Impact of response shift effects in the assessment of self-reported depression during treatment: Insights from a rTMS versus Venlafaxine randomized controlled trial.

PURPOSE: Patient-Reported Outcomes are essential to properly assess treatment effectiveness in randomized clinical trial (RCT) for Major Depressive Disorder (MDD). MDD self-assessment may vary over time depending on change in the meaning of patients' self-evaluation of depression, i.e. Response Shift (RS). Our aim was to investigate RS and its impact on different depression domains in a clinical trial comparing rTMS versus Venlafaxine. METHODS: The occurrence and type of RS was determined using Structural Equation Modeling applied to change over time in 3 domains (Sad Mood, Performance Impairment, Negative Self-Reference) of the short-form Beck Depression Inventory (BDI-13) in a secondary analysis of a RCT on 170 patients with MDD treated by rTMS, venlafaxine or both. RESULTS: RS was evidenced in the venlafaxine group in the Negative Self-Reference and Sad Mood domains. CONCLUSION: RS effects differed between treatment arms in self-reported depression domains in patients with MDD. Ignoring RS would have led to a slight underestimation of depression improvement, depending on treatment group. Further investigations of RS and advancing new methods are needed to better inform decision making based on Patient-Reported Outcomes.

Venlafaxine XR treatment for older patients with major depressive disorder: decision trees for when to change treatment.

BACKGROUND: Predictors of antidepressant response in older patients with major depressive disorder (MDD) need to be confirmed before they can guide treatment. OBJECTIVE: To create decision trees for early identification of older patients with MDD who are unlikely to respond to 12 weeks of antidepressant treatment, we analysed data from 454 older participants treated with venlafaxine XR (150-300 mg/day) for up to 12 weeks in the Incomplete Response in Late-Life Depression: Getting to Remission study. METHODS: We selected the earliest decision point when we could detect participants who had not yet responded (defined as >50% symptom improvement) but would do so after 12 weeks of treatment. Using receiver operating characteristic models, we created two decision trees to minimise either false identification of future responders (false positives) or false identification of future non-responders (false negatives). These decision trees integrated baseline characteristics and treatment response at the early decision point as predictors. FINDING: We selected week 4 as the optimal early decision point. Both decision trees shared minimal symptom reduction at week 4, longer episode duration and not having responded to an antidepressant previously as predictors of non-response. Test negative predictive values of the leftmost terminal node of the two trees were 77.4% and 76.6%, respectively. CONCLUSION: Our decision trees have the potential to guide treatment in older patients with MDD but they require to be validated in other larger samples. CLINICAL IMPLICATIONS: Once confirmed, our findings may be used to guide changes in antidepressant treatment in older patients with poor early response.

Successfully treated patients with vortioxetine versus venlafaxine: a simplified cost-effectiveness analysis based on a head-to-head study in Asian patients with major depressive disorder.

Objective: To compare the rates of successfully treated patients (STPs) with vortioxetine versus venlafaxine in major depressive disorder (MDD), using dual endpoints that combine improvement of mood symptoms with optimal tolerability or functional remission, and conduct a simplified cost-effectiveness analysis.Methods: The 8-week SOLUTION study (NCT01571453) assessed the efficacy and safety of vortioxetine (10 mg/day) versus venlafaxine XR (150 mg/day) in adult Asian patients with MDD. Rates were calculated post-hoc of STP Mood and Tolerability (≥50% reduction from baseline in Montgomery-Åsberg Depression Rating Scale [MADRS] total score and no treatment-emergent adverse events) and STP Mood and Functioning (≥50% reduction from baseline in MADRS total score and Sheehan Disability Scale total score ≤6). The incremental costs per STP were assessed using the 2018 pharmacy purchase prices for branded vortioxetine/branded venlafaxine in China as the base case.Results: STP Mood and Tolerability rates were 28.9% for vortioxetine and 19.9% for venlafaxine (p = .028); the corresponding STP Mood and Functioning rates were 28.0% and 23.5% (p = .281). Drug costs for the 8-week treatment period were CN¥1954 for vortioxetine and CN¥700 for venlafaxine. The incremental cost per STP for vortioxetine versus venlafaxine was CN¥13,938 for Mood and Tolerability and CN¥27,876 for Mood and Functioning.Conclusions: Higher rates of dual treatment success were seen with vortioxetine versus venlafaxine. Although vortioxetine was not dominant in the base case, the incremental cost per STP for vortioxetine versus venlafaxine were overall within acceptable ranges. These results support the benefits previously reported with vortioxetine versus other antidepressants in broad efficacy, tolerability profile and cost-effectiveness.

The Concise Health Risk Tracking Self-Report (CHRT-SR) assessment of suicidality in depressed outpatients: A psychometric evaluation.

BACKGROUND: The 12-item Concise Health Risk Tracking Self-Report (CHRT-SR12 ) is a brief, self-report measure that systematically assesses both suicidal thinking and associated thoughts that may indicate the propensity for suicidal acts. It can be used as a tool to both assess risk and guide treatment interventions targeting associated cognitions. METHODS: This report used acute treatment data from a clinically representative sample of outpatients with nonpsychotic major depressive disorder (N = 665) participating in the Combining Medications to Enhance Depression Outcomes trial, who received up to 12 weeks of escitalopram, escitalopram plus bupropion SR, or venlafaxine XR plus mirtazapine. Outcome assessors and patients were masked to treatment. RESULTS: Factor analysis of CHRT-SR12 confirmed that the 12 items have higher order structure with two subscales (Propensity, Suicidal Thoughts) and a total score. Internal consistencies were acceptable for both subscales and total score. All three scales were modestly correlated with overall depression severity (r = 0.54 to r = 0.21) and highly discriminating among patients grouped by suicide item ratings on three different depressive symptom ratings. The three scales also distinguished change over the acute phase treatment for those with different levels of baseline suicidal ideation (measured by 30-item Inventory of Depressive Symptomatology (item 18) and for those with change in suicidal ideation (baseline to last visit). CONCLUSIONS: The CHRT-SR12 has good to excellent psychometric properties and is sensitive to change in suicidal thinking and propensity toward suicidal behavior in outpatients with major depressive disorder. It allows for the monitoring of thoughts and feelings associated with increased suicidal risk as well as levels of thoughts about suicide.

Assessment of the relationship of spiritual well-being to depression and quality of life for persons with spinal cord injury.

OBJECTIVE: This study sought to describe the association between spiritual well-being, demographic characteristics, quality of life (QOL) and depressive symptoms following spinal cord injury (SCI). We hypothesized QOL and depressed mood would both be explained by extent of spiritual well-being, and meaning-focused (M&P) spirituality would have a stronger impact than faith-focused spirituality. METHODS: 210 individuals with SCI were screened as part of a randomized control trial of venlafaxine XR for major depressive disorder (MDD). 204 completed all measures: Patient Health Questionniare-9 (PHQ-9) assessed depression, the FACIT-Sp assessed spiritual well-being, the Neuro-QOL PAWB scale assessed QOL, and the PANAS assessed affect. RESULTS: Approximately 26% had major depression. Bivariate correlations of scores on PAWB and PANAS and FACIT-Sp showed that all four scales had strong associations with those on PAWB (p < 0.0005). As hypothesized, both the M&P and Faith scales of the FACIT-Sp were significant predictors of QOL (ß = 0.544; p < 0.0005 and ß = 0.151; p = 0.004), though only the M&P scale was an independently significant predictor of likely MDD. CONCLUSION: The findings support that spirituality, as measured by the FACIT-Sp, is strongly associated with QOL and likelihood of MDD. Assessment of spirituality should be included along with more traditional psychological measurements to better inform treatment. Implications for Rehabilitation Spiritual beliefs can contribute to quality of life and may help moderate depressive symptoms that accompany chronic illness and disability, suggesting that rehabilitation professionals should address spirituality in working with their patients with spinal cord injury (SCI). While spiritual issues are often deferred to pastoral counselors during hospitalization, it is clear that addressing these is not the domain of one discipline and does not end upon inpatient discharge. In addressing spirituality, clinicians should tap the spiritual strengths present in their clients, whether meaning/peace-focused or religious, understanding that spirituality involves more than religiosity and also that having a sense of meaning and peace appears to be of great importance.

Análisis de costo-efectividad de los medicamentos utilizados para el tratamiento de pacientes con dolor neuropático en Colombia / Cost-effectiveness analysis of drugs used for the treatment of patients with neuropathic pain in Colombia

INTRODUCCIÓN: El análisis de costo-efectividad de ácido tióctico, acetaminofén y tramadol, acetaminofén e hidrocodona, tramadol, amitriptilina, imipramina, valproato, acetaminofén y codeína, buprenorfina, capsaicina, carbamazepina, parches de fentanyl, tapentadol, duloxetina, gabapentina, parches de lidocaína, oxcarbazepina, pregabalina para el tratamiento de pacientes con dolor neuropatico en Colombia, se desarrolla en el marco del mecanismo técnico-científico para la ampliación progresiva del plan de beneficios y la definición de la lista de exclusiones, establecido en el artículo 15 de la Ley 1751 de 2015. Estas tecnologías fueron seleccionadas por la Dirección de Beneficios, Costos y Tarifas del Aseguramiento en Salud del Ministerio de Salud y Protección Social (MinSalud), y remitidas al Instituto de Evaluación Tecnológica en Salud (IETS) para su evaluación. Con respecto a la condición de salud de interés, la asociación internacional para el estudio del dolor (IASP 2011) definió el dolor neuropático como dolor causado por consecuencia directa de una lesión o enfermedad del sistema nervioso somatosensitivo. El mecanismo generador del dolor neuropático se halla en cualquier sitio a lo largo del recorrido de las vías nociceptivas (las vías que conducen la información de tipo doloroso), sin estimular inicialmente a los nociceptores (los receptores de dolor), a diferencia de lo que sucede con el dolor nociceptivo o fisiológico. El dolor neuropático es causado por diversos trastornos que afectan el sistema nervioso central y perifér

Análisis de impacto presupuestal de escitalopram, paroxetina y venlafaxina como terapia de mantenimiento para pacientes adultos con trastorno de ansiedad generalizada en Colombia / Budget impact analysis of escitalopram, paroxetine and venlafaxine as maintenance therapy for adult patients with generalized anxiety disorder in Colombia

Tecnologías evaluadas: Nuevas: escitalopram, paroxetina y venlafaxina, Actuales: sertralina y fluoxetina. Población: Pacientes mayores de 18 años con trastorno de ansiedad generalizada en Colombia. Perspectiva: La perspectiva del presente AIP corresponde al tercero pagador, que en este caso es el Sistema General de Seguridad Social en Salud (SGSSS) en Colombia. Horizonte temporal: El horizonte temporal de este AIP en el caso base corresponde a un año. Adicionalmente se reportan las estimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión en el POS en el año 1. Costos incluidos: Costos por mg de los medicamentos analizados. Fuente de costos: Los precios de cada tecnologías considerada fueron calculados con la base de datos SISMED. Escenarios: En el escenario 1 se considera una igualación progresiva de las participaciones de mercado de todos los medicamentos analizados, igualándose en el año 3. En el escenario 2, además de dicha igualación de participaciones de mercado, se asumen un precio común para las nuevas alternativas, siguiendo las metodologías de inclusión fe grupos terapéuticos definidas\r\npor el Ministerio de Salud y Protección Social. Resultados: Para la inclusión en el POS de escitalopram, paroxetina y venlafaxina como terapia de mantenimiento para pacientes con trastorno de ansiedad\r\ngeneralizada en Colombia, se requeriría una inversión de $5.874.138.950 en el año 1 y de $5.795.867.954 en el año 3. En el caso en el que los medicamentos del escenario nuevo sean incluidos con un precio común\r\nbasado en las metodologías de grupos terapéuticos del Ministerio de Salud y protección Social, el impacto presupuestal se reduciría a $664.806.300 en el año 1 y $631.634.228, en el año 3.(AU)

Análisis de impacto presupuestal de escitalopram, paroxetina y venlafaxina como terapia de mantenimiento para pacientes adultos con trastorno de fobia social en Colombia / Budget impact analysis of escitalopram, paroxetine and venlafaxine as maintenance therapy for adult patients with social phobia disorder in Colombia

Tecnologías evaluadas: Nuevas: escitalopram, paroxetina y venlafaxina, Actuales: sertralina y fluoxetina. Población:\tPacientes mayores de 18 años con trastorno de fobia social en Colombia. Perspectiva: La perspectiva del presente AIP corresponde al tercero pagador, que en este caso es el Sistema General de Seguridad Social en Salud (SGSSS) en Colombia. Horizonte temporal: El horizonte temporal de este AIP en el caso base corresponde a un año. Adicionalmente se reportan las estimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión en el POS en el año 1. Costos incluidos: Costos por mg de los medicamentos analizados. Fuente de costos: Los precios de cada tecnologías considerada fueron calculados con la base de datos SISMED. Escenarios: En el escenario 1 se considera una igualación progresiva de las participaciones de mercado de todos los medicamentos analizados, igualándose en el año 3. En el escenario 2, además de dicha igualación de participaciones de mercado, se asumen un precio común para las nuevas alternativas, siguiendo las metodologías de inclusión fe grupos terapéuticos definidas\r\npor el Ministerio de Salud y Protección Social. Resultados: Para la inclusión en el POS de escitalopram, paroxetina y venlafaxina como terapia de mantenimiento para pacientes con trastorno de fobia social en\r\nColombia, se requeriría una inversión de $44.181.317.390 en el año 1 y de $34.102.843.305 en el año 3. En el caso en el que los medicamentos del escenario nuevo sean incluidos con un precio común basado en las\r\nmetodologías de grupos terapéuticos del Ministerio de Salud y protección Social, el impacto presupuestal se reduciría a $5.822.672.775 en el año 1 y $3.330.318.162, en el año 3.(AU)

Cost-effectiveness of vortioxetine versus venlafaxine (extended release) in the treatment of major depressive disorder in South Korea.

OBJECTIVE: To assess the cost-effectiveness of vortioxetine versus venlafaxine XR (extended-release) in major depressive disorder (MDD) patients in South Korea. METHODS: A 1-year cost-effectiveness analysis from a limited societal perspective was performed using a combined model consisting of a decision-tree and a Markov model. Patients entered the model when initiating or switching antidepressant treatment following inadequate response to previous treatment. Remission, relapse and recovery were the main health states. RESULTS: Vortioxetine dominated venlafaxine XR, with quality-adjusted life year (QALY) gains of 0.0131 and cost savings of KRW 623,229/year [US$530/year] from a limited societal perspective. Safety contributed more than efficacy to the incremental QALY gains. More patients were in recovery after initial treatment and after 1 year with vortioxetine (31%, 40%) compared to venlafaxine XR (23%, 36%). Vortioxetine remained dominant in 98% of probabilistic simulations. CONCLUSION: Vortioxetine dominated venlafaxine XR in South Korea and is a relevant treatment option for MDD patients initiating or switching therapy.

[Economic evaluation of desvenlafaxine in the treatment of major depressive disorder in Spain]. / Evaluación económica de la desvenlafaxina en el tratamiento de la depresión mayor en España.

INTRODUCTION: The objective of this analysis was to evaluate the clinical and economic value of the use of 50mg-desvenlafaxine compared to the usual care (mix of duloxetine and venlafaxine) in the outpatient treatment of major depressive disorder after first line treatment failure (relapse) in Spain. MATERIALS AND METHODS: A Markov model was used to follow up a cohort of major depressive disorder patients for one year after failure of first-line treatment with a serotonin-specific reuptake inhibitor and estimate outcome measures (percentage remission and depression-free days) and accrued and direct costs incurred during outpatient treatment of major depressive disorder. In order to obtain the efficacy data related to the treatment alternatives, a literature review of clinical trials was performed. A panel of clinical experts validated the use of clinical resources employed in the estimation of economic outcomes together with model assumptions. The analysis was performed in 2014 from the perspective of the National Health System. RESULTS: Due to fewer discontinuations, initiating second line treatment with desvenlafaxine was associated with more depression-free days and a higher percentage of patients in remission versus usual care: 1.7 days and 0.5%, respectively. This was translated into lower drug and events management costs, and an overall cost reduction of €108 for the National Health System. CONCLUSIONS: In patients who have not responded to a first-line serotonin-specific reuptake inhibitor therapy, desvenlafaxine-50mg was clinically similar in effectiveness, but a less costly option, compared with a weighted average of duloxetine and venlafaxine for the second-line treatment of major depressive disorder patients from a payer (National Health System) perspective in Spain.

Effects and cost-effectiveness of pharmacogenetic screening for CYP2D6 among older adults starting therapy with nortriptyline or venlafaxine: study protocol for a pragmatic randomized controlled trial (CYSCEtrial).

BACKGROUND: Nortriptyline and venlafaxine are commonly used antidepressants for treatment of depression in older patients. Both drugs are metabolized by the polymorphic cytochrome P450-2D6 (CYP2D6) enzyme and guidelines for dose adaptations based on the CYP2D6 genotype have been developed. The CYP2D6 Screening Among Elderly (CYSCE) trial is designed to address the potential health and economic value of genotyping for CYP2D6 in optimizing dose-finding of nortriptyline and venlafaxine. METHODS/DESIGN: In a pragmatic randomized controlled trial, patients diagnosed with a major depressive disorder according to the DSM-IV and aged 60 years or older will be recruited from psychiatric centers across the Netherlands. After CYP2D6 genotyping determined in peripheral blood obtained by finger-prick, patients will be grouped into poor, intermediate, extensive, or ultrarapid metabolizers. Patients with deviant genotype (that is poor, intermediate or ultrarapid genotype) will be randomly allocated to an intervention group in which the genotype and dosing advice is communicated to the treating physician, or to a control group in which patients receive care as usual. Additionally, an external reference group of patients with the extensive metabolizer genotype is included. Primary outcome in all groups is time needed to obtain an adequate blood level of the antidepressant drug. Secondary outcomes include adverse drug reactions measured by a shortened Antidepressant Side-Effects Checklist (ASEC), and cost-effectiveness of the screening. DISCUSSION: Results of this trial will guide policy-making with regard to pharmacogenetic screening prior to treatment with nortriptyline or venlafaxine among older patients with depression. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01778907 ; registration date: 22 January 2013.

Management of Newer Antidepressant Medications in U.S. Commercial Health Plans.

BACKGROUND: Private health insurance plays a large role in the U.S. health system, including for many individuals with depression. Private insurers have been actively trying to influence pharmaceutical utilization and costs, particularly for newer and costlier medications. The approaches that insurers use may have important effects on patients' access to antidepressant medications. AIMS OF THE STUDY: To report which approaches (e.g., tiered copayments, prior authorization, and step therapy) commercial health plans are employing to manage newer antidepressant medications, and how the use of these approaches has changed since 2003. METHODS: Data are from a nationally representative survey of commercial health plans in 60 market areas regarding alcohol, drug abuse and mental health services in 2010. Responses were obtained from 389 plans (89% response rate), reporting on 925 insurance products. For each of six branded antidepressant medications, respondents were asked whether the plan covered the medication and if so, on what copayment tier, and whether it was subject to prior authorization or step therapy. Measures of management approach were constructed for each medication and for the group of medications. Bivariate and multivariate analyses were used to test for association of the management approach with various health plan characteristics. RESULTS: Less than 1% of health plan products excluded any of the six antidepressants studied. Medications were more likely to be subjected to restrictions if they were newer, more expensive or were reformulations. 55% of products used placement on a high cost-sharing tier (3 or 4) as their only form of restriction for newer branded antidepressants. This proportion was lower than in 2003, when 71% of products took this approach. In addition, only 2% of products left all the newer branded medications unrestricted, down from 25% in 2003. Multivariate analysis indicated that preferred provider organizations were more likely than other product types to use tier 3 or 4 placement. DISCUSSION: We find that U.S. health plans are using a variety of strategies to manage cost and utilization of newer branded antidepressant medications. Plans appear to be finding that approaches other than exclusion are adequate to meet their cost-management goals for newer branded antidepressants, although they have increased their use of administrative restrictions since 2003. Limitations include lack of information about how administrative restrictions were applied in practice, information on only six medications, and some potential for endogeneity bias in the regression analyses. CONCLUSION: This study has documented substantial use of various restrictions on access to newer branded antidepressants in U.S. commercial health plans. Most of these medications had generic equivalents that offered at least some substitutability, reducing access concerns. At the same time, it is worth noting that high copayments and administrative requirements can nonetheless be burdensome for some patients. IMPLICATIONS FOR HEALTH POLICY: Health plans' pharmacy management approaches may concern policymakers less than in the early 2000s, due to the lesser distinctiveness of today's branded medications. This may change depending on future drug introductions. IMPLICATIONS FOR FURTHER RESEARCH: Future research should examine the impact of plans' pharmacy management approaches, using patient-level data.

Eficácia e segurança da venlafaxina, duloxetina e trazodona no tratamento da depressão / Efficacy and safety of venlafaxine, duloxetine and trazodone in the treatment of depression / Eficacia y seguridad de la venlafaxina, de la duloxetina y de la trazodona en el tratamiento de la depresíon

TECNOLOGIAS: Duloxetina, venlafaxina e trazodona. INDICAÇÃO: Depressão moderada ou grave. CARACTERIZAÇÃO DA TECNOLOGIA: A duloxetina e a venlafaxina fazem parte do grupo de antidepressivos inibidores da recaptação de serotonina e noradrenalina (IRSN). A trazodona é um antidepressivo atípico, atua inibindo a recaptação da serotonina e bloqueia os receptores adrenérgicos e histaminérgicos. Esses medicamentos aumentam a quantidade de serotonina e/ ou noradrenalina na fenda sináptica, aumentando, portanto, a estimulação sináptica e a atividade destas monoaminas no SNC. PERGUNTA: Os medicamentos duloxetina, venlafaxina e trazodona são mais eficazes e seguros para o tratamento da depressão maior em adultos do que a fluoxetina? BUSCA E ANÁLISE DE EVIDÊNCIAS CIENTÍFICAS: Foram pesquisadas as bases Medline (via Pubmed), Centre for Reviews and Dissemination (CRD), The Cochrane Library e LILACS. Buscaram-se revisões sistemáticas (RS) de ensaios clínicos que comparassem a eficácia e segurança dos medicamentos duloxetina, venlafaxina e trazodona comparados à fluoxetina para o tratamento do Transtorno Depressivo Maior, que utilizaram como critério de diagnóstico as classificações internacionais CID-10 e o DSM IV. A qualidade da evidência foi avaliada pelo sistema GRADE. Para avaliar desfechos secundários relacionados ao abandono do tratamento e efeitos adversos, dados de estudos observacionais presentes nas RS foram considerados. Avaliações de Tecnologias de Saúde e guias terapêuticos foram pesquisadas em sites de agências internacionais e na Rede Brasileira de Avaliação de Tecnologia em Saúde. RESUMO DOS RESULTADOS DOS ESTUDOS SELECIONADOS: Foram incluídas doze revisões sistemáticas (RS) com meta-análise. Na avaliação da eficácia, os resultados das RS demonstraram uma discreta superioridade da venlafaxina frente à fluoxetina. Na avaliação da segurança, ao verificar as taxas de abandono do tratamento e incidência de eventos adversos, grande parte dos estudos se mostrou inconclusiva ou levemente desfavorável à duloxetina ou venlafaxina comparados à fluoxetina. A maioria das RS apresentou evidência de baixa qualidade e todas contribuíram para uma recomendação fraca a favor da venlafaxina. Foram incluídos três guias terapêuticos que não fizeram distinção entre os medicamentos antidepressivos de segunda geração (ex. duloxetina, venlafaxina e trazodona) e os ISRS (ex. fluoxetina) para o desfecho de eficácia. RECOMENDAÇÕES: Os resultados de eficácia encontrados neste PTC apontam para a indicação da venlafaxina em caso de resposta inadequada ao tratamento com ISRS. Ao mesmo tempo em que o mecanismo de ação da venlafaxina parece estar relacionado à sua superioridade terapêutica, também estaria relacionado às suas limitações clinicas, principalmente em pacientes hipertensos ou com problemas cardíacos. A escolha inicial do medicamento deve ser pautada em vários critérios como: potenciais reações adversas e o custo do tratamento. Considerando a baixa qualidade da evidência dos resultados apresentados e o maior custo de tratamento frente às alternativas terapêuticas existentes, a fluoxetina ainda se apresenta como medicamento de primeira escolha para o tratamento do TDM em pacientes adultos, uma vez que sua eficácia é comparável às tecnologias avaliadas, com melhor tolerância. Ressalta-se que apesar de não ter sido objeto de comparação neste PTC outros ISRS, tais como: sertralina, citalopram ou escitalopram parecem possuir eficácia comparável entre si. Quanto a duloxetina e trazodona, não foram encontradas evidências de comparação direta com fluoxetina.(AU)

TECHNOLOGIES: duloxetine, venlafaxine and trazodone. INDICATION: moderate or major depression. CHARACTERIZATION OF THE TECHNOLOGY: Duloxetine and venlafaxine are part of the group of antidepressants reuptake of serotonin and norepinephrine (IRSR). Trazodone is an atypical antidepressant, works by inhibiting the reuptake of serotonin and blocks the adrenergic and histaminergic. These drugs increase the amount of serotonin and / or noradrenaline in the synaptic cleft, thereby increasing synaptic stimulation and the activity of these monoamines in the CNS. QUESTION: Are duloxetine, venlafaxine and trazodone more effective and safe than fluoxetine for the treatment of major depression in adults? SEARCH AND ANALYSIS OF SCIENTIFIC EVIDENCE: We searched Medline (via Pubmed) Centre for Reviews and Dissemination (CRD), The Cochrane Library and LILACS. Sought to systematic reviews (SR) clinical trials that compared the efficacy and safety of duloxetine drugs, venlafaxine and trazodone compared to fluoxetine for the treatment of Major Depressive Disorder, which used as a diagnostic criterion the international classifications ICD-10 and DSM IV. The quality of evidence was evaluated by the GRADE system. To evaluate secondary endpoints related to the abandonment of treatment and adverse effects data from observational studies present in the SR were considered. Health Technology Assessments and therapeutic guidelines were searched in international agency sites and the Brazilian Network for Health Technology Assessment. SUMMARY OF THE RESULTS OF THE SELECTED STUDIES: Twelve systematic reviews with meta-analysis were included. In assessing effectiveness, the results of SR showed a slight superiority of venlafaxine front of fluoxetine. In safety assessment, to check the dropout rates of treatment and incidence of adverse events, most studies proved inconclusive or slightly unfavorable to duloxetine or venlafaxine compared to fluoxetine. Most SR presented evidence of low quality and all contributed to a weak recommendation in favor of venlafaxine. Were included three therapeutic guides who didn't distinguish between second-generation antidepressant medications (eg, duloxetine, venlafaxine and trazodone) and SSRIs (eg, fluoxetine) for efficacy endpoint. RECOMMENDATIONS: Efficacy results of this study point to the indication of venlafaxine in case of inadequate response to treatment with SSRIs. While the mechanism of action of venlafaxine seems to be related to its therapeutic superiority it could also be related to its clinical limitations, especially in hypertensive patients or in patients with heart problems. The initial choice of drug should be based on various criteria such as potential adverse reactions and the cost of treatment. Given the low quality of the evidence and the higher cost of treatment in face of existing treatment alternatives, fluoxetine still presents itself as the first choice drug for the treatment of MDD in adult patients, since its effectiveness is comparable to the evaluated technologies and it is better tolerated. We emphasize that despite not having been the object of comparison in this study other SSRIs such as sertraline, citalopram or escitalopram seem to have comparable efficacy to each other. As for duloxetine and trazodone, we found no evidence of direct comparison with fluoxetine.(AU)

TECNOLOGÍA: Duloxetina, venlafaxina y trazodona. INDICACIÓN: Depresión moderada o grave. CARACTERIZACIÓN DE LA TECNOLOGÍA: La parte venlafaxina y duloxetina del grupo antidepresivos de la recaptación de serotonina y norepinefrina (IRSN). La trazodona es un antidepresivo atípico, actúa mediante la inhibición de la recaptación de serotonina y bloquea los receptores adrenérgicos e histamina. Estos fármacos aumentan la cantidad de serotonina y/o norepinefrina en la hendidura sináptica, lo que aumenta la estimulación sináptica y la actividad de estas monoaminas en el SNC. PREGUNTA: ¿Las drogasduloxetina, venlafaxina, trazodona y son más eficaces para el tratamiento de la depresión mayor en adultos que la fluoxetina? BÚSQUEDA Y ANÁLISIS DE LA EVIDENCIA CIENTÍFICA: Se hicieron búsquedas en las bases de datos Medline (viaPubmed), Centre for Reviews and Dissemination (CRD), The Cochrane Library y en LILACS. Mucha demanda hasta Revisiones Sistemáticas (RS) de ensayos clínicos que compararon la eficacia y seguridad de medicamentos duloxetina, venlafaxina, trazodona en comparación con la para el tratamiento de la depresión moderada o grave, que utiliza como criterio diagnóstico de las clasificaciones internacionales de la CID-10 y DSM IV. Para evaluar los objetivos secundarios relacionados con el abandono del tratamiento y los efectos adversos, se consideraron los datos de estudios observacionales presentes en el RS. La calidad de la evidencia se evaluaron utilizando el sistema GRADE. Evaluación de Tecnologías Sanitarias y las guias terapéuticas fueron encuestados en las agencias y sitios web internacionales de la Red Brasileña de Evaluación de Tecnologías Sanitarias. RESUMEN DE LOS RESULTADOS DE LOS ESTUDIOS SELECCIONADOS: Se incluyeron doce RS con y meta-análisis. En la evaluación de la eficacia, los resultados de RS mostraron una ligera superioridad de venlafaxina frente de la fluoxetina. Una evaluación de la seguridad, para comprobar las tasas de abandono del tratamiento y la incidencia de eventos adversos, la mayoría de los estudios demostró inconclusa o ligeramente desfavorable a la duloxetina o venlafaxina en comparación con la fluoxetina. La mayoría de RS mostraron evidencia de baja calidad y contribuyeron a una recomendación débil a favor de la venlafaxina. Se incluyeron tres guías terapéuticas que no hacía distinciones entre los antidepresivos de segunda generación (por ejemplo, duloxetina, venlafaxina y trazodona) y los ISRS (por ejemplo fluoxetina) para los resultados de eficacia. RECOMENDACIONES: Los resultados de eficacia de este estudio apuntan para la indicación de la venlafaxina en caso de respuesta inadecuada al tratamiento con ISRS. Mientras que el mecanismo de acción de la venlafaxina parece estar relacionada con su superioridad terapéutica también se relacionó con sus limitaciones clínicas, especialmente en pacientes hipertensos o con problemas del corazón. La elección inicial de drogas debe basarse en diversos criterios, tales como reacciones adversas potenciales y el costo del tratamiento. Dada la baja calidad de la evidencia de los resultados presentados y el mayor costo del tratamiento en frente a de las alternativas de tratamiento existentes, la fluoxetina todavía presentase como el fármaco de primera elección para el tratamiento del trastorno depresivo mayor en adultos, ya que su eficacia es comparable a las tecnologías evaluadas con mejor tolerancia. Es de destacar que a pesar de no haber sido objeto de comparación en este estudio otros ISRS tales como sertralina, citalopram o escitalopram parecen tener una eficacia comparable entre ellos. Cuanto a la duloxetina y la trazodona, no se encontraron pruebas de comparación directa con la fluoxetina.(AU)

Influence of the CYP2D6 isoenzyme in patients treated with venlafaxine for major depressive disorder: clinical and economic consequences.

BACKGROUND: Antidepressant drugs are the mainstay of drug therapy for sustained remission of symptoms. However, the clinical results are not encouraging. This lack of response could be due, among other causes, to factors that alter the metabolism of the antidepressant drug. OBJECTIVE: to evaluate the impact of concomitant administration of CYP2D6 inhibitors or substrates on the efficacy, tolerability and costs of patients treated with venlafaxine for major depressive disorder in clinical practice. METHODS: We designed an observational study using the medical records of outpatients. Subjects aged ≥ 18 years who started taking venlafaxine during 2008-2010 were included. Three study groups were considered: no combinations (reference), venlafaxine-substrate, and venlafaxine-inhibitor. The follow-up period was 12 months. The main variables were: demographic data, comorbidity, remission (Hamilton <7), response to treatment, adverse events and costs. The statistical analysis included logistic regression models and ANCOVA, with p values <0.05 considered significant. RESULTS: A total of 1,115 subjects were recruited. The mean age was 61.7 years and 75.1% were female. Approximately 33.3% (95% CI: 30.5 to 36.1) were receiving some kind of drug combination (venlafaxine-substrate: 23.0%, and venlafaxine-inhibitor: 10.3%). Compared with the venlafaxine-substrate and venlafaxine-inhibitor groups, patients not taking concomitant drugs had a better response to therapy (49.1% vs. 39.9% and 34.3%, p<0.01), greater remission of symptoms (59.9% vs. 50.2% and 43.8%, p<0.001), fewer adverse events (1.9% vs. 7.0% and 6.1%, p<0.05) and a lower mean adjusted cost (€2,881.7 vs. €4,963.3 and €7,389.1, p<0.001), respectively. All cost components showed these differences. CONCLUSIONS: The patients treated with venlafaxine alone showed a better response to anti-depressant treatment, greater remission of symptoms, a lower incidence of adverse events and lower healthcare costs.

Prediction of antidepressant response to venlafaxine by a combination of early response assessment and therapeutic drug monitoring.

INTRODUCTION: Early assessment of a therapeutic response is a central goal in antidepressant treatment. The present study examined the potential for therapeutic drug monitoring and symptom rating to predict venlafaxine treatment efficacy (measured by overall patient response and remission). METHODS: 88 patients were uptitrated homogenously to 225 mg/day venlafaxine. Serum concentrations of venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODV) were measured at week 2. Continuous psychopathometric ratings were measured for up to 6 weeks by independent study raters. RESULTS: An early improvement was significantly more common in venlafaxine responders than non-responders (χ(2); p=0.007). While ODV serum levels were significantly higher in responders (t test; p=0.006), VEN serum levels, sum level of VEN+ODV and the ratio of ODV/VEN levels were not. Moreover, patients who showed an early response combined with an ODV serum level above the median of 222 ng/mL were significantly more likely to achieve full response (binary logistic model; p<0.01). Sensitivity (84% for early response) and specificity (81% for combination of early response and therapeutic drug monitoring) were sufficient to qualify as a reasonable screening instrument. CONCLUSION: Our results indicate that early improvement and ODV serum concentration are predictive of therapeutic outcome and can thus be used to guide use of the antidepressant venlafaxine.

Transtornos de Ansiedade I: eficácia e segurança de sertralina, citalopram e venlafaxina no tratamento de estresse pós-traumático e fobia social / Anxiety Disorders I: efficacy and safety of sertraline, citalopram and venlafixine in the treatment of posttraumatic stress disorder and social phobia / Trastornos de Ansiedad I: eficacia y seguridad de la sertralina, citalopram y venlafaxina en el tratamiento del trastorno por estrés postraumático y fobia social

TECNOLOGIAS: Venlafaxina, citalopram e sertralina. INDICAÇÃO: Tratamento de transtorno de estresse pós-traumático (TEPT) e transtorno de ansiedade social (fobia social) (TAS). CARACTERIZAÇÃO DA TECNOLOGIA: As tecnologias citalopram e sertralina pertencem à classe dos Inibidores Seletivos da Recaptação da Serotonina (ISRS) e a venlafaxina pertence à classe dos Inibidores da Recaptação de Serotonina e Norepinefrina (IRSN). PERGUNTA: Venlafaxina, citalopram e sertralina são mais eficazes e seguras no tratamento de pacientes com TEPT e TAS do que as tecnologias disponíveis no SUS (clomipramina, diazepam, clonazepam, clobazam e fluoxetina? BUSCA E ANÁLISE DE EVIDÊNCIAS CIENTÍFICAS: Foram pesquisadas as bases The Cochrane Library (via Bireme), Medline (via Pubmed), Lilacs, APA PsycNET (via PsychINFO) e Centre for Reviews and Dissemination (CRD). Buscaram-se revisões sistemáti cas (RS) de ensaios clínicos que comparassem os medicamentos entre si e com outras opções terapêuticas disponíveis no Sistema Único de Saúde para o tratamento de transtornos de ansiedade. Foram selecionadas também avaliações de tecnologias em saúde (ATS) em websites de agências internacionais e da Rede Brasileira de Avaliação de Tecnologia em saúde. Foram selecionados estudos publicados em inglês, português ou espanhol. RESUMO DOS RESULTADOS DOS ESTUDOS SELECIONADOS: Foram incluídas três RS sobre TEPT, e três RS sobre TAS. Em nenhuma das revisões foram encontrados estudos científicos que comparassem estes medicamentos diretamente entre si ou entre as alternativas incorporadas no Sistema Único de Saúde (SUS) sendo que, de maneira geral, nas comparações versus placebo os medicamentos demonstraram eficácia estatisticamente significante. Foram consideradas ainda Avaliações de Tecnologias em Saúde (ATS) de organismos internacionais acerca do tema. Em nenhuma dessas avaliações houve indicação de terapia farmacológica como primeira opção sendo que esses estudos preconizavam intervenções psicológicas. Estas avaliações indicaram antidepressivos como segunda linha para o tratamento demonstraram sua eficácia. Os estudos não recomendaram a terapia com benzodiazepínicos (BZD) e an psicóticos. RECOMENDAÇÕES: Nas atuais indicações terapêuticas listadas no Formulário Terapêutico Nacional ou nos Protocolos Clínicos e Diretrizes Terapêuticas, não há opção de tratamento farmacológico para os pacientes com TEPT e TAS no Sistema Único de Saúde. A fluoxetina apresentou eficácia e segurança comparáveis às alternativas avaliadas nesse PTC. Considerando indicações aprovadas em bula e os resultados das RS incluídas, bem como os custos estimados, recomenda-se o uso de sertralina para TEPT e TAS.(AU)

TECHNOLOGIES: venlafaxine, citalopram and sertraline. INDICATION: Treatment of post-trauma c stress disorder and social anxiety disorder (social phobia). TECHNOLOGY CHARACTERIZATION: Technologies citalopram and sertraline belong to the class of Selec ve Serotonin Reuptake Inhibitors (SSRIs) and venlafaxine belongs to the class of Serotonin Reuptake Inhibitors and norepinephrine (SNRI). QUESTION: venlafaxine, citalopram and sertraline are safer and more effective in treating patients suffering from post-trauma c stress disorder and social anxiety than the technologies available in SUS (clomipramine, diazepam, clonazepam, clobazam and fluoxe ne? SEARCH AND ANALYSIS OF SCIENTIFIC EVIDENCE: the foundations The Cochrane Library (via BIREME), Medline (via Pubmed), Lilacs, APA PsycNET (via PsychINFO) and Centre for Reviews and Dissemination (CRD) were surveyed. We searched for systematic reviews (SR) of clinical trials that compared the drugs with each other and with other therapeutic options available in the Health System for the treatment of anxiety disorders. Reviews of health technologies (ATS) in international agencies and the Brazilian Network for Health Technology Assessment websites were also selected. Studies published in English, Portuguese or Spanish were selected. SUMMARY OF RESULTS OF SELECTED STUDIES: We included three RS on PTSD, and three RS on TAS. In none of the revisions scien fic studies comparing these drugs directly between themselves or between alterna ve incorporated into the Unified Health System (SUS) and, in general, the comparisons versus placebo medica ons demonstrated sta s cally significant efficacy were found. S ll Health Technology Assessments (HTA) were considered of interna onal organiza ons on the subject. In none of these ra ngs was no indica on of drug therapy as first choice and these studies advocated psychological interven ons. These evalua ons indicated as second -line an depressants for the treatment and demonstrated its effec veness. The studies did not recommend therapy with benzodiazepines (BZD) and an psycho cs. SUMMARY OF RESULTS OF SELECTED STUDIES: We included three RS on PTSD, and three RS on TAS. In none of the revisions scientific studies comparing these drugs directly between themselves or between alternative incorporated into the Unified Health System (SUS) and, in general, the comparisons versus placebo medications demonstrated statiscally significant efficacy were found. S ll Health Technology Assessments (HTA) were considered of international organizations on the subject. In none of these ratings was no indication of drug therapy as first choice and these studies advocated psychological interventions. These evaluations indicated as second -line an depressants for the treatment and demonstrated its effec veness. The studies did not recommend therapy with benzodiazepines (BZD) and an psycho cs. RECOMMENDATIONS: In the current therapeutic indications listed in the National Formulary or the Therapeutic Guidelines and Clinical Protocols, there is no pharmacological treatment option for patients with PTSD and SAD in the Unified Health System. Fluoxe ne showed efficacy and safety comparable to the alternatives evaluated in this PTC. Considering approved indications in bull and results of RS included, as well as es mated costs, it is recommended the use of sertraline for PTSD and SAD.(AU)

TECNOLOGÍAS: Venlafaxina, citalopram y la sertralina, INDICACIÓN: Tratamiento del trastorno de estrés postraumático y trastorno de ansiedad social (fobia social). TECNOLOGÍA CARACTERIZACIÓN : Tecnologías de citalopram y la sertralina pertenecen a la clase de inhibidores de la recaptación selectiva de serotonina (ISRS) y venlafaxina pertenece a la clase de inhibidores de la recaptación de serotonina y norepinefrina (IRSN). PREGUNTA: Venlafaxina, citalopram y la sertralina son más seguros y más eficaces en el tratamiento de pacientes que sufren de trastorno de estrés postraumático y la ansiedad social de las tecnologías disponibles en el SUS (clomipramina, diazepam, clonazepam, clobazam y fluoxe na? BÚSQUEDA Y ANÁLISIS DE LA EVIDENCIA CIENTIFICA: Las fundaciones La Biblioteca Cochrane (a través de BIREME), MEDLINE (vía PubMed), Lilas, APA PsycNET (vía PsychINFO) y Centro de Revisiones y Difusión (CRD) fueron encuestados. Se realizaron búsquedas de revisiones sistemáticas (RS) de los ensayos clínicos que compararon los fármacos entre sí y con otras opciones terapéuticas disponibles en el Sistema de Salud para el tratamiento de los trastornos de ansiedad. También se seleccionaron Avaliaciones de Tecnologías Sanitarias (ATS) en los organismos internacionales y la Red Brasileña por si os web Evaluación de Tecnologías Sanitarias. Se seleccionaron los estudios publicados en Inglés, Español o Portugués. RESUMEN DE LOS RESULTADOS DE LOS ESTUDIOS SELECCIONADOS: Tres RS fueron incluidas sobre trastorno de estrés postraumático, y tres RS en TAS. En ninguna de las revisiones de estudios cientificos que comparan estos fármacos directamente entre sí o entre alternativas incorporado en el Sistema Único de Salud (SUS) y, en general, se encontro que las comparaciones frente a los medicamentos de placebo demostró una eficacia estadíscamente significa va. Aún Evaluación de Tecnologías Sanitarias (HTA) se consideró de organizaciones internacionales en la materia. En ninguna de estas clasificaciones hubo indicación de la terapia con medicamentos como primera opción y estos estudios abogó intervenciones psicológicas. Estas evaluaciones indican que los an depresivos de segunda línea para el tratamiento y demostraron su eficacia. Los estudios no recomiendan el tratamiento con benzodiazepinas (BZD) y an psicóticos. RECOMENDACIONES: En las indicaciones terapéuticas actuales que figuran en el Formulario Nacional o las directrices terapéuticas terapéuticas y protocolos clínicos, no hay ninguna opción de tratamiento farmacológico para los pacientes con trastorno de estrés postraumático y SAD en el Sistema de Salud. Fluoxetina mostró una eficacia y una seguridad comparables a las alternativas evaluadas en este PTC. Teniendo en cuenta las indicaciones aprobadas por la Agencia Nacional de Vigilancia Sanitaria y los resultados de RS incluidos, así como los costos es mados, se recomienda el uso de sertralina para el trastorno de estrés postraumático y TAS.(AU)

Transtornos de Ansiedade III: eficácia e segurança de sertralina, citalopram e venlafaxina no tratamento de Transtorno Obsessivo-Compulsivo e Síndrome do Pânico / Anxiety Disorders III: efficacy and safety of sertraline, citalopram and venlafaxine in the treatment of Obsessive-Compulsive Disorder and Panic Disorder / Trastornos de Ansiedad III: eficacia y seguridad de la sertralina, citalopram y venlafaxina en el tratamiento del Trastorno Obsesivo-Compulsivo y Trastorno de Pánico

TECNOLOGIAS: Venlafaxina, citalopram e sertralina. INDICAÇÃO: Tratamento de Síndrome do Pânico e Transtorno Obsessivo-Compulsivo. CARACTERIZAÇÃO DA TECNOLOGIA: As tecnologias citalopram e sertralina pertencem à classe dos Inibidores Seletivos da Recaptação da Serotonina (ISRS) e a venlafaxina pertence à classe dos Inibidores da Recaptação de Serotonina e Norepinefrina (IRSN). PERGUNTA: Venlafaxina, citaloprame sertralina são mais eficazes e seguras no tratamento de pacientes com Síndrome do Pânico e Transtorno Obsessivo-Compulsivo do que as tecnologias disponíveis no SUS (clomipramina, diazepam, clonazepam, clobazam e fluoxetina)? BUSCA E ANÁLISE DE EVIDÊNCIAS CIENTÍFICAS: Foram pesquisadas as bases The Cochrane Library (via Bireme), Medline (via Pubmed), Lilacs, APA PsycNET (via PsychINFO) e Centre for Reviews and Dissemination (CRD). Buscaram-se revisões sistemáticas (RS) de ensaios clínicos que comparassem os medicamentos entre si e com outras opções terapêuticas disponíveis no Sistema Único de Saúde para o tratamento de transtornos de ansiedade. Foram selecionadas também avaliações de tecnologias em saúde (ATS) em websites de agências internacionais e da Rede Brasileira de Avaliação de Tecnologia em Saúde . Foram selecionados estudos publicados em inglês, português ou espanhol. RESUMO DOS RESULTADOS DOS ESTUDOS SELECIONADOS: Foram incluídas seis revisões sistemáticas: uma acerca da Síndrome do Pânico (SP) e cinco de Transtorno Obsessivo-Compulsivo (TOC). Em nenhuma das revisões foram encontrados estudos científicos que comparassem estes medicamentos diretamente entre si ou entre as alternativas incorporadas no Sistema Único de Saúde (SUS) sendo que, de maneira geral, nas comparações versus placebo, os medicamentos demonstraram eficácia estatisticamente significante. Foram consideradas ainda seis Avaliações de Tecnologias em Saúde (ATS) de organismos internacionais acerca do tema. Em nenhuma dessas avaliações houve indicação de terapia farmacológica como primeira opção sendo que esses estudos preconizavam intervenções psicológicas. Estas avaliações indicaram antidepressivos como segunda linha para o tratamento. Os estudos não recomendaram a terapia com benzodiazepínicos e antipsicóticos. RECOMENDAÇÕES: Os medicamentos venlafaxina, citalopram e sertralina apresentaram perfil de eficácia e segurança semelhantes aos dos medicamentos clomipramina e fluoxetina, disponíveis no SUS. Dessa forma, recomenda-se o uso de clomipramina para síndrome do pânico e de fluoxe na ou clomipramina para TOC.(AU)

TECHNOLOGIES: Venlafaxine, Citalopram and Sertraline. INDICATION: Treatment of panic disorder and obsessive-compulsive disorder. CHARACTERIZATION OF TECHNOLOGY: Citalopram and Sertraline belong to the class of Selective Serotonin Reuptake Inhibitors (SSRIs) and Velafaxine belong the class of Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs). Question: Venlafaxine, Citalopram and Sertraline are safer and more effective in trea ng pa ents with panic disorder and obsessive-compulsive disorder than the technologies incorporated into the Brazilian Public Health System (SUS)? Search And Analysis Of Scien Fic Evidence: The databases The Cochrane Library (via Bireme), Medline (via Pubmed), Lilacs, APA PsycNET (via PsychINFO) and Centre for Reviews and Dissemination (CRD) were inves gated. We searched for systematic reviews (SR) of clinical trials that compared the drugs within each other and with other therapeutic options incorporated in SUS for the treatment of anxiety disorders. Health Technology Assessments (HTA) in international agencies sites and in Brazilian Network for Health Technology Assessment (REBRATS) were also selected. Studies published in English, Portuguese or Spanish were selected. SUMMARY OF RESULTS OF THE SELECTED STUDIES: Six systema c reviews, one about panic disorder and 5 about obsessive-compulsive, were included. None of the reviews of scien fic studies compared these drugs directly between themselves or between the alterna ves incorporated into SUS and, in general, was found statistically significant efficacy in studies comparing drugs versus placebo. SixHTA´s of international organizations on the subject were considered. These HTA´sfound no indication of drug therapy as first choice and these studies advocated psychological interventions. These evaluations have demonstrated the effectiveness of an depressants as second choice for the treatment of anxiety disorders. The studies did not recommend therapy with benzodiazepines (BZD) and an"psycho cs. RECOMMENDATIONS: Venlafaxine, citalopram and sertraline presented similar efficacy and safety profiles when compared to clomipramine and fluoxetine, available in SUS. Thus, we recommend the use of clomipramine for panic disorder and fluoxetine or clomipramine for OCD.(AU)

TECNOLOGÍAS: La venlafaxina, citalopram y sertralina. INDICACIÓN: Tratamiento de Trastorno Obsesivo Compulsivo y trastorno de pánico. CARACTERIZACIÓN DE LA TECNOLOGÍA: Las tecnologías de citalopram y sertralina pertenecen a la clase de los inhibidores selec vos de la recaptación de serotonina (ISRS) y Venlafaxina pertenece a la clase de los inhibidores de la recaptación de serotonina y norepinefrina (IRSN). PREGUNTA: ¿La venlafaxina, citalopram y sertralina son más seguros y más eficaces en el tratamiento de pacientes con Trastorno Obsesivo Compulsivo y trastorno de pánico que las tecnologías incorporadas en el SNS? BÚSQUEDA Y ANÁLISIS DE LA EVIDENCIA CIENTÍFICA: las fundaciones The Cochrane Library (vía Bireme), MEDLINE (vía PubMed), Lilacs, APA PsycNET (vía PsychINFO) y Centro de Revisiones y Difusión (CRD) fueron inves gados. Hemos tratado de revisiones sistemá cas (RS) de los ensayos clínicos que compararon los fármacos entre sí y con otras opciones terapéu cas incorporadas en el sistema nacional de salud para el tratamiento de los trastornos de ansiedad. También fueron seleccionados comentarios de tecnologías sanitarias (ATS) en las agencias de un si o y la Red Brasileña de Evaluación de Tecnologías Sanitarias. Los estudios publicados en inglés, se seleccionaron portugués o español. RESUMEN DE LOS RESULTADOS DE LOS ESTUDIOS SELECCIONADOS: Fueran incluidas seis revisiones sistemá cas, una acerca de lo trastorno de pánico e cinco acerca de lo trastorno obsesivo compulsivo. En ninguna de las revisiones de estudios cien ficos que comparan estos fármacos directamente entre sí o entre las alterna vas incluidas en el Sistema Único de Salud (SUS) y, en general, las comparaciones frente a los medicamentos de placebo demostraron estadís camente se encontraron una eficacia significa va. Seis estudios de Tecnologías en Salud (ATS) de las organizaciones internacionales en la materia fueron considerados. En ninguno de estos exámenes hubo indicación de la terapia con medicamentos como primera opción y estos estudios abogó intervenciones psicológicas. Estas evaluaciones han demostrado la eficacia de los an depresivos en general, como segunda opción para el tratamiento de trastornos de ansiedad. Los estudios no recomiendan el tratamiento con benzodiacepinas (BZD) y an psicó cos. RECOMENDACIONES: La venlafaxina, el citalopram y la sertralinapresentaron eficacia y seguridad semejante a de laclomipramina y la fluoxe na,disponibles enSUS. Por lo tanto, se recomienda el uso de clomipramina para el trastorno de pánico y la fluoxe na o clomipramina para el TOC.(AU)

Transtornos de ansiedade II: eficácia e segurança de sertralina, citalopram e venlafaxina no tratamento de ansiedade generalizada / Trastornos de ansiedad II: Eficacia y seguridad de la sertralina, citalopram y venlafaxina en el tratamiento de la ansiedad generalizada / Anxiety disease II: efficacy and safety of sertraline, citalopram and venlafaxine in the treatment of generalized anxiety

TECNOLOGIAS: Venlafaxina, citalopram e sertralina. INDICAÇÃO: Tratamento de transtornos de ansiedade generalizada. CARACTERIZAÇÃO DA TECNOLOGIA: As tecnologias citalopram e sertralina pertencem à classe dos Inibidores Seletivos da Recaptação da Serotonina (ISRS) e a venlafaxina pertence à classe dos Inibidores da Recaptação de Serotonina e Norepinefrina (IRSN). PERGUNTA: Venlafaxina, citalopram e sertralina são mais eficazes e seguras no tratamento de pacientes com transtorno de ansiedade generalizada do que as tecnologias disponíveis no SUS? BUSCA E ANÁLISE DE EVIDÊNCIAS CIENTÍFICAS: : Foram pesquisadas as bases The Cochrane Library (via Bireme), Medline (via Pubmed), Lilacs, APA PsycNET (via PsychINFO) e Centre for Reviews and Dissemination (CRD). Buscaram-se revisões sistemáticas (RS) de ensaios clínicos que comparassem os medicamentos entre si e com outras opções terapêuticas disponíveis no Sistema Único de Saúde para o tratamento de transtornos de ansiedade. Foram selecionadas também avaliações de tecnologias em saúde (ATS) em websites de agências internacionais e da Rede Brasileira de Avaliação de Tecnologia em saúde. Foram selecionados estudos publicados em inglês, português ou espanhol. RESUMO DOS RESULTADOS DOS ESTUDOS SELECIONADOS: Foram incluídas duas revisões sistemáticas acerca de Transtorno de Ansiedade generalizada (TAG). Em nenhuma das revisões foram encontrados estudos científicos que comparassem o citalopram para o tratamento do TAG. Para os outros medicamentos, não houve estudos que os comparassem diretamente entre si ou entre as alternavas incorporadas no Sistema Único de Saúde (SUS) sendo que, de maneira geral, nas comparações versus placebo os medicamentos demonstraram eficácia estatisticamente significante. Foram consideradas ainda Avaliações de Tecnologias em Saúde (ATS) e guias terapêuticos de organismos internacionais acerca do tema. Em nenhuma dessas avaliações houve indicação de terapia farmacológica como primeira opção sendo que esses estudos preconizavam intervenções psicológicas. Estas avaliações indicaram antidepressivos como segunda linha para o tratamento, com exceção para os casos de fobias específicas e demonstraram sua efetividade. Os estudos não recomendaram a terapia com benzodiazepínicos e antipsicóticos. RECOMENDAÇÕES: Sertralina, venlafaxina e fluoxena, esta última disponível no SUS, demonstraram eficácia para o tratamento de TAG. Dessas três alternativas, somente a ve nlafaxina tem indicação em bula para TAG aprovada pela ANVISA, pelo FDA e pela EMA. Desta forma, recomenda-se a utilização de venlafaxina para o tratamento de TAG.(AU)

TECHNOLOGIES:Venlafaxine, citalopram and sertraline. INDICATION: Treatment of generalized anxiety disorder. TECHNOLOGY CHARACTERIZAON: Citalopram and sertraline belong to the class of Selecve Serotonin Reuptake Inhibitors (SSRIs) and venlafaxine belongs to the class of Serotonin Reuptake Inhibitors and norepinephrine (SNRI). QUESTION: Venlafaxine, citalopram and sertraline are more effecve and safe in the treatment of paents with generalized anxiety disorder than the technologies available in SUS? SEARCH AND ANALYSIS OF SCIENFIC EVIDENCE: the foundations The Cochrane Library (via BIREME), Medline (via Pubmed), Lilacs, APA PsycNET (via PsychINFO) and Centre for Reviews and Dissemination (CRD) were surveyed. We searched for systemac reviews (SR) of clinical trials that compared the drugs with each other and with other therapeutic options available in the Health System for the treatment of anxiety disorders. Reviews of health technologies (ATS) in international agencies and the Brazilian Network for Health Technology Assessment websites were also selected. Studies published in English, Portuguese or Spanish were selected. SUMMARY OF RESULTS OF SELECTED STUDIES: two systematic reviews about generalized anxiety disorder (GAD) were included. In none of the reviews scientific studies comparing citalopram for the treatment of TAG found. For other drugs, there were no studies that compared directly with each other or between alternative incorporated into the Unified Health System (SUS) and, in general, the comparisons versus placebo medications demonstrated stascally significant efficacy. Were sll considered to Health Technology Assesstiments and therapeutic guidelines of international organizations on the subject. In none of these rangs was no indication of drug therapy as first choice and these studies advocated psychological interventions. These evaluations indicated antidepressants as a second line treatment, except for cases of specific phobias and demonstrated its effectiveness. The studies did not recommend therapy with benzodiazepines and anpsychocs. RECOMMENDATIONS: Sertraline, venlafaxine and fluoxene, the laer available in SUS, have demonstrated efficacy for the treatment of GAD. Of these three alternatives, only venlafaxine has indicated labeling for TAG approved by ANVISA, FDA and the EMA. Thus, we recommend the use of venlafaxine in the treatment of GAD.(AU)

TECNOLOGÍAS: Venlafaxina, citalopram y la sertralina Indicación: Tratamiento de los trastorno de ansiedad generalizada Caracterización de la tecnología: Citalopram y la sertralina pertenecen a la clase de inhibidores de la recaptación selectiva de serotonina (ISRS) y venlafaxina pertenece a la clase de inhibidores de la recaptación de serotonina y norepinefrina (IRSN). PREGUNTA: ¿Venlafaxina, citalopram y la sertralina son más eficaces y seguros en el tra tamiento de pacientes con trastorno de ansiedad generalizada que las tecnologías disponibles en el SUS? BÚSQUEDA Y ANÁLISIS DE LA EVIDENCIA CIENTIFICA: Las fundaciones La Biblioteca Cochrane (a través de BIREME), MEDLINE (vía PubMed), Lilas, APA PsycNET (vía PsychINFO) y Centro de Revisiones y Difusión (CRD) fueron encuestados. Se realizaron búsquedas de revisiones sistemáticas (RS) de los ensayos clínicos que compararon los fármacos entre sí y con otras opciones terapéuticas disponibles en el Sistema de Salud para el tratamiento de los trastornos de ansiedad. También se seleccionaron Críticas de tecnologías sanitarias (ATS) en los organismos internacionales y la Red Brasileña por sitios web Evaluación de Tecnologías Sanitarias. Se seleccionaron los estudios publicados en Inglés, Español o Portugués. RESUMEN DE LOS RESULTADOS DE LOS ESTUDIOS SELECCIONADOS: dos revisiones sistemáticas sobre el trastorno de ansiedad generalizada (TAG) se incluyeron. En ninguna de las revisiones de estudios cientificos que comparan citalopram para el tratamiento del TAG encontrado. Para otros fármacos, no se realizaron estudios que compararon directamente entre sí o entre alternativas incorporado en el Sistema Único de Salud (SUS) y, en general, las comparaciones frente a los medicamentos de placebo demostraron una eficacia estadíscamente significava. Todavía se consideraban Evaluación de Tecnologías Sanitarias (HTA) y las directrices terapéuticas de las organizaciones internacionales en la materia. En ninguna de estas clasificaciones hubo indicación de la terapia con medicamentos como primera opción y estos estudios abogó intervenciones psicológicas. Estas evaluaciones indican antidepresivos como tratamiento de segunda línea, a excepción de los casos de fobias específicas y demostraron su eficacia. Los estudios no recomiendan el tratamiento con benzodiazepinas y anpsicócos. RECOMENDACIONES: La sertralina, venlafaxina y fluoxena, este último disponible en SUS, han demostrado eficacia para el tratamiento de TAG. De estas tres alternativas, sólo venlafaxina ha indicado equetado para TAG aprobado por la ANVISA, la FDA y la EMA. Por lo tanto, se recomienda el uso de venlafaxina en el tratamiento de TAG.(AU)