A register-based approach to identifying treatment-resistant depression—Comparison with clinical definitions

BACKGROUND: Several definitions of treatment-resistant depression (TRD) are used for clinical research, but no verified model for use in register data exists. We aimed to compare a novel model created for use in register data—the Karolinska Institutet Model (KIM)–to the clinical definitions regarding the proportion of patients identified with TRD, their characteristics and clinical outcomes. METHODS: All patients in Sweden initiating antidepressant treatment with a diagnosis of depression in specialized healthcare 2006–2014 were identified and followed in national registers. In KIM, patients who initiated a third sequential, >28-day antidepressant treatment trial were defined as having TRD. Proportion of TRD and patient characteristics were compared with register adaptations of the European Staging Model (ESM), Massachusetts General Hospital Staging Method (MGH-s), and Maudsley Staging Model (MSM). Differences in patient characteristics were assessed with Chi-square tests and one-way ANOVAs. Hazard ratios for psychiatric hospitalization and for death from external causes were estimated by Cox proportional hazard regressions. RESULTS: Out of 127,108 antidepressant initiators with depression, the highest proportion of TRD was found using the MGH-s (19.0%), followed by MSM (15.3%), KIM (12.9%), and ESM (9.5%). Clinical characteristics were similar across the models. Compared with TRD patients identified by KIM, those identified by ESM had a marginally higher risk for psychiatric hospitalization (adjusted hazard ratio [aHR] 1.03, 95%CI 1.00–1.05), whereas those identified by MGH-s (aHR 0.92; 0.90–0.94) and MSM (aHR 0.95; 0.94–0.97) had a slightly reduced risk. Patients identified by MGH-s showed a reduced mortality compared with KIM (aHR 0.84; 0.72–0.98). CONCLUSIONS: This study provides insight into the differing characteristics of patients captured by various TRD models when used for register research. Models yielding lower proportions of TRD seemed to identify patients with greater morbidity. The KIM may be useful for register based research in TRD.