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.

Latin American consensus recommendations for the management and treatment of patients with treatment-resistant depression (TRD).

Despite the abundance of literature on treatment-resistant depression (TRD), there is no universally accepted definition of TRD, and available treatment pathways for the management of TRD vary across the Latin American region, highlighting the need for a uniform definition and treatment principles to optimize the management of TRD in Latin America. METHODS: Following a thematic literature review and pre-meeting survey, a Latin America expert panel comprising 14 psychiatrists with clinical experience in managing patients with TRD convened and utilized the RAND/UCLA appropriateness method to develop consensus-based recommendations on the appropriate definition of TRD and principles for its management. RESULTS: The expert panel agreed that 'treatment-resistant depression' (TRD) is defined as 'failure of two drug treatments of adequate doses, for 4-8 weeks duration with adequate adherence, during a major depressive episode'. A stepwise treatment approach should be employed for the management of TRD - treatment strategies can include maximizing dose, switching to a different class, and augmenting or combining treatments. Nonpharmacological treatments, such as electroconvulsive therapy, are also appropriate options for patients with TRD. CONCLUSION: These consensus recommendations on the operational definition of TRD and approved treatments for its management can be adapted to local contexts in the Latin American countries but should not replace clinical judgement. Individual circumstances and benefit-risk balance should be carefully considered while determining the most appropriate treatment option for patients with TRD.

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.

Sensitivity and specificity of the mood disorder questionnaire and the bipolar spectrum diagnostic scale in Argentinean patients with mood disorders.

OBJECTIVE: To assess the sensitivity and specificity of two self-report instruments for detection of bipolarity in a sample of Argentinean patients. METHOD: Spanish versions of the MDQ and the BSDS were administered over four months at 11 sites in Argentina. Diagnoses were made using DSM-IV criteria and the MINI. The study sample consisted of patients diagnosed with Bipolar Disorder (BD) Types I, II, or NOS. BDNOS diagnoses were made using extended guidelines for bipolar spectrum symptoms. Unipolar patients were used as a control group. Of 493 patients screened, 354 completed evaluation by MDQ and MINI, and 363 by BSDS and MINI. RESULTS: Specificity of MDQ was 0.97 and BSDS was 0.81. MDQ sensitivity was 0.70 for bipolar type I (BD-I), 0.52 for bipolar II (BD-II) and 0.31 for bipolar not otherwise specified (BDNOS). BSDS sensitivities were 0.75, 0.70 and 0.51 respectively. LIMITATIONS: This study was performed in specialized outpatient settings and thus its results are not necessarily representative for other clinical settings. There was not a systematic evaluation of comorbid psychiatric disease or test-retest reliability. CONCLUSION: The local versions of the MDQ and the BSDS showed a sensitivity and specificity comparable to previous research. Our results indicate that in this sample, MDQ was more specific for BD and BSDS was more sensitive to detect BD-II and NOS. Since BD-I is more readily recognized than bipolar spectrum disorders, enhanced sensitivity of BSDS for soft bipolarity may be an advantage.

Bipolar disorders and affective temperaments: a national family study testing the "endophenotype" and "subaffective" theses using the TEMPS-A Buenos Aires.

BACKGROUND: The purpose of this study is to examine the prevalence of affective temperaments between clinically unaffected relatives of bipolar patients and secondarily to investigate the impact of these "subaffective" forms on their quality of life (QoL). METHODS: The study was performed in seven sites across Argentina. We administered the scales TEMPS-A and Quality of Life Index to a sample of 114 non-ill first degree relatives of bipolar disorder patients ("cases") and 115 comparison subjects without family history of affective illness ("controls"). We used The Mood Disorder Questionnaire to rule out clinical bipolarity. RESULTS: Mean scores on all TEMPS-A subscales were significantly higher in cases, except for hyperthymia. The prevalence of affective temperaments, according to Argentinean cut-off points, was also higher, with statistical significance for cyclothymic and anxious temperaments. Regarding QoL, we found no significant differences between both groups, except for interpersonal functioning, which was better in controls. A detailed subanalysis showed significant effects of QoL domains for all temperaments, except for the hyperthymic. LIMITATIONS: We used self-report measures. A larger sample size would have provided us greater statistical power for certain analyses. CONCLUSIONS: Our findings support the concept of a spectrum of subthreshold affective traits or temperaments - especially for the cyclothymic and anxious - in bipolar pedigrees. We further demonstrated that, except for the hyperthymic, quality of life was affected by these temperaments in "clinically well" relatives. Overall, our data are compatible with the "endophenotype" and "subaffective" theses for affective temperaments.