BACKGROUND: Chronic pain is common in adults, and often has a detrimental impact upon physical ability, well-being, and quality of life. Previous reviews have shown that certain antidepressants may be effective in reducing pain with some benefit in improving patients' global impression of change for certain chronic pain conditions. However, there has not been a network meta-analysis (NMA) examining all antidepressants across all chronic pain conditions.
OBJECTIVES: To assess the comparative efficacy and safety of antidepressants for adults with chronic pain (except headache).
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, AMED and PsycINFO databases, and clinical trials registries, for randomised controlled trials (RCTs) of antidepressants for chronic pain conditions in January 2022.
SELECTION CRITERIA: We included RCTs that examined antidepressants for chronic pain against any comparator. If the comparator was placebo, another medication, another antidepressant, or the same antidepressant at different doses, then we required the study to be double-blind. We included RCTs with active comparators that were unable to be double-blinded (e.g. psychotherapy) but rated them as high risk of bias. We excluded RCTs where the follow-up was less than two weeks and those with fewer than 10 participants in each arm. DATA COLLECTION AND ANALYSIS: Two review authors separately screened, data extracted, and judged risk of bias. We synthesised the data using Bayesian NMA and pairwise meta-analyses for each outcome and ranked the antidepressants in terms of their effectiveness using the surface under the cumulative ranking curve (SUCRA). We primarily used Confidence in Meta-Analysis (CINeMA) and Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) to assess the certainty of the evidence. Where it was not possible to use CINeMA and ROB-MEN due to the complexity of the networks, we used GRADE to assess the certainty of the evidence. Our primary outcomes were substantial (50%) pain relief, pain intensity, mood, and adverse events. Our secondary outcomes were moderate pain relief (30%), physical function, sleep, quality of life, Patient Global Impression of Change (PGIC), serious adverse events, and withdrawal.
MAIN RESULTS: This review and NMA included 176 studies with a total of 28,664 participants. The majority of studies were placebo-controlled (83), and parallel-armed (141). The most common pain conditions examined were fibromyalgia (59 studies); neuropathic pain (49 studies) and musculoskeletal pain (40 studies). The average length of RCTs was 10 weeks. Seven studies provided no useable data and were omitted from the NMA. The majority of studies measured short-term outcomes only and excluded people with low mood and other mental health conditions. Across efficacy outcomes, duloxetine was consistently the highest-ranked antidepressant with moderate- to high-certainty evidence. In duloxetine studies, standard dose was equally efficacious as high dose for the majority of outcomes. Milnacipran was often ranked as the next most efficacious antidepressant, although the certainty of evidence was lower than that of duloxetine. There was insufficient evidence to draw robust conclusions for the efficacy and safety of any other antidepressant for chronic pain. Primary efficacy outcomes Duloxetine standard dose (60 mg) showed a small to moderate effect for substantial pain relief (odds ratio (OR) 1.91, 95% confidence interval (CI) 1.69 to 2.17; 16 studies, 4490 participants; moderate-certainty evidence) and continuous pain intensity (standardised mean difference (SMD) -0.31, 95% CI -0.39 to -0.24; 18 studies, 4959 participants; moderate-certainty evidence). For pain intensity, milnacipran standard dose (100 mg) also showed a small effect (SMD -0.22, 95% CI -0.39 to 0.06; 4 studies, 1866 participants; moderate-certainty evidence). Mirtazapine (30 mg) had a moderate effect on mood (SMD -0.5, 95% CI -0.78 to -0.22; 1 study, 406 participants; low-certainty evidence), while duloxetine showed a small effect (SMD -0.16, 95% CI -0.22 to -0.1; 26 studies, 7952 participants; moderate-certainty evidence); however it is important to note that most studies excluded participants with mental health conditions, and so average anxiety and depression scores tended to be in the 'normal' or 'subclinical' ranges at baseline already. Secondary efficacy outcomes Across all secondary efficacy outcomes (moderate pain relief, physical function, sleep, quality of life, and PGIC), duloxetine and milnacipran were the highest-ranked antidepressants with moderate-certainty evidence, although effects were small. For both duloxetine and milnacipran, standard doses were as efficacious as high doses. Safety There was very low-certainty evidence for all safety outcomes (adverse events, serious adverse events, and withdrawal) across all antidepressants. We cannot draw any reliable conclusions from the NMAs for these outcomes.
AUTHORS' CONCLUSIONS: Our review and NMAs show that despite studies investigating 25 different antidepressants, the only antidepressant we are certain about for the treatment of chronic pain is duloxetine. Duloxetine was moderately efficacious across all outcomes at standard dose. There is also promising evidence for milnacipran, although further high-quality research is needed to be confident in these conclusions. Evidence for all other antidepressants was low certainty. As RCTs excluded people with low mood, we were unable to establish the effects of antidepressants for people with chronic pain and depression. There is currently no reliable evidence for the long-term efficacy of any antidepressant, and no reliable evidence for the safety of antidepressants for chronic pain at any time point.
OBJECTIVE: To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip osteoarthritis pain and physical function to enable effective and safe use of these drugs at their lowest possible dose.
DESIGN: Systematic review and network meta-analysis of randomised trials.
DATA SOURCES: Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, regulatory agency websites, and ClinicalTrials.gov from inception to 28 June 2021.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised trials published in English with ≥100 patients per group that evaluated NSAIDs, opioids, or paracetamol (acetaminophen) to treat osteoarthritis.
OUTCOMES AND MEASURES: The prespecified primary outcome was pain. Physical function and safety outcomes were also assessed.
REVIEW METHODS: Two reviewers independently extracted outcomes data and evaluated the risk of bias of included trials. Bayesian random effects models were used for network meta-analysis of all analyses. Effect estimates are comparisons between active treatments and oral placebo.
RESULTS: 192 trials comprising 102 829 participants examined 90 different active preparations or doses (68 for NSAIDs, 19 for opioids, and three for paracetamol). Five oral preparations (diclofenac 150 mg/day, etoricoxib 60 and 90 mg/day, and rofecoxib 25 and 50 mg/day) had ≥99% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. Topical diclofenac (70-81 and 140-160 mg/day) had ≥92.3% probability, and all opioids had ≤53% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. 18.5%, 0%, and 83.3% of the oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of dropouts due to adverse events. 29.8%, 0%, and 89.5% of oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of any adverse event. Oxymorphone 80 mg/day had the highest risk of dropouts due to adverse events (51%) and any adverse event (88%).
CONCLUSIONS: Etoricoxib 60 mg/day and diclofenac 150 mg/day seem to be the most effective oral NSAIDs for pain and function in patients with osteoarthritis. However, these treatments are probably not appropriate for patients with comorbidities or for long term use because of the slight increase in the risk of adverse events. Additionally, an increased risk of dropping out due to adverse events was found for diclofenac 150 mg/day. Topical diclofenac 70-81 mg/day seems to be effective and generally safer because of reduced systemic exposure and lower dose, and should be considered as first line pharmacological treatment for knee osteoarthritis. The clinical benefit of opioid treatment, regardless of preparation or dose, does not outweigh the harm it might cause in patients with osteoarthritis.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO number CRD42020213656.
OBJECTIVE: Despite an extensive body of research on NSAIDs in osteoarthritis, the duration of their efficacy and timeline of adverse event (AE) onset have been understudied. We conducted a systematic review and meta-analyses from 2 to 26 weeks to characterize the efficacy and AE trajectories of oral NSAIDs in knee osteoarthritis.
METHODS: We searched MEDLINE, EMBASE, Web of Science, Google Scholar, and the Cochrane Database from inception to May 2018. RCTs assessing the efficacy and/or safety of FDA-approved NSAIDs in knee osteoarthritis patients were included. Two independent reviewers assessed quality and extracted data. We calculated standardized mean differences and risk ratios with 95% confidence intervals.
RESULTS: We included 72 RCTs (26,424 participants). NSAIDs demonstrated moderate, statistically significant effects on pain that peaked at 2 weeks (SMD -0.43 [-0.48, -0.38]), but the magnitude of the effects decreased over time. The results for function were similar. The incidence of GI AEs was significantly higher in NSAID users than placebo users as early as 4 weeks (RR 1.38 [1.21, 1.57]). The incidence of CV AEs in NSAID users was not significantly different from placebo. Most GI and CV AEs were transient and of minor severity.
CONCLUSION: NSAIDs produced significant pain and function improvements that peaked at 2 weeks but decreased over time. The incidence of minor GI and CV AEs consistently rose, reaching significance as early as 4 weeks. Clinicians should weigh the durability of efficacy with the early onset of minor AEs along with patient tolerability and preferences when formulating an NSAID regimen. This article is protected by copyright. All rights reserved.
OBJECTIVE: Despite an extensive body of research on nonsteroidal antiinflammatory drugs (NSAIDs) in osteoarthritis, the duration of their efficacy and timeline of adverse event (AE) onset have been understudied. We conducted a systematic review and meta-analyses from 2 to 26 weeks to characterize the efficacy and AE trajectories of oral NSAIDs in knee osteoarthritis.METHODS: We searched MEDLINE, Embase, Web of Science, Google Scholar, and the Cochrane Database from inception to May 2018. Randomized controlled trials assessing the efficacy and/or safety of Federal Drug Administration-approved NSAIDs in knee osteoarthritis patients were included. Two independent reviewers assessed quality and extracted data. We calculated standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (95% CIs).RESULTS: We included 72 randomized controlled trials (26,424 participants). NSAIDs demonstrated moderate, statistically significant effects on pain that peaked at 2 weeks (SMD -0.43 [95% CI -0.48, -0.38]), but the magnitude of the effects decreased over time. The results for function were similar. The incidence of gastrointestinal (GI) AEs was significantly higher in NSAID users than placebo users as early as 4 weeks (RR 1.38 [95% CI 1.21, 1.57]). The incidence of cardiovascular (CV) AEs in NSAID users was not significantly different from placebo. Most GI and CV AEs were transient and of minor severity.CONCLUSION: NSAIDs produced significant pain and function improvements that peaked at 2 weeks but decreased over time. The incidence of minor GI and CV AEs consistently rose, reaching significance as early as 4 weeks. Clinicians should weigh the durability of efficacy with the early onset of minor AEs along with patient tolerability and preferences when formulating an NSAID regimen.
BACKGROUND: Pain comorbid with depression is frequently encountered in clinical settings and often leads to significant impaired functioning. Given the complexity of comorbidities, it is important to address both pain and depressive symptoms when evaluating treatment options.
AIM: To review studies addressing pain comorbid with depression, and to report the impact of current treatments.
METHOD: A systematic search of the literature databases was conducted according to predefined criteria. Two authors independently conducted a focused analysis of the full-text articles and reached a consensus on 28 articles to be included in this review.
RESULTS: Overall, studies suggested that pain and depression are highly intertwined and may co-exacerbate physical and psychological symptoms. These symptoms could lead to poor physical functional outcomes and longer duration of symptoms. An important biochemical basis for pain and depression focuses on serotonergic and norepinephrine systems, which is evident in the pain-ameliorating properties of serotonergic and norepinephrine antidepressants. Alternative pharmacotherapies such as ketamine and cannabinoids appear to be safe and effective options for improving depressive symptoms and ameliorating pain. In addition, cognitive-behavioral therapy may be a promising tool in the management of chronic pain and depression.
CONCLUSION: The majority of the literature indicates that patients with pain and depression experience reduced physical, mental, and social functioning as opposed to patients with only depression or only pain. In addition, ketamine, psychotropic, and cognitive-behavioral therapies present promising options for treating both pain and depression.
OBJETIVO: Actualizar nuestras revisiones sistemáticas anteriores que evaluaron todos los ensayos controlados aleatorios publicados (ECA) que evaluaban terapias farmacológicas y no farmacológicas en pacientes con osteoartritis de la mano (OA). Las terapias quirúrgicas no fueron evaluadas. DISEÑO: Los ECA publicados entre marzo de 2008 y diciembre de 2015 se agregaron a las revisiones sistemáticas anteriores. RESULTADOS: En esta actualización se analizaron un total de 95 ECA que evaluaron diversas terapias farmacológicas y no farmacológicas en OA manual. En general, la calidad metodológica de estos ECA ha mejorado desde la última actualización, con más estudios describiendo sus métodos de asignación al azar, cegamiento y ocultamiento de la asignación. Sin embargo, los ECA continúan debilitados por la falta de una definición de caso consistente y la falta de evaluaciones de resultados estandarizadas específicas para la OA manual. El número y la ubicación de las articulaciones manuales evaluadas continúan siendo subnotificadas, y sólo el 25% de los ECA describieron adecuadamente el método utilizado para garantizar el ocultamiento de la asignación. Estas siguen siendo las principales debilidades de los ECA publicados. No se pudo realizar un metanálisis debido a la marcada heterogeneidad del estudio, datos estadísticos insuficientes disponibles en los ECA publicados y un pequeño número de comparadores idénticos. Conclusión: La OA manual es un área compleja en la que estudiar la eficacia de las terapias. Ha habido una mejora en el diseño y la conducta general de los ECA, sin embargo, se necesitan ECA adicionales grandes con un enfoque metodológico más robusto específico para la OA manual, con el fin de hacer conclusiones clínicamente relevantes sobre la eficacia de las diversas opciones de tratamiento disponibles.
Antecedentes: Los fármacos antiinflamatorios no esteroideos (AINE) son la columna vertebral del tratamiento del dolor de la osteoartritis. Para este metanálisis de la red, se consideraron los ensayos aleatorios que compararon cualquiera de las siguientes intervenciones: AINEs, paracetamol o placebo, con el fin de evaluar la eficacia de diferentes preparaciones y dosis de AINEs en el dolor de osteoartritis en un metaanálisis de red. Para el tratamiento del dolor de la osteoartritis. Se realizaron búsquedas en el Registro Cochrane Central de Ensayos Controlados (CENTRAL) y en las listas de referencias de artículos relevantes para ensayos publicados entre el 1 de enero de 1980 y el 24 de febrero de 2015, con al menos 100 pacientes por grupo. Los resultados preespecificados primarios y secundarios fueron dolor y función física, y se extrajeron por duplicado hasta siete puntos de tiempo después del inicio del tratamiento. Utilizamos una extensión de modelos de efectos aleatorios bayesianos multivariables para comparaciones mixtas de tratamiento múltiple con un efecto aleatorio a nivel de ensayos. Para el análisis primario, una caminata aleatoria de primer orden se utilizó para dar cuenta de múltiples resultados de seguimiento de resultados dentro de un ensayo. Los preparados que utilizaron diferentes dosis diarias totales se consideraron por separado en el análisis. Para evaluar una posible relación dosis-respuesta, se utilizaron covariables específicos de la preparación asumiendo la linealidad en la dosis relativa log. RECOLECCIONES: Se identificaron 8973 manuscritos de nuestra búsqueda, de los cuales 76 ensayos aleatorios con un total de 58 451 pacientes fueron incluidos en este análisis. Se consideraron 23 ganglios en relación con siete AINE diferentes o paracetamol con dosis diaria específica de administración o placebo. Todas las preparaciones, independientemente de la dosis, mejoraron las estimaciones puntuales de los síntomas del dolor en comparación con el placebo. Para seis intervenciones (diclofenaco 150 mg / día, etoricoxib 30 mg / día, 60 mg / día y 90 mg / día y rofecoxib 25 mg / día y 50 mg / día), la probabilidad de que la diferencia con el placebo sea de Por debajo de un mínimo preespecificado efecto clínicamente importante para la reducción del dolor (tamaño del efecto [ES] -0 · 37) fue de al menos el 95%. Entre las dosis diarias máximas aprobadas, diclofenaco 150 mg / día (ES -0,57, 95% de intervalo de credibilidad [CrI] -0,69 a -0,45) y 60 mg de etoricoxib / día (ES -0,58, -0 · 74 a -0 · 43) tuvieron la mayor probabilidad de ser la mejor intervención, ambos con un 100% de probabilidad de alcanzar la mínima diferencia clínicamente importante. Los efectos del tratamiento aumentaron a medida que aumentó la dosis de fármaco, pero las pruebas correspondientes para un efecto de dosis lineal fueron significativas sólo para el naproxeno (p = 0, 034). No se encontró evidencia de que los efectos del tratamiento variaran durante la duración del tratamiento. El ajuste del modelo fue bueno, y la heterogeneidad entre los ensayos y la inconsistencia fueron bajas en todos los análisis. Se consideró que todos los ensayos tenían un bajo riesgo de sesgo para el cegamiento de los pacientes. Las estimaciones de los efectos no cambiaron en los análisis de sensibilidad con dos modelos estadísticos adicionales y en la contabilidad de los criterios de calidad metodológica en el análisis de metarregresión.INTERPRETACIÓN: Sobre la base de los datos disponibles, no se observa papel del paracetamol monoterapia para el tratamiento de pacientes con Osteoartritis independientemente de la dosis. Proporcionamos pruebas sólidas de que el diclofenaco 150 mg / día es el AINE más efectivo disponible en la actualidad, en términos de mejorar tanto el dolor como la función. Sin embargo, teniendo en cuenta el perfil de seguridad de estos fármacos, los médicos deben considerar nuestros resultados junto con toda la información de seguridad conocida al seleccionar la preparación y la dosis para pacientes individuales.Fundación: Swiss National Science Foundation (subvención número 405340-104762) y Arco Foundation , Suiza.
INTRODUCCIÓN: Hay discusión sobre los beneficios y los riesgos de las drogas para el tratamiento del dolor musculoesquelético crónico. Este estudio comparó la eficacia, seguridad y tolerabilidad de diclofenac, ibuprofeno, naproxeno, celecoxib, etoricoxib y para los pacientes con dolor causado por la osteoartritis (OA) o la artritis reumatoide (RA).
MÉTODOS: Una revisión sistemática de la literatura utilizada en Medline y EMBASE para identificar ensayos controlados aleatorios. Resultados de eficacia evaluados incluyeron: el alivio del dolor medido por escala analógica visual (VAS); Western Ontario McMaster Universidades Artritis Index (WOMAC) VAS o escala WOMAC Likert; funcionamiento físico medido por WOMAC VAS o escala de Likert; y la evaluación global del paciente (PGA) de la gravedad de la enfermedad medida en VAS o escala de Likert de 5 puntos. Los resultados de seguridad incluyen: Colaboración antiplaquetarios Trialists '(APTC), importante cardiovasculares (CV) y (GI) grandes eventos gastrointestinales superiores, y los retiros. Los datos para cada resultado fueron sintetizados por un meta-análisis de la red bayesiana (NMA). Para las evaluaciones de eficacia, se utilizaron dosis etiquetarse para el tratamiento de OA para el caso base mientras que dosis etiquetarse para el tratamiento de la RA también se incluyeron en el análisis de sensibilidad. Los datos agrupados a través de intervalos de dosis se utilizaron para la seguridad.
Resultados de eficacia, seguridad y tolerabilidad de datos se encontraron resultados para 146.524 pacientes en 176 estudios incluidos en la NMA. Diclofenac (150 mg / día) era probable que sea más eficaz en el alivio del dolor que celecoxib (200 mg / día), naproxeno (1000 mg / día), y el ibuprofeno (2400 mg / día), y similar a etoricoxib (60 mg / día); una dosis más baja de diclofenac (100 mg / día) era comparable a todos los otros tratamientos para aliviar el dolor. Mejora de la función física con diclofenaco (100 y 150 mg / día) era comparable a la mayoría de todos los otros tratamientos. PGA con diclofenaco (100 y 150 mg / día) era probable que sea más eficaz o comparable a todos los otros tratamientos. Todos los tratamientos activos fueron similares para APTC y los principales eventos CV. Eventos gastrointestinales superiores mayores con diclofenaco fue menor en comparación con el naproxeno y el ibuprofeno, comparable a celecoxib, y más alto que el etoricoxib. Riesgo de retirada con diclofenac fue menor en comparación con el ibuprofeno, similar a celecoxib y naproxeno, y más alto que etoricoxib.
Conclusiones: El perfil beneficio-riesgo de diclofenaco era comparable a otros tratamientos utilizados para aliviar el dolor en la OA y RA; beneficios y riesgos varían en los individuos y necesitan cuenta al tomar decisiones de tratamiento.
Fármacos anti-inflamatorios no esteroideos (AINE), tales como los AINE no selectivos (nsNSAIDs) o selectivos de la ciclooxigenasa-2 (COX-2) inhibidores, se prescriben comúnmente para el alivio del dolor de artritis en pacientes con osteoartritis (OA), artritis reumatoide ( RA), o la espondilitis anquilosante (AS). Las guías de tratamiento para la terapia crónica de AINE incluyen la consideración de gastroprotección para aquellos en riesgo de úlceras gástricas (GUS) asociados con el tratamiento con AINE crónica. La Administración de Alimentos y Medicamentos de los Estados ha aprobado tabletas de magnesio naproxeno / esomeprazol para el alivio de los signos y síntomas de la artrosis, AR y AS, y para disminuir el riesgo de desarrollo de GUS en los pacientes con riesgo de desarrollar Gus asociadas a AINE. La Asociación Médica Europea ha aprobado esta terapia para el tratamiento sintomático de la OA, AR, y como en los pacientes que están en riesgo de desarrollar asociadas a AINE, GUS y / o úlceras duodenales, para los que el tratamiento con dosis más bajas de naproxeno u otros AINE no es considerado suficiente. Tabletas de magnesio Naproxeno / esomeprazol se han comparado con naproxeno y celecoxib para esas indicaciones en ensayos de cabeza a cabeza. Esta revisión sistemática de la literatura y la red de los meta-análisis de los datos de los ensayos controlados aleatorios se realizó para comparar las tabletas de magnesio naproxeno / esomeprazol con un número de comparadores pertinentes adicionales. Para este estudio, un examen inicial examinó MEDLINE ®, Embase ®, y en el Cochrane Controlled Trials Register desde el principio de base de datos al 14 de abril de 2009. Utilizando la misma metodología, una actualización de la revisión se llevó a cabo el 21 de diciembre de 2009. El examen sistemático y análisis de la red mostraron tabletas de magnesio naproxeno / esomeprazol tienen un mejor perfil de tolerabilidad gastrointestinal superior (dispepsia y úlcera gástrica o gastroduodenal) durante varios comparadores activos (naproxeno, ibuprofeno, diclofenaco, ketoprofeno, etoricoxib, y de dosis fija diclofenac sódico más misoprostol ), y son igualmente eficaces como todos los comparadores activos en el tratamiento de los síntomas de artritis en los pacientes con OA, AR, y AS. Tabletas de magnesio Naproxeno / esomeprazol son por lo tanto una opción valiosa para el tratamiento de los síntomas de artritis en pacientes elegibles con artrosis, AR y AS.
ANTECEDENTES: El tratamiento del dolor es una gran prioridad para los pacientes con artritis reumatoide (AR). Los antidepresivos se utilizan en ocasiones como agentes coadyuvantes para aumentar el alivio del dolor, ayudar con el sueño y reducir la depresión. Estos antidepresivos incluyen los antidepresivos tricíclicos (ATC), los inhibidores de la monoaminooxidasa (IMAO), los inhibidores selectivos de la recaptación de serotonina (ISRS), los inhibidores selectivos de la recaptación de serotonina noradrenalina (ISRSN) y los inhibidores de la recaptación de norepinefrina (IRN). Desafortunadamente la prescripción de antidepresivos en esta población aún es polémica debido a las pruebas científicas contradictorias.
OBJETIVOS: El objetivo de esta revisión fue determinar la eficacia y la seguridad de los antidepresivos para el tratamiento del dolor en pacientes con AR.
MÉTODOS DE BÚSQUEDA: Se realizó una búsqueda electrónica en el Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials, CENTRAL) ( Cochrane Library 2010, cuarto trimestre); MEDLINE (1950 hasta noviembre, semana 1, 2010); EMBASE (2010, semana 44); y en PsycINFO (1806 hasta noviembre, semana 2, 2010). También se buscó en los resúmenes del American College of Rheumatology (ACR) de 2008 a 2009 y de la European League Against Rheumatism (EULAR) y se realizó una búsqueda manual de las listas de referencias de los artículos.
CRITERIOS DE SELECCIÓN: Se incluyeron ensayos controlados con asignación aleatoria (ECAs) que compararon un tratamiento antidepresivo con otro tratamiento (activo o placebo, incluidos los tratamientos no farmacológicos) en pacientes adultos con AR que tenían al menos una medida de resultado clínicamente relevante. Las medidas de resultado de interés fueron dolor, efectos adversos, función, sueño, depresión y calidad de vida.
OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos revisores cegados extrajeron los datos y evaluaron el riesgo de sesgo de los ensayos de forma independiente. Se realizaron metanálisis para examinar la eficacia de los antidepresivos en el dolor, la depresión y la función, así como su seguridad.
RESULTADOS PRINCIPALES: Se incluyeron ocho ECAs (652 participantes) en esta revisión. Todos los ensayos evaluaron los ATC y dos ensayos evaluaron un ISRS como comparador. Siete de los ocho ensayos tuvieron un alto riesgo de sesgo. No hubo datos suficientes para calcular el número necesario a tratar para un resultado beneficioso adicional (NNTB) para el resultado primario de dolor. Los análisis cualitativos no encontraron pruebas de un efecto de los antidepresivos sobre la intensidad del dolor ni la depresión a corto plazo (menos de una semana) y encontraron pruebas contradictorias de un efecto beneficioso a medio (de una a seis semanas) o largo plazo (más de seis semanas). Hubo significativamente más eventos adversos leves en los pacientes que recibieron ATC comparados con los que recibieron placebo (cociente de riesgos [CR] 2,27; intervalo de confianza [IC] del 95%: 1,17 a 4,42), pero no hubo un aumento significativo de los retiros debido a un evento adverso (CR 1,09; IC del 95%: 0,49 a 2,42).
CONCLUSIONES DE LOS AUTORES: Actualmente no hay pruebas suficientes para apoyar la prescripción habitual de antidepresivos como analgésicos en los pacientes con AR, ya que no es posible establecer conclusiones confiables acerca de su eficacia a partir de ocho ECAs con placebo. El uso de estos agentes se puede asociar con eventos adversos que son generalmente leves y no dan lugar a la interrupción del tratamiento. Se necesitan más ensayos de alta calidad en esta área.
Chronic pain is common in adults, and often has a detrimental impact upon physical ability, well-being, and quality of life. Previous reviews have shown that certain antidepressants may be effective in reducing pain with some benefit in improving patients' global impression of change for certain chronic pain conditions. However, there has not been a network meta-analysis (NMA) examining all antidepressants across all chronic pain conditions.
OBJECTIVES:
To assess the comparative efficacy and safety of antidepressants for adults with chronic pain (except headache).
SEARCH METHODS:
We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, AMED and PsycINFO databases, and clinical trials registries, for randomised controlled trials (RCTs) of antidepressants for chronic pain conditions in January 2022.
SELECTION CRITERIA:
We included RCTs that examined antidepressants for chronic pain against any comparator. If the comparator was placebo, another medication, another antidepressant, or the same antidepressant at different doses, then we required the study to be double-blind. We included RCTs with active comparators that were unable to be double-blinded (e.g. psychotherapy) but rated them as high risk of bias. We excluded RCTs where the follow-up was less than two weeks and those with fewer than 10 participants in each arm.
DATA COLLECTION AND ANALYSIS:
Two review authors separately screened, data extracted, and judged risk of bias. We synthesised the data using Bayesian NMA and pairwise meta-analyses for each outcome and ranked the antidepressants in terms of their effectiveness using the surface under the cumulative ranking curve (SUCRA). We primarily used Confidence in Meta-Analysis (CINeMA) and Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) to assess the certainty of the evidence. Where it was not possible to use CINeMA and ROB-MEN due to the complexity of the networks, we used GRADE to assess the certainty of the evidence. Our primary outcomes were substantial (50%) pain relief, pain intensity, mood, and adverse events. Our secondary outcomes were moderate pain relief (30%), physical function, sleep, quality of life, Patient Global Impression of Change (PGIC), serious adverse events, and withdrawal.
MAIN RESULTS:
This review and NMA included 176 studies with a total of 28,664 participants. The majority of studies were placebo-controlled (83), and parallel-armed (141). The most common pain conditions examined were fibromyalgia (59 studies); neuropathic pain (49 studies) and musculoskeletal pain (40 studies). The average length of RCTs was 10 weeks. Seven studies provided no useable data and were omitted from the NMA. The majority of studies measured short-term outcomes only and excluded people with low mood and other mental health conditions. Across efficacy outcomes, duloxetine was consistently the highest-ranked antidepressant with moderate- to high-certainty evidence. In duloxetine studies, standard dose was equally efficacious as high dose for the majority of outcomes. Milnacipran was often ranked as the next most efficacious antidepressant, although the certainty of evidence was lower than that of duloxetine. There was insufficient evidence to draw robust conclusions for the efficacy and safety of any other antidepressant for chronic pain. Primary efficacy outcomes Duloxetine standard dose (60 mg) showed a small to moderate effect for substantial pain relief (odds ratio (OR) 1.91, 95% confidence interval (CI) 1.69 to 2.17; 16 studies, 4490 participants; moderate-certainty evidence) and continuous pain intensity (standardised mean difference (SMD) -0.31, 95% CI -0.39 to -0.24; 18 studies, 4959 participants; moderate-certainty evidence). For pain intensity, milnacipran standard dose (100 mg) also showed a small effect (SMD -0.22, 95% CI -0.39 to 0.06; 4 studies, 1866 participants; moderate-certainty evidence). Mirtazapine (30 mg) had a moderate effect on mood (SMD -0.5, 95% CI -0.78 to -0.22; 1 study, 406 participants; low-certainty evidence), while duloxetine showed a small effect (SMD -0.16, 95% CI -0.22 to -0.1; 26 studies, 7952 participants; moderate-certainty evidence); however it is important to note that most studies excluded participants with mental health conditions, and so average anxiety and depression scores tended to be in the 'normal' or 'subclinical' ranges at baseline already. Secondary efficacy outcomes Across all secondary efficacy outcomes (moderate pain relief, physical function, sleep, quality of life, and PGIC), duloxetine and milnacipran were the highest-ranked antidepressants with moderate-certainty evidence, although effects were small. For both duloxetine and milnacipran, standard doses were as efficacious as high doses. Safety There was very low-certainty evidence for all safety outcomes (adverse events, serious adverse events, and withdrawal) across all antidepressants. We cannot draw any reliable conclusions from the NMAs for these outcomes.
AUTHORS' CONCLUSIONS:
Our review and NMAs show that despite studies investigating 25 different antidepressants, the only antidepressant we are certain about for the treatment of chronic pain is duloxetine. Duloxetine was moderately efficacious across all outcomes at standard dose. There is also promising evidence for milnacipran, although further high-quality research is needed to be confident in these conclusions. Evidence for all other antidepressants was low certainty. As RCTs excluded people with low mood, we were unable to establish the effects of antidepressants for people with chronic pain and depression. There is currently no reliable evidence for the long-term efficacy of any antidepressant, and no reliable evidence for the safety of antidepressants for chronic pain at any time point.
Pregunta de la revisión sistemática»Revisión sistemática de intervenciones
