Treatment-Resistant Depression in Argentina: results from a longitudinal analysis of the TRAL Study / Depresión resistente al tratamiento en Argentina: resultados de un análisis longitudinal del estudio TRAL.

Literature concerning patients with Treatment-Resistant Depression (TRD) treatment response and patient report outcomes (PROs) -such as QoL or disability- in Argentina is scarce. In the scope of the Treatment-Resistant Depression in America Latina (TRAL) study which previous results highlighted the burden of TRD compared to non-TRD patients as well as essential epidemiological data in the region, this paper reports on the outcomes of Standard-of-Care (SOC) over a 1-year follow-up of TRD patients in the subsample for Argentina. From a sample of 220 MDD patients identified in 5 sites in Argentina, 72 patients were diagnosed with TRD. Exclusion criteria included patients with psychosis, schizophrenia, bipolar disorder, schizoaffective disorder, dementia, with severe chemical dependence or currently participating in another clinical trial. MADRS, PHQ-9 and PROs (EQ-5D and SDS) were used as outcomes. Patients' mean age was 54.7 years and 70.3% of the patients were female. Around 61% of the patients achieved a response (reduction of MADRS score ≥ 50%), but over 33% did not achieve a remission (MADRS total score ≤12). Almost 67% of the patients still felt anxious/depressed at the end of the study (EQ-5D), while disruption affected patients in diverse areas -71% in work/school, 69.7% in social life/leisure and 66.6% in their family life/personal responsibilities. The burden of TRD is significant in Argentina, and more effort should be put in the implementation of treatment protocols with better outcomes.

La literatura disponible en relación a la respuesta al tratamiento de los pacientes con Depresión Resistente al Tratamiento (TRD) y los resultados del informe del paciente (PRO) -como la calidad de vida o la discapacidad- es escasa en Argentina. A partir de la submuestra de Argentina del estudio de depresión resistente al tratamiento en América Latina (TRAL), cuyos resultados anteriores destacaron la carga de TRD en comparación con los pacientes sin DRT, así como datos epidemiológicos esenciales en la región, este documento informa sobre los resultados del estándar de atención (Standard-of-Care, SOC) durante un seguimiento de 1 año de pacientes con DRT De una muestra de 220 pacientes con TDM de 5 centros de Argentina, 72 pacientes fueron diagnosticados con DRT. El criterio de exclusión excluyó a los pacientes con psicosis, esquizofrenia, trastorno bipolar, trastorno esquizoafectivo, demencia, dependencia química grave o que estaban participando en otro ensayo clínico. La MADRS, el PHQ-9 y los PRO (EQ-5D y SDS) se utilizaron como resultados. La edad media de los pacientes fue de 54,7 años y el 70,3 % de los pacientes eran mujeres. Alrededor del 61 % de los pacientes lograron una respuesta (reducción del ≥50 % en el puntaje total de MADRS), pero más del 33 %  no logró una remisión (puntuación total MADRS ≤12). Casi el 67 % de los pacientes seguían sintiéndose ansiosos/ deprimidos al final del estudio (EQ-5D), mientras que dicho trastorno afectó a los pacientes en diversas áreas: el 71 % en el trabajo/la escuela, el 69,7 % en la vida social/el tiempo libre y el 66,6 % en su vida familiar/las responsabilidades personales. La carga de la DRT es significativa en Argentina, y se debe hacer más esfuerzo en la implementación de protocolos de tratamiento con mejores resultados.

Gravidade da depressão, resposta ao tratamento e PRO (incapacidade e QoL) em pacientes com DRT em um ano de acompanhamento com tratamento padrão: análise do subgrupo brasileiro do estudo observacional multinacional TRAL / Depression severity, treatment response and PRO (disability and QoL) in TRD patients over a 1-year follow-up with standard of care: Analysis of the Brazilian subset of the multicenter, observational TRAL study

Objetivo: A depressão resistente ao tratamento (DRT) é uma preocupação primária no Brasil devido à sua natureza onerosa e complexa, enquanto o diagnóstico e o tratamento geralmente são desafiadores. O presente manuscrito apresenta os resultados clínicos de um ano de acompanhamento em pacientes com DRT em tratamento padrão (SOC) no subgrupo brasileiro do estudo de Depressão Resistente ao Tratamento na América Latina (TRAL). Métodos: Essa fase longitudinal do estudo TRAL tinha como meta caracterizar alterações nos resultados clínicos e outras variáveis de interesse (p. ex., qualidade de vida, incapacidade) em um ano de acompanhamento em pacientes com DRT em 10 centros no Brasil. Os pacientes incluídos tinham diagnóstico clínico de DRT com base nos critérios DSM-5 e confirmado por MINI. A Escala de Depressão de Montgomery-Asberg (MADRS) era usada para avaliar a gravidade da doença e os resultados clínicos. Outras escalas de depressão e instrumentos classificados pelo paciente eram usadas para medir resultados correlacionados. Resultados: Cento e cinquenta e oito pacientes com DRT, na maioria mulheres (84,4%) com idade média de 48,55 anos, foram incluídos na análise. Apenas 31,4% dos pacientes apresentaram uma resposta clinicamente significativa, 10,3% tiveram recidiva e 26,7% alcançaram remissão, conforme medido pela MADRS no final do estudo (EOS). Aproximadamente 55% dos pacientes apresentavam depressão grave/moderadamente grave no EOS. Problemas de mobilidade, cuidados pessoais, problemas nas atividades usuais e dor e desconforto foram relatados pela maioria dos pacientes no EOS, assim como comprometimento marcado/extremo das atividades no trabalho/escola e da vida social/das atividades de lazer no EOS. Conclusões: Os resultados clínicos alcançados atualmente ainda são notavelmente insatisfatórios para DRT. Portanto, o envolvimento de todas as partes interessadas é essencial para implementar protocolos de tratamento mais eficazes no Brasil.

Objective: Treatment-resistant depression (TRD) is a primary concern in Brazil due to its burdensome and complex nature, while diagnosis and treatment is often challenging. The current manuscript presents the clinical outcomes in a one-year follow-up of TRD patients under Standard-of-care (SOC) in the Brazilian subset of the Treatment-Resistant Depression in America Latina (TRAL) study. Methods: This longitudinal phase of TRAL aimed to characterize changes in the clinical outcomes and other variables of interest (e.g. quality of life, disability) in a one-year follow-up of TRD patients in 10 centers in Brazil. Included patients were clinically diagnosed with TRD based on DSM-5 criteria and confirmed by MINI. Montgomery-Asberg Depression Rating Scale (MADRS) was used to assess disease severity and clinical outcomes. Other depression scales and patient rated instruments were used to measure correlated outcomes. Results: One hundred fifty-eight TRD patients, mostly female (84.4%), averaging 48.55 years, were included in the analysis. Only 31.4% of the patients showed a clinically significant response, 10.3% had a relapse and 26.7% achieved remission, as measured through MADRS at end-of-study (EOS). Almost 55% of the patients showed moderately severe/severe depression at EOS. Mobility issues, self-care, problems with usual activities and pain and discomfort were reported by the majority of the patients at EOS, as well as marked/extreme disruption of school/work and social life/leisure activities at EOS. Conclusions: Currently achieved clinical outcomes are still remarkably unsatisfactory for TRD. Therefore, the involvement of all relevant stakeholders is essential to implement more effective treatment protocols in Brazil.

Depression and suicidality severity among TRD patients after 1-year under standard of care: Findings from the TRAL study, a multicenter, multinational, observational study in Latin America.

INTRODUCTION: Treatment resistant depression (TRD) is one of the most pressing issues in mental healthcare in LatAm. However, clinical data and outcomes of standard of care (SOC) are scarce. The present study reported on the Treatment-Resistant Depression in America Latina (TRAL) project 1-year follow-up of patients under SOC assessing clinical presentation and outcomes. MATERIALS AND METHODS: 420 patients with clinical diagnoses of TRD from Argentina, Brazil, Colombia and Mexico were included in a 1-year follow-up to assess clinical outcomes of depression (MADRS) and suicidality (C-SSRS), as well as evolution of clinical symptoms of depression. Patients were assessed every 3 months and longitudinal comparison was performed based on change from baseline to each visit and end of study (12 months). Socio demographic characterization was also performed. RESULTS: Most patients were female (80.9%), married (42.5%) or single (34.4%), with at least 10 years of formal education (71%). MDD diagnosis was set at 37.29 (SD=14.00) years, and MDD duration was 11.11 years (SD=10.34). After 1-year of SOC, 79.1% of the patients were still symptomatic, and 40% of the patients displayed moderate/severe depression. Only 44.1% of the patients achieved a response (≥50% improvement in MADRS), and 60% of the sample failed to achieve remission. Suicidal ideation was reported by more than half of the patients at the end of study. CONCLUSIONS: Depression and suicidality symptoms after a 1-year of SOC is of great concern. Better therapeutic options are needed to tackle this debilitating and burdensome disease.

[Major depressive disorder and treatment-resistant depression: an epidemiological analysis in Argentina of the Study of Treatment-Resistant Depression in Latin America]. / Trastorno depresivo mayor y depresión resistente al tratamiento: un análisis epidemiológico en Argentina del estudio de Depresión resistente al tratamiento en América Latina.

Treatment-Resistant Depression (TRD) prevalence varies considerable between regions and epidemiology of TRD in Argentina is lacking. Based on the Treatment-Resistant Depression in America Latina (TRAL) study, epidemiology and burden of TRD in MDD patients from Argentina is reported in this paper. A sample of adult MDD patients (n=396) from 5 sites in Argentina, with clinical diagnosis were included. Patients with psychosis, schizophrenia, bipolar disorder, schizoaffective disorder, dementia, with severe chemical dependence or currently participating in another clinical trial were excluded. Patient reported outcomes and clinical assessment scales were used as outcomes. The prevalence of TRD in MDD patients in Argentina is 33.2%, based on TRAL data. Patients in TRD are older compared to those without TRD, and was more evident in married/consensual union MDD patients. Higher suicidality, greater comorbidity based on MINI, and worse scores in MADRS and PHQ-9 were identified in TRD patients. The prevalence identified in TRAL study for Argentina is substantial comparing with other Latin American countries and worldwide prevalence. TRD represents a disproportional burden to society, and efforts should be placed on reducing the burden of MDD and TRD in Argentina by improving early diagnosis, therapeutic management and ensuring that all patients have better access to mental healthcare.

Suicidality and Quality of Life in Treatment-Resistant Depression Patients in Latin America: Secondary Interim Analysis of the TRAL Study.

Background: A large proportion of patients with major depressive disorder (MDD) have treatment-resistant depression (TRD). The TRAL study examines the impact of TRD on suicidality and health-related quality of life (HRQoL) among MDD patients in 4 Latin American countries. Methods: In this multicenter, prospective, observational study, MDD patients were recruited from 33 sites in Mexico, Colombia, Brazil, and Argentina. Patients were assessed for TRD, defined as failure to respond to ≥2 antidepressant medications of adequate dose and duration. Other assessments included current disease status, Mini International Neuropsychiatric Interview (MINI), Columbia-Suicide Severity Rating Scale (C-SSRS), 5 Level EQ-5D (EQ-5D-5L), Patient Health Questionnaire-9 (PHQ-9), and Sheehan Disability Scale (SDS). Results: 1,475 MDD patients were included in the analysis (mean age, 45.6 years; 78% women), and 429 met criteria for TRD. Thoughts of suicide and suicide attempts were more common among TRD patients (38.7%) compared with non-TRD patients (24.9%; P < 0.0001), according to the current disease status questionnaire. The C-SSRS showed that lifetime suicidal behavior was significantly more common among TRD patients than non-TRD patients (13.8 vs. 10.0%; P = 0.0384). Compared with non-TRD patients, TRD patients showed significantly greater adverse impacts on QoL (EQ-5D-5L), more severe depression (PHQ-9), and greater functional impairment (SDS). Conclusion: TRD patients in clinical sites from Mexico, Colombia, Brazil, and Argentina were more likely to experience suicidality and negative effects on HRQoL than non-TRD patients.

Prevalence and Impact of Treatment-Resistant Depression in Latin America: a Prospective, Observational Study.

Approximately one-third of patients with major depressive disorder (MDD) have treatment-resistant depression (TRD). The TRAL study will evaluate the prevalence and impact of TRD among patients with MDD in four Latin American countries. In this multicenter, prospective, observational study, patients with MDD were recruited from 33 reference sites in Mexico, Colombia, Brazil, and Argentina. Patients were assessed for TRD, defined as failure to respond to ≥ 2 antidepressant medications of adequate dose and duration. Demographics, previous/current treatments, depressive symptoms, functioning, healthcare resource utilization, and work impairment were also collected and evaluated using descriptive statistics, chi-square test, Fisher exact test, t-test for independent samples, or the Mann-Whitney nonparametric test, as appropriate. 1475 patients with MDD were included in the analysis (mean age, 45.6 years; 78% women); 89% were receiving relevant psychiatric treatment. 429 patients met criteria for TRD, and a numerically higher proportion of patients with TRD was present in public versus private sites of care (31% vs 27%). The mean Montgomery-Asberg Depression Rating Scale score was 25.0 among all MDD patients and was significantly higher for patients with TRD versus non-TRD (29.4 vs 23.3; P < 0.0001). Patients with TRD, versus those with non-TRD, were significantly more likely to be older, have a longer disease duration, have more comorbidities, be symptomatic, have a higher median number of psychiatric consultations, and report greater work impairment. Patients with TRD have a disproportionate burden of disease compared to those with non-TRD. Appropriate treatment for TRD is a substantial unmet need in Latin America. https://www.ClinicalTrials.gov identifier NCT03207282, 07/02/2017.

Epidemiologia e ônus da depressão resistente ao tratamento no Brasil: análise do subgrupo brasileiro do estudo de observação multicêntrico TRAL / Epidemiology and burden of treatment-resistant depression in Brazil: analysis of the Brazilian subset of multicenter observational TRAL study

Objetivos: A epidemiologia da depressão resistente ao tratamento (DRT) varia mundialmente, mas é incerta na América Latina. Este artigo relata a epidemiologia e o ônus da DRT em pacientes com transtorno depressivo maior (TDM) no Brasil, no estudo observacional multinacional, multicêntrico, de DRT na América Latina (TRAL). Métodos: Trezentos e noventa e seis pacientes adultos com TDM (tratados ou não) no Brasil, com diagnóstico de TDM usando o Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) e confirmado por MINI Entrevista Neuropsiquiátrica Internacional v7.0.2, foram incluídos em 10 centros. Os pacientes forneceram consentimento e concluíram as avaliações. Os critérios de exclusão incluíram pacientes com psicose, esquizofrenia, transtorno bipolar, transtorno esquizoafetivo, demência, transtorno de uso de substância ou participação atual em outro estudo. A MADRS foi usada para gravidade da doença. Escalas de depressão e instrumentos classificados pelos pacientes foram usados para medir os resultados. Resultados: A prevalência de DRT em pacientes com TDM na América Latina corresponde a 29,1% (IC 95% [26,8%; 31,4%]), embora no Brasil corresponda a 40,4% (IC 95%: 35,6%-45,2%), a mais alta no estudo TRAL. Os pacientes com DRT são mais velhos e apresentam maior proporção de divórcios e menor nível educacional, com pontuação mais alta na Escala de Classificação da Depressão de Montgomery-Asberg (MADRS), comparados a pacientes sem DRT. Os custos de saúde foram maiores em pacientes com DRT, com menor qualidade de vida e maiores custos de saúde e comprometimento laboral. Conclusões: Estes achados confirmam que a DRT apresenta alta prevalência no Brasil, consistentemente com estudos anteriores sobre transtornos depressivos. Globalmente, os pacientes com DRT apresentam maior ônus da doença, sugerindo a necessidade de melhorar os cuidados para pacientes com DRT no Brasil

Objectives: Treatment-resistant depression (TRD) epidemiology varies worldwide, but uncertain in Latin America (LatAm). This paper reports on the epidemiology and burden of TRD in major depressive disorder (MDD) patients in Brazil from the TRD in America Latina (TRAL) multicenter, multinational, observational study. Methods: 396 adult patients (treated or untreated) with MDD diagnosis in Brazil using Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) and confirmed by MINI International Neuropsychiatric Interview v7.0.2 were consecutively enrolled from 10 clinical sites in Brazil. Patients provided consent and complete assessments. Exclusion criteria included patients with psychosis, schizophrenia, bipolar disorder, schizoaffective disorder, dementia, with substance use disorder or currently participating in another clinical trial. Montgomery-Asberg Depression Rating Scale (MADRS) was used for disease severity. Depression scales and patient rated instruments were used to measure outcomes. Results: The prevalence of TRD in MDD patients in LatAm is 29.1% (95%CI [26.8%; 31.4%]), though the values for Brazil are 40.4% (95%CI: 35.6%-45.2%), the highest in the TRAL study. TRD patients are older, have higher proportion of divorce and lower education, with higher MADRS score compared to non-TRD patients. Healthcare costs were higher in TRD patients, with lower quality of life (QoL) and higher work impairment and healthcare costs. Conclusions: Present findings confirms that TRD is highly prevalent in Brazil, which is consistent with previous studies concerning depressive disorders. Globally, TRD patients experience higher burden of the disease. These findings suggest the need to improve care among TRD patients in Brazil