Abstract
Modifications in serotonin and dopamine metabolism were evaluated in 13 children with autistic behavior and related to their responsiveness to fenfluramine treatment. A double-blind medication-placebo crossover design was used. Each patient received 1.5 mg/kg fenfluramine daily for 3 months followed and preceded by placebo for 1 month. Clinical improvement was observed in 6 children (responders). It included reduction of behavioral symptoms such as motor activity, anxiety, mood disturbances, and distractibility. Modifications of serotonin (5-HT), dopamine (DA), and DA metabolites [homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC)] were assessed at urinary levels. Responders and nonresponders showed a significant decrease of urinary 5-HT levels on fenfluramine. The main differences between the two groups of subjects were found with HVA, the major metabolite of DA. Fenfluramine significantly increased HVA levels in responders whereas no significant modification was found in nonresponders. Moreover the initial level of HVA (lower in responders) significantly differentiated the two groups. These results suggest that the clinical response to fenfluramine could be related to the dopaminergic action of this drug and that urinary DA metabolite levels could be considered as indicators of the responsiveness to fenfluramine treatment in children with autistic behavior.
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References
American Psychiatric Association. (1980).Diagnostic and statistical manual for mental disorders (3rd ed.). Washington, DC: Author.
Anderson, L. T., Campbell, M., Grega, D. M., Perry, R., Small, A. M., & Green, W. M. (1984). Haloperidol in the treatment of infantile autism: effects on learning and behavioral symptoms.American Journal of Psychiatry, 141, 1195–1202.
August, G. J., Raz, N., & Baird, T. D. (1985). Effects of fenfluramine on behavioral, cognitive and affective disturbances in autistic children.Journal of Autism and Developmental Disorders, 15, 97–107.
August, G. J., Raz, N., Papanicolaou, A. C., Baird, T. D., Hirsh, S. L., & Hsu, L. L. (1984). Fenfluramine treatment in infantile autism. Neurochemical, electrophysiological and behavioral effects.The Journal of Nervous and Mental Disease, 172, 604–612.
Barthélémy, C. (1986). Evaluations cliniques quantitatives en pédopsychiatrie.Neuropsychiatrie de l'Enfance, 34, 63–91.
Barthélémy, C., Bruneau, N., Cottet-Eymard, J. M., Jouve, J., Garreau, B., Lelord, G., Muh, J. P., & Peyrin, L. (1988). Urinary free and conjugated catecholamines and metabolies in autistic children.Journal of Autism and Developmental Disorders, 18, 583–591.
Barthélémy, C., Martineau, J., Jouve, J., Moraine, J. P., & Lejeune, J. (1987). Methodologies de'études thérapeutiques controlées (vitamine B6-Magnesium-Halopéridol-folatesfenfluramine) chez l'enfant autistique. In F. Gremy, S. Tomkiewicz, P. Ferrari, & G. Lelord (Eds.), Autisme infantile/Infantile autism. Colloque INSERM, Vol. 146, pp. 265–272.
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.
Bruneau, N., Barthélémy, C., Jouve, J., & Lelord, G. (1986). Frontal auditory-evoked potential augmenting-reducing and urinary homovanillic acid.Neuropsychobiology, 16, 78–84.
Cambell, M., Deutsch, S. I., Perry, R., Wolsky, B. B., & Palij, M. (1986). Short-term efficacy and safety of fentluramine in hospitalised preschol-age autistic children: An open study.Psychopharmacology Bulletin, 22, 141–147.
Du Verglas, G., Banks, S. R., & Guyer, K. E. (1988). Clinical effects of fenfluramine on children with autism: A review of the research.Journal of Autism and Developmental Disorders, 18, 297–308.
Garattini, S., Buczko, W., Jori, A., & Samanin. (1975). The mechanism of action of fenfluramine.Postgraduate Medical Journal, 51(Suppl. 1): 27–35.
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 autistics boys.New England Journal of Medicine, 307, 165–169.
Ho, H. H., Lockitch, G., Eaves, L., & Jacobson, B. (1986). Blood serotonin concentrations and fenfluramine therapy in autistic children.The Journal of Pediatrics, 108, 465–469.
Jouve, J., Martineau, J., Mariotte, N., Barthelemy, C., Muh, J. P., & Lelord, G. (1986). Determination of urinary serotonin using liquid chromatography with electrochemical detection.Journal of Chromatography, 378, 437–443.
Klykylo, W. M., Feldis, D., O'Grady, D., Ross, D. L., & Halloran, C. (1985). Brief report: Clinical effects of fenfluramine in ten autistic subjects.Journal of Autism and Developmental Disorders, 15, 417–423.
Martineau, J., Bruneau, N., Barthélémy, C., Garreau, B., Muh, J. P., & Lelord, G. (1987). Developmental changes in ERPs and monoamines metabolites in normal, mentally retarded and autistic children. In R. Johnson, Jr., J. W. Rohrbaugh, & R. Parasuraman (Eds.),Current trends in event-related potential research. (Supplement 40 toElectroencephalography and Clinical Neurophysiology) (1987), 609–616.
Muh, J. P., Barthélémy, C., Jouve, J., Martineau, J., Mariotte, N., & Bruneau, N. (1987). Les monoamines urinaires dans l'autisme de l'enfant. In F. Grémy, S. Tomkiewicz, P. Ferrari, & G. Lelord (Eds.),Autisme infantile/Infantile autism. Colloque INSERM, Vol. 146, pp. 129–136.
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.
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., Piggot, L., Realmuto, G., Stubbs, E. G., & Umansky, R. (1986). Fenfluramine therapy for autism: Promise and precaution.Psychopharmacology Bulletin, 22, 133–140.
Ritvo, E. R., Freeman, B. J., Yuwiler, A., Geller, E., Yokota, A., Schroth, P., & Novak, P. (1984). Study of fenfluramine in out patients with the syndrome of autism.The Journal of Pediatrics, 105, 823–828.
Stubbs, E. G., Budden, S. S., Jackson, R. H., Terdal, L. G., & Ritvo, E. R. (1986). Effects of fenfluramine on eight out patients with the syndrome of autism.Developmental Medicine and Child Neurology, 28, 229–235.
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This study was supported by CNRS (UA 596) “Biology and Neuropsychiatry,” INSERM 85-90-14, INSERM U 316, and Fondation Langlois. The authors thank the Servier Laboratory for supplying fenfluramine and placebo tablets, Ms. M. Barre and Ms. A. Lardeux for their technical assistance, and Ms. L. Crespin for the manuscript preparation.
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Barthelemy, C., Bruneau, N., Jouve, J. et al. Urinary dopamine metabolites as indicators of the responsiveness to fenfluramine treatment in children with autistic behavior. J Autism Dev Disord 19, 241–254 (1989). https://doi.org/10.1007/BF02211844
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DOI: https://doi.org/10.1007/BF02211844