Pharmacotherapy for the Treatment of Major Depressive Disorder in Late Life—A Narrative Review

This narrative review summarizes the evidence supporting the selection of a first-line, second-line, and third-line pharmacotherapy for major depressive disorder (MDD) in an older adult. Controlled trials support the short- and long-term efficacy of first-generation antidepressants, ie, monoamine oxidase inhibitors and tricyclic antidepressants, and of second-generation antidepressants, ie, selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Based on the strongest available evidence, guidelines, and expert opinion, the recommended first-line antidepressant is an SSRI, with a preference for sertraline; the recommended second-line antidepressants are the SNRIs duloxetine or venlafaxine XR; and the recommended third-line pharmacotherapy is augmentation of a second-line antidepressant with the atypical antipsychotic aripiprazole. Alternative choices for each of these agents (eg, escitalopram, vortioxetine, or bupropion augmentation) are supported by some weaker evidence. When this stepwise pharmacotherapy is combined with measurement-based care, one can expect MDD to remit in the vast majority of older patients.