BACKGROUND: This study aimed to identify targeted interventions for the prevention and treatment of harmful alcohol use. Umbrella review methodology was used to summarise the effectiveness across a broad range of interventions, in order to identify which interventions should be considered for inclusion within universal health coverage schemes in low- and middle-income countries.
METHODS AND FINDINGS: We included systematic reviews with meta-analysis of randomised controlled trials (RCTs) on targeted interventions addressing alcohol use in harmful drinkers or individuals with alcohol use disorder. We only included outcomes related to alcohol consumption, heavy drinking, binge drinking, abstinence, or alcohol-attributable accident, injury, morbidity or mortality. PubMed, Embase, PsycINFO, Cochrane Database of Systematic Reviews, and the International HTA Database were searched from inception to 3 September 2021. Risk of bias of reviews was assessed using the AMSTAR2 tool. After reviewing the abstracts of 9,167 articles, results were summarised narratively and certainty in the body of evidence for each intervention was assessed using GRADE. In total, 86 studies met the inclusion criteria, of which the majority reported outcomes for brief intervention (30 studies) or pharmacological interventions (29 studies). Overall, methodological quality of included studies was low.
CONCLUSIONS: For harmful drinking, brief interventions, cognitive behavioural therapy, and motivational interviewing showed a small effect, whereas mentoring in adolescents and children may have a significant long-term effect. For alcohol use disorder, social network approaches and acamprosate showed evidence of a significant and durable effect. More evidence is required on the effectiveness of gamma-hydroxybutyric acid (GHB), nalmefene, and quetiapine, as well as optimal combinations of pharmacological and psychosocial interventions. As an umbrella review, we were unable to identify the extent to which variation between studies stemmed from differences in intervention delivery or variation between country contexts. Further research is required on applicability of findings across settings and best practice for implementation. Funded by the Thai Health Promotion Foundation, grant number 61-00-1812.
BACKGROUND: Guidelines about post-traumatic stress disorder (PTSD) recommend broad categories of drugs, but uncertainty remains about what pharmacological treatment to select among all available compounds.
METHODS: Cochrane Central Register of Controlled Trials register, MEDLINE, PsycINFO, National PTSD Center Pilots database, PubMed, trial registries, and databases of pharmaceutical companies were searched until February 2016 for double-blind randomised trials comparing any pharmacological intervention or placebo as oral therapy in adults with PTSD. Initially, we performed standard pairwise meta-analyses using a random effects model. We then carried out a network meta-analysis. The main outcome measures were mean change on a standardised scale and all-cause dropout rate. Acute treatment was defined as 8-week follow up.
RESULTS: Desipramine, fluoxetine, paroxetine, phenelzine, risperidone, sertraline, and venlafaxine were more effective than placebo; phenelzine was better than many other active treatments and was the only drug, which was significantly better than placebo in terms of dropouts (odds ratio 7.50, 95% CI 1.72-32.80). Mirtazapine yielded a relatively high rank for efficacy, but the respective value for acceptability was not among the best treatments. Divalproex had overall the worst ranking.
CONCLUSIONS: The efficacy and acceptability hierarchies generated by our study were robust against many sources of bias. The differences between drugs and placebo were small, with the only exception of phenelzine. Considering the small amount of available data, these results are probably not robust enough to suggest phenelzine as a drug of choice. However, findings from this review reinforce the idea that phenelzine should be prioritised in future trials in PTSD.
QUESTION: Network meta-analyses (NMAs) of treatment efficacy across different pharmacological treatments help inform clinical decision-making, but their methodological quality may vary a lot depending also on the quality of the included primary studies. We therefore conducted a systematic review of NMAs of pharmacological treatment for common mental disorders in order to assess the methodological quality of these NMAs, and to relate study characteristics to the rankings of efficacy and tolerability.
STUDY SELECTION AND ANALYSIS: We searched three databases for NMAs of pharmacological treatment used in major depression, generalised anxiety disorder (GAD), social anxiety disorder (SAD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD) and specific phobia.Studies were appraised using the International Society for Pharmacoeconomics and Outcomes Research checklist of good research practices for indirect-treatment-comparison and network-meta-analysis studies.
FINDINGS: Twenty NMAs were eligible for inclusion. The number of randomised controlled trials per NMA ranged from 11 to 234, and included between 801 to more than 26 000 participants. Overall, antidepressants were found to be efficacious and tolerable agents for several disorders based on rankings (45%) or statistical significance (55%). The majority of NMAs in this review adhered to guidelines by including a network diagram (70%), assessing consistency (75%), making use of a random effects model (75%), providing information on the model used to fit the data (75%) and adjusting for covariates (75%).
CONCLUSIONS: The 20 NMAs of depression and anxiety disorders, PTSD and/or OCD included in this review demonstrate some methodological strengths in comparison with the larger body of published NMAs for medical disorders, support current treatment guidelines and help inform clinical decision-making.
IMPORTANCIA: Existe un debate acerca de la efectividad de los tratamientos psiquiátricos y si la farmacoterapia o psicoterapia se destinarán, principalmente.
OBJETIVOS: Realizar una revisión sistemática sobre la eficacia de tratamientos farmacológicos y psicoterapias para los principales trastornos psiquiátricos y para comparar la calidad de los ensayos de farmacoterapia y psicoterapia.
Revisión de la evidencia: Se realizaron búsquedas en MEDLINE, EMBASE, PsycINFO, y la Biblioteca Cochrane (abril de 2012, sin límite de tiempo o idioma) para revisiones sistemáticas sobre la farmacoterapia o psicoterapia versus placebo, la farmacoterapia versus psicoterapia, y su combinación vs solos modalidad. Dos revisores seleccionaron de forma independiente los metanálisis y extrajeron los tamaños del efecto de eficacia. Se evaluó la calidad de los ensayos individuales incluidos en la farmacoterapia y la psicoterapia metanálisis con el riesgo Cochrane de herramienta de sesgo.
RESULTADOS: La búsqueda produjo 45.233 resultados. Se incluyeron 61 meta-análisis sobre 21 trastornos psiquiátricos, que contenían 852 ensayos individuales y 137.126 participantes. El tamaño del efecto promedio de los metanálisis fue medio (media, 0,50; IC del 95%, 0,41-0,59). Los tamaños del efecto de las psicoterapias vs placebo tendieron a ser mayores que los de los medicamentos, pero las comparaciones directas, aunque por lo general basado en unos pocos ensayos, no revelaron diferencias consistentes. Ensayos de farmacoterapia individuales eran más propensos a tener muestras de gran tamaño, el cegamiento, los grupos de control y análisis de intención de tratar. Por el contrario, los ensayos de psicoterapia tenían menores tasas de deserción y datos de seguimiento previstas. En los estudios de psicoterapia, en lista de espera diseños mostraron efectos más grandes que hizo comparaciones con placebo.
Conclusiones y relevancia: Muchos tratamientos farmacológicos y psicoterapias son eficaces, pero no hay mucho margen de mejora. Debido a las múltiples diferencias en los métodos utilizados en los ensayos de farmacoterapia y psicoterapia, las comparaciones indirectas de sus tamaños del efecto en comparación con placebo o ningún tratamiento son problemáticas. Comparaciones directas bien diseñados, que son escasos, necesitan financiación pública. Dado que los pacientes a menudo se benefician de ambas formas de terapia, la investigación también debe centrarse en cómo ambas modalidades pueden ser mejor combinan para maximizar la sinergia en lugar de debatir sobre el uso de un tratamiento sobre el otro.
This study aimed to identify targeted interventions for the prevention and treatment of harmful alcohol use. Umbrella review methodology was used to summarise the effectiveness across a broad range of interventions, in order to identify which interventions should be considered for inclusion within universal health coverage schemes in low- and middle-income countries.
METHODS AND FINDINGS:
We included systematic reviews with meta-analysis of randomised controlled trials (RCTs) on targeted interventions addressing alcohol use in harmful drinkers or individuals with alcohol use disorder. We only included outcomes related to alcohol consumption, heavy drinking, binge drinking, abstinence, or alcohol-attributable accident, injury, morbidity or mortality. PubMed, Embase, PsycINFO, Cochrane Database of Systematic Reviews, and the International HTA Database were searched from inception to 3 September 2021. Risk of bias of reviews was assessed using the AMSTAR2 tool. After reviewing the abstracts of 9,167 articles, results were summarised narratively and certainty in the body of evidence for each intervention was assessed using GRADE. In total, 86 studies met the inclusion criteria, of which the majority reported outcomes for brief intervention (30 studies) or pharmacological interventions (29 studies). Overall, methodological quality of included studies was low.
CONCLUSIONS:
For harmful drinking, brief interventions, cognitive behavioural therapy, and motivational interviewing showed a small effect, whereas mentoring in adolescents and children may have a significant long-term effect. For alcohol use disorder, social network approaches and acamprosate showed evidence of a significant and durable effect. More evidence is required on the effectiveness of gamma-hydroxybutyric acid (GHB), nalmefene, and quetiapine, as well as optimal combinations of pharmacological and psychosocial interventions. As an umbrella review, we were unable to identify the extent to which variation between studies stemmed from differences in intervention delivery or variation between country contexts. Further research is required on applicability of findings across settings and best practice for implementation. Funded by the Thai Health Promotion Foundation, grant number 61-00-1812.
