OBJECTIVES: Major depressive disorder (MDD) contributes to a significant burden in the US, where it is the third leading cause of disability. For patients with MDD who benefit from anti-depressant therapies (ADTs), time to (and in) response or remission can vary greatly. Prior studies have indicated that those who experience response or remission earlier have better long-term MDD-related outcomes. This study sought to quantify the relationship between time to acute treatment-induced remission and the risk of relapse of MDD symptoms in the STAR*D trial (NCT00021528).

METHODS: The STAR*D dataset was analyzed to assess whether early remitters (i.e, patients experiencing remission ≤28 days following step start) exhibited reduced risk of a subsequent relapse during a 12-month naturalistic follow-up compared to late remitters (>28 days). A self-reported Quick Inventory of Depressive Symptomatology (QIDS-SR₁₆) score of ≤5 sustained until the end of any treatment step and a score of ≥11 during the 12-month follow-up defined remission and relapse, respectively. A hazard ratio quantifying the relationship between remission timing and risk of subsequent MDD relapse was estimated using Cox regression modeling, adjusted for patient’s age, treatment step, QIDS-SR₁₆ score at step start, and additional forward-selected demographic factors.

RESULTS: Among 1130 patients with MDD who achieved remission (n=231 early remitters; n=899 late remitters), a significantly greater proportion of late remitters (39.3%) relapsed during the 12-month follow-up phase compared to early remitters (24.7%, P<0.0001). Late remitters had a nearly 50% higher risk of relapse than early remitters during the 12-month follow-up phase (adjusted hazard ratio=1.48, P=0.01).

CONCLUSIONS: Patients in STAR*D who remitted earlier showed significantly reduced risk of relapse compared to those remitting later. These findings highlight the importance of quickly inducing remission– both for the immediate relief of symptoms and the improvement of long-term outcomes.