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.

Understanding the journey of patients with depression in Brazil: A systematic review.

Despite having an organized mental health law and policy, a majority of patients with depression remain underreported and undertreated in Brazil. The study aimed to quantitatively map and identify the deficiencies in patient journey touchpoints in terms of awareness, screening, diagnosis, treatment, adherence, and control for depression in Brazil using a semi-systematic approach highlighting the knowledge gaps in the existing literature. A structured search of Embase, MEDLINE, and BIOSIS databases was conducted to identify the relevant studies published in English, Portuguese, and Spanish from 2006 to 2021. An unstructured search was also conducted on Google or government websites with no restrictions. To address the data gaps, anecdotal data were also considered. Weighted or simple means were calculated for the pooled data. Of 3175 articles retrieved, 10 articles met the inclusion criteria. Synthesized evidence indicates that the pooled prevalence of depression in Brazil ranged from 4.1% to 21.8%; 42.4% of patients had awareness of depression, 37.5% underwent screening, 18.7% had a diagnosis, and 54.4% received treatment. No data on adherence and control were available. The study findings highlight the need for more research to accurately estimate the common patient journey touchpoints for depression to achieve better clinical outcomes in Brazil.

Seasonality of suicide in the city of Sao Paulo, Brazil, 1979-2003.

OBJECTIVE: To evaluate suicide seasonality in the city of São Paulo within an urban area and tropical zone. METHOD: Suicides were evaluated using the chi-square test and analysis of variance (ANOVA) by comparing monthly, quarterly and half-yearly variations, differentiating by gender. Analyses of time series were carried out using the autocorrelation function and periodogram, while the significance level for seasonality was confirmed with the Fisher's test. RESULTS: The suicides of the period between 1979 and 2003 numbered 11,434 cases. Differences were observed in suicides occurring in Spring and Autumn for the total sample (ANOVA: p-value = 0.01), and in the male sample (ANOVA: p-value = 0.02). For the analysis of time series, seasonality was significant only for the period of 7 months in the male sample (p-value = 0.04). DISCUSSION: In this study, no significant seasonal differences were observed in the occurrences of suicides, with the exception of the male sample. The differences observed did not correspond with the pattern described in studies carried out in temperate zones. Some of the climatic particularities of the tropical zone might explain the atypical pattern of seasonality of suicides found in large populations within an urban area and tropical zone.

The impact of patients with generalized anxiety disorder in the Brazilian Private Healthcare System: a claim database study with expert's perspective / O impacto de pacientes com transtorno de ansiedade generalizada no Sistema Único de Saúde: um estudo de base de sinistros com a perspectiva de especialistas

This study describes the healthcare resource use and costs associated with anxiety assessing claim database outcomes and expert opinion from the perspective of the Brazilian Private Healthcare System. A retrospective analysis of the Orizon database was conducted, containing claims data of anxiety patients reported in Private Healthcare Systems (2015-2017) according to the ICD-10 code (F40 or F41 and their subtypes). Further, a 3-hour online meeting brought together five anxiety and Health Insurance Companies experts to discuss their perspectives. The total cost of the 18,069 patients identified in the database was BRL 490 million: related to medical appointments (2%), exams (16%), emergency room (5%), and others (77%). The mean number of appointments was 5.1 in a 4-year period, performed by 61% of the patients. Approximately 2,595 visits were made to psychiatrists by 923 patients, and 95% underwent at least one examination (100.6 examinations per patient, on average). The identification of anxiety patients and their corresponding burden is challenging to estimate. The higher impact is related to the frequency of healthcare use before the diagnosis than the treatment itself. These outcomes may help plan and implement adequate healthcare programs for patients with anxiety.

Este estudo descreve o uso de recursos de saúde e os custos relacionados à ansiedade associando resultados de uma base de dados administrativa e opinião de especialistas na perspectiva do Sistema Privado de Saúde Brasileiro. Foi realizada uma análise retrospectiva da base de dados da Orizon de pacientes com ansiedade em atendimento hospitalizar ou ambulatorial no Sistema Privado de Saúde (2015 - 2017) com o código CID-10 (F40 ou F41 e os seus subtipos), adicionalmente promovemos uma reunião online de 3 horas com cinco especialistas em ansiedade e em seguros de saúde para discutir as suas perspectivas. O custo total dos 18.069 pacientes identificados no banco de dados foi de R$ 490 milhões, relacionados a consultas médicas (2%), exames (16%), pronto-socorro (5%) e outros (77%). A média de consultas foi de 5,1 em um período de 4 anos, realizadas por 61% dos pacientes. Aproximadamente 2.595 visitas foram feitas a psiquiatras por 923 pacientes, e 95% realizaram pelo menos um exame (média de 100,6 exames por paciente. É desafiador identificar e estimar o impacto da doença no Sistema Privado de Saúde Brasileiro. O impacto maior está relacionado à frequência de uso de serviços de saúde antes do diagnóstico, em comparação com o próprio tratamento. Esses resultados podem ajudar a planejar e implementar programas de saúde adequados para pacientes com ansiedade.

Understanding the journey of patients with depression in Brazil: A systematic review

Abstract Despite having an organized mental health law and policy, a majority of patients with depression remain underreported and undertreated in Brazil. The study aimed to quantitatively map and identify the deficiencies in patient journey touchpoints in terms of awareness, screening, diagnosis, treatment, adherence, and control for depression in Brazil using a semi-systematic approach highlighting the knowledge gaps in the existing literature. A structured search of Embase, MEDLINE, and BIOSIS databases was conducted to identify the relevant studies published in English, Portuguese, and Spanish from 2006 to 2021. An unstructured search was also conducted on Google or government websites with no restrictions. To address the data gaps, anecdotal data were also considered. Weighted or simple means were calculated for the pooled data. Of 3175 articles retrieved, 10 articles met the inclusion criteria. Synthesized evidence indicates that the pooled prevalence of depression in Brazil ranged from 4.1% to 21.8%; 42.4% of patients had awareness of depression, 37.5% underwent screening, 18.7% had a diagnosis, and 54.4% received treatment. No data on adherence and control were available. The study findings highlight the need for more research to accurately estimate the common patient journey touchpoints for depression to achieve better clinical outcomes in Brazil.

Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression: a randomized double-blind trial in a Brazilian sample.

OBJECTIVE: Hypericum perforatum has demonstrated antidepressant efficacy when compared to placebo, but comparisons with other antidepressants remain controversial. We assessed the efficacy and safety of Hypericum perforatum in comparison with fluoxetine, in a 8-week double-blind trial in patients with mild to moderate depression. METHOD: Seventy-two outpatients were randomly assigned to receive Hypericum perforatum 900 mg/day, fluoxetine 20 mg/day or placebo. Efficacy measures included the HAM-D21 scale, the Montgomery-Asberg Rating Scale, and the Clinical Global Impression. Safety was assessed with the UKU Side Effect Rating Scale. RESULTS: Intention-to-treat analysis showed no differences between the mean scores of the three groups. In the analyses of observed cases, patients receiving Hypericum perforatum had the lowest remission rates (12%, p = 0.016) compared to fluoxetine (34.6%) and placebo (45%). CONCLUSIONS: Hypericum perforatum was less efficacious than both fluoxetine and placebo. Both drugs were safe and well-tolerated. Larger trials are needed for definite conclusions.

Neuromodulation approaches for the treatment of major depression: challenges and recommendations from a working group meeting.

UNLABELLED: The use of neuromodulation as a treatment for major depressive disorder (MDD) has recently attracted renewed interest due to development of other non-pharmacological therapies besides electroconvulsive therapy (ECT) such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). METHOD: We convened a working group of researchers to discuss the updates and key challenges of neuromodulation use for the treatment of MDD. RESULTS: The state-of-art of neuromodulation techniques was reviewed and discussed in four sections: [1] epidemiology and pathophysiology of MDD; [2] a comprehensive overview of the neuromodulation techniques; [3] using neuromodulation techniques in MDD associated with non-psychiatric conditions; [4] the main challenges of neuromodulation research and alternatives to overcome them. DISCUSSION: ECT is the first-line treatment for severe depression. TMS and tDCS are strategies with a relative benign profile of side effects; however, while TMS effects are comparable to antidepressant drugs for treating MDD; further research is needed to establish the role of tDCS. DBS and VNS are invasive strategies with a possible role in treatment-resistant depression. In summary, MDD is a chronic and incapacitating condition with a high prevalence; therefore clinicians should consider all the treatment options including invasive and non-invasive neuromodulation approaches.

Premenstrual dysphoric symptoms amongst Brazilian college students: factor structure and methodological appraisal.

OBJECTIVES: The present study aims to assess the factor structure of the DSM-IV Premenstrual Dysphoric Disorder (PMDD) symptoms and its relationship with depressive symptoms. METHODS: We evaluated retrospectively PMDD symptoms in 513 female college students, through a self-reporting questionnaire based on DSM-IV criteria, in addition to the Beck Depression Inventory (BDI). Principal component analysis on PMDD symptom data was performed to assess its dimensional structure. RESULTS: In this non-clinical sample, the analysis indicated a higher importance of the dysphoric dimension, but physical symptoms as well as "being out of control" or "overwhelmed" should also be viewed as major symptoms of PMDD. Behavioural symptoms are of secondary importance. The mean BDI score of PMDD group was significantly higher (p < 0.05) than non-PMDD group. CONCLUSION: The factor structure of the total sample was similar to the symptom structure suggested by DSM-IV diagnostic criteria. Depressive symptoms should be viewed as a confounding variable in PMDD.

Neuromodulation approaches for the treatment of major depression: challenges and recommendations from a working group meeting / Estratégias de neuromodulação para o tratamento da depressão maior: desafios e recomendações de uma força-tarefa

The use of neuromodulation as a treatment for major depressive disorder (MDD) has recently attracted renewed interest due to development of other non-pharmacological therapies besides electroconvulsive therapy (ECT) such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). METHOD: We convened a working group of researchers to discuss the updates and key challenges of neuromodulation use for the treatment of MDD. RESULTS: The state-of-art of neuromodulation techniques was reviewed and discussed in four sections: [1] epidemiology and pathophysiology of MDD; [2] a comprehensive overview of the neuromodulation techniques; [3] using neuromodulation techniques in MDD associated with non-psychiatric conditions; [4] the main challenges of neuromodulation research and alternatives to overcome them. DISCUSSION: ECT is the first-line treatment for severe depression. TMS and tDCS are strategies with a relative benign profile of side effects; however, while TMS effects are comparable to antidepressant drugs for treating MDD; further research is needed to establish the role of tDCS. DBS and VNS are invasive strategies with a possible role in treatment-resistant depression. In summary, MDD is a chronic and incapacitating condition with a high prevalence; therefore clinicians should consider all the treatment options including invasive and non-invasive neuromodulation approaches.

O uso de técnicas de neuromodulação para o tratamento do transtorno depressivo maior (TDM) tem despertado um renovado interesse nos últimos anos com o desenvolvimento de outras intervenções não-farmacólogicas além da eletroconvulsoterapia (ECT), como a estimulação magnética transcraniana (EMT), a estimulação transcraniana por corrente continua (ETCC), a estimulação cerebral profunda (DBS) e a estimulação de nervo vago (VNS). MÉTODO: Nós organizamos um grupo de trabalho com vários pesquisadores para discutir os avanços recentes e os principais desafios para o uso da neuromodulação no tratamento do TDM. RESULTADOS: O estado-da-arte da neuromodulação foi revisado e discutido em quatro seções: [1] epidemiologia e fisiopatologia do TDM; [2] uma revisão das técnicas de neuromodulação; [3] o uso das técnicas de neuromodulação na depressão que ocorre associada ou em virtude de condições não-psiquiátricas; [4] os principais desafios da pesquisa na neuromodulação e alternativas para superá-los. DISCUSSÃO: ECT é o tratamento de primeira linha para depressão grave. EMT e ETCC são estratégias com um perfil benigno de efeitos adversos; contudo, enquanto os efeitos da EMT são comparáveis ao das drogas antidepressivas para o tratamento da TDM, a eficácia da ETCC ainda precisa ser estabelecida por mais pesquisas clínicas. DBS e VNS são intervenções invasivas com um papel possível para a depressão refratária. Em resumo, TDM é uma condição crônica, incapacitante e de alta prevalência; portanto na prática clínica todas as opções de tratamento possíveis, incluindo as farmacológicas e não-farmacológicas, devem ser consideradas.

Seasonality of suicide in the city of Sao Paulo, Brazil, 1979-2003 / Sazonalidade do suicídio na cidade de São Paulo, Brasil, 1979-2003

OBJECTIVE: To evaluate suicide seasonality in the city of São Paulo within an urban area and tropical zone. METHOD: Suicides were evaluated using the chi-square test and analysis of variance (ANOVA) by comparing monthly, quarterly and half-yearly variations, differentiating by gender. Analyses of time series were carried out using the autocorrelation function and periodogram, while the significance level for seasonality was confirmed with the Fisher's test. RESULTS: The suicides of the period between 1979 and 2003 numbered 11,434 cases. Differences were observed in suicides occurring in Spring and Autumn for the total sample (ANOVA: p-value = 0.01), and in the male sample (ANOVA: p-value = 0.02). For the analysis of time series, seasonality was significant only for the period of 7 months in the male sample (p-value = 0.04). DISCUSSION: In this study, no significant seasonal differences were observed in the occurrences of suicides, with the exception of the male sample. The differences observed did not correspond with the pattern described in studies carried out in temperate zones. Some of the climatic particularities of the tropical zone might explain the atypical pattern of seasonality of suicides found in large populations within an urban area and tropical zone.

OBJETIVO: Avaliar a sazonalidade do suicídio na cidade de São Paulo, uma área urbana em zona tropical. MÉTODO: Os suicídios foram avaliados pelo teste de qui-quadrado e análise de variância (ANOVA), comparando variações mensais, trimestrais e semestrais, diferenciando por gênero. Também foi realizada a análise de séries temporais, utilizando a função de autocorrelação e periodograma, além da confirmação, com o teste de Fisher de significância para sazonalidade. RESULTADOS: Os suicídios do período entre 1979 e 2003 totalizaram 11.434 casos. Foram observadas diferenças apenas nos suicídios ocorridos na primavera e outono na amostra total (ANOVA: p-valor = 0,01), e na amostra para o sexo masculino (ANOVA: p-valor = 0,02). Pela análise de séries temporais, a sazonalidade foi significativa apenas para o período de sete meses, na amostra para o sexo masculino (p-valor = 0,04). DISCUSSÃO: Neste estudo não foram observadas diferenças sazonais significativas na ocorrência de suicídios, com exceção da amostra masculina. Tais diferenças não correspondem ao padrão descrito nos estudos realizados em zona temperada. Algumas das particularidades climáticas da zona tropical poderiam explicar o padrão atípico de sazonalidades de suicídios em uma grande população de área urbana e zona tropical.

Síndrome de burnout ou estafa profissional e os transtornos psiquiátricos: [revisão] / Burnout syndrome and psychiatric disorders: [review]

CONTEXTO: A síndrome de burnout é conseqüente a prolongados níveis de estresse no trabalho e compreende exaustão emocional, distanciamento das relações pessoais e diminuição do sentimento de realização pessoal. OBJETIVO: O objetivo deste artigo foi realizar uma revisão bibliográfica a respeito da síndrome no Brasil e em outros países, considerando sua prevalência, possíveis fatores de risco para seu desenvolvimento, sua associação com outros transtornos psiquiátricos e conseqüências para o indivíduo e a organização em que trabalha. MÉTODOS: Realizou-se uma revisão bibliográfica utilizando-se a base de dados da MedLine, Scielo, American Psychiatry Association, Evidence-Based Mental Health, American College of Physicians, Agency for Healthcare Research and Quality, National Guideline Clearinghouse e da Organização Mundial da Saúde no período compreendido entre 1985 e 2006. CONCLUSÃO: A prevalência da síndrome de burnout ainda é incerta, mas dados sugerem que acomete um número significativo de indivíduos, variando de aproximadamente 4 por cento a 85,7 por cento, conforme a população estudada. Pode apresentar comorbidade com alguns transtornos psiquiátricos, como a depressão. Os efeitos do burnout podem prejudicar o profissional em três níveis: individual (físico, mental, profissional e social), profissional (atendimento negligente e lento ao cliente, contato impessoal com colegas de trabalho e/ou pacientes/clientes) e organizacional (conflito com os membros da equipe, rotatividade, absenteísmo, diminuição da qualidade dos serviços). Mais pesquisas devem ser realizadas para que mudanças positivas nas organizações de trabalho sejam baseadas em evidências científicas.

BACKGROUND: Burnout syndrome is consequent of prolonged levels of stress in the work’s environment. OBJECTIVE: The aims of this article are to obtain information about the syndrome’s prevalence in Brazil and in other countries, the risk factors responsible for its development, its association with psychiatric disorders and consequences for the individual and for the organization. METHODS: It was carried out a review using database from MedLine, Scielo, American Psychiatry Association, Evidence-Based Mental Health, American College of Physicians, Agency for Healthcare Research and Quality, National Guideline Clearinghouse and from World Health Organization, between 1985 and 2006. CONCLUSION: The prevalence is still uncertain, but data suggest that it could affect a significant number of individuals, range from aproximately 4 percent to 85.7 percent according to the studied population. It could be presented as a comorbidity with some psychiatric illnesses like depressive disorder. The effects of burnout could interfere negatively in the individual level (physical, mental, professional and social); professional level (slow and negligent service to the patient/customer, impersonal contact with colleagues and/or patient/customers); and organizational level (conflict with the team’s members, turnover, absenteeism, diminishing of service’s quality). More researches should be carried out to organizations make positive changes based in scientific evidences.

Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression: a randomized double-blind trial in a Brazilian sample / Hypericum perforatum versus fluoxetina no tratamento da depressão leve a moderada: estudo duplo-cego randomizado em uma amostra brasileira

OBJETIVE: Hypericum perforatum has demonstrated antidepressant efficacy when compared to placebo, but comparisons with other antidepressants remain controversial. We assessed the efficacy and safety of Hypericum perforatum in comparison with fluoxetine, in a 8-week double-blind trial in patients with mild to moderate depression. METHOD: Seventy-two outpatients were randomly assigned to receive Hypericum perforatum 900 mg/day, fluoxetine 20 mg/day or placebo. Efficacy measures included the HAM-D21 scale, the Montgomery-Åsberg Rating Scale, and the Clinical Global Impression. Safety was assessed with the UKU Side Effect Rating Scale. RESULTS: Intention-to-treat analysis showed no differences between the mean scores of the three groups. In the analyses of observed cases, patients receiving Hypericum perforatum had the lowest remission rates (12 percent, p = 0.016) compared to fluoxetine (34.6 percent) and placebo (45 percent). CONCLUSIONS: Hypericum perforatum was less efficacious than both fluoxetine and placebo. Both drugs were safe and well-tolerated. Larger trials are needed for definite conclusions.

OBJETIVO: Hypericum perforatum demonstrou eficácia antidepressiva em comparação ao placebo, mas comparações com outros antidepressivos permanecem controversas. Avaliamos a eficácia e a tolerabilidade do Hypericum perforatum em comparação com fluoxetina e placebo, em um estudo duplo-cego de oito semanas em pacientes com depressão leve a moderada. MÉTODO: Setenta e dois pacientes ambulatoriais receberam aleatoriamente doses fixas de Hypericum perforatum 900 mg/dia, fluoxetina 20 mg/dia ou placebo. Medidas de eficácia incluíram a HAM-D21, Escala de Montgomery-Asberg e Impressão Clínica Global. A segurança foi avaliada por meio da Escala UKU de Efeitos Colaterais. RESULTADOS: A análise por intenção de tratar não demonstrou diferenças entre os três grupos. Na análise por casos observados, os pacientes que receberam Hypericum perforatum tiveram as menores taxas de remissão (12 por cento, p = 0,016), em comparação à fluoxetina (34,6 por cento) e ao placebo (45 por cento). CONCLUSÕES: Hypericum perforatum foi menos eficaz que fluoxetina e placebo. Ambas as drogas foram seguras e bem toleradas. Estudos conclusivos com uma maior amostra são necessários.

Depressão / Depression

Os transtornos depressivos são um grave problema de saúde pública, pela alta prevalência na população, e grande impacto na morbidade, mortalidade e qualidade de vida dos afetados. Apesar disso, a maioria dos pacientes segue sem diagnóstico ou sem tratamento adequado. Dificuldades diagnósticas como o reconhecimento da bipolaridade em pacientes depressivos e os preconceitos em relação às doenças mentais, por parte de pacientes e médicos, devem ser conhecidas e contornadas na prática clínica. Os médicos de todas as especialidades necessitam adquirir a capacidade de utilizar corretamente ao menos dois antidepressivos de classes farmacológicas diferentes, em doses e tempo adequados, antes de encaminhar para um médico psiquiatra especialista em transtornos do humor. Informações atualizadas sobre o diagnóstico e tratamento dos transtornos depressivos devem ser oferecidas regularmente em programas de educação médica.

Depressão e comorbidades clínicas / Depression and medical comorbidity

A associação entre depressão e doenças clínicas é muito freqüente, levando a pior evolução tanto do quadro psiquiátrico como da doença clínica, com menor aderência às orientações terapêuticas, além de maior morbidade e mortalidade. A depressão muitas vezes é subdiagnosticada e subtratada, principalmente pela presença de sintomas depressivos, que também podem ocorrer em doenças crônicas, como fadiga e anorexia. Diversas doenças estão claramente associadas à depressão, com maior destaque para as doenças cardiovasculares, endocrinológicas, neurológicas, renais, oncológicas e outras síndromes dolorosas crônicas. Os autores discutem as evidências na literatura que demonstram essa associação, com enfoque nos avanços em fisiopatologia e terapêutica psiquiátrica.