CLINICAL AND NEUROCHEMICAL EFFECTS OF FENFLURAMINE IN CHILDREN WITH AUTISM

Fifteen children with autism were treated with 60 mg d,1-fenfluramine (FEN) or placebo in a double-blind A-B-A protocol followed immediately by double-blind placebo-controlled crossover administration of FEN (t otal duration 62 weeks). Both biochemical and clinical outcomes were e xamined. Biochemically, FEN led to an increase in dihydroxyphenylaceti c acid (DOPAC) and decreases in whole-blood serotonin (5-HT), plasma n orepinephrine (NE), and plasma 3-methoxy-4-hydroxyphenylglycol (MHPG). The decrease in whole-blood 5-HT was seen only during treatment with FEN. However, NE levels did wt return to baseline as long as 8 weeks a fter the first FEN treatment period. Increases in DOPAC were greater d uring the second FEN treatment period than the first. Persistent chang es in catecholamine regulation may be related to previously reported l ong-term effects on central nervous system 5-HT after FEN. Clinically, FEN led to a modest decrease in parent, but wt teacher, ratings of hy peractivity and to a small reduction in sensorimotor abnormalities. Ab normal social and affectual responses also decreased, but this was not directly related to FEN treatment. Effects on cognition were equivoca l. Hyperserotonemic subjects did not differ from normoserotonemic subj ects in clinical response. Overall, no significant advantage for the u se of FEN could be established.