Clinical characteristics of treatment-resistant depression in adults in Hungary: Real-world evidence from a 7-year-long retrospective data analysis

Fig 1. Schematic of patient inclusion and determination of TRD. The treatment pattern of patients was considered on three different levels. Individual prescriptions were compiled into drug use periods, which were then compiled into PTD episodes. Then, the whole follow-up period for patients was broken down stepwise to determine TRD. Step A–MDD patient identification: Patients are identified based on the inclusion and exclusion criteria. All patients with AD prescriptions in 2007 and 2008 are excluded. Step B–PTD identification: The PTD episodes needed to be identified as treatment failures were only considered within a single PTD episode. Step C–TRD determination: The failure of a treatment (corresponding to a drug use period) was evaluated at the start of the subsequent treatment (regardless of the previous treatment having ended or not). After the second failure was identified (within a PTD episode), the patient was identified to have TRD (up to the end of follow-up). AD, antidepressant; MDD, major depressive disorder; PTD, pharmaceutically treated depression; TRD, treatment-resistant depression.

Fig 2. Algorithm for treatment failure evaluation. The figure illustrates all the possible scenarios for evaluating of failure of a treatment (A). The evaluation occurs at the start of the next event [initiation of the next treatment (B) or hospitalisation in a psychiatric ward (H)]. The dashed line at the end of treatment A illustrates that the evaluation result was independent of whether treatment A was being received at this time point. X represents the number of days elapsed. The category of treatments (on a scale of 1–3) was determined based on the Hungarian reimbursement guidelines (see S7 Appendix in S3 File).

Fig 3. Number of new MDD and TRD cases by year. New MDD patients were identified at the patient’s first AD prescription (MDD index date). New patients with TRD were identified at the date of the second treatment failure within the same PTD (TRD index date). The same patient could have the MDD index date and TRD index date in different years. *Data for 2015 only available up to 31 August 2015. AD, antidepressant; PTD, pharmaceutically treated depression; MDD, major depressive disorder; TRD, treatment resistant depression.

Fig 4. Overall survival of TRD and non-TRD patients. Start: TRD index date for patients with TRD, “matched date” for non-TRD patients; event: death; censoring: at the study end (31 August 2015) or when matched non-TRD patients develop TRD. TRD, treatment-resistant depression.

Fig 5. Distribution of patients by the number of different treatment ingredients used throughout the whole study period. This analysis includes antidepressant and add-on therapies. Only the number of different treatment ingredients was counted, so a patient using the same treatment multiple times would only count as one treatment. The numbers are counted within the whole study period (and not within a single PTD episode). PTD, pharmaceutically treated depression.

Fig 6. Use of specific drug classes during the whole study period. Both antidepressant treatments and add-on therapies are included. A patient was considered to use a certain class of treatment if they had at least one prescription filled from the given class of treatment. Lithium is not included in the figure due to very low patient counts. ‘Other’ includes other antidepressant treatments not included in the classes stated. AANTIP, atypical antipsychotics; ANTIE, antiepileptics; BUSP, buspirone; MAOI, monoamine oxidase inhibitors; SNRI, serotonin-norepinephrine reuptake inhibitors; SSRI, selective serotonin reuptake inhibitors; T3/T4, thyroid therapy; TCA, tricyclic antidepressants.

Fig 7. Top 10 most frequently used antidepressant treatments during the whole study period for non-TRD and TRD patients. Treatments are presented in descending order by the frequency of patients with TRD using them. For patients with TRD, the antidepressants used also include those used prior to identification of TRD. TRD, treatment-resistant depression.