OBJECTIVES: To understand the association between timing of augmentation of antidepressants (AD) with antipsychotics (AP) and overall healthcare costs in patients with major depressive disorder (MDD) inadequately responding to first-line AD (Inadequate Responders).

METHODS: Using the Truven Health Analytics MarketScan® Medicaid, Commercial, and Medicare Supplemental databases (07/01/2009-12/31/2015), adult Inadequate Responders were identified if they had one of the following qualifying events indicating incomplete response to their initial AD treatment: psychiatric hospitalization or ED visit, initiating psychotherapy, or switching to or adding on a different AD. Two mutually exclusive cohorts were identified based on time from first qualifying event date to first date of augmentation with an AP (index date): ≤6 months (early add-on) and 7-12 months (late add-on). Patients were further required to be continuously enrolled 1 year before (baseline) and 1 year after (follow-up) the index date. Patients with schizophrenia or bipolar disorder diagnoses were excluded. General linear regression was used to estimate the adjusted healthcare cost in the early add-on cohort versus the late add-on cohort, controlling for demographic and clinical characteristics, insurance type, baseline medications, and baseline ED visits or hospitalizations.

RESULTS: Of the 6,935 identified Inadequate Responders meeting study criteria, 68.7% started an AP early and 31.3% late. At baseline, before AP augmentation, patients in the early add-on cohort had higher psychiatric comorbid disease burden (47.3% vs. 42.5%; p<0.001) and higher inpatient utilization [mean (SD) 0.41 (0.72) vs. 0.27 (0.67); p<0.001], compared to those in the late add-on cohort. During the 1-year follow-up, the adjusted total all-cause healthcare cost was significantly lower in the early add-on cohort than in the late add-on cohort ($18,864 vs. $20,452; p=0.046).

CONCLUSIONS: Findings of this real-world study suggest that, in patients with MDD who inadequately responded to first-line AD treatment, adding an AP earlier reduces overall healthcare costs.