There is a growing literature exploring the placebo response within specific mental disorders, but no overarching quantitative synthesis of this research has analyzed evidence across mental disorders. We carried out an umbrella review of meta-analyses of randomized controlled trials (RCTs) of biological treatments (pharmacotherapy or neurostimulation) for mental disorders. We explored whether placebo effect size differs across distinct disorders, and the correlates of increased placebo effects. Based on a pre-registered protocol, we searched Medline, PsycInfo, EMBASE, and Web of Knowledge up to 23.10.2022 for systematic reviews and/or meta-analyses reporting placebo effect sizes in psychopharmacological or neurostimulation RCTs. Twenty meta-analyses, summarising 1,691 RCTs involving 261,730 patients, were included. Placebo effect size varied, and was large in alcohol use disorder (g = 0.90, 95% CI [0.70, 1.09]), depression (g = 1.10, 95% CI [1.06, 1.15]), restless legs syndrome (g = 1.41, 95% CI [1.25, 1.56]), and generalized anxiety disorder (d = 1.85, 95% CI [1.61, 2.09]). Placebo effect size was small-to-medium in obsessive-compulsive disorder (d = 0.32, 95% CI [0.22, 0.41]), primary insomnia (g = 0.35, 95% CI [0.28, 0.42]), and schizophrenia spectrum disorders (standardized mean change = 0.33, 95% CI [0.22, 0.44]). Correlates of larger placebo response in multiple mental disorders included later publication year (opposite finding for ADHD), younger age, more trial sites, larger sample size, increased baseline severity, and larger active treatment effect size. Most (18 of 20) meta-analyses were judged ‘low’ quality as per AMSTAR-2. Placebo effect sizes varied substantially across mental disorders. Future research should explore the sources of this variation. We identified important gaps in the literature, with no eligible systematic reviews/meta-analyses of placebo response in stress-related disorders, eating disorders, behavioural addictions, or bipolar mania.
Síntesis amplia/ Revisión panorámica de revisiones sistemáticas
BACKGROUND: As a source of readily available evidence, rigorously synthesized and interpreted by expert clinicians and methodologists, clinical guidelines are part of an evidence-based practice toolkit, which, transformed into practice recommendations, have the potential to improve both the process of care and patient outcomes. In Brazil, the process of development and updating of the clinical guidelines for the Brazilian Unified Health System (Sistema Único de Saúde, SUS) is already well systematized by the Ministry of Health. However, the implementation process of those guidelines has not yet been discussed and well structured. Therefore, the first step of this project and the primary objective of this study was to summarize the evidence on the effectiveness of strategies used to promote clinical practice guideline implementation and dissemination.
METHODS: This overview used systematic review methodology to locate and evaluate published systematic reviews regarding strategies for clinical practice guideline implementation and adhered to the PRISMA guidelines for systematic review (PRISMA).
RESULTS: This overview identified 36 systematic reviews regarding 30 strategies targeting healthcare organizations, healthcare providers and patients to promote guideline implementation. The most reported interventions were educational materials, educational meetings, reminders, academic detailing and audit and feedback. Care pathways-single intervention, educational meeting-single intervention, organizational culture, and audit and feedback-both strategies implemented in combination with others-were strategies categorized as generally effective from the systematic reviews. In the meta-analyses, when used alone, organizational culture, educational intervention and reminders proved to be effective in promoting physicians' adherence to the guidelines. When used in conjunction with other strategies, organizational culture also proved to be effective. For patient-related outcomes, education intervention showed effective results for disease target results at a short and long term.
CONCLUSION: This overview provides a broad summary of the best evidence on guideline implementation. Even if the included literature highlights the various limitations related to the lack of standardization, the methodological quality of the studies, and especially the lack of conclusion about the superiority of one strategy over another, the summary of the results provided by this study provides information on strategies that have been most widely studied in the last few years and their effectiveness in the context in which they were applied. Therefore, this panorama can support strategy decision-making adequate for SUS and other health systems, seeking to positively impact on the appropriate use of guidelines, healthcare outcomes and the sustainability of the SUS.
Síntesis amplia/ Revisión panorámica de revisiones sistemáticas
We summarized and compared meta-analyses of pharmacological and non-pharmacological interventions targeting physical health outcomes among people with schizophrenia spectrum disorders. Major databases were searched until June 1, 2018. Of 3,709 search engine hits, 27 meta-analyses were included, representing 128 meta-analyzed trials and 47,231 study participants. While meta-analyses were generally of adequate or high quality, meta-analyzed studies were less so. The most effective weight reduction interventions were individual lifestyle counseling (standardized mean difference, SMD=–0.98) and exercise interventions (SMD=–0.96), followed by psychoeducation (SMD=–0.77), aripiprazole augmentation (SMD=–0.73), topiramate (SMD=–0.72), d-fenfluramine (SMD=–0.54) and metformin (SMD=–0.53). Regarding waist circumference reduction, aripiprazole augmentation (SMD=–1.10) and topiramate (SMD=–0.69) demonstrated the best evidence, followed by dietary interventions (SMD=–0.39). Dietary interventions were the only to significantly improve (diastolic) blood pressure (SMD=–0.39). Switching from olanzapine to quetiapine or aripiprazole (SMD=–0.71) and metformin (SMD=–0.65) demonstrated best efficacy for reducing glucose levels, followed by glucagon-like peptide-1 receptor agonists (SMD=–0.39), dietary interventions (SMD=–0.37) and aripiprazole augmentation (SMD=–0.34), whereas insulin resistance improved the most with metformin (SMD=–0.75) and rosiglitazone (SMD=–0.44). Topiramate had the greatest efficacy for triglycerides (SMD=–0.68) and low-density lipoprotein (LDL)-cholesterol (SMD=–0.80), whereas metformin had the greatest beneficial effects on total cholesterol (SMD=–0.51) and high-density lipoprotein (HDL)-cholesterol (SMD=0.45). Lifestyle interventions yielded small effects for triglycerides, total cholesterol and LDL-cholesterol (SMD=–0.35 to –0.37). Only exercise interventions increased exercise capacity (SMD=1.81). Despite frequent physical comorbidities and premature mortality mainly due to these increased physical health risks, the current evidence for pharmacological and non-pharmacological interventions in people with schizophrenia to prevent and treat these conditions is still limited and more larger trials are urgently needed.
Síntesis amplia/ Revisión panorámica de revisiones sistemáticas
BACKGROUND:: Treatment options for clozapine resistance are diverse whereas, in contrast, the evidence for augmentation or combination strategies is sparse.
AIMS:: We aimed to extract levels of evidence from available data and extrapolate recommendations for clinical practice.
METHODS:: We conducted a systematic literature search in the PubMed/MEDLINE database and in the Cochrane database. Included meta-analyses were assessed using Scottish Intercollegiate Guidelines Network criteria, with symptom improvement as the endpoint, in order to develop a recommendation grade for each clinical strategy identified.
RESULTS:: Our search identified 21 meta-analyses of clozapine combination or augmentation strategies. No strategies met Grade A criteria. Strategies meeting Grade B included combinations with first- or second-generation antipsychotics, augmentation with electroconvulsive therapy for persistent positive symptoms, and combination with certain antidepressants (fluoxetine, duloxetine, citalopram) for persistent negative symptoms. Augmentation strategies with mood-stabilisers, anticonvulsants, glutamatergics, repetitive transcranial magnetic stimulation, transcranial direct current stimulation or cognitive behavioural therapy met Grades C-D criteria only.
CONCLUSION:: More high-quality clinical trials are needed to evaluate the efficacy of add-on treatments for symptom improvement in patients with clozapine resistance. Applying definitions of clozapine resistance would improve the reporting of future clinical trials. Augmentation with second-generation antipsychotics and first-generation antipsychotics can be beneficial, but the supporting evidence is from low-quality studies. Electroconvulsive therapy may be effective for clozapine-resistant positive symptoms.
QUESTION: Network meta-analyses (NMAs) of treatment efficacy across different pharmacological treatments help inform clinical decision-making, but their methodological quality may vary a lot depending also on the quality of the included primary studies. We therefore conducted a systematic review of NMAs of pharmacological treatment for common mental disorders in order to assess the methodological quality of these NMAs, and to relate study characteristics to the rankings of efficacy and tolerability.
STUDY SELECTION AND ANALYSIS: We searched three databases for NMAs of pharmacological treatment used in major depression, generalised anxiety disorder (GAD), social anxiety disorder (SAD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD) and specific phobia.Studies were appraised using the International Society for Pharmacoeconomics and Outcomes Research checklist of good research practices for indirect-treatment-comparison and network-meta-analysis studies.
FINDINGS: Twenty NMAs were eligible for inclusion. The number of randomised controlled trials per NMA ranged from 11 to 234, and included between 801 to more than 26 000 participants. Overall, antidepressants were found to be efficacious and tolerable agents for several disorders based on rankings (45%) or statistical significance (55%). The majority of NMAs in this review adhered to guidelines by including a network diagram (70%), assessing consistency (75%), making use of a random effects model (75%), providing information on the model used to fit the data (75%) and adjusting for covariates (75%).
CONCLUSIONS: The 20 NMAs of depression and anxiety disorders, PTSD and/or OCD included in this review demonstrate some methodological strengths in comparison with the larger body of published NMAs for medical disorders, support current treatment guidelines and help inform clinical decision-making.
Síntesis amplia/ Revisión panorámica de revisiones sistemáticas
BACKGROUND: A key function of health systems is implementing interventions to improve health, but coverage of essential health interventions remains low in low-income countries. Implementing interventions can be challenging, particularly if it entails complex changes in clinical routines; in collaborative patterns among different healthcare providers and disciplines; in the behaviour of providers, patients or other stakeholders; or in the organisation of care. Decision-makers may use a range of strategies to implement health interventions, and these choices should be based on evidence of the strategies' effectiveness.
OBJECTIVES: To provide an overview of the available evidence from up-to-date systematic reviews about the effects of implementation strategies for health systems in low-income countries. Secondary objectives include identifying needs and priorities for future evaluations and systematic reviews on alternative implementation strategies and informing refinements of the framework for implementation strategies presented in the overview.
METHODS: We searched Health Systems Evidence in November 2010 and PDQ-Evidence up to December 2016 for systematic reviews. We did not apply any date, language or publication status limitations in the searches. We included well-conducted systematic reviews of studies that assessed the effects of implementation strategies on professional practice and patient outcomes and that were published after April 2005. We excluded reviews with limitations important enough to compromise the reliability of the review findings. Two overview authors independently screened reviews, extracted data and assessed the certainty of evidence using GRADE. We prepared SUPPORT Summaries for eligible reviews, including key messages, 'Summary of findings' tables (using GRADE to assess the certainty of the evidence) and assessments of the relevance of findings to low-income countries.
MAIN RESULTS: We identified 7272 systematic reviews and included 39 of them in this overview. An additional four reviews provided supplementary information. Of the 39 reviews, 32 had only minor limitations and 7 had important methodological limitations. Most studies in the reviews were from high-income countries. There were no studies from low-income countries in eight reviews.Implementation strategies addressed in the reviews were grouped into four categories – strategies targeting:1. healthcare organisations (e.g. strategies to change organisational culture; 1 review);2. healthcare workers by type of intervention (e.g. printed educational materials; 14 reviews);3. healthcare workers to address a specific problem (e.g. unnecessary antibiotic prescription; 9 reviews);4. healthcare recipients (e.g. medication adherence; 15 reviews).Overall, we found the following interventions to have desirable effects on at least one outcome with moderate- or high-certainty evidence and no moderate- or high-certainty evidence of undesirable effects.1.Strategies targeted at healthcare workers: educational meetings, nutrition training of health workers, educational outreach, practice facilitation, local opinion leaders, audit and feedback, and tailored interventions.2.Strategies targeted at healthcare workers for specific types of problems: training healthcare workers to be more patient-centred in clinical consultations, use of birth kits, strategies such as clinician education and patient education to reduce antibiotic prescribing in ambulatory care settings, and in-service neonatal emergency care training.3. Strategies targeted at healthcare recipients: mass media interventions to increase uptake of HIV testing; intensive self-management and adherence, intensive disease management programmes to improve health literacy; behavioural interventions and mobile phone text messages for adherence to antiretroviral therapy; a one time incentive to start or continue tuberculosis prophylaxis; default reminders for patients being treated for active tuberculosis; use of sectioned polythene bags for adherence to malaria medication; community-based health education, and reminders and recall strategies to increase vaccination uptake; interventions to increase uptake of cervical screening (invitations, education, counselling, access to health promotion nurse and intensive recruitment); health insurance information and application support.
AUTHORS' CONCLUSIONS: Reliable systematic reviews have evaluated a wide range of strategies for implementing evidence-based interventions in low-income countries. Most of the available evidence is focused on strategies targeted at healthcare workers and healthcare recipients and relates to process-based outcomes. Evidence of the effects of strategies targeting healthcare organisations is scarce.
Síntesis amplia/ Revisión panorámica de revisiones sistemáticas
BACKGROUND: One target of the Sustainable Development Goals is to achieve "universal health coverage, including financial risk protection, access to quality essential health-care services and access to safe, effective, quality and affordable essential medicines and vaccines for all". A fundamental concern of governments in striving for this goal is how to finance such a health system. This concern is very relevant for low-income countries.
OBJECTIVES: To provide an overview of the evidence from up-to-date systematic reviews about the effects of financial arrangements for health systems in low-income countries. Secondary objectives include identifying needs and priorities for future evaluations and systematic reviews on financial arrangements, and informing refinements in the framework for financial arrangements presented in the overview.
METHODS: We searched Health Systems Evidence in November 2010 and PDQ-Evidence up to 17 December 2016 for systematic reviews. We did not apply any date, language, or publication status limitations in the searches. We included well-conducted systematic reviews of studies that assessed the effects of financial arrangements on patient outcomes (health and health behaviours), the quality or utilisation of healthcare services, resource use, healthcare provider outcomes (such as sick leave), or social outcomes (such as poverty, employment, or financial burden of patients, e.g. out-of-pocket payment, catastrophic disease expenditure) and that were published after April 2005. We excluded reviews with limitations important enough to compromise the reliability of the findings. Two overview authors independently screened reviews, extracted data, and assessed the certainty of evidence using GRADE. We prepared SUPPORT Summaries for eligible reviews, including key messages, 'Summary of findings' tables (using GRADE to assess the certainty of the evidence), and assessments of the relevance of findings to low-income countries.
MAIN RESULTS: We identified 7272 reviews and included 15 in this overview, on: collection of funds (2 reviews), insurance schemes (1 review), purchasing of services (1 review), recipient incentives (6 reviews), and provider incentives (5 reviews). The reviews were published between 2008 and 2015; focused on 13 subcategories; and reported results from 276 studies: 115 (42%) randomised trials, 11 (4%) non-randomised trials, 23 (8%) controlled before-after studies, 51 (19%) interrupted time series, 9 (3%) repeated measures, and 67 (24%) other non-randomised studies. Forty-three per cent (119/276) of the studies included in the reviews took place in low- and middle-income countries. Collection of funds: the effects of changes in user fees on utilisation and equity are uncertain (very low-certainty evidence). It is also uncertain whether aid delivered under the Paris Principles (ownership, alignment, harmonisation, managing for results, and mutual accountability) improves health outcomes compared to aid delivered without conforming to those principles (very low-certainty evidence). Insurance schemes: community-based health insurance may increase service utilisation (low-certainty evidence), but the effects on health outcomes are uncertain (very low-certainty evidence). It is uncertain whether social health insurance improves utilisation of health services or health outcomes (very low-certainty evidence). Purchasing of services: it is uncertain whether increasing salaries of public sector healthcare workers improves the quantity or quality of their work (very low-certainty evidence). Recipient incentives: recipient incentives may improve adherence to long-term treatments (low-certainty evidence), but it is uncertain whether they improve patient outcomes. One-time recipient incentives probably improve patient return for start or continuation of treatment (moderate-certainty evidence) and may improve return for tuberculosis test readings (low-certainty evidence). However, incentives may not improve completion of tuberculosis prophylaxis, and it is uncertain whether they improve completion of treatment for active tuberculosis. Conditional cash transfer programmes probably lead to an increase in service utilisation (moderate-certainty evidence), but their effects on health outcomes are uncertain. Vouchers may improve health service utilisation (low-certainty evidence), but the effects on health outcomes are uncertain (very low-certainty evidence). Introducing a restrictive cap may decrease use of medicines for symptomatic conditions and overall use of medicines, may decrease insurers' expenditures on medicines (low-certainty evidence), and has uncertain effects on emergency department use, hospitalisations, and use of outpatient care (very low-certainty evidence). Reference pricing, maximum pricing, and index pricing for drugs have mixed effects on drug expenditures by patients and insurers as well as the use of brand and generic drugs. Provider incentives: the effects of provider incentives are uncertain (very low-certainty evidence), including: the effects of provider incentives on the quality of care provided by primary care physicians or outpatient referrals from primary to secondary care, incentives for recruiting and retaining health professionals to serve in remote areas, and the effects of pay-for-performance on provider performance, the utilisation of services, patient outcomes, or resource use in low-income countries.
AUTHORS' CONCLUSIONS: Research based on sound systematic review methods has evaluated numerous financial arrangements relevant to low-income countries, targeting different levels of the health systems and assessing diverse outcomes. However, included reviews rarely reported social outcomes, resource use, equity impacts, or undesirable effects. We also identified gaps in primary research because of uncertainty about applicability of the evidence to low-income countries. Financial arrangements for which the effects are uncertain include external funding (aid), caps and co-payments, pay-for-performance, and provider incentives. Further studies evaluating the effects of these arrangements are needed in low-income countries. Systematic reviews should include all outcomes that are relevant to decision-makers and to people affected by changes in financial arrangements.
Síntesis amplia/ Revisión panorámica de revisiones sistemáticas
OBJECTIVE: To assess the available scientific evidence regarding the efficacy of interventions aimed to enhance medication adherence in patients with multiple chronic conditions (PMCC).
DESIGN: Overview of systematic reviews.
DATA SOURCES: The following databases were consulted (September 2013): Pubmed, EMBASE, the Cochrane Library, CRD and WoS to identify interventions aimed to enhance medication adherence in PMCC, or otherwise, patients with chronic diseases common in the PMCC, or polypharmacy.
STUDY SELECTION: Systematic reviews of clinical trials focused on PMCC or similar were included. They should compare the efficacy of any intervention aimed to improve compliance to prescribed and self-administered medications with clinical practice or other interventions.
DATA EXTRACTION: Information about the study population, nature of intervention and efficacy in terms of improved adherence was extracted.
RESULTS: 566 articles were retrieved of which 9 systematic reviews were included. None was specifically focused on PMCC but considered patients with chronic diseases common in the PMCC, patients with more than one chronic disease and polypharmacy. The overall effectiveness of interventions was modest without relevant differences between behavioural, educational and combined interventions. Some components of these interventions including patient counselling and regimen simplification appear to be effective tools in improving adherence in this population group.
CONCLUSION: There is a large heterogeneity of interventions aimed to improve adherence with modest efficacy, none in PMCC.
La clozapina es considerada el antipsicótico más efectivo en el manejo de la esquizofrenia resistente. A pesar de esto, hasta un tercio de los pacientes no responde a tratamiento, por lo que se han planteado múltiples estrategias terapéuticas, entre ellas la terapia electroconvulsiva, aunque aún no está claro si es efectiva y segura en estos casos. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos seis revisiones sistemáticas que en conjunto incluyen 55 estudios, entre los cuales hay seis estudios aleatorizados que evalúan esquizofrenia resistente a clozapina. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que la terapia electroconvulsiva probablemente aumenta la respuesta a tratamiento en pacientes con esquizofrenia resistente que usan clozapina, sin embargo no es posible determinar si produce efectos adversos a nivel cognitivo porque la certeza de la evidencia es muy baja.
ANTECEDENTES: Muchos países están desarrollando estrategias de prevención del suicidio para las cuales se requiere evidencia actualizada y de alta calidad. MÉTODOS: Se realizaron búsquedas en PubMed y en la Biblioteca Cochrane utilizando múltiples términos relacionados con la prevención del suicidio para los estudios publicados entre el 1 de enero de 2005 y el 31 de diciembre de 2014. Se evaluaron siete intervenciones: La educación pública y médica, las estrategias de los medios de comunicación, el cribado, la restricción del acceso a los medios de suicidio, los tratamientos y el apoyo por internet o por línea telefónica. Se extrajeron datos sobre los resultados primarios de interés, a saber, comportamiento suicida (suicidio, intento o ideación) y resultados intermedios o secundarios (búsqueda de tratamiento, identificación de individuos en riesgo, tasas de prescripción o uso de antidepresivos o referencias). 18 expertos en prevención de suicidios de 13 países europeos revisaron todos los artículos y evaluaron la fuerza de la evidencia utilizando los criterios de Oxford. Debido a que la heterogeneidad de las poblaciones y la metodología no permitieron metanálisis formal, presentamos un análisis narrativo. RESULTADOS: Se identificaron 1797 estudios, incluyendo 23 revisiones sistemáticas, 12 metaanálisis, 40 ensayos controlados aleatorios (ECA), 67 estudios de cohortes y 22 estudios ecológicos o basados en la población. La evidencia de restricción del acceso a medios letales en la prevención del suicidio se ha fortalecido desde 2005, especialmente en lo que se refiere al control de los analgésicos (disminución general del 43% desde 2005) y los puntos calientes de suicidio por salto (reducción del 86% A 91%). Se ha demostrado que los programas de concienciación en la escuela reducen los intentos de suicidio (odds ratio [OR] 0 · 45, IC del 95% 0 · 24-0 85], p = 0, 014) y la ideación suicida (0, 5, -0 · 92; p = 0 · 025). Los efectos anti-suicidas de la clozapina y el litio han sido probados, pero podrían ser menos específicos de lo que se pensaba anteriormente. Los tratamientos farmacológicos y psicológicos eficaces de la depresión son importantes en la prevención. No existen pruebas suficientes para evaluar los posibles beneficios de la prevención del suicidio en la atención primaria, en la educación general del público y en las directrices de los medios de comunicación. Otros enfoques que necesitan más investigación incluyen la formación de guardián, la educación de los médicos, y el apoyo de Internet y ayuda. La escasez de ECA es una limitación importante en la evaluación de las intervenciones preventivas. INTERPRETACIÓN: En la búsqueda de iniciativas eficaces de prevención del suicidio, ninguna estrategia única claramente está por encima de las demás. Las combinaciones de estrategias basadas en la evidencia a nivel individual y el nivel de población deben ser evaluadas con diseños de investigación sólidos. FINANCIACIÓN: Plataforma de Expertos en Salud Mental, Foco en la Depresión, y el Colegio Europeo de Neuropsicofarmacología.
There is a growing literature exploring the placebo response within specific mental disorders, but no overarching quantitative synthesis of this research has analyzed evidence across mental disorders. We carried out an umbrella review of meta-analyses of randomized controlled trials (RCTs) of biological treatments (pharmacotherapy or neurostimulation) for mental disorders. We explored whether placebo effect size differs across distinct disorders, and the correlates of increased placebo effects. Based on a pre-registered protocol, we searched Medline, PsycInfo, EMBASE, and Web of Knowledge up to 23.10.2022 for systematic reviews and/or meta-analyses reporting placebo effect sizes in psychopharmacological or neurostimulation RCTs. Twenty meta-analyses, summarising 1,691 RCTs involving 261,730 patients, were included. Placebo effect size varied, and was large in alcohol use disorder (g = 0.90, 95% CI [0.70, 1.09]), depression (g = 1.10, 95% CI [1.06, 1.15]), restless legs syndrome (g = 1.41, 95% CI [1.25, 1.56]), and generalized anxiety disorder (d = 1.85, 95% CI [1.61, 2.09]). Placebo effect size was small-to-medium in obsessive-compulsive disorder (d = 0.32, 95% CI [0.22, 0.41]), primary insomnia (g = 0.35, 95% CI [0.28, 0.42]), and schizophrenia spectrum disorders (standardized mean change = 0.33, 95% CI [0.22, 0.44]). Correlates of larger placebo response in multiple mental disorders included later publication year (opposite finding for ADHD), younger age, more trial sites, larger sample size, increased baseline severity, and larger active treatment effect size. Most (18 of 20) meta-analyses were judged ‘low’ quality as per AMSTAR-2. Placebo effect sizes varied substantially across mental disorders. Future research should explore the sources of this variation. We identified important gaps in the literature, with no eligible systematic reviews/meta-analyses of placebo response in stress-related disorders, eating disorders, behavioural addictions, or bipolar mania.
Síntesis amplia»Revisión panorámica de revisiones sistemáticas
