Clonidine trial in tardive dyskinesia. Therapeutic response, MHPG, and plasma DBH

The a2-adrenergic receptor agonist clonidine has a beneficial effect on tardive dyskinetic symptomatology (TDS), in the pathophysiology of which the involvement of noradrenergic mechanisms, among others, has been proposed. The authors investigated possible relationships between the therapeutic efficacy of clonidine in patients with tardive dyskinesia (TD) and concentrations in urine and plasma of the main noradrenaline (NA) metabolite methoxyhydroxyphenylglycol (MHPG), and of the NA biosynthetic enzyme dopamine-b-hydroxylase (DBH) in plasma. Clonidine was administered to twelve chronic schizophrenic patients with TDS in a double-blind, cross-over, single-dose trial. MHPG was measured in urine samples collected before and after administration. MHPG and DBH were also measured in plasma of blood samples taken three hours after administration. Ten patients then received clonidine in addition to neuroleptics for a period of two weeks. Clonidine caused significant amelioration in TDS both in the single-dose and the two-week trials. The degree of amelioration was, however, not correlated with the MHPG or DBH baseline values, or with the differences between placebo and drug in the single-dose trial.