Clinical Features and Outcomes of 124 Italian Patients With Treatment Resistant Depression: A Real-World, Prospective Study

Abstract

Introduction: Treatment-resistant depression (TRD) is a debilitating condition affecting 20–30% of patients with major depressive disorders (MDD). Currently, there is no established standard of care for TRD, and wide variation in the clinical approach for disease management has been documented. Real-world data could help describe TRD clinical features, disease burden, and treatment outcome and identify a potential unmet medical need.Methods: We analyzed the Italian data from a European, prospective, multicentric, observational cohort study of patients fulfilling TRD criteria by the European Medicine Agency, with moderate to severe major depressive episode, and starting a new antidepressant treatment according to routinary clinical practice. They were followed up for minimum 6 months. Treatments received throughout the study period, disease severity, health-related quality of life and functioning were prospectively recorded and analyzed.Results: The Italian subcohort included 124 TRD patients (30.2% of patients of the European cohort; mean age 53.2 [sd = 9.8], women: 82, 66.1%). At enrollement, the mean (SD) duration of MDD was 16 years (sd = 11.1) and the mean duration of the ongoing major depressive episode (MDE) was 97.5 weeks (sd = 143.5); low scores of quality of life and functioning were reported. The most frequently antidepressant classes started at baseline (data available for 98 subjects) were selective serotonin reuptake inhibitors (SSRI, 42 patients [42.9%]) and serotonin-norepinephrine reuptake inhibitors (SNRI, 32 patients [32.7%]). In terms of treatment strategies, 50 patients (51%) started augmentation therapies, 18 (18.4%) combination therapies and 24 (24.5%) monoterapies (6 patients [6%] started a non-antidepressant drug only). Fourteen patients (11.3%) were treated with a psychosocial approach, including psychotherapy. After 6 months of treatment, clinical assessments were collected for 89 patients: 64 (71.9%) showed no response, 9 (10.1%) response without remission and 16 (18.0%) were in remission; non-responder patients showed lower quality of life and higher disability scores than responder patients.Conclusions: In our sample of TRD patients, we documented substantial illness burden, low perceived quality of life and poor outcome, suggesting an unmet treatment need in TRD care in Italy.Registration Number:ClinicalTrials.gov, number: NCT03373253.

Nationwide consensus on the clinical management of treatment-resistant depression in Italy: a Delphi panel

“…Regarding the "Treatment journey and its organizational implications" (statements 4,5,6,13,16,17), the surveyed physicians agreed on the need for long-term treatment and providing TRD patients with appropriate and approved treatments. However, there was low consensus and indecision about waiting 3-4 weeks before modifying an ineffective antidepressant treatment (statement 6).…”

“…TRD is a complex condition influenced by genetic, clinical and environmental factors, as well as comorbidities and psychosocial factors [4]. Patients with TRD experience a higher burden of illness compared to responders, including more severe symptoms, greater disability, and reduced quality of life [2,5]. The economic burden of TRD is also significant, with higher direct and indirect costs compared to nontreatment-resistant depression [6].…”

“…Pharmacological options, that include selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA), monoamine oxidase inhibitors (MAOIs), and atypical antidepressants and non-pharmacological treatments (neurostimulation, psychotherapeutic interventions) could be used, alone or in combination, with different strategies, such as dose escalation, medication switching, combination therapy, and augmentation/additional therapy. The everyday Italian clinical practice is not different from the European context; in Italy it can be documented, on the one hand the frequent use of SSRI, SNRI and augmentation strategies, and on the other hand the rare utilization of psychosocial approaches [5].…”

Treatment-Resistant Depression in America Latina study: one-year follow-up of treatment resistant depression patients under standard of care reveals insights on quality of life, disability, work impairment, and depressive symptoms

“…A thorough description of TRAL’s methodology can be found in previous publications of the project ( 12 , 39 ). This study followed a similar approach to other real-world studies set on characterizing the clinical and non-clinical outcomes of TRD based on the routine standard of care ( 16–18 , 33 , 40 ). The importance of real-world evidence in this context should not be understated given the differences between clinical trials and the routine management of TRD patients, in which real-world evidence better depicts the treatment unmet needs.…”

“…In this regard, the impact on instrumental activities of daily living (IADLs) should be considered, which should desirably be returned to the state previous to the episode of MDD/TRD. Previous real-word evidence has shown that outcomes of MDD/TRD are significant in dimensions such as quality of life and disability, and this is more evident in non-responders to treatment ( 16 ). The significanlty high indirect effect of absenteeism should not be discarded, as it accounts for 70% of the costs associated with a major depressive episode in a study in Belgium ( 37 ).…”