BackgroundThis naturalistic follow-up study examines outcomes for youth with depression (n = 25) or subsyndromal bipolar disorder (n = 13) 2–5 years after participation in randomized clinical trials (RCTs) of omega-3 fatty acids (Ω3), individual family psychoeducational psychotherapy (IF-PEP), and their combination MethodsForty percent (38/95) of RCT families completed a follow-up assessment ResultsRelapse rates and conversion to bipolar disorder were consistent with published literature. Original treatment assignment did not impact current functioning. Overall, participants’ mood severity, executive functioning, and global functioning continued to be better than at RCT baseline. Depressive symptoms increased significantly from end of RCT. Manic symptom severity, executive functioning, and global functioning remained comparable to end of RCT. The majority of parents and youth reported improved youth emotion regulation skills and family communication. They considered study participation beneficial, with increased understanding of mood disorders being the top reason. Half of youth commenced or continued Ω3 and 58% commenced or continued psychotherapy post-RCT, suggesting some degree of consumer satisfaction; these youth had lower depression severity than other participants. LimitationsOnly 40% returned to this naturalistic follow-up; they were less likely to have an African-American parent, were of higher income, and youth were more symptomatic at end of RCT than those who did not return ConclusionsImprovement from RCT baseline continued although depressive symptom severity increased from end of RCT to follow-up. Meaningful improvements in youth and family functioning persisted 2–5 years later. Interventions that prevent relapse or conversion to BPSD are still needed for these vulnerable populations.