Journal of Autism and Developmental Disorders

, Volume 19, Issue 4, pp 511–532 | Cite as

Fenfluramine treatment of twenty children with autism

  • Gunnar Ekman
  • Fredrika Miranda-Linné
  • Christopher Gillberg
  • Mats Garle
  • Lennart Wetterberg


The effects of fenfluramine were examined on 20 children with autism over a 48-week period utilizing a double-blind placebo-controlled crossover design. Blood and urine samples and psychological tests (Griffith's Developmental Scales and Real Life Rating Scale) were obtained at each crossover period. The only significant improvement was a decrease in abnormal motor behavior. We did not find any significant improvement in intellectual functioning or any correlation between good clinical response and low baseline serotonin levels or high baseline IQ. Serotonin decreased 53% after fenfluramine treatment and rebounded to a level 35% higher than baseline following a placebo period. Fenfluramine and the active metabolite norfenfluramine were determined in plasma samples.


Serotonin Crossover Design Fenfluramine Psychological Test Serotonin Level 
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  1. Alin-Åkerman, B., & Nordberg, L. (1980).Griffiths' utvecklingsskalor I och II. Stockholm: Psykologiförlaget AB.Google Scholar
  2. American Psychiatric Association. (1980).Diagnostic and statistical manual of mental disorders. (3rd ed.). Washington DC: Author.Google Scholar
  3. American Psychiatric Association. (1985).Draft DSM III-R in development (Work group to revise DSM-III). Washington, DC: Author.Google Scholar
  4. Anderson, G. M., Volkmar, F. R., Hoder, E. L., Paul, R., McPhedran, P., Minderaa, R. B., Young, J. G., Hansen, C. R., & Cohen, D. J. (1987). Whole blood serotonin in autistic and normal subjects.Journal of Child Psychology and Psychiatry, 28, 885–900.PubMedGoogle Scholar
  5. Anderson, L. T., Campbell, M., Grega, D. M., Perry, R., Small, A. M., & Green, W. H. (1984). Haloperidol in infantile autism: Effects on learning and behavioural symptoms.American Journal of Psychiatry, 141, 1195–1201.PubMedGoogle Scholar
  6. August, G. J., Raz, N., Papanicolaou, C., Baird, M. A., Hirsh, S., & Hsu, L. L. (1984). Fenfluramine treatment in infantile autism: Neurochemical, electrophysiological, and behavioral effects.Journal of Nervous and Mental Disease, 172, 604–612.PubMedGoogle Scholar
  7. August, G. J., Raz, N., & Baird, T. B. (1985). Effects of fenfluramine on behavioral, cognitive, and affective disturbances in autistic children.Journal of Autism and Developmental Disorders, 15, 97–106.PubMedGoogle Scholar
  8. Beeghly, J. H. L., Kuperman, S., Perry, P. J., Wright, G. J., & Tsai, L. Y. (1987). Fenfluramine treatment of autism: Relationship of treatment response to blood levels of fenfluramine and norfenfluramine.Journal of Autism and Developmental Disorders, 17, 541–548.PubMedGoogle Scholar
  9. Brownell, K. D., & Stunkard, A. J. (1982). The double-blind in danger: Untoward consequences of informed consent.American Journal of Psychiatry, 139, 1487–1489.PubMedGoogle Scholar
  10. Campbell, D. B. (1971). Plasma concentrations of fenfluramine and its metabolite, norfenfluramine after single and repeated oral administration.British Journal of Pharmacology, 43, 465–466.Google Scholar
  11. Campbell, D. B. (1973). Absorption, distribution, and metabolism of fenfluramine.La Vie Medicale au Canada Francais, 2, 34.PubMedGoogle Scholar
  12. Campbell, M., Friedman, E., Green, W. H., Collins P. J., Small, A. M., & Breuer, H. (1975). Blood serotonin in schizophrenic children. A preliminary study.International Pharmacopsychiatry, 10, 213–221.PubMedGoogle Scholar
  13. Campbell, M., Perry, R., Polonsky, B. B., Deutsch, S. I., Palij, M., & Lukashok, D. (1986). An open study of fenfluramine in hospitalized young autistic children.Journal of Autism and Developmental Disorders, 16, 495–505.PubMedGoogle Scholar
  14. 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.PubMedGoogle Scholar
  15. Freeman, B. J., Ritvo, E. R., Yokota, A., & Ritvo, A. (1986). A scale for rating symptoms of patients with the syndrome of autism of in real life settings.Journal of the American Academy of Child Psychiatry, 25, 130–136.PubMedGoogle Scholar
  16. Garattini, S., Buczko, W., Jori, A., & Samanin, R. (1975). The mechanism of action of fenfluramine.Postgraduate Medical Journal (Suppl. 1),51, 27–35.Google Scholar
  17. Geller, E., Ritvo, E. R., Freeman, B. J., & Yuwiler, A. (1982). Preliminary observations on the effect of fenfluramine on blood serotonin and symptoms in three autistic boys.New England Journal of Medicine, 307, 165.PubMedGoogle Scholar
  18. Gillberg, C., Wahlström, J., Johansson, R., Törnblom, M., & Albertsson-Wikland, K. (1986). Folic acid as an adjunct in the treatment of children with the autism Fragile-X syndrome (AFRAX).Developmental Medicine and Child Neurology, 28, 624–627.PubMedGoogle Scholar
  19. Goldstein, M., Mahanand, P., Lee, J., & Coleman, M. (1976). Dopamine-beta-hydroxylase and endogenous total 5-hydroxyindole levels in autistic patients and controls. In M. Coleman (Ed.),The autistic syndrome (pp. 57–63). Amsterdam: Elsevier/North Holland.Google Scholar
  20. Hanley, H. G., Stahl, S. M., & Freedman, D. X. (1977). Hyperserotonemia and amine metabolites in autistic and retarded children.Archives of General Psychiatry, 34, 521–531.PubMedGoogle Scholar
  21. Ho, H., Lockitch, G., Eaves, L., & Jacobson, B. (1986). Blood serotonim concentrations and fenfluramine therapy in autistic children.Pediatric Pharmacology and Therapeutics, 108, 465–469.Google Scholar
  22. Hoshino, Y., Kumashiro, H., & Kancko, M. (1979). Serum proteins, free tryptophan plasma cyclic AMP levels in autistic children.Fukushima Journal of Medical Science, 26, 79–91.PubMedGoogle Scholar
  23. Hoshino, Y., Yamamoto, T., Kaneko, M., Tachibana, R., Watanabe, M., Ono, Y., & Kumashiro, H. (1984). Blood serotonin and free tryptophan concentration in autistic children.Neuropsychobiology, 11, 22–27.PubMedGoogle Scholar
  24. Innes, J. A., Watson, M. L., Ford, M. J., Munro, J. F., Stoddart, M. E., & Campbell, D. B. (1977). Plasma fenfluramine levels, weight loss, and side effects.British Medical Journal, 2, 1322–1325.PubMedGoogle Scholar
  25. Klykylo, W. M., Feldis, D., O'Grady, D., Ross, D. L., & Halloran, C. (1985). Clinical effects of fenfluramine in ten autistic subjects.Journal of Autism and Developmental Disorders, 15, 417–423.PubMedGoogle Scholar
  26. Kohler, J. (1985). Is autism a biochemical abnormality?Communication, 19, 13.Google Scholar
  27. Krug, D. A., Arick, J., & Almond, P. (1980). Behavior checklist for identifying severely handicapped individuals with high levels of autistic behavior.Journal of Child Psychology and Psychiatry, 21, 221–229.PubMedGoogle Scholar
  28. Minderaa, R. B., Anderson, G. M., Volkmar, F. R., Akkerhuis, G. W., & Cohen, D. J. (1987). Urinary 5-hydroxyindoleactic acid and whole blood serotonin and tryptophan in autistic and normal subjects.Biological Psychiatry, 22, 933–940.PubMedGoogle Scholar
  29. Ritvo, E. R., & Freeman, B. J., (1978) National Society for Autistic Children definition of the syndrome of autism.Journal of Autism and Childhood Schizophrenia, 8, 162–169.PubMedGoogle Scholar
  30. Ritvo, E. R., Freeman, B. J., Geller, E., & Yuwiler, A. (1983). Effects of fenfluramine on 14 outpatients with the syndrome of autism.Journal of the American Academy of Child Psychiatry, 22, 549–558.PubMedGoogle Scholar
  31. Ritvo, E. R., Freeman, B. J., Yuwiler, A., Geller, E., Schroth, P., Yokota, A. Mason-Brothers, A., August, G. J., Klykylo, W., Leventhal, B., Lewis, K., Piggott, L., Realmuto, G., Stubbs, G., & Umansky, R. (1986). Fenfluramine treatment of autism: UCLA-collaborative study of 81 patients at nine medical centers.Psychopharmacology Bulletin, 22, 133–140.PubMedGoogle Scholar
  32. Ritvo, E. R., Freeman, B. J., Yuwiler, A., Geller, E., Yokota, A., Schroth, P., & Novak, P. (1984). Study of fenfluramine in outpatients with the syndrome of autism.Journal of Pediatrics, 105, 823–828.PubMedGoogle Scholar
  33. Ritvo, E. R., Rabin, K., Yuwiler, A., Freeman, B. J., & Geller, E. (1980). Biochemical and hematologic studies of children with the syndrome of autism, childhood schizophrenia, and related developmental disabilities: A critical review. In M. Rutter & E. Schopler (Eds.), Autism: A reappraisal of concepts (pp. 163–183). New York: Plenum Press.Google Scholar
  34. Ritvo, E. R., Yuwiler, A., Geller, E., Ornitz, E. M., Saeger, K., & Plotkin, S. (1970). Increased blood serotonin and platelets in early infantile autism.Archives of General Psychiatry, 23, 566–572.PubMedGoogle Scholar
  35. Ritvo, E. R., Yuwiler, A., Geller, E., Kales, A., Rashkis, S., Schicor, A., Plotkin, S., Axelrod, R., & Howard, C. (1971). Effects of L-dopa in autism.Journal of Autism and Childhood Schizophrenia, 1, 190–205.PubMedGoogle Scholar
  36. Rutter, M. (1978). Diagnosis and definition. In M. Rutter, & E. Schopler (Eds.),Autism: A reappraisal of concepts and treatment (pp. 1–25). London: Plenum Press.Google Scholar
  37. Schain, R. J., & Freedman, D. X. (1961). Studies on 5-hydroxyindole metabolism in autistic and other mentally retarded children.Journal of Pediatrics, 58, 315–320.PubMedGoogle Scholar
  38. Steffenburg, S., & Gillberg, C. (1986). Autism and autistic-like conditions: Swedish rural and urban areas: A population study.British Journal of Psychiatry, 149, 81–87.PubMedGoogle Scholar
  39. Stubbs, E. G., Budden, S. S., Jackson, R. H., Terdal, L. G., & Ritvo, E. R. (1986). Effects of fenfluramine on eight outpatients with the syndrome of autism.Developmental Medicine and Child Neurology, 28, 229–235.PubMedGoogle Scholar
  40. Swedish Central Bureau of Statistics. (1982).Swedish socioeconomic classification. Stockholm: Statistics Sweden.Google Scholar
  41. Takahashi, S., Kanai, H., & Miyamoto, Y. (1976). Reassessment of elevated serotonin levels in blood platelets in early infantile autism.Journal of Autism and Childhood Schizophrenia, 6, 317–326.PubMedGoogle Scholar
  42. Volkmar, F. R., Cicchetti, D. V., Dykens, E., Sparrow, S. S., Leckmen, J. F., & Cohen, D. J. (1988). An evaluation of the Autism Behavior Checklist.Journal of Autism and Developmental Disorders, 18, 81–97.PubMedGoogle Scholar
  43. Young, J. G., Kavanaugh, M. E., Anderson, G. M., Shaywitz, B. A., & Cohen, D. J. (1982). Clinical neurochemistry of autism and associated disorders.Journal of Autism and Developmental Disorders 12, 147–165.PubMedGoogle Scholar
  44. Yuwiler, A., Plotkin, S., Geller, E., & Ritvo, E. R. (1970). A rapid accurate procedure for the determination of serotonin in whole human blood.Biochemical Medicine, 3, 426–436.PubMedGoogle Scholar
  45. Yuwiler, A., Ritvo, E. R., Bald, D., Kipper, D., & Kipper, A. (1971). Examination of circadian rhythmicity of blood serotonin and platelets in autistic and non-autistic children.Journal of Autism and Childhood Schizophrenia, 1, 421–435.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1989

Authors and Affiliations

  • Gunnar Ekman
    • 1
  • Fredrika Miranda-Linné
    • 1
  • Christopher Gillberg
    • 2
  • Mats Garle
    • 3
  • Lennart Wetterberg
    • 1
  1. 1.Department of PsychiatryKarolinska InstituteStockholmSweden
  2. 2.Department of Child and Adolescent PsychiatryUniversity of GöteborgGöteborgSweden
  3. 3.Department of Clinical Pharmacology, Karolinska InstituteHuddinge HospitalHuddingeSweden

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