Fenfluramine and dextroamphetamine treatment of childhood hyperactivity. Clinical and biochemical findings.
Twenty boys (mean age, 9 +/- 2 years) with attention deficit disorder with hyperactivity received three weeks each of dextroamphetamine sulfate (0.5 mg/kg/d), fenfluramine hydrochloride (0.6 mg/kg/d increased to 2.0 mg/kg/d), and placebo in a double-blind, random-order, crossover design. Half the boys also met criteria for conduct disorder. Dextroamphetamine produced immediate and marked improvement in disruptive, overactive behaviors. Fenfluramine had no effect on any behavioral measure at either the low or high dosage. Both drugs decreased levels of urinary norepinephrine, 3-methoxy-4-hydroxyphenylglycol (MHPG), and vanillylmandelic acid. Fenfluramine, however, also produced a significant decrease in plasma MHPG levels and a larger decrease in urinary norepinephrine levels. It reduced urinary epinephrine levels as well, an effect opposite to that of dextroamphetamine. These findings suggest that different mechanisms of action are involved in the ability of the two drugs to reduce levels of MHPG and vanillylmandelic acid. Fenfluramine increased plasma prolactin levels and decreased platelet serotonin levels. Despite the structural similarity of the two drugs, some common overall effects on catecholamine metabolism, and similar effects on weight, fenfluramine had none of the motor activity or therapeutic effects of dextroamphetamine.
Donnelly
M
M
Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Md 20892.
Rapoport
J L
JL
Potter
W Z
WZ
Oliver
J
J
Keysor
C S
CS
Murphy
D L
DL
D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D001792:Blood Platelets / Q000032:analysis; D002648:Child; D002986:Clinical Trials as Topic; D003913:Dextroamphetamine / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005277:Fenfluramine / Q000494:pharmacology / Q000627:therapeutic use*; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D011388:Prolactin / Q000097:blood; D011569:Psychiatric Status Rating Scales; D012701:Serotonin / Q000097:blood / Q000378:metabolism; D013329:Structure-Activity Relationship; D014642:Vanilmandelic Acid / Q000378:metabolism
D005277:Fenfluramine; D012701:Serotonin; D008734:Methoxyhydroxyphenylglycol; D014642:Vanilmandelic Acid; D011388:Prolactin; D003913:Dextroamphetamine; D009638:Norepinephrine; D006719:Homovanillic Acid