Abstract
Major depressive disorder (MDD) in adolescents is a significant public health concern. When left untreated, it can lead to poor academic performance, substance use, and a heightened risk of suicide. The U.S. Food and Drug Administration (FDA) issued a black box warning on selective serotonin reuptake inhibitors (SSRIs) for patients under 18 due to concerns about increased suicidality - a decision that remains debated given SSRIs' role as first-line treatment for depression and the inherent suicide risk of untreated MDD. This systematized literature review examined the current evidence on the association between SSRI use and suicidality in adolescents with MDD following the FDA black box warning. Following a comprehensive PubMed search, studies were selected using predefined inclusion and exclusion criteria. Eight studies were selected for further data extraction and synthesis. Overall, observational studies found a small but measurable increase in suicidal risk with SSRI use, particularly during the early treatment phase, highlighting the need for close monitoring. Two randomized controlled trials (RCTs) reported increased treatment-emergent suicidality with SSRI monotherapy compared to cognitive behavioral therapy (CBT) or combination therapy, while two other RCTs found no significant association. Across studies, combination therapy with SSRIs and CBT tended to yield better outcomes and lower rates of suicidality. Current evidence reveals that SSRI treatment in childhood and adolescent MDD is associated with a small but measurable increase in suicidality, particularly in early treatment, underscoring the need for close clinical monitoring and concurrent psychotherapy. Clinicians are encouraged to monitor closely for suicidality during early treatment and to carefully weigh the benefits of SSRIs against the risks of untreated depression.