Introduction
depressive disorder, depression, MDD, depressive symptoms
DISORDER
Major depressive disorder (MDD) is a mental health disorder associated with significant mortality, serious functional impairment, and reduced quality of life (QoL) [Standard-of-care (SOC) antidepressant therapies (ADTs), such as selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs), are efficacious but generally take weeks or months to improve depressive symptoms, which may lead to an increased risk of suicide and treatment discontinuation [In the pursuit for novel treatments, different mechanisms of depression are being investigated, particularly disruption in the balance between excitatory glutamate and inhibitory γ-aminobutyric acid (GABA) signaling [As part of the LANDSCAPE program, the ongoing phase 3 SHORELINE Study (NCT03864614; publication of a manuscript describing interim data currently under review) was designed to assess the safety and tolerability of an open-label, 14-day treatment course of zuranolone 30 or 50 mg, as well as the need for repeat treatment courses for up to 1 year. Interim results from SHORELINE showed that most treatment-emergent AEs (TEAEs) were mild or moderate, and ~80% of patients who responded to the first course of zuranolone 50 mg and continued beyond Day (D)28 received a total of 1 or 2 treatment courses through ≤1 year of follow-up [Understanding the potential of zuranolone to rapidly improve depressive symptoms, including when co-initiated with an ADT, is important, because previous literature shows that individuals with MDD who achieve early treatment responses are likely to achieve better outcomes than those who do not achieve an early response or who have lingering or unresolved symptoms [