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.

Introduction: Depressive Disorders are on the rise worldwide. This is also the case in Latin America (LatAm). Treatment-Resistant Depressive Disorder (TRD) poses additional burden to patients with depression. Impacts quality of life (QoL) and other dimensions, and standard of care (SOC) is insufficient to achieve the desired clinical outcomes. Evidence from LatAm is, however, lacking. The present study was devised as a 1-year follow-up of the SOC in TRD patients in LatAm to explore the burden of TRD. Methods: This was an observational, multinational, longitudinal study. Patients with clinical diagnosis of TRD in LatAm were included in a 1-year follow-up with SOC. Beyond the Sociodemographic characterization, outcome measures were QoL (EQ-5D-5L), disability (Sheehan Disability Scale - SDS), work productivity (Work Productivity and Activity Incapacity Questionnaire: depression - WPAI:D) and depression severity (Patient Health Questionnaire-PHQ9). Patients were assessed every 3-months and comparison was performed based on change from baseline to each visit and end of study (EOS - 12 months). Results: Patients averaged 48 (± 13.12) years, mostly female (80.9%) and married/consensual union (42.5%) or single patients (34.4%). Despite the SOC treatment, three-quarters of the patients remained symptomatic at EOS, regardless of the significant longitudinal decrease (p ≤ 0.001). Similar trends were found for disability (p ≤ 0.001) -82.2% of the patients reporting work/school disruption at EOS-, percentage of work (34%) and activity impairment (40%) at EOS (p ≤ 0.001) and only 29.2% of patients with depressive severity "none" at EOS (p ≤ 0.001). The results portray the need to improve clinical outcomes in this complex and burdensome disease in LatAm. Discussion: Here we show that the burden of TRD remains significant in essential dimensions of everyday life at EOS underlining the need for better therapeutic solutions. The improvements in most patients do not provide the desired outcome of return to the state before the condition. Further research should focus on identifying which treatments provide better outcomes in a real-world context.

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.

[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.

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.

[Study of Flexible Doses of Paliperidone ER in Pacients with Schizophrenia who Have Undergone Inefficient Treatment with other Antipsychotics]. / Estudio de dosis flexibles de paliperidona ER en pacientes con esquizofrenia previamente tratados sin efectividad con otros antipsicóticos.

BACKGROUND: Extended-release (ER) paliperidone is an innovative atypical antipsychotic that allows minimal peak-to-through fluctuations with once-daily dosing. OBJECTIVE: To evaluate effectiveness, safety and tolerability of flexible, once-daily doses of paliperidone ER (3-12 mg/day) in patients with schizophrenia from Argentina and Colombia who had previously failed treatment with other antipsychotic agents. METHODS: The authors conducted a 6-month, open-label, prospective and multicentric study. Effectiveness was assessed with Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance scale (PSP). Other measures of effectiveness, safety and tolerability, were also conducted. RESULTS: Paliperidone ER 3-12 mg/day improved Positive and Negative Syndrome Scale (PANSS) total scores (primary endpoint) from baseline to study end (p < 0,001). In the PANSS total score, the mean change from baseline (83, 9 units) to end point (53,7 units) was significant (p < 0,001). Flexible doses of paliperidone ER demonstrated a ≥20% reduction in the PANSS total score (p<0.001) in almost two-thirds of patients. PSP mean change from baseline (52 units) to end point (85 units) was significant (p < 0,001). Secondary effectiveness assessments, as well as safety and tolerability measures, demonstrated favourable results throughout the study. CONCLUSIONS: Flexible doses of paliperidone ER over 6 months were effective, safe and well tolerated in patients with schizophrenia from Argentina and Colombia.

[2nd Argentine consensus on the treatment of bipolar disorders 2010]. / II Consenso argentino sobre el tratamiento de los trastornos bipolares 2010.

The consensus guidelines of Argentine experts in the treatment of bipolar disorders are the result of three days of work of the 9 main local experts under the organization of the Argentine Association of Mood Disorders (ASATHU). This work is an update of the guidelines published on this journal in 2006. It was adopted a mixed criterion for its preparation: all the recent data of the evidence medicine based published until now were discussed and were balanced with the knowledge acquired from clinical experience of the local experts on the bipolar field. It presents general recommendations and suggested therapeutic sequences for maintenance, manic/hypomanic or mixed episode and depressive episode treatments. Bipolar disorders have been divided according to the international classifications in type I and II; with or without rapid cycling. This work also includes a series of recommendations for early and differential diagnosis of bipolar disorders.

[Acute mania. Clinical features and pharmacological treatment]. / Manía aguda. Características clínicas y tratamiento farmacológico.

The bipolar disorder is a chronic disease and often a devastating one. The Physical and psychosocial impairments which are associated with a high percentage of medical and psychiatric care, family dysfunction, divorces, drug abuse and suicides are common. One of the mayor difficulties is the diagnosis. Numerous studies show the course of time that takes to reach a diagnosis. Empirical studies have tried to evaluate the characteristics of the atypical mania. Different authors have found that atypical mania features may coexist in some patients with mania, particularly those who experience a severe mania phase. The identification of factors and subtypes may be useful to identify atypical characteristics in patients with acute mania. This concept may be used for research developments that tend to establish rational strategies of treatment and the underlying biological substrates of every clinical subtype. There are several agents that may be used in treating acute mania, however, of practical importance is to determine which one is the most effective when deciding which one to choose. It is important to point out that in the daily practice multiple medication is the rule rather then the exception. The use of mood stabilizers is recommended in all phases of treatment with mono-therapy or combined therapies. Its is convenient to establish cathagoric ranks that include first line treatments as the preferred option, second line as the alternative choice and a third line as the inappropriate one.

Manía aguda. Características clínicas y tratamiento farmacológico. / [Acute mania. Clinical features and pharmacological treatment]

The bipolar disorder is a chronic disease and often a devastating one. The Physical and psychosocial impairments which are associated with a high percentage of medical and psychiatric care, family dysfunction, divorces, drug abuse and suicides are common. One of the mayor difficulties is the diagnosis. Numerous studies show the course of time that takes to reach a diagnosis. Empirical studies have tried to evaluate the characteristics of the atypical mania. Different authors have found that atypical mania features may coexist in some patients with mania, particularly those who experience a severe mania phase. The identification of factors and subtypes may be useful to identify atypical characteristics in patients with acute mania. This concept may be used for research developments that tend to establish rational strategies of treatment and the underlying biological substrates of every clinical subtype. There are several agents that may be used in treating acute mania, however, of practical importance is to determine which one is the most effective when deciding which one to choose. It is important to point out that in the daily practice multiple medication is the rule rather then the exception. The use of mood stabilizers is recommended in all phases of treatment with mono-therapy or combined therapies. Its is convenient to establish cathagoric ranks that include first line treatments as the preferred option, second line as the alternative choice and a third line as the inappropriate one.

Manía aguda. Características clínicas y tratamiento farmacológico / [Acute mania. Clinical features and pharmacological treatment]

The bipolar disorder is a chronic disease and often a devastating one. The Physical and psychosocial impairments which are associated with a high percentage of medical and psychiatric care, family dysfunction, divorces, drug abuse and suicides are common. One of the mayor difficulties is the diagnosis. Numerous studies show the course of time that takes to reach a diagnosis. Empirical studies have tried to evaluate the characteristics of the atypical mania. Different authors have found that atypical mania features may coexist in some patients with mania, particularly those who experience a severe mania phase. The identification of factors and subtypes may be useful to identify atypical characteristics in patients with acute mania. This concept may be used for research developments that tend to establish rational strategies of treatment and the underlying biological substrates of every clinical subtype. There are several agents that may be used in treating acute mania, however, of practical importance is to determine which one is the most effective when deciding which one to choose. It is important to point out that in the daily practice multiple medication is the rule rather then the exception. The use of mood stabilizers is recommended in all phases of treatment with mono-therapy or combined therapies. Its is convenient to establish cathagoric ranks that include first line treatments as the preferred option, second line as the alternative choice and a third line as the inappropriate one.