Tratamentos farmacológicos para transtornos de ansiedade, transtorno obsessivo-compulsivo e transtorno de estresse pós-traumático : uma meta-regressão e metanálise em rede mulinível

Anxiety, obsessive-compulsive, and stress-related disorders frequently co-occur, and patients often exhibit symptoms from multiple domains. However, meta-analyses typically limit the statistical analysis to specific symptom domains. Consequently, the efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) on multiple mental health domains has not yet been studied through meta-analyses in this field. While SSRIs and SNRIs are the first-line pharmacological treatments, many patients are non-compliant due to their fear of potential adverse events, which is the second leading cause of nonadherence. Therefore, comparing the rates of adverse events and tolerability profiles of each medication may help improve adherence. Despite this, no large-scale quantitative review has evaluated the comparative tolerability and rates of most adverse events associated with all SSRIs and SNRIs. The articles that comprise this thesis aim to compare the efficacy in multiple symptom domains and tolerability profiles of SSRIs and SNRIs in the treatment of children and adults diagnosed with anxiety, obsessive-compulsive, or stress-related disorders. To achieve this, data are gathered from a systematic review of published and unpublished randomized controlled trials that assessed the efficacy of SSRIs or SNRIs in individuals diagnosed with any anxiety, obsessive-compulsive, or stress-related disorder. Searches were conducted in MEDLINE, PsycINFO, Embase, Cochrane, publicly accessible clinical trial registries, and pharmaceutical companies' databases. No restrictions were imposed regarding comorbidities with any other mental disorder, as well as specific assessment instruments, participants' age and sex, date of publication, or study language. Article #1 estimates the acceptability and efficacy of SSRIs and SNRIs in internalizing symptoms of children and adults, also exploring the multilevel structure of efficacy in all symptom domains related to the diagnoses of anxiety, obsessive-compulsive, or stress-related disorders. Article #2 expands on the findings from article #1 by investigating the tolerability of SSRIs and SNRIs, estimating the incidence rates of 17 specific adverse events, and determining treatment rankings for those events. In both articles, data were pooled through three-level network meta-analyses and multiple meta-regression analyses, accounting for clinical and methodological differences. Results of the efficacy analysis, which included 469 outcome measures from 135 studies, support the efficacy of these medications in the overall measure of internalizing symptoms, across all symptom domains, and in patients from all diagnostic categories. Head-to-head comparisons revealed only minor differences between medications in terms of efficacy and acceptability. Tolerability analyses, including 799 outcome measures of adverse events from 80 studies, indicate that participants in medication groups experienced higher rates of adverse events compared to placebo groups. Significant differences in tolerability of medications were identified and distinct tolerability profiles were estimated for each SSRI or SNRI. This three-level network meta-analysis contributes to the ongoing discussion about the true benefits of antidepressants, providing robust evidence due to the significantly larger quantity of data, higher statistical power compared to previous studies, and the assessment of the multilevel structure of transdiagnostic efficacy. Furthermore, the tolerability findings presented here may guide clinical decision-making when clinicians consider one medication over another, potentially enhancing treatment acceptability and compliance.Transtornos de ansiedade, transtorno obsessivo-compulsivo e transtornos relacionados ao estresse frequentemente coocorrem, e os pacientes frequentemente apresentam sintomas de vários domínios; no entanto, metanálises geralmente limitam-se a análises de domínios de sintomas específicos. Consequentemente, a eficácia dos inibidores seletivos da recaptação de serotonina (ISRSs) e dos inibidores da recaptação de serotonina e noradrenalina (IRSNs) em múltiplos domínios de saúde mental ainda não foi avaliada por metanálises relacionadas a esses diagnósticos. Embora os ISRSs e IRSNs sejam os tratamentos farmacológicos de primeira escolha, muitos pacientes não aderem ao tratamento devido ao medo de potenciais eventos adversos, segunda causa mais comum para não adesão; portanto, estimar incidências de eventos adversos e perfis de tolerabilidade de cada medicamento pode ajudar a melhorar a adesão. Apesar disso, nenhuma metanálise avaliou a tolerabilidade comparativa e incidências da maioria dos eventos adversos associados a diversos ISRSs e IRSNs. Os artigos que compõem esta tese têm como objetivo comparar a eficácia nos múltiplos domínios de sintomas e os perfis de tolerabilidade dos ISRSs e IRSNs no tratamento de crianças e adultos diagnosticados com transtornos de ansiedade, obsessivo-compulsivo ou relacionados ao estresse. Para isso, os dados foram coletados por meio de uma revisão sistemática de ensaios clínicos randomizados desenvolvidos para estimar a eficácia de ISRSs ou IRSNs em indivíduos diagnosticados com os transtornos em estudo. As buscas foram realizadas no MEDLINE, PsycINFO, Embase, Cochrane, registros de ensaios clínicos e bancos de dados de empresas farmacêuticas. Não houve restrições com relação a comorbidades ou escalas específicas. O Artigo #1 avalia a aceitabilidade e eficácia de ISRSs e IRSNs nos sintomas internalizantes, explorando a estrutura multinível da eficácia em todos os domínios de sintomas. O Artigo #2 expande os achados do Artigo #1 investigando a tolerabilidade de ISRSs e IRSNs, estimando as taxas de incidência de 17 eventos adversos e ranqueando as medicações para esses eventos. Em ambos artigos, os dados foram analisados por meio de metanálises de rede multinível e modelos múltiplos de meta-regressão, considerando características clínicas e metodológicas. Resultados das análises de eficácia, as quais incluíram 469 desfechos de 135 estudos, demonstram eficácia no desfecho global de sintomas internalizantes, em todos os domínios de sintomas e em pacientes com todas categorias diagnósticas. Comparações pareadas revelaram apenas pequenas diferenças entre medicamentos quanto a eficácia e aceitabilidade. As análises de tolerabilidade, envolvendo 799 desfechos de eventos adversos de 80 estudos, indicam que participantes tratados com medicamentos apresentaram maiores taxas de incidência de eventos adversos quando comparados com grupos em uso de placebo. Foram identificadas diferenças significativas na tolerabilidade dos medicamentos e foram estimados perfis de tolerabilidade distintos para cada fármaco. Esta metanálise de rede multinível contribui para discussões sobre os verdadeiros benefícios dos antidepressivos, fornecendo evidências robustas devido à quantidade significativamente maior de desfechos, maior poder estatístico e avaliação da estrutura multinível de eficácia transdiagnóstica. Além disso, resultados de tolerabilidade podem orientar a tomada de decisão quando médicos consideram um medicamento em relação a outro, potencialmente melhorando a aceitabilidade e a adesão ao tratamento

Translating measurement into practice: Brazilian norms for the Patient Health Questionnaire (PHQ-9) for assessing depressive symptoms

OBJECTIVES: To provide practical norms for measuring depressive symptoms with the Patient Health Questionnaire 9 (PHQ-9) in Brazil through a state-of-the-art psychometrics analysis. METHODS: We used a large representative dataset from the 2019 Brazilian National Health Survey (Pesquisa Nacional de Saúde - 2019), which included 90,846 Brazilian citizens. To assess scale structure, we assessed a unidimensional model using confirmatory factor analysis. Item response theory was used to characterize the distribution of depressive symptoms. Summed- and mean-based PHQ-9 scores were then linked using item response theory-based scores in generalized additive models. Finally, percentiles, T scores, and a newly developed score, called the decimal score (D score), were generated to describe PHQ-9 norms for the Brazilian population. RESULTS: Confirmatory factor analysis revealed a good fit to the unidimensional model, being invariant to age and sex. Item response theory captured item-level information about the latent trait (reliable from 1 to 3 SDs above the mean). Brazilian norms were presented using summed scores, T scores, and D scores. CONCLUSION: This is the first study to determine Brazilian norms for the PHQ-9 among a large representative sample using robust psychometric tools. More precise PHQ-9 scores are now available and may be widely used in primary and specialized clinical care settings

Selective serotonin reuptake inhibitors, and serotonin and norepinephrine reuptake inhibitors for anxiety, obsessive-compulsive, and stress disorders : a 3-level network metaanalysis

Background: Anxiety, obsessive-compulsive, and stress-related disorders frequently co-occur, and patients often present symptoms of several domains. Treatment involves the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), but data on comparative efficacy and acceptability are lacking. We aimed to compare the efficacy of SSRIs, SNRIs, and placebo in multiple symptom domains in patients with these diagnoses over the lifespan through a 3-level network meta-analysis. Methods and findings: We searched for published and unpublished randomized controlled trials that aimed to assess the efficacy of SSRIs or SNRIs in participants (adults and children) with diagnosis of any anxiety, obsessive-compulsive, or stress-related disorder in MEDLINE, PsycINFO, Embase, and Cochrane Library from inception to 23 April 2015, with an update on 11 November 2020. We supplemented electronic database searches with manual searches for published and unpublished randomized controlled trials registered in publicly accessible clinical trial registries and pharmaceutical companies’ databases. No restriction was made regarding comorbidities with any other mental disorder, participants’ age and sex, blinding of participants and researchers, date of publication, or study language. The primary outcome was the aggregate measure of internalizing symptoms of these disorders. Secondary outcomes included specific symptom domains and treatment discontinuation rate. We estimated standardized mean differences (SMDs) with 3-level network meta-analysis with random slopes by study for medication and assessment instrument. Risk of bias appraisal was performed using the Cochrane Collaboration’s risk of bias tool. This study was registered in PROSPERO (CRD42017069090). We analyzed 469 outcome measures from 135 studies (n = 30,245). All medications were more effective placebo for the aggregate measure of internalizing symptoms (SMD −0.56, 95% CI −0.62 to −0.51, p < 0.001), for all symptom domains, and in patients from all diagnostic categories. We also found significant results when restricting to the most used assessment instrument for each diagnosis; nevertheless, this restriction led to exclusion of 72.71% of outcome measures. Pairwise comparisons revealed only small differences between medications in efficacy and acceptability. Limitations include the moderate heterogeneity found in most outcomes and the moderate risk of bias identified in most of the trials. Conclusions: In this study, we observed that all SSRIs and SNRIs were effective for multiple symptom domains, and in patients from all included diagnostic categories. We found minimal differences between medications concerning efficacy and acceptability. This three-level network meta-analysis contributes to an ongoing discussion about the true benefit of antidepressants with robust evidence, considering the significantly larger quantity of data and higher statistical power when compared to previous studies. The 3-level approach allowed us to properly assess the efficacy of these medications on internalizing psychopathology, avoiding potential biases related to the exclusion of information due to distinct assessment instruments, and to explore the multilevel structure of transdiagnostic efficacy

Behaviour of the foramen ovale flow in fetuses with intrauterine growth restriction

Foramen ovale (FO) flow may be altered in IUGR. .is study was designed to test this hypothesis. Methods. Forty pregnant women (24–38 weeks) were divided into 3 groups: group I (IUGR), group II (adequate growth and maternal hypertension), and group III (normal controls). Impedance across the FO was assessed by the FO pulsatility index (FOPI): (systolic velocity − presystolic velocity)/mean velocity. Statistical analysis utilized ANOVA, Tukey test, and ROC curves. Results. Mean FOPI in IUGR fetuses (n=15) was 3.70 ± 0.99 (3.15–4.26); in the group II (n=12), it was 2.84 ± 0.69 (2.40–3.28), and in the group III (n=13), it was 2.77 ± 0.44 (2.50–3.04) (p=0.004). FOPI and UtA RI were correlated (r= 0.375, p= 0.017), as well as FOPI and UA RI (r= 0.356, p= 0.024) and, inversely, FOPI and MCA RI (r= −0.359, p= 0.023). Conclusions. .e FO flow pulsatility index is increased in fetuses with IUGR, probably as a result of impaired left ventricular diastolic functio

Mental health care delivery and quality of service provision in Brazil

Public mental health system in Brazil is structured through “The Psychosocial Care Network (Rede de Atenção Psicossocial, RAPS)''. This coordinated system comprises primary care, specialized mental health care, crisis management services, inpatient units, deinstitutionalization initiatives, and psychosocial rehabilitation programs. In this narrative review, we aim to provide an overview of mental health care delivery in Brazil by assessing three aspects of the RAPS: structure, operationalization, and current state. For reviewing its structure, we start by overviewing the public health system, then examining the psychiatric reform, as well as the law and policy that established the components of the community-based mental health system in the country. Regarding the operationalization, we review recommendations for how the different components of the system should be coordinated, as well as directions for practices at the assistance level. Finally, we review the results of the mental health system, including official data and academic publications assessing coverage, funding, and quality of care. Drawing on the results from this review, we highlight fragilities that indicate three future directions for strengthening the mental health provision in Brazil: establishing appropriate mechanisms for systematic assessment of the mental health system, improving the recommendations regarding the coordination and integration of services, and promoting evidence-based practices across the different levels of care provision