For the first-line treatment of major depressive disorder (MDD), physicians most commonly prescribe a selective serotonin reuptake inhibitor (SSRI), serotonin/norepinephrine reuptake inhibitor (SNRI), or bupropion (various brands and generics) within one year of a patient’s diagnosis. Most of the drugs in these classes are currently available as low-priced generics; Eli Lilly’s Cymbalta became generically available in early December 2013. Our quantitative analysis of patient-level claims data indicates that the patient shares of more recently launched antidepressants including Actavis’s (formerly Forest Laboratories’) Viibryd (vilazodone) among newly diagnosed MDD patients continue to be much lower than those of generic products in first- and even second-line therapy—demonstrating the increasing difficulty that new products are having penetrating the MDD market. As a result of this environment, marketers of MDD products have turned their attention to those patients who fail to respond adequately to first-line SSRIs and SNRIs. This patient population is substantial: More than 40% of newly diagnosed MDD patients move to a second-line therapy within the first year of diagnosis, according to our analysis, and more than one-half of these patients move to a third-line therapy in the first year, a trend that is consistent with the fact that patients are less likely to respond to a subsequent drug after each failed treatment attempt. These data highlight the market potential for therapies approved to treat MDD patients with an inadequate response to SSRIs and/or SNRIs, such as Bristol-Myers Squibb/Otsuka’s atypical antipsychotic Abilify (aripiprazole) and AstraZeneca’s Seroquel XR (quetiapine XR). Very recently-launched agents for MDD, which include Lundbeck/Takeda’s Brintellix (vortioxetine) and Actavis/Pierre Fabre’s Fetzima (levomilnacipran), will also compete for second-line share in patients who fail first-line SSRI/SNRI use, despite the lack of specific regulatory approval for this patient population. This report uses national patient-level claims data to explore the position of the leading maintenance therapies in the treatment of newly diagnosed MDD patients with a quantitative analysis of treatment patterns and share by line of therapy, as well as progression between lines, duration of treatment on each line, and use of concomitant treatment. The report also quantifies a drug’s source of business among recently treated MDD patients compared with its competitors and details which drugs precede others through an analysis of add-versus-switch patterns. Additional analyses explore persistency and compliance by brand.