OBJECTIVES. To determine the real-life incidence of treatment-resistant depression (TRD) in Spain, and their associated economic burden.

METHODS. A retrospective observational study was carried out using data from the BIG-PAC database^® (http://www.encepp.eu/encepp/viewResource.htm?id=29236). Patients with a depressive disorder (DD) diagnose, aged ≥ 18 years who initiated a new antidepressant treatment (AD; index date) during 2015-2017 were included in the study. Patient follow-up was 18 months. Patients were classified as: a) TRD, and b) non-TRD, based on the criteria defined by Cepeda et al. 2018 and Edwards et al. 2013. Variables of interest: epidemiological, demographic, comorbidity, antidepressants administered, resource use and healthcare direct and indirect costs (temporary and permanent occupational disability; mean/patient). Two sensitivity analyses were made varying the degree of temporality of TRD.

RESULTS. 21,630 DD patients aged ≥ 18 years (mean age: 53.2 years; female: 67.2%) were analyzed: 18,071 were non-TRD and 3,559 (16.5% [95% CI: 16%-17%]) were TRD patients. The population prevalence of TRD was 0.09% (95%CI: 0.07–0.11%). The annual incidence rate was 0.59, 1.02 and 1.18 per 1,000 person-years. Mortality was higher in TRD than in non-TRD patients (2.4% vs.1.3%; p<0.001), as were suicide attempts (4.5% vs 3.3%, p<0.001). The mean total cost per patient in 18 months were € 4,147.9. Costs were higher for TRD patients than for non-TRD patients (€ 5,878.8 vs. € 3,801.8; p<0.001; difference: € 2,077.0). Similar differences were found when comparing specific cost components: direct healthcare costs (€ 1,327.2 vs. € 625.5, p<0.001), costs due to loss of productivity (€ 1,148.5 vs. € 754.8; p<0.001) and to permanent disability (€ 3,403.1 vs. € 2,421.5; p<0.001). Sensitivity analyses showed similar results.

CONCLUSIONS. Treatment-resistant depression (TRD) is associated with a high increase of resource use and costs, especially indirect costs.