In a recently published study, Dr clothes, Researchers have evaluated the effectiveness and compared the relative effectiveness of various pharmacological treatments for alcohol use disorder (AUD).
Background
Unhealthy alcohol consumption is the third leading cause of preventable death in the United States (US), killing 145,000 people annually. More than 28 million Americans aged 12 years and older fit DSM-5 criteria for AUD in 2020, with rates likely to increase due to the coronavirus disease-2019 (COVID-19) pandemic.
Further research is needed. Despite the high prevalence and mortality associated with AUD, only a small proportion of affected individuals receive pharmacotherapy, underscoring a significant treatment gap that may widen during the COVID-19 pandemic.
About the study
The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) and followed a strategy to review the effectiveness of pharmacotherapy for alcohol use disorders as detailed in a comprehensive technical report.
Searches were conducted across several databases, including PubMed, the Cochrane Library, and others, with peer review by a librarian using the Peer Review of Electronic Search Strategies (PRESS) checklist. Inclusion criteria focused on adults with AUD in studies evaluating Food and Drug Administration (FDA) approved medications or certain off-label medications for a minimum duration of 12 weeks.
Eligible studies for this systematic review and meta-analysis were required to report alcohol consumption, health outcomes, or adverse events. For efficacy, only double-blind, randomized clinical trials were considered, whereas, for adverse effects, a wider range of study design was allowed due to the limitations of randomized controlled trials (RCTs) in detecting rare harms. Two reviewers independently screened studies, with any conflicts resolved by discussion or by a third reviewer.
Data extraction was thorough, and risk of bias was rigorously assessed using predefined criteria, with the strength of evidence graded from high to insufficient, considering the consistency, directness and precision of the studies. For substances with at least minimal evidence of benefit, results were pooled, focusing primarily on alcohol consumption as the primary outcome.
Meta-analyses were performed using random-effects models, and various statistical tools were employed to assess heterogeneity, in addition to calculating differences and proportions. Subgroup analysis identifies potential variables that influence outcomes. When meta-analysis was not possible, a qualitative synthesis was provided instead.
Results of the study
A thorough database search yielded 2,860 citations, and through a rigorous initial review process focusing on titles and abstracts, the majority of these, 2,543 citations, were discarded. Further examination of 317 full-text articles excluded 267 articles, resulting in a focused selection of 156 articles that reported on outcomes from 118 RCTs. Of this group, 81 RCTs were included in a comprehensive 2014 systematic review, and another 37 RCTs were new contributions to the field.
These recently added RCTs had a wide range of participant numbers, ranging from 12 to 921, and treatment durations varied from 12 weeks to a full year. Most studies focus on individuals diagnosed with alcohol dependence. Recruitment methods were varied, reflecting the wide interest in the field and different research paths.
Most trials integrated psychosocial interventions, noting that medications combined with psychological support seemed to provide additional benefits, which were reflected in effect sizes, thereby suggesting an enhanced efficacy when combining medical and psychosocial treatments to address alcohol dependence.
Research on acamprosate and naltrexone was conducted mainly in Europe and the United States, often alongside psychosocial support. Drugs such as varenicline, ondansetron, and prazosin have shown limited evidence of efficacy. Acamprosate and naltrexone, approved by the FDA for alcohol use disorders, significantly improved drinking outcomes, but acamprosate did not significantly reduce relapse to heavy drinking. Oral naltrexone has been shown to be beneficial, unlike its injectable version.
Further analysis showed that other non-FDA-prescribed drugs such as topiramate and baclofen demonstrated significant benefits in reducing drinking rates. The strength of evidence for these findings was moderate to low, with gabapentin not showing a significant association with lower drinking rates. A direct comparison between acamprosate and naltrexone showed no significant difference in improvement of alcohol use outcomes. Health outcomes associated with drug treatment are not adequately reported in RCTs, making it difficult to assess any significant improvements in areas such as quality of life or mortality.
Adverse effects were not consistently detected across drugs due to non-standardized collection methods, which were often not reported in trials. However, it has been observed that dizziness is the most common mild side effect of the medication. Acamprosate and naltrexone were more likely to cause gastrointestinal problems than placebo.
Other drugs, such as baclofen and topiramate, were associated with higher instances of drowsiness, numbness, and cognitive dysfunction. A direct comparison between acamprosate and oral naltrexone highlighted a lower incidence of nausea with acamprosate.