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Clinical and Biochemical Findings

Maureen Donnelly, MD; Judith L. Rapoport, MD; William Z. Potter, MD, PhD; Jerry Oliver; Cynthia S. Keysor; Dennis L. Murphy, MD

Arch Gen Psychiatry. 1989;46(3):205-212.

Abstract
• 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-methoxy4-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.

Author Affiliations
From the Child Psychiatry Branch (Drs Donnelly and Rapoport and Ms Keysor) and Laboratory of Clinical Science (Drs Potter and Murphy and Mr Oliver), National Institute of Mental Health, Bethesda, Md. Dr Donnelly is now with Georgetown University School of Medicine, Washington, DC.

Footnotes
Accepted for publication March 25, 1988.

Reprint requests to Child Psychiatry Branch, Bldg 10, Room 6N-240, NIMH, 9000 Rockville Pike, Bethesda, *MD 20892 (Dr Rapoport).

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