BackgroundTreatment resistant depression (TRD) is a burdensome condition with a severe impact on patients’ everyday lives. Therapeutics have improved in the last decade, however, outcomes remain poor. Real-world characterization has become increasingly important to accurately depict the clinical setting. ResisToday was an observational, prospective, multicenter study that aimed to increase available real-world evidence by evaluating clinical and socio-demographics, treatment patterns and clinical and patient-reported outcomes (PROs) of patients with TRD in Portugal.MethodsPatients with a clinical diagnosis of TRD and moderate to severe depression (Montgomery-Åsberg Depression Rating Scale [MADRS] score ≥22), who were initiating a new treatment for TRD could enroll in ResisToday. Clinical outcomes were evaluated using the MADRS and the Clinical Global Impression-Severity scale (CGI-S). PROs were reported using the Patient Health Questionnaire-9 (PHQ-9) and EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire. Outcomes were assessed at baseline, Week 4 (primary endpoint) and Week 20.ResultsOf 153 patients, 123 (80.4%) were female and the mean age was 53.9 years. The mean age of onset of clinical depression symptoms was 38.0 years, and the mean time since diagnosis of major depressive disorder (MDD) was 11.8 years. TRD treatments initiated at baseline were varied; the most common treatments initiated or ongoing at baseline were mirtazapine (43.1%), venlafaxine (42.5%), quetiapine (25.5%), and trazodone (20.9%). Most patients’ antidepressant treatment was augmented with an antipsychotic (36.6%), combined with additional antidepressants (22.2%), or combined with another augmentation strategy (19.0%). Improvements in MADRS were observed from baseline to Week 4 and Week 20 (both p<0.001). Clinical response and remission, assessed by MADRS, were achieved by 14.9% and 3.1% of patients, respectively, at Week 4, and 40.5% and 25.3% at Week 20. Improvements were observed across CGI-S, PHQ-9, and EQ-5D-5L measures through Week 20 (all p<0.001).ConclusionsOutcomes for patients with TRD in real-world clinical practice remain poor, with most patients not responding after 20 weeks of treatment. Treatment heterogeneity highlights a lack of clinical consensus, and the need for novel therapeutics and improved treatment protocols for TRD in real-world clinical practice in Portugal.