Advances in the treatment of depression.

SUMMARY: Depression is a highly prevalent and disabling condition associated with significant morbidity and mortality. Currently available treatments for depression include tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, various atypical antidepressants, and electroconvulsive therapy. Although these treatments are effective, a significant number of patients do not respond or achieve sustained remission despite aggressive management. Advances in the neurobiology of depression have suggested a number of novel targets for antidepressant treatment. Based on an improved understanding of the neurobiology of depression, several novel pharmacologic and nonpharmacologic interventions are being developed. Pharmacologic developments include CRF antagonists, glucocorticoid receptor antagonists, substance P receptor antagonists, NMDA glutamate receptor antagonists, transdermal selegiline, so-called "triple" reuptake inhibitors, and augmentation of typical antidepressant medications with atypical antipsychotics. Nonpharmacologic advances have largely involved focal brain stimulation techniques including vagus nerve stimulation, transcranial magnetic stimulation, magnetic seizure therapy, and deep brain stimulation. For the most part, the data on these treatments are preliminary, and more study is needed to clarify their potential clinical benefit. However, it is clear that further study of the neurobiology of depression will continue to provide a rationale for developing innovative targets for antidepressant therapies.