OBJECTIVE: Patients with schizophrenia have higher cardio-metabolic risk, partially from antipsychotic-induced weight-gain. Glucagon-like-peptide-1 receptor-agonists (GLP-1RAs) may reduce antipsychotic-associated weight-gain, however, safety and efficacy in schizophrenia has not been systematically reviewed.
MATERIALS AND METHODS: We systematically searched PubMed/EMBASE/PsycINFO/Cochrane, using the search terms "(antipsychotic and GLP-1RA)". Individual participant data from studies randomizing patients to GLP-1RA or control were meta-analysed. Primary outcome was difference in body weight between GLP-1RA and control; secondary outcomes included cardio-metabolic parameters and adverse drug reactions (ADRs). Multiple linear regression was conducted including sex, age, psychosis severity, metabolic parameter, ADRs, and GLP-1RA-agent.
RESULTS: Three studies (exenatide once-weekly=2; liraglutide once-daily=1) provided participant-level data (n=164, age=40.0±11.1years, weight=105.8±20.8kg). After 16.2±4.0 weeks of treatment, weight loss was 3.71 kg (95% CI=2.44-4.99 kg) greater for GLP-1RA vs. control (p<0.001), number-needed-to-treat ≥5% weight-loss=3.8 (95%CI=2.6-7.2). Waist, BMI, HbA1c, fasting-glucose and visceral-adiposity were each significantly lower with GLP-1RA. Sex, age, psychosis severity, nausea, any ADR, and GLP-1RA-agent did not significantly impact outcomes. Weight loss with GLP-1RAs was greater for clozapine-/olanzapine-treated patients (n=141) than other antipsychotics (n=27) (4.70kg, 95%CI=3.13-6.27 vs 1.5kg 95%CI=-1.47-4.47) (p<0.001). Nausea was more common with GLP-1RAs than control (53.6% vs 27.5%, p=0.002, number-needed-to-harm=3.8).
CONCLUSION: GLP-1RAs are effective and tolerable for antipsychotic-associated weight-gain, particularly clozapine-/olanzapine-treated patients. With few included patients, further studies are required before making routine use recommendations for GLP-1RAs. This article is protected by copyright. All rights reserved.
INTRODUCTION: Weight gain is a common antipsychotic (AP)-related adverse drug reaction (ADR) that can increase the risk of cardiovascular diseases and premature mortality. This meta-analysis examined the efficacy and tolerability of combining metformin and lifestyle intervention for AP-related weight gain in schizophrenia.
METHODS: Randomized controlled trials (RCTs) with meta-analyzable data were searched and retrieved by 2 independent investigators. RevMan software (version 5.3) was used to synthesize data, and to calculate the standardized or weighted mean differences and risk ratio with their 95% confidence intervals.
RESULTS: Six RCTs (n=732) were included and meta-analyzed. The metformin and lifestyle combination (MLC) group had significant reduction in weight and body mass index compared with the metformin group, lifestyle group, and placebo group. There was less frequent weight gain of≥7% in the MLC group over placebo. No other group differences in ADRs, total psychopathology, and all-cause discontinuation were found. In terms of study quality, 5 RCTs were open-labelled, 1 RCT had low risk allocation concealment, and 3 RCTs specifically described randomization methods.
CONCLUSION: Combining metformin and lifestyle intervention shows significant effect in reducing AP-related weight gain. Higher quality and larger RCTs are needed to confirm these findings.Review registration: CRD42017059198.
OBJECTIVE: Weight gain is one of the most challenging issues in patients with schizophrenia treated with antipsychotics. Several meta-analyses have been conducted to review the efficacy of topiramate in reducing weight, however, several issues regarding the methodology had arisen of which make the results remain ambiguous.
METHODS: We conducted a meta-analysis of randomised controlled trials about the use of topiramate in patients with schizophrenia for weight reduction. Ten double-blinded randomised placebo-controlled trials and seven open-label randomised controlled trials included 905 patients.
RESULTS: Patients treated with topiramate experienced a greater reduction in body weight and BMI. Patients in countries of the lower overweight population showed more significant BMI reduction. Besides, studies from the Middle East and South Asia showed the greatest effect in body weight change, followed by East Asia, then Europe/America. Topiramate group was outperformed control group with significant psychopathology improvement. No difference between two groups regarding the overall side effects.
CONCLUSIONS: Topiramate was significantly superior to control group in mitigating weight gain and psychopathology in antipsychotic-treated patients with schizophrenia. The effects of topiramate augmentation need further investigations in larger definitive studies using methodological rigor and thorough assessments.
This study was a meta-analysis of randomized controlled trials (RCTs) of ranitidine as an adjunct for antipsychotic-induced weight gain in patients with schizophrenia. RCTs reporting weight gain or metabolic side effects in patients with schizophrenia were included. Case reports/series, non-randomized or observational studies, reviews, and meta-analyses were excluded. The primary outcome measures were body mass index (BMI) (kg/m(2)) and body weight (kg). Four RCTs with five study arms were identified and analyzed. Compared with the control group, adjunctive ranitidine was associated with marginally significant reductions in BMI and body weight. After removing an outlier study for BMI, the effect of ranitidine remained significant. Adjunctive ranitidine outperformed the placebo in the negative symptom score of the Positive and Negative Syndrome Scale. Although ranitidine was associated with less frequent drowsiness, other adverse events were similar between the two groups. Adjunctive ranitidine appears to be an effective and safe option for reducing antipsychotic-induced weight gain and improving negative symptoms in patients with schizophrenia. Larger RCTs are warranted to confirm these findings. Trial registration PROSPERO: CRD42016039735.
Antipsychotic polypharmacy in schizophrenia is much debated, since it is common and costly with unclear evidence for its efficacy and safety. We conducted a systematic literature search and a random effects meta-analysis of randomized trials comparing augmentation with a second antipsychotic vs. continued antipsychotic monotherapy in schizophrenia. Co-primary outcomes were total symptom reduction and study-defined response. Antipsychotic augmentation was superior to monotherapy regarding total symptom reduction (16 studies, N=694, standardized mean difference, SMD=–0.53, 95% CI: −0.87 to −0.19, p=0.002). However, superiority was only apparent in open-label and low-quality trials (both p<0.001), but not in double-blind and high-quality ones (p=0.120 and 0.226, respectively). Study-defined response was similar between antipsychotic augmentation and monotherapy (14 studies, N=938, risk ratio = 1.19, 95% CI: 0.99 to 1.42, p=0.061), being clearly non-significant in double-blind and high-quality studies (both p=0.990). Findings were replicated in clozapine and non-clozapine augmentation studies. No differences emerged regarding all-cause/specific-cause discontinuation, global clinical impression, as well as positive, general and depressive symptoms. Negative symptoms improved more with augmentation treatment (18 studies, N=931, SMD=–0.38, 95% CI: −0.63 to −0.13, p<0.003), but only in studies augmenting with aripiprazole (8 studies, N=532, SMD=–0.41, 95% CI: −0.79 to −0.03, p=0.036). Few adverse effect differences emerged: D2 antagonist augmentation was associated with less insomnia (p=0.028), but more prolactin elevation (p=0.015), while aripiprazole augmentation was associated with reduced prolactin levels (p<0.001) and body weight (p=0.030). These data suggest that the common practice of antipsychotic augmentation in schizophrenia lacks double-blind/high-quality evidence for efficacy, except for negative symptom reduction with aripiprazole augmentation.
ANTECEDENTES: Las intervenciones nutricionales parecen fundamentales para el control del peso y la reducción del riesgo cardiometabólico en personas con enfermedades mentales graves (SMI). Falta una evaluación completa de las intervenciones nutricionales. OBJETIVOS: Someter ensayos controlados aleatorios de intervenciones nutricionales en personas con SMI a revisión sistemática y metaanálisis, y medir parámetros antropométricos y bioquímicos y consumo nutricional. MÉTODO: Una búsqueda en la base de datos electrónica identificó ensayos con componentes de intervención nutricional. Los ensayos se agruparon para metanálisis. Se realizaron análisis de la meta-regresión sobre moderadores antropométricos. RESULTADOS: Las intervenciones condujeron a pérdida significativa de peso (19 estudios), reducción del índice de masa corporal (17 estudios), disminución de la circunferencia de la cintura (10 estudios) y menor nivel de glucosa en la sangre (5 estudios). Las intervenciones dirigidas por dietistas (6 estudios) y los estudios realizados con iniciación antipsicótica (4 estudios) tuvieron tamaños de efecto mayores. CONCLUSIONES: La evidencia apoya intervenciones de nutrición como atención estándar en la prevención y el tratamiento del aumento de peso entre las personas que experimentan SMI.
OBJETIVO: El aumento de peso asociado con los antipsicóticos en la esquizofrenia ha sido una preocupación constante. Este metanálisis examinó la eficacia y la seguridad de la amantadina como tratamiento complementario del aumento de peso en la esquizofrenia mediante la búsqueda sistemática y el análisis de ensayos controlados aleatorios (ECA). En el metanálisis se incluyeron ECAs que compararon amantadina con placebo en pacientes adultos con esquizofrenia. MÉTODOS: Dos investigadores independientes investigaron la literatura y extrajeron los datos. Se calcularon las diferencias de medias ponderadas y estandarizadas (ADM / SMD) y la razón de riesgo ± 95% de los intervalos de confianza. Resultados Se incluyeron en el análisis cinco ECA (n = 265) con diseño doble ciego de 8,2 ± 5,9 semanas. Amantadina superó el placebo en cuanto a la reducción de peso con un tamaño de efecto moderado (ensayos, 3, n = 205, DMP -2,22 kg, P = 0,001, I² = 45%). Amantadina también superó al placebo en el punto final en el síntoma negativo (Escala de Síndrome Positivo y Negativo [PANSS] [1 ensayo] y la Escala para la Evaluación de Síntomas Negativos [1 ensayo]) resultados (ensayos 2, n = 84, SMD, Pero no en las puntuaciones totales de PANSS (ensayos, 2) (SMD, -0,31; P = 0,16, I² = 0%) y el síntoma positivo (PANSS [1 ensayo], p = 0,01, Y la Escala para la Evaluación de Síntomas Positivos [1 ensayo]) puntuaciones (DME, 0,13, P = 0,54, I² = 0%). Exceptuando el insomnio (P = 0,007, el número necesario para dañar, 6, el intervalo de confianza del 95%, 4-16), la interrupción de todas las causas (relación de riesgo 1,12, P = 0,54, I² = 0%) y otros eventos adversos fueron similares Entre los grupos amantadina y placebo. CONCLUSIONES: Según este metaanálisis de 5 ECA, la amantadina complementaria parece ser una opción eficaz para atenuar el aumento de peso relacionado con el antipsicótico en pacientes con esquizofrenia. Se necesitan más ECA para informar las recomendaciones clínicas. (PsycINFO Database Record (c) 2017 APA, todos los derechos reservados)
Las complicaciones metabólicas se encuentran comúnmente en las personas tratadas con clozapina. Las revisiones sobre el manejo de este problema generalmente han sacado conclusiones agrupando diferentes tipos de estudios que involucran pacientes tratados con diferentes antipsicóticos diferentes. Realizamos una revisión sistemática y metaanálisis de tratamientos farmacológicos y no farmacológicos para la obesidad inducida por clozapina o el síndrome metabólico. Dos investigadores investigaron PubMed y Embase de forma independiente para ensayos controlados aleatorios (ECA) de tratamientos para la obesidad inducida por clozapina o el síndrome metabólico. Se excluyeron todos los demás tipos de estudios. Sólo incluimos ECA en los que más del 50% de los participantes estaban tomando clozapina. Se identificaron 15 ECA. Los tratamientos farmacológicos efectivos para la obesidad inducida por clozapina y el síndrome metabólico incluyen metformina, aripiprazol y Orlistat (sólo en hombres). El metanálisis de tres estudios mostró un efecto robusto de la metformina en la reducción del índice de masa corporal y la circunferencia de la cintura, pero sin efectos sobre la glucemia, los niveles de triglicéridos o los niveles de HDL. Además, existen limitadas pruebas de la restricción combinada de calorías y el ejercicio como una alternativa no farmacológica para el tratamiento de la obesidad inducida por clozapina, pero sólo en un entorno hospitalario. La rosiglitazona, el topiramato, la sibutramina, la fenilpropanolamina, el modafinilo y la atomoxetina no han demostrado ser beneficiosos, a pesar de los informes de eficacia en otras poblaciones tratadas con diferentes antipsicóticos. Se concluye que los datos de ensayos controlados aleatorios apoyan el uso de metformina, aripiprazol y Orlistat (en hombres solamente) para tratar la obesidad inducida por clozapina. La restricción de calorías en combinación con un programa de ejercicio puede ser eficaz como una alternativa no farmacológica. Los hallazgos de ensayos en diferentes poblaciones no deben extrapolarse a las personas que están siendo tratadas con clozapina.
ANTECEDENTES: A pesar de que la clozapina es el estándar de oro para el tratamiento de la esquizofrenia refractaria, tiene el perfil metabólico peor de todos los antipsicóticos. Esto es mediado en parte por el impacto de la clozapina en el péptido similar al glucagón (GLP-1). Hay una ausencia de evidencia sólida para tratamientos efectivos para la clozapina asociado el aumento de peso y síndrome metabólico. La metformina, con su papel en el aumento de GLP-1 puede ayudar a la pérdida de peso entre las personas en la clozapina.
MÉTODOS: Se realizó una revisión sistemática y meta-análisis de la metformina versus placebo para el cambio en el peso y el síndrome metabólico para la gente en la clozapina sin diabetes mellitus. Se realizaron búsquedas en el Registro del Grupo Cochrane de Esquizofrenia juicio, PubMed y Embase, así como las siguientes bases de datos chinas: el sistema chino Biomédica Servicio Literatura y Base de Datos de Conocimiento de China integrada de los recursos. Esto se complementó con búsquedas manuales en los papeles principales.
RESULTADOS: Ocho estudios, de los cuales tres eran de bases de datos chinas, con 478 participantes fueron incluidos. Se encontró que la metformina fue superior al placebo en términos de pérdida de peso (-3.12kg, 95% CI -4.88kg a -1.37kg) y el índice de masa corporal (-1.18kg / m2, 95% IC -1.76kg / m2 a -0.61kg / m2). La metformina mejoró significativamente tres de los cinco componentes del síndrome metabólico; circunferencia de la cintura, glucosa en ayunas y triglicéridos. El análisis de sensibilidad sobre la calidad del estudio y la duración no afectó en gran medida los resultados.
CONCLUSIONES: La metformina dio lugar a la pérdida de peso clínicamente significativa entre las personas que la clozapina, y puede reducir las tasas de síndrome metabólico. La inclusión de la metformina en los protocolos de tratamiento de la gente en la clozapina, según la tolerancia, debe ser considerado.
Prueba de registro: número de registro PRÓSPERO CRD42015029723.
This meta-analysis of randomized controlled trials (RCTs) evaluated the efficacy and safety of adding aripiprazole to other antipsychotics in schizophrenia. A systematic computer search identified 55 RCTs including 4457 patients who were randomized to aripiprazole (14.0 ± 7.0 mg/d) versus placebo (18 RCTs) or open antipsychotic treatment (37 RCTs). Aripiprazole significantly outperformed the comparison interventions based on psychiatric scales: (1) total score in 43 RCTs (N = 3351) with a standardized mean difference (SMD) of −0.48 (95% confidence interval [CI], −0.68 to −0.28; P < 0.00001; I² = 88%), (2) negative symptom score in 30 RCTs (N = 2294) with an SMD of −0.61(95% CI, −0.91 to −0.31; P < 0.00001; I² = 91%), and (3) general psychopathology score in 13 RCTs (N = 1138) with a weighted mean difference (WMD) of −4.02 (95% CI, −7.23 to −0.81; P = 0.01; I² = 99%), but not in positive symptoms in 29 RCTs (N = 2223) with a SMD of −0.01 (95% CI, 0.26 to 0.25; P = 0.95; I² = 88%). Differences in total score based on psychiatric scales may be explained by the use of an antipsychotic for comparison rather than placebo in 31 RCTs with a nonblind design. Aripiprazole outperformed the comparison interventions for body weight in 9 RCTs (N = 505) with a WMD of −5.08 kg (95% CI, −7.14 to −3.02; P < 0.00001; I² = 35%) and for body mass index (BMI) in 14 RCTs (N = 809) with a WMD of −1.78 (CI: −2.25 to −1.31; P < 0.00001; I² = 54%). The BMI meta-regression analysis indicated aripiprazole's association with lower BMI was stronger in females. Adjunctive aripiprazole appears safe but better RCTs are needed to demonstrate efficacy. Chinese journals and scientific societies should encourage the publication of high-quality RCTs and require registration in a centralized Chinese database. (PsycINFO Database Record (c) 2017 APA, all rights reserved)
Patients with schizophrenia have higher cardio-metabolic risk, partially from antipsychotic-induced weight-gain. Glucagon-like-peptide-1 receptor-agonists (GLP-1RAs) may reduce antipsychotic-associated weight-gain, however, safety and efficacy in schizophrenia has not been systematically reviewed.
MATERIALS AND METHODS:
We systematically searched PubMed/EMBASE/PsycINFO/Cochrane, using the search terms "(antipsychotic and GLP-1RA)". Individual participant data from studies randomizing patients to GLP-1RA or control were meta-analysed. Primary outcome was difference in body weight between GLP-1RA and control; secondary outcomes included cardio-metabolic parameters and adverse drug reactions (ADRs). Multiple linear regression was conducted including sex, age, psychosis severity, metabolic parameter, ADRs, and GLP-1RA-agent.
RESULTS:
Three studies (exenatide once-weekly=2; liraglutide once-daily=1) provided participant-level data (n=164, age=40.0±11.1years, weight=105.8±20.8kg). After 16.2±4.0 weeks of treatment, weight loss was 3.71 kg (95% CI=2.44-4.99 kg) greater for GLP-1RA vs. control (p<0.001), number-needed-to-treat ≥5% weight-loss=3.8 (95%CI=2.6-7.2). Waist, BMI, HbA1c, fasting-glucose and visceral-adiposity were each significantly lower with GLP-1RA. Sex, age, psychosis severity, nausea, any ADR, and GLP-1RA-agent did not significantly impact outcomes. Weight loss with GLP-1RAs was greater for clozapine-/olanzapine-treated patients (n=141) than other antipsychotics (n=27) (4.70kg, 95%CI=3.13-6.27 vs 1.5kg 95%CI=-1.47-4.47) (p<0.001). Nausea was more common with GLP-1RAs than control (53.6% vs 27.5%, p=0.002, number-needed-to-harm=3.8).
CONCLUSION:
GLP-1RAs are effective and tolerable for antipsychotic-associated weight-gain, particularly clozapine-/olanzapine-treated patients. With few included patients, further studies are required before making routine use recommendations for GLP-1RAs. This article is protected by copyright. All rights reserved.
