Economic impact of treatment-resistant depression: A retrospective observational study

•Major depressive disorder it is one of the most common psychiatric diagnoses in the general population.•Lack of remission and treatment-resistant depression is associated with a worse quality of life, higher comorbidity, increased resource use, social and occupational disability and worse therapeutic outcomes.•The population-based Treatment-Resistant Depression incidence in Spain is 0.93/1000 person-years.•Treatment-Resistant Depression is associated with greater resource use and higher costs compared with non-TRD patients.•Comorbidity, cumulative mortality and suicide-related behaviors were also significantly higher in Treatment-Resistant Depression patients. To determine the incidence of Treatment-Resistant Depression (TRD) in Spain and to estimate its economic burden, using real world data. A retrospective, observational-study was carried out using data from the BIG-PAC database®. Patients aged ≥18 years with a diagnosis of major depressive-disorder (MDD) who initiated a new antidepressant treatment in 2015–2017 were included. The patients were classified as TRD and non-TRD. Patients were classified as TRD if they had, during the first year of antidepressant treatment: a) failure with ≥2 antidepressants including the prescription of ≥3 antidepressants (N06A) or ≥2 antidepressant and ≥1 antipsychotic (N05A; including lithium) b) antidepressants administered for ≥ 4 weeks each, and c) the time between the end of one treatment and the initiation of the next was ≤ 90 days. Inherent limitations of data collection from databases should also be considered in this analysis (e.g., lack of information about adherence to treatment). Follow-up period: 18 months. The incidence rate was calculated as the number of TRD patients per 1,000 persons-year divided by the population attended. Outcomes: direct healthcare and indirect costs. Two sensitivity analyses were performed varying the index date and the period used to define TRD patients (6 vs.12 months). 21,630 patients with MDD aged ≥ 18 years (mean age: 53.2 years; female: 67.2%) were analyzed, of whom 3,559 met TRD criteria, yielding a 3-year cumulative incidence of 16.5% (95%CI: 16%-17%) among MDD patients. The annual population incidence rate of TRD in 2015–2017, was 0.59, 1.02 and 1.18/1,000 person-years, respectively (mean: 0.93/1,000 person-year). Overall, mean total costs per MDD patient were €4,147.9, being higher for TRD than for non-TRD patients (€6,096 vs. €3,846; p