Major depressive disorder is highly prevalent, recurrent, and associated with inter-episodic dysfunction. Individuals with severe depression exhibit profound morbidity, co-morbidity, disability, cost, and mortality. Severe depression is a heterogeneous phenotype with a lack of standardized definition. The chronic and heterogeneous nature of severe depression results in a lower probability of spontaneous remission and often a chronic course. The complicated course of illness in severe depression results in frequent clinical visits and longer courses of therapy. Pharmacological treatment strategies for severe depression are selective serotonin reuptake inhibitors, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, norepinephrine-serotonin reuptake inhibitors, and monoamine oxidase inhibitors. These agents, alone and in various combinations, as well as psychosocial treatments, electroconvulsive therapy, transcranial magnetic stimulation, vagal nerve stimulation, and...

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