Noradrenergic function and clinical outcome in antidepressant pharmacotherapy

Controversy remains regarding the role of noradrenergic systems in determining clinical response to antidepressant pharmacotherapy. Pineal gland production of melatonin can serve as a physiologic index of noradrenergic function. The aim of this study was to examine the effects of antidepressant treatment on 24-hour urinary excretion of the principle metabolite of melatonin, 6-sulfatoxymelatonin in treatment responders and nonresponders. Twenty-four outpatients meeting DSM-III-R criteria for Major Depression received treatment with either fluvoxamine or imipramine for 6 weeks while participating in a placebo-controlled double-blind clinical trial. Twenty-four hour excretion of 6-sulfatoxymelatonin was measured at baseline and at the conclusion of the treatment trial. Changes in urinary excretion of 6-sulfatoxymelatonin distinguished antidepressant responders from nonresponders, with a significant increase observed in the former group and a significant decrease in the latter. The degree of clinical response was correlated with the change in 6-sulfatoxymelatonin excretion. These results suggest that enhanced noradrenergic function may play an important role in determining clinical response to antidepressant pharmacotherapy.