, L. (1984). Antiautistic or desinhibitory effects of low dosages of sulpiride (versus high dosages): A controlled study in hebephrenic patients.Encéphale, 10, 25–28.Google Scholar
  37. Petit, M., Zann, M., Colonna, L., & Lesieur, P. (1987). The effect of sulpiride on negative symptoms of schizophrenia.British Journal of Psychiatry, 150, 270.Google Scholar
  38. Pichot, P., & Boyer, P. (1988a). A double blind controlled multicenter trial of low dose amisulpride (Solian 50) versus low dose fluphenazine in the treatment of negative symptoms in chronic schizophrenia.Annals of Psychiatry, 3(3 bis), 312–320.Google Scholar
  39. Pichot, P., & Boyer, P. (1988b). A double blind, controlled multicenter trial of amisulpride versus high dose haloperidol in an acute psychotic disorder.Annals of Psychiatry, 3(3 bis), 326–332.Google Scholar
  40. Post, R. M., Gerner, R. H., Carman, J. S., & Bunney, W. E. (1976). Effects of low doses of a dopamine receptor stimulation in mania.Lancet, 1, 203–204.Google Scholar
  41. Ritvo, E. P., Yuwiler, A., Geller, E., Kales, A., Raskins, S., Schico, A., Plotkin, S., Axelrod, R., & Howard, C. (1971). Effects of L. Dopa in autism.Journal of Autism and Childhood Schizophrenia, 1, 190–205.Google Scholar
  42. Schopler, E., Reichler, R. J., DeVellis, R. F., & Daly, K. (1980). Toward objective classification of childhood autism: Childhood Autism Rating Scale (CARS).Journal of Autism and Developmental Disorders, 10, 91–103.Google Scholar
  43. Schwartz, J. C., Delandre, M., Martres, M. P., Sokoloff, P., Protais, P., Vasse, M., Costentin, J., Laibe, P., Mann, A., Wermuth, C. G., Gulat, C., & Lafitte, A. (1984). Biochemical and behavioral identification of discriminant benzamide derivatives: New tools to differentiate subclasses of dopamine receptors.Neurology and Neurobiology, 8b, 59–72.Google Scholar
  44. Simon Soret, C., & Borenstein, P. (1987). Essai de la bromocriptine dans le traitement de l'austisme infantile.Presse Médicale, 16(26), 1286.Google Scholar
  45. Sokoloff, P., Giros, B., Martres, M. P., Bouthenet, M. L., & Schwartz, J. C. (1990). Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics.Nature, 347, 146–151.Google Scholar
  46. Sokoloff, P., Martres, M. P., Delandre, M., Schwartz, J. C., Protais, P., & Costentin, J. (1983). Two classes of dopamine receptors distinguishable by substituted benzamides. In M. Ackenheil and N. Matussek (Eds.),Special aspects of psychopharmacology (pp. 131–143). Paris: Expansion Scientifique Française.Google Scholar
  47. Sokoloff, P., Martres, M. P., Redouane, K., Schwartz, J. C., Protais, P., Vasse, M., Dubuc, I., Costentin, J., Hamdi, P., Mann, A., & Wermuth, C. G. (1987). Behavior and neurochemical profiles of discriminant benzamide derivatives.Psychiatry and Psychobiologie, 2, 253–264.Google Scholar
  48. Trabucchi, M., Andreoli, V. M., Frahola, L., & Spano, P. F. (1977). Pre and post synaptic action of bromocriptine: Its pharmacological effects in schizophrenia and neurological diseases.Advances in Biochemical Psychopharmacology, 16, 661–665.Google Scholar
  49. Van Kammen, D. P., Hommer, D. W., & Malas, K. L. (1987). Effect of pimozide on positive and negative symptoms in schizophrenic patients: Are negative symptoms state dependant?Neuropsychobiology, 18, 113–117.Google Scholar
  50. Vasse, M., Protais, P., Costentin, J., & Schwartz, J. C. (1985). Unexpected potentialisation by discriminant benzamide derivatives of stereotyped behaviours elicited by dopamine agonists in mice.Archives of Pharmacology, 329, 108–116.Google Scholar
  51. Winsberg, B. G., Sverd, J., Castell, S., Hurwie, M., & Perel, J. M. (1980). Estimation of monoamine and cyclic AMP turnover and aminoacid concentration of spinal fluid in autistic children.Neuropediatrics, 11, 250–261.Google Scholar

Copyright information

© Plenum Publishing Corporation 1992

Authors and Affiliations

  • Sonia Dollfus
    • 1
  • Michel Petit
    • 1
  • Jean F. Menard
    • 2
  • Philippe Lesieur
    • 3
  1. 1.Department of PsychiatryUniversity of RouenRouenFrance
  2. 2.Department of BiophysicsUniversity of RouenRouenFrance
  3. 3.Department of ResearchHospital of Sotteville Les RouenSotteville Les RouenFrance

Personalised recommendations