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The mainstay of treatment for late-life depression is antidepressant medication, although recently there have been some psychotherapies that have been developed specifically for the older patient, e.g. problem solving therapy, that have proved effective. Although tricyclic antidepressants (TCAs) are used much less frequently in younger patients, they still have a very important role in the treatment of late-life depression. The selective serotonin reuptake inhibitors (SSRIs) are the most prescribed class of antidepressants for late-life depression. Given the number of patients with late-life depression who do not respond to a trial of an antidepressant there is considerable opportunity to study augmentation strategies. This chapter discusses dysthymic disorder and sub-syndromal depressive disorder, which is a heterogenous group of milder forms of depression. In patients with depression and cognitive impairment, there is a need to understand pathophysiology, determine early prognostic indicators, and develop optimal treatment strategies.