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.

Potencial de disparidad o Mismatch negativity y P3a en pacientes con esquizofrenia / Mismatch negativity and P3a in patients with Schizophrenia

Resumen Antecedentes: la esquizofrenia es una enfermedad crónica que genera gran discapacidad, para la cual se han reportado biomarcadores potenciales, pero sin suficiente validez clínica. El mismatch negativity (MMN) y el P3a son potenciales relacionados con eventos que han demostrado ser indicadores neurofisiológicos del procesamiento auditivo pre-atencional y potenciales biomarcadores. Objetivo: evaluar el MMN y P3a en pacientes con diagnóstico de esquizofrenia y su relación con variables sociodemográficas y clínicas. Método: estudio cuantitativo transversal de 23 sujetos con esquizofrenia (ESQ) y 22 controles sanos (SN). Las amplitudes promedio y latencias del MMN/P3a para la condición infrecuente en duración y frecuencia fueron obtenidas mediante un paradigma oddball auditivo en un EEG de 32 canales. Resultados: se encontraron diferencias para la condición frecuencia en la amplitud del MMN (p=0.046; CI 95% 0.009; 0.87) y la amplitud del P3a (p=0.042; CI 95% 0.025; 1.24) entre los grupos; la amplitud del MMN fue menor en el grupo ESQ (-0.36 DE 0.51 µV) en comparación con los participantes del grupo de SN (-0.81 DE 0.89 µV), mientras que la amplitud del P3a fue menor en el grupo SN (0.18 DE 0.97 µV) versus el grupo ESQ (0.82 DE 1.05 µV). En relación con las variables sociodemográficas y clínicas, las asociaciones con el P3a fueron moderadas y con el MMN débiles. Conclusiones: la reducción de la amplitud del MMN a la condición frecuencia exhibe mayor utilidad que el P3a como medida de alta estabilidad en pacientes con esquizofrenia, lo que reitera su posible uso como biomarcador.

Abstract Background: schizophrenia is a chronic disease that generates great disability, which currently has potential biomarkers but without sufficient clinical validity. Mismatch negativity (MMN) and P3a are event-related potentials that have been shown to be neurophysiological indicators of pre-attentional auditory processing and potential biomarkers. Objective: to evaluate MMN and P3a in patients with a diagnosis of schizophrenia and their relationship with sociodemographic and clinical variables. Method: a quantitative cross-sectional study of 23 subjects with schizophrenia and 22 healthy controls was performed. The average amplitudes and latencies of the MMN/P3a for the condition infrequent in duration and infrequent in frequency were obtained using an auditory oddball paradigm on a 32-channel EEG. Results: differences were found for the frequency condition in the amplitude of the MMN (p=0.046; 95% CI 0.009; 0.87) and the amplitude of the P3a (p=0.042; 95% CI 0.025; 1.24) between the groups; MMN amplitude was lower in schizophrenia (-0.36 SD 0.51 µV) compared to healthy controls (-0.81 SD 0.89 µV), while P3a amplitude was lower in healthy controls (0.18 SD 0.97 µV) versus the group with schizophrenia (0.82 SD 1.05 µV). In regard to sociodemographic and clinical variables, the associations with P3a were moderate, and showed weak MMN. Conclusions: MMN amplitude reduction to the frequency condition exhibits greater utility than P3a as a measure of high stability in schizophrenia, restating its potential use as a biomarker.

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.