Acute and Chronic CLonidine Treatment in Tourette's Syndrome: A Preliminary Report on Clinical Response and Effect on Plasma and Urinary Catecholamine Metabolites, Growth Hormone, and Blood Pressure

Abstract

Tourette's syndrome (TS) is a chronic neuropsychiatric disorder of unknown etiology characterized by simple and complex motor and phonic symptoms and behavioral difficulties. Clonidine, an α 2-adrenergic receptor agonist, is useful in the treatment of TS. We report the preliminary results of a series of biological studies undertaken during an open 12-week clinical trial of oral clonidine (2–3 μg/kg/day) in six TS patients. These studies focus on the functional status of central noradrenergic and dopaminergic systems. Specifically, we report the effectgs of a single dose of clonidine (3 μg/kg) p.o., given under double-blind, placebo-controlled conditions, on plasma-free and urinary total 3-methoxy-4-hydroxyphenthyleneglycol (MHPG), plasma homovanillic acid (HVA), plasma human growth hormone (HGH), blood pressure, and sedation under baseline conditions, and after 12 weeks of clonidine therapy. The data do no clearly support the hypothesis that presynaptic noradrenergic receptors are subsensitive in TS or that chronic clonidine treatment increases their sensitivity. However, a significant increase in baseline HVA following chronic clonidine treatment was observed. These preliminary findings are suggestive of a central noradrenergic-dopaminergic interaction in TS. In addition, the clinical response data at 12 weeks, 10–12 months, and following double-blind, placebo-controlled withdrawal of clonidine are presented, and the usefulness of the pretreatment biological measures in predicting the clinical response to clonidine is assessed.