Department of Psychiatry, Amsterdam Neuroscience, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Vergio, Clichy, France.
Department of Psychiatry, Amsterdam Neuroscience, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Int Rev Neurobiol. 2024;178:213-281. doi: 10.1016/bs.irn.2024.07.005. Epub 2024 Oct 20.
Alcohol dependence (AD) significantly impacts public health, affecting 3.4% of people aged 18-64 and contributing to around 12% of overall mortality. Individuals with AD have a markedly reduced life expectancy, dying up to 28 years earlier than the general population. Current treatments for AD show limited efficacy, with many patients not responding to these interventions, highlighting the need for new therapeutic options with novel mechanisms of action. Sodium oxybate (SMO), the sodium salt of GHB, is one such candidate, pharmacologically similar to alcohol; it acts on several neurotransmitters including GABA, potentially mitigating withdrawal symptoms and craving for alcohol. SMO has been clinically used in Italy and Austria since the 1990s, approved for treating alcohol withdrawal syndrome (AWS) and for maintaining abstinence in AD patients. Several randomized clinical trials (RCTs) and meta-analyses showed evidence of SMO to be effective and safe in these indications. For AWS, SMO was more effective than placebo and as effective as benzodiazepines in reducing withdrawal symptoms. For maintaining abstinence, SMO significantly improved continuous abstinence duration and abstinence rate compared to placebo. Comprehensive clinical data indicate that SMO is well-tolerated, with main adverse effects being mild, such as dizziness and vertigo, and serious adverse events being rare. The effectiveness and safety of SMO, coupled with its approval in two EU countries affirm its potential as a treatment option for AD, particularly in severe cases. Further RCTs, especially with stratification by severity of dependence, are suggested to refine our understanding of its efficacy across different patient subgroups.
酒精依赖（AD）显著影响公共健康，影响 18-64 岁人群的 3.4%，并导致约 12%的总死亡率。AD 患者的预期寿命明显缩短，比普通人群早死 28 年。目前 AD 的治疗方法效果有限，许多患者对这些干预措施没有反应，这凸显了需要具有新作用机制的新治疗选择。GHB 的钠盐——羟丁酸钠（SMO）就是这样一种候选药物，它在药理学上与酒精相似；它作用于几种神经递质，包括 GABA，可能减轻戒断症状和对酒精的渴望。自 20 世纪 90 年代以来，SMO 已在意大利和奥地利临床使用，被批准用于治疗酒精戒断综合征（AWS）和维持 AD 患者的戒酒状态。几项随机临床试验（RCT）和荟萃分析表明，SMO 在这些适应证中具有有效性和安全性。对于 AWS，SMO 比安慰剂更有效，与苯二氮䓬类药物一样有效，可减轻戒断症状。对于维持戒酒状态，SMO 与安慰剂相比，显著延长了持续戒酒时间和戒酒率。综合临床数据表明，SMO 耐受性良好，主要不良反应轻微，如头晕和眩晕，严重不良事件罕见。SMO 的有效性和安全性，加上它在两个欧盟国家的批准，肯定了它作为 AD 治疗选择的潜力，特别是在严重病例中。建议进行更多的 RCT，特别是按依赖严重程度进行分层，以进一步了解其在不同患者亚组中的疗效。
