Fig. 1. Identification of overall cohort, exposure groups, cases and controls in the retrospective cohort study and nested case-control study.

All diagnoses were captured across all settings including outpatient, inpatient and emergency services.^aValid incident patients were patients older than 10 years old without records of depression from 1993 to the date of the first recorded depression diagnosis, and who did not die immediately after cohort entry.^bPrescription records of antidepressants between the date of first depression diagnosis and 31 December 2020 were extracted to define patients' TRD status. Antidepressant treatment regimens could be either monotherapy or combination therapies with antipsychotics and/or mood stabilisers. TRD treatment-resistant depression.