, Volume 19, Issue 2, pp 241-254

Urinary dopamine metabolites as indicators of the responsiveness to fenfluramine treatment in children with autistic behavior

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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.

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.