Twenty-one drug free patients fulfilling the DSM-111-R criteria for major depressive disorder were administered an alpha2 adrenoceptor challenge test. They were then treated with an antidepressant or ECT. Six weeks later, alpha2 function was again tested and found to be universally downregulated in treatment responders. Those who failed to respond to treatment (33%) had evidence of continuing alpha2 adrenoceptor activity. These results suggest central noradrenergic overactivity as a possible mechanism for depression, which runs counter to the classic catecholamine hypothesis.
