Treatment of dissociative symptoms with opioid antagonists: a systematic review.

BACKGROUND: The clinical guidelines for the treatment of dissociation focus primarily on psychotherapy. However, different psychoactive drugs are used in clinical practice. The use of opioid antagonists has been proposed as a therapeutic option based on the theory that dissociation might be a phenomenon mediated by dysregulation of the endogenous opioid system. OBJECTIVE: To review and meta-analyse the available evidence on the efficacy of the opioid antagonists naltrexone, naloxone, and nalmefene as treatments for dissociative symptoms and disorders. METHOD: The PRISMA guidelines were followed, and this review was registered in Prospero with reference number CRD42021280976. The search was performed in the PubMed, Scopus, Web of Science, EMBASE, PsycINFO, and PubPsych databases. RESULTS: 1,798 citations were obtained. After removing duplicates and applying inclusion and exclusion criteria, we included 5 comparative studies with 9 dissociation measures that had included a total of 154 participants, of whom 134 had been treated with an opioid antagonist. The results of the meta-analysis showed a treatment effect for dissociation when using opioid antagonists [pooled d = 1.46 (95% CI: 0.62-2.31)]. However, the studies we included were very heterogeneous [Q = 66.89 (p < .001)] and there may have been publication bias. CONCLUSIONS: Although more research is needed and the results must be interpreted with caution because of the limited amount of data and heterogeneity in the studies and their methodological qualities, opioid antagonists (particularly naltrexone) are promising candidates for the treatment of dissociative symptoms and showed a moderate - large effect size in reducing these symptoms.

The results of the meta-analysis showed a treatment effect for dissociation when using opioid antagonists [pooled d = 1.46 (95% CI: 0.62­2.31)].The results must be interpreted with caution because of the limited amount of data and heterogeneity in the studies and their methodological qualities.Opioid antagonists (particularly naltrexone) are promising candidates for the treatment of dissociative symptoms and showed a moderate ­ large effect size in reducing these symptoms.

Una visión actual del tratamiento farmacológico para la obesidad / A current vision of the pharmacological treatment for obesity

Fundamentos: La obesidad es una patología muy prevalente a nivel mundial. La prevención, modificación deestilo de vida, tratamiento nutricional, psicológico y tratamiento farmacológico son estrategias para combatiresta enfermedad. El objetivo de esta revisión es analizar las evidencias existentes sobre la eficacia de losfármacos en la reducción del peso corporal y otros parámetros antropométricos y metabólicos relacionados.Métodos: Se ha realizado una búsqueda en PubMed y ScienceDirect de los artículos publicados en los últimos10 años seleccionando ensayos clínicos con fármacos en hombres y mujeres adultos obesos.Resultados: La naltrexona-bupropión es la asociación de fármacos contra la obesidad que obtiene mejoresresultados en la reducción de los parámetros antropométricos y metabólicos (perfil lipídico y presión arterial),seguida de la liraglutida 3,0 mg y el orlistato; la semaglutida es el hipoglucemiente que reduce más estosparámetros. La mejora de la calidad de vida no es relevante y los efectos adversos muy similares entre losfármacos. En fármacos nuevos o en estudio no se observan mejores resultados.Conclusiones: Los fármacos indicados para la obesidad en nuestro entorno son eficaces y seguros, lasemaglutida puede ser otra opción para el tratamiento. Hace falta más evidencia para incluir nuevos fármacosentre los comercializados contra la obesidad. (AU)

Background: Obesity is a very prevalent disease worldwide. Prevention, lifestyle modification, nutritional,psychological and pharmacological treatment are strategies to combat this disease. The objective of this reviewis to analyze the existing evidence on the efficacy of drugs in reducing body weight and other relatedanthropometric and metabolic parameters.Methods: A search was made in PubMed and ScienceDirect of the last 10 years, selecting clinical trials withdrugs in obese adult men and women.Results: Naltrexone-bupropion is the anti-obesity drug association that obtains the best results in reducinganthropometric and metabolic parameters (lipid profile and blood pressure), followed by liraglutide 3.0 mg andorlistato; semaglutide is the hypoglycemic agent that reduces these parameters the most. The improvement inquality of life is not relevant and the adverse effects are very similar between the drugs. Better results are notobserved in new or in-study drugs.Conclusions: The drugs indicated for obesity in our country are effective and safe, and semaglutide can alsobe a good option for obesity treatment. More evidence is needed to include new drugs among those marketedagainst obesity. (AU)

Guía de práctica clínica para el tratamiento farmacológico y psicológico de los pacientes adultos con un trastorno de ansiedad y un diagnóstico comórbido de trastorno por uso de sustancias / Clinical practice guideline on pharmacological and psychological management of adult patients with an anxiety disorder and comorbid substance use

Esta revisión resume las intervenciones farmacológicos y psicosociales que han sido llevadas a cabo en trastornos de ansiedad con un diagnóstico comórbido de trastorno por uso de sustancias y además proporciona recomendaciones clínicas respecto de cuáles elementos de intervención son útiles para hacer frente a los síntomas del uso de sustancias y los síntomas de ansiedad en pacientes con estas afecciones concurrentes. Se utilizó la mejor evidencia de ensayos controlados aleatorizados para evaluar las opciones de tratamiento. La fuerza de las recomendaciones se describió mediante el enfoque GRADE. Hay ensayos clínicos disponibles únicamente para el trastorno por estrés postraumático (TEPT) y para el trastorno de ansiedad. En cuanto al diagnóstico comórbido de trastorno por uso de sustancias, todos los estudios han incluido pacientes con consumo de alcohol, ninguno de ellos ha abordado el consumo de cocaína, cannabis o nicotina. Aunque algunos tratamientos han mostrado beneficios para los síntomas de ansiedad sin beneficios para el consumo de alcohol u otras sustancias, solo se han ensayado enfoques farmacológicos limitados (sertralina, desipramina, paroxetina, buspirona, naltrexona y disulfiram).(AU)

This review synthesizes the pharmacological and psychosocial interventions that have been conducted in comorbid anxiety disorders and SUDs while also providing clinical recommendations about which intervention elements are helpful for addressing substance use versus anxiety symptoms in patients with these co-occurring conditions. The best evidence from randomized controlled trials was used to evaluate treatment options. The strength of recommendations was described using the GRADE approach. Clinical trials are only available for post-traumatic stress disorder (PTSD) and for social anxiety. Concerning the comorbid substance use, all the studies have included patients with alcohol use, none of them have dealt with cocaine, cannabis or nicotine use. Although some treatments have shown benefit for anxiety symptoms without benefits for alcohol or other substance use, only limited pharmacological approaches have been assayed (sertraline, desipramine, paroxetine, buspirone, naltrexone and disulfiram).(AU)

Naltrexona para trastornos asociados al uso de alcohol / Naltrexone for alcohol use disorders

INTRODUCCIÓN: Los trastornos asociados al uso de alcohol (antes clasificados como abuso de alcohol y dependencia de alcohol) tienen un gran impacto en la población. A. Cuadro clínico: La Organización Mundial de la Salud reporta que 3 millones de muertes en el mundo son atribuidas al uso nocivo de alcohol, representando un 5.3% de todas las defunciones. El tratamiento del trastorno asociado al uso del alcohol tiene como objetivo disminuir el consumo de alcohol y disminuir el deseo o ansias de consumir alcohol y disminuir las recaídas de consumo. B. Tecnologia: Naltrexona es un antagonista opiáceo que actúa por competición específica con los receptores localizados en el sistema nervioso central y periférico. De esta forma, inhibe la acción de los opiáceos de administración exógena. Este receptor ha sido asociado con el efecto gratificante del alcohol y de las ansias para consumir alcohol. Se postula que el uso de naltrexona en pacientes con trastorno asociado al uso de alcohol sería beneficioso en el manejo ya que contribuiría a disminuir el efecto gratificante del alcohol, disminuyendo las recaídas después de la abstinencia. OBJETIVO: Evaluar la eficacia y seguridad, así como documentos relacionados a la decisión de cobertura de naltrexona para trastornos asociados al uso de alcohol. METODOLOGÍA: Se realizó una búsqueda en las principales bases de datos bibliográficas: MEDLINE, LILACS, COCHRANE, así como en buscadores genéricos de Internet incluyendo Google Scholar y TRIPDATABASE. Adicionalmente, se hizo una búsqueda dentro de la información generada por las principales instituciones internacionales de psiquiatrías y agencias de tecnologías sanitarias que realizan revisiones sistemáticas (RS), evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC). RESULTADOS: Se identificaron tres RS que evaluaban el uso naltrexona vía oral comparado con placebo en pacientes con dependencia de alcohol o desorden asociado a consumo de alcohol. Además, se identificaron tres GPC que mencionaban a la tecnología. No se encontraron ETS, ni EE de la región. CONCLUSIONES: La evidencia con respecto a naltrexona para trastorno asociado al uso de alcohol es abundante y de moderada calidad metodológica. La evidencia de eficacia y seguridad se basa en tres RS. Si bien una RS menciona no encontrar diferencias de efectividad de naltrexona versus placebo, una RS que incluye mayor número de estudios muestra una diferencia en el riesgo de pacientes que retornan a consumir alcohol y excesivamente consumir alcohol comparado con placebo. Además, se encuentra una disminución en el porcentaje de días de consumo de alcohol. Tres GPC recabadas consideran naltrexona o acamprosato como primera línea de tratamiento en pacientes con trastorno asociado al uso de alcohol moderado a severo.

[Pharmacological treatment of obesity for Primary Care physicians]. / Tratamiento farmacológico de la obesidad para médicos de Atención Primaria.

Obesity is a disease of high prevalence in Primary Care clinics. It is associated with major comorbidities (dyslipidaemia, diabetes, hypertension) that increase morbidity and mortality, health expenditure, and reduces the quality of life of patients. Changes in lifestyle are still the pillars of the treatment of excess weight. Pharmacological treatment should be considered when there are difficulties in achieving weight loss goals. In this article, a review is presented on the currently authorised drugs for the treatment of obesity and overweight with major comorbidities.

Relevance of weight in the management of patients with type 2 diabetes mellitus: towards an adipocentric approach to diabetes. / Importancia del peso en el control del paciente con diabetes mellitus tipo 2: hacia una visión adipocéntrica del abordaje de la diabetes.

In recent decades, there has been a worldwide parallel increase in the prevalence of obesity and type 2 diabetes mellitus (T2DM), which is not surprising, given that increased visceral fat is the main risk factor for the development of T2DM in genetically predisposed individuals. An intervention focused on intensive blood glucose control in T2DM with classic drugs increases the risk of weight gain and the rate of hypoglycaemia. In contrast, weight loss through lifestyle changes, drugs and/or surgery simultaneously improves most cardiovascular (CV) risk factors, including hyperglycemia. Intensive intervention on lifestyle induces an overall benefit in patients with T2DM, but long-term weight loss is modest and has not been shown to reduce CV morbidity and mortality. The emergence of new therapeutic classes for T2DM and obesity, which simultaneously improve HbA1c, weight and other CV risk factors without inducing hypoglycaemia, represents a major change in the management of patients with diabesity. A sodium-glucose cotransporter-2 inhibitor and a GLP-1 receptor agonist have recently been shown to decrease CV and total mortality in type 2 diabetic patients with CV disease. Furthermore, bariatric surgery rapidly induces remission or improvement of T2DM in a large percentage of patients and reduces diabetes-related mortality. The emergence of new therapies raises the possibility of changing the current glucose-centred therapeutic strategy for a weight-centred approach.

Do opioid receptors play a role in the pathogenesis of the inflammatory response in acute pancreatitis? / Os receptores opioides desempenham papel na patogênese da resposta inflamatória na pancreatite aguda?

PURPOSE: To investigate the effect of the opioid blocker naltrexone in the inflammatory response in acute pancreatitis (AP). METHODS: Acute pancreatitis was induced in anesthetized male Wistar rats by retrograde injection of 2.5% sodium taurocholate diluted in 0.5ml saline into the main pancreatic duct. Animals were randomized to the following experimental groups: Control Group (n=9): animals received an intraperitoneal injection of saline solution (0.5ml), 15 minutes before the induction of AP. Naltrexone Group (n=9): animals received an intraperitoneal injection of naltrexone 0.5ml (15 mg/kg), 15 minutes before induction of AP. Peritoneal levels of TNF-α and serum levels of IL-6 and amylase were determined The volume of the ascitic fluid was also evaluated. Myeloperoxidase (MPO) activities were analyzed in homogenates of pulmonary tissue. RESULTS: There were no significant differences in the ascitic fluid volume, nor in TNF-a and IL-6 levels in the naltrexone group compared to controls. Treatment with naltrexone did not affect the lung MPO activity compared to control group. CONCLUSIONS: The opioid receptors don't play an important role in the pathogenesis of the inflammatory response in acute pancreatitis. If opioids affect leukocytes inflammatory signaling, there are no major implications in the pathogenesis of acute pancreatitis.

OBJETIVO: Investigar o efeito do bloqueador opióide naltrexone na resposta inflamatória da pancreatite aguda. METODOS: Pancreatite aguda foi induzida em ratos machos Wistar, através de injeção retrógada de solução de taurocolato de sódio a 2,5% nos ductos pancreáticos. Os animais foram alocados em dois grupos: Grupo controle (n=9) animais receberam 0,5 ml de solução salina intra-peritonial 15 minutos antes da indução da pancreatite aguda e Grupo naltrexone (n=9) animais receberam naltrexone (15mg/kg de peso), em 0,5 ml de volume final por via intraperitoneal, 15 minutos antes da indução da pancreatite aguda. Foram avaliados o volume de ascite, os níveis séricos de amilase e IL-6, assim como TNF-α peritoneal e a atividade da mieloperoxidase (MPO) no tecido pulmonar. RESULTADOS: Não foram encontradas diferenças significantes nos parâmetros analisados entre o grupo que recebeu solução salina e o que recebeu naltrexone . CONCLUSÕES: Os receptores opióides não desempenham papel importante na resposta inflamatória sistêmica associada à pancreatite aguda. Se os opioides alteram a sinalização inflamatória nos leucócitos está ação não se reflete na patogênese da pancreatite aguda.

Eficacia de la naltrexona en el tratamiento de prurito severo / Effectiveness of naltrexone in the treatment of severe pruritus

Introducción. El prurito es una complicación frecuente de las patologías hepáticas, que puede llegar a ser de difícil manejo. El incremento en el tono opioide cerebral se ha postulado como mecanismo fisiopatológico causal del prurito. Es así como el antagonismo opioide causa mejoría y resolución sintomática en estos pacientes. Objetivo. Describir el manejo de prurito severo con antagonismo opioide en una paciente refractaria a manejo médico convencional, y hacer una revisión de la literatura. Metodología y resultados. Este es el caso de una paciente de 50 años de edad, con antecedente de hepatitis autoinmune, quien se presenta con historia de cinco años de prurito severo secundario a colestasis, manejada con antihistamínicos, esteroides, ácido ursodeoxicólico y colestiramina sin mejoría. Se decide manejo con antagonismo opioide; se inicia con naloxona infusión por 24 horas, con dosis ascendentes desde 0,002 mcg/ kg/min, hasta 0,2 mcg/kg/min, y posteriormente naltrexona, hasta dosis de 50 mg día. Se evalúo la respuesta terapéutica por medio de escala visual análoga (EVA). Desde el inicio de la infusión se obtiene disminución en la EVA hasta valores de 0/10 durante las primeras 24 horas, con mejoría clínica y sintomática.Conclusiones. En el enfoque de la paciente con prurito refractario debe considerarse el uso de antagonismo opioide como alternativa terapéutica.

Introduction. Pruritus is a frequent complication in liver disease and may be difficult to manage. Increased cerebral opiod tone has been proposed as the physiological mechanism that causes pruritus. Opiod antagonism, therefore, leads to an improvement and resolution of symptoms in these patients. Objective. Describe the management of severe pruritus using opiod antagonists in a patient who does not respond to conventional medical management, and conduct a review of the literature.Methodology and results. This is the case of a 50 year-old female patient with a history of autoimmune hepatitis with a five-year history of severe pruritus secondary to cholestasis whichdoes not improve after management with antihistamines, steroids, ursodeoxycholic acid and cholestyramine. It is decided to initiate management with opiod antagonists, starting with an infusion of naloxone for 24 hours with dose escalation from 0.002 μg/kg/min up to 0.2 μg/kg/min, followed by naltrexone up to a dose of 50 mg/day. The therapeutic response was assessed using the visual analog scale (VAS). Within 24 hours ofinitiating the infusion, there is a reduction in the VAS score down to 0/10, with clinical and symptomaticimprovement. Conclusions. The approach to patients with refractorypruritus should include the use of opioidantagonists as a therapeutic option.

Ensaio clínico duplo-cego randomizado e placebocontrolado com naltrexona e intervenção breve no tratamento ambulatorial da dependência de álcool / A double blind, randomized and placebo-controlled clinical trial with naltrexone and brief intervention in outpatient treatment of alcohol dependence

OBJETIVO: O objetivo deste estudo é avaliar a eficácia da naltrexona com intervenção breve em pacientes com dependência de álcool. MÉTODO: Este estudo é um ensaio clínico randomizado, duplo-cego, placebo-controlado de 12 semanas. A amostra de 71 pacientes foi dividida randomicamente em dois grupos (um recebendo naltrexona e outro placebo). Sujeitos dependentes de álcool foram tratados com 50 mg de naltrexona ou placebo diariamente por 12 semanas. Ambos os grupos de tratamento receberam intervenção breve. Os desfechos clínicos primários para este estudo foram taxa de recaída e mudança no padrão de consumo de álcool. RESULTADOS: Na intenção de tratar, menor porcentagem de sujeitos tratados com naltrexona recaíram (3 por cento 21 por cento; p = 0,054). Naltrexona com intervenção breve não foi superior ao placebo para diminuir os dias de consumo (6,2 + 10,6 3,05 + 7,3; p = 0,478), os dias de consumo moderado (0 2,2 + 6,9; p = 0,345) e os dias de consumo pesado (0,03 + 0,2 0,3 + 0,9; p = 0,887). Naltrexona foi bem tolerada. Os efeitos adversos mais frequentes na presente amostra foram: cefaleia (25,4 por cento), sonolência (20,9 por cento), náuseas (16,4 por cento), hiperfagia (16,4 por cento), anorexia (14,9 por cento), ansiedade (10,4 por cento), pirose (10,4 por cento) e irritabilidade (10,4 por cento). CONCLUSÕES: Embora o grupo naltrexona tenha demonstrado tendência para reduzir taxa de recaída (> 5 doses/dia), não foi encontrada nenhuma diferença em outras variáveis de consumo de álcool entre os grupos naltrexona e placebo. Estudos futuros devem examinar a eficácia desse tipo de combinação de tratamento nos cuidados primários de saúde.

OBJECTIVE: The objective of this study is to evaluate the efficacy of naltrexone with brief intervention among patients with alcohol dependence. METHOD: This study is a 12-week randomized, double blind, placebo-controlled clinical trial. The sample of 71 patients was randomly divided in two groups (one receiving naltrexone and the other placebo). Alcohol-dependent subjects were treated with 50 mg of naltrexone or placebo daily for 12 weeks. Both treatment groups received brief intervention. The primary results for this study were relapse rate and change in drinking behaviors. RESULTS: In the intention-to-treat fewer naltrexone treated subjects relapsed (3 percent 21 percent; p = 0.054). Naltrexone with brief intervention was not effective in decreasing drinking days (6.2 + 10.6 3.05 + 7.3; p = 0.478), moderate drinking days (0 2.2 + 6.9; p = 0.345) and heavy drinking days (0.03 + 0.2 0.3 + 0.9; p = 0.887). Naltrexone was well tolerated. The most frequent adverse effects in our sample were: headache (25.4 percent), drowsiness (20.9 percent), nausea (16.4 percent), hyperphagia (16.4 percent), anorexia (14.9 percent), anxiety (10.4 percent), heartburn (10.4 percent) and irritability (10.4 percent). CONCLUSIONS: Although the naltrexone group showed a tendency to reduce relapse rate (> 5 drinks/day), no differences were found in other alcohol consumption variables between naltrexone and placebo groups. Further studies should examine the efficacy of this kind of treatment combination in the primary health care.

Actualización del tratamiento farmacológico de la dependencia alcohólica / Pharmacological review of alcoholic dependence treatment

El objetivo de la presente actualización farmacológica es abordar la problemática de la dependencia alcohólica. Partiendo de las bases biológicas y del impacto del etanol sobre los sistemas neurobiológicos y de neurotransmisión, se hará una revisión de las principales herramientas farmacológicas para el tratamiento de la dependencia alcohólica. El disulfiram, la naltrexona y el acamprosato, todas ellas con aprobación por la FDA (Food and Drug Administration) han mostrado mecanismos de acción, perfiles de eficacia, tolerabilidad y adherencia dispares. También nos referiremos al topiramato, el que está siendo estudiado actualmente con relación a esta indicación.

The aim of the present pharmacological update is to revise the problem of alcohol dependence. Starting from the biological bases and the impact of alcohol on the neurobiological and neurotransmission systems, a revision of the main pharmacological tools for alcohol dependence treatment will be done. Disulfiram, naltrexone, acamprosate, all of them approved by the FDA (Food and Drug Administration), have shown mechanisms of action, efficacy, tolerance and adherence dissimilar. We will also refer to topiramate, which is being studied for this indication.