Antidepressant mechanism of add-on repetitive transcranial magnetic stimulation in medication-resistant depression using cerebral glucose metabolism

Background: Add-on repetitive transcranial magnetic stimulation (rTMS) is effective in treating medication-resistant depression (MRD), but little is known about the rTMS antidepressant mechanism and pathophysiology underlying MRD. Methods: Twenty MRD patients received 2 weeks of navigated add-on rTMS to the left dorsolateral prefrontal cortex (DLPFC). Treatment response was defined as a >= 50% decrease in HDRS after treatment. Cerebral glucose metabolism was measured from all MRD patients twice, before and 3 months after rTMS, and from 20 healthy controls once at baseline. Results: At baseline, MRD subjects presented significant hypometabolism at the bilateral DLPFC and anterior cingulum, as well as hypermetabolism at several limbic and subcortical regions compared to the controls. Higher metabolism at the medial PFC and rostral anterior cingulum, and lower metabolism at the limbic structures, including the left parahippocampus and fusiform gyrus, predicted a response to rTMS. After successful rTMS treatment, the abnormally elevated metabolism in the left middle temporal cortex and fusiform gyrus decreased significantly, suggesting a reversal of metabolic imbalances. However, the overall metabolic pattern was still abnormal, even after their depression was under control. In contrast, the non-responders showed a worsening pattern of increased metabolism in the bilateral temporal cortex and fusiform gyrus. Conclusions: The antidepressant mechanism of add-on rTMS may be reflected as suppression of hyperactivity in the left temporal cortex and fusiforrn gyrus, perhaps through enhancing the function of the medial prefrontal cortex and anterior cingulum. The limbic-cortical dysregulation of glucose metabolism might be a trait of an underlying mechanism of MRD. (C) 2010 Elsevier B.V. All rights reserved.