Noradrenergic function and clinical outcome in antidepressant pharmacotherapy

Controversy remains regarding the role of noradrenergic systems in determin ing clinical response to antidepressant pharmacotherapy. Pineal gland produ ction of melatonin can serve as a physiologic index of noradrenergic functi on. The aim of this study was to examine the effects of antidepressant trea tment on 24-hour urinary excretion of the principle metabolite of melatonin , 6-sulfatoxymelatonin in treatment responders and nonresponders. Twenty-fo ur outpatients meeting DSM-III-R criteria for Major Depression received tre atment with either fluvoxamine or imipramine for 6 weeks while participatin g in a placebo-controlled double-blind clinical trial. Twenty-four hour exc retion of 6-sulfatoxymetaltonin was measured at baseline and at the conclus ion of the treatment trial. Changes in urinary excretion of 6-sulfatoxymela tonin distinguished antidepressant responders from nonresponders, with a si gnificant increase observed in the former group and a significant decrease in the latter. The degree of clinical response was correlated with the chan ge in 6-sulfatoxymelatonin excretion. These results suggest that enhanced n oradrenergic function may play an important role in determining clinical re sponse to antidepressant pharmacotherapy. (C) 2001 American College of Neur opsychopharmacology. Published by Elsevier Science Inc.