The Revised Monoamine Theory of Depression: A Modulatory Role for Monoamines, Based on New Findings From Monoamine Depletion Experiments in Humans

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Abstract
The original hypothesis that brain monoamine systems have a primary direct role in depression has been through several modifications during the past 30 years. In order to test this hypothesis and more fully characterize the role of serotonin and catecholamines in the pathophysiology of depression and the mechanism of action of antidepressant treatments, our research group has conducted a series of studies evaluating monoamine depletion induced brief clinical relapse following different types of antidepressant treatment of depressed patients. We have also studied the effects of monoamine depletion (SD) on depressive symptoms in depressed and recovered patients off medication and in healthy controls. Relapse to serotonin depletion or to catecholamine depletion (CD) was found to be specific to the type of antidepressant treatment, i.e., patients responding to selective serotonin reuptake inhibilitors relapsed more frequently following SD than CD and patients responding to selective catecholamine reuptake inhibitors relapsed more frequently following CD than SD. Neither CD or SD increased depressive symptoms in clinically ill patients off treatment, or produced clinical depression in normal controls. However, recovered patients with a prior history of depression had a relapse with SD. Patients with obsessive compulsive disorder who improved on SSRI treatment, did not have an increase in OCD symptoms but those with prior depressive symptoms did have an increase in depressive symptoms with SD.

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