Effects of Fenfluramine on Eight Outpatients With the Syndrome of Autism

Abstract

SUMMARY Fenfluramine was administered to eight autistic outpatients in a double‐blind study to determine its effects on symptomatic behavior, developmental scores, blood serotonin levels and platelet counts. Two children benefited substantially according to academic and cognitive tests, parental and teacher reports and the principal investigator's clinical impressions. They also manifested behavioral and mood swings. The remaining six children showed varying degrees of response; one was withdrawn during the study by his parents. The greatest improvement occurred in children with an IQ above 40; the more severely retarded improved little, and primarily in the motor sphere. RÉSUMÉ Effets de la fenfluramine sur huit enfants autistiques La fenfluramine a été administerée a huit enfants autistiques vivant à domicile dans une étude en double aveugle pour déterminer les effets du produit sur le comportement symptomatique, les scores de développement, les taux de la sérotonine sanguine et le nombre de plaquettes. Deux enfants ont bénéficié significativement du traitement selon les tests scolaires et cognitifs, les rapports des parents et des professeurs, et les impressions cliniques du conducteur de I'étude. IIs ont montréégalement des variations de comportement et d'humeur. Les réponses furent varites chez les six autres enfants; l'un avait été retiré de I'ttude par ses parents. Les améliorations les plus marquées ont été observtes chez les enfants avec un QI de plus de 40; l'ameAlioration a été prédominante dans la sphére motrice pour les enfants présentant le retard mental le plus sévére. ZUSAMMENFASSUNG Die Wirkung von Fenfluramin bei acht ambulanten Patienten mit autistischem Syndrom Im Rahmen einer Doppelblindstudie wurden acht ambulante autistische Patienten mit Fenfluramin behandelt um festzustellen, welche Wirkung es auf das charakteristische Verhalten, die Entwicklungsscores, die Serotoninspiegel im Blut und die Thrombocytenzahlen hat. Zwei Kinder zeigten eine deutliche Besserung, was durch akademische und cognitive Tests, durch Berichte von Eltern und Lehrern und durch die klinischen Befunde des ersten Untersuchers belegt wurde. AuBerdem zeigten sie Verhaltens– und Stimmungswandlungen. Die restlichen sechs Kinder reagierten unterschiedlich; eins wurde wahrend der Studie von den Eltern herausgenommen. Die deutlichste Besserung wurde bei Kindern mit einem IQ iiber 40 festgestellt; die schwerer retardierten besserten sich hauptsachlich im motorischen Bereich. RESUMEN Efectos de la fenfluramina en ocho pacientes con autismo Se administerô Fenfluramina a ocho pacientes autisticos en vista de dispensario en un estudio doble ciego para determinar sus efectos sobre el comportamiento sintomitico, los puntajes de desarrollo, los niveles en sangre de serotonina y el contaje de plaquetas. Dos niños mejoraron de acuerdo con los tests cognitivos y académicos, los comentarios de los padres y de los maestros y las principales impresiones clinicas del investigador. Tambitn manifestaron vaivenes en el comportamiento y en el ...

Review Paper: Current Strategies in the Development of Anti-obesity Drugs and Their Safety Concerns

“…32, 51 However, other reports have shown that fenfluramine actually lowers blood 5HT and does not increase plasma 5HT in humans. 86, 123 5HT effects are mediated extracellularly through 5HT1B and 5HT2B receptors and intracellularly via cellular capture of 5HT through the 5HT uptake transporter (5HTT). 66 A reduction in 5HT uptake has been shown to produce increased concentrations of 5HT in the pulmonary vasculature, which might contribute to the pathogenesis of lung injury.…”

ELECTROPHYSIOLOGICAL EFFECTS OF FENFLURAMINE OR COMBINED VITAMIN B6 AND MAGNESIUM ON CHILDREN WITH AUTISTIC BEHAVIOUR

“…Our previous study reported global improvement in the behaviour of children sensitive to this treatment, with particular improvement in responsiveness to other people, communication, bizarre responses to the environment, and selfgenerated behaviour . In a subsequent study of 14 autistic children, significant improvements in sensory and motor behaviour were noted (Ritvo et al 1983), although other studies showed that fenfluramine does not ameliorate the symptoms of all patients (August et al 1984(August et al , 1985Klykylo et al 1985;Ho et al 1986;Stubbs et al 1986). In a subsequent study of 14 autistic children, significant improvements in sensory and motor behaviour were noted (Ritvo et al 1983), although other studies showed that fenfluramine does not ameliorate the symptoms of all patients (August et al 1984(August et al , 1985Klykylo et al 1985;Ho et al 1986;Stubbs et al 1986).…”

“…Geller et al (1982) reported that fenfluramine improved the IQ scores and some clinical signs of three autistic patients. In a subsequent study of 14 autistic children, significant improvements in sensory and motor behaviour were noted (Ritvo et al 1983), although other studies showed that fenfluramine does not ameliorate the symptoms of all patients (August et al 1984(August et al , 1985Klykylo et al 1985;Ho et al 1986;Stubbs et al 1986). A more recent study showed that some children also had improvement in behavioural signs such as motor activity, anxiety, mood difficulties and attention disturbances (Barthelemy et al 1988a).…”

Overview of current models and research.

“…For example, over the past 15 years a number of theoretical papers have emerged that have a common theme: The impact of the environment on development will depend on the nature of the organism on whom the environment impinges (e.g., Horowitz, 1987, Plomin et al, 1977Rutter, 1983;Thomas & Chess, 1976;Wachs, 1986). Within the biomedical literature, individual differences in reactivity to specific drugs are commonplace (Neims, 1986;Rapport, Stoner, DePaul, Birmingham, & Tucker, 1985;Stubbs, Budden, Jackson, Terdal, & Ritvo, 1986), as are individual differences in physiological reactivity to stress (Falkner & Rogonessi, 1986;Kasl & Cobb, 1970;Magnusson, 1988;Mason, 1968aMason, , 1968b and diet (Kawasaki, Delea, Barter, & Smith, 1978). At a behavioral level, for infrahuman populations, differential reactivity to objectively similar environments is seen as a function of species differences (Henderson, 1980;Hinde & Stevenson-Hinde, 1973), strain differences within species (Freedman, 1974;Fuller, 1967;Sackett, Rupenthal, Fahrenburch, Holm, & Greenough, 1981), or differences in nutritional history of the organism (Findley, Ng, Reid, & Armstrong, 1981;Weinberg, Dallman, & Levine, 1980).…”