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Objective: The study aimed to estimate 5-year recurrence rates of first-episode major depressive disorder (MDD) and assess the impact of adolescence on recurrence likelihood after the first episode, compared to adults.

Methods: A pre-registered retrospective cohort study that utilized epidemiological data from the Stockholm MDD Cohort (1997–2018), including all individuals registered with a depression diagnosis in Region Stockholm from 2010 to 2018. This dataset combines longitudinal information from primary and secondary care, socioeconomic data, drug dispensations, psychotherapy sessions, brain stimulation treatments, and inpatient treatment. The study included 9124 individuals (1727 adolescents aged 13–17 and 7397 adults aged 18–40) who experienced their first MDD episode between 2011 and 2012, with at least three months of remission. Propensity score weighting balanced cohorts for biological sex, socioeconomic status, depression severity, psychiatric comorbidities, and treatments.

Results: The 5-year recurrence rates were 46.1% for adolescents and 49.0% for adults. The study had over 80% power to detect a minimum absolute difference in recurrence rates of approximately 5.5 percentage points. No significant difference in recurrence likelihood (p = 0.364) or time from remission to recurrence (median 379 days for adolescents, 326 days for adults, p = 0.836) was found between groups. Findings were consistent across bootstrap replicates and sensitivity analyses with extended remission periods.

Conclusions: Approximately half of individuals with a first MDD episode experience recurrence within five years. Recurrence rates were higher than expected for adults but consistent with expectations for adolescents. The study underscores the need for relapse prevention from adolescence through adulthood and indicates a similar clinical course of MDD across age groups.