Garbutt James C, Kranzler Henry R, O'Malley Stephanie S, Gastfriend David R, Pettinati Helen M, Silverman Bernard L, Loewy John W, Ehrich Elliot W
Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill 27599-7160, USA.
JAMA. 2005 Apr 6;293(13):1617-25. doi: 10.1001/jama.293.13.1617.
Alcohol dependence is a common disorder associated with significant morbidity and mortality. Naltrexone, an opioid antagonist, has been shown to be effective for treatment of alcohol dependence. However, adherence to daily oral pharmacotherapy can be problematic, and clinical acceptance and utility of oral naltrexone have been limited.
To determine efficacy and tolerability of a long-acting intramuscular formulation of naltrexone for treatment of alcohol-dependent patients.
DESIGN, SETTING, AND PARTICIPANTS: A 6-month, randomized, double-blind, placebo-controlled trial conducted between February 2002 and September 2003 at 24 US public hospitals, private and Veterans Administration clinics, and tertiary care medical centers. Of the 899 individuals screened, 627 who were diagnosed as being actively drinking alcohol-dependent adults were randomized to receive treatment and 624 received at least 1 injection.
An intramuscular injection of 380 mg of long-acting naltrexone (n = 205) or 190 mg of long-acting naltrexone (n = 210) or a matching volume of placebo (n = 209) each administered monthly and combined with 12 sessions of low-intensity psychosocial intervention.
The event rate of heavy drinking days in the intent-to-treat population.
Compared with placebo, 380 mg of long-acting naltrexone resulted in a 25% decrease in the event rate of heavy drinking days (P = .02) [corrected] and 190 mg of naltrexone resulted in a 17% decrease (P = .07). Sex and pretreatment abstinence each showed significant interaction with the medication group on treatment outcome, with men and those with lead-in abstinence both exhibiting greater treatment effects. Discontinuation due to adverse events occurred in 14.1% in the 380-mg and 6.7% in the 190-mg group and 6.7% in the placebo group. Overall, rate and time to treatment discontinuation were similar among treatment groups.
Long-acting naltrexone was well tolerated and resulted in reductions in heavy drinking among treatment-seeking alcohol-dependent patients during 6 months of therapy. These data indicate that long-acting naltrexone can be of benefit in the treatment of alcohol dependence.
酒精依赖是一种常见疾病，与显著的发病率和死亡率相关。纳曲酮是一种阿片类拮抗剂，已被证明对酒精依赖的治疗有效。然而，坚持每日口服药物治疗可能存在问题，口服纳曲酮的临床接受度和效用有限。
确定长效肌肉注射用纳曲酮治疗酒精依赖患者的疗效和耐受性。
设计、地点和参与者：2002年2月至2003年9月在美国24家公立医院、私立及退伍军人管理局诊所和三级医疗中心进行的一项为期6个月的随机、双盲、安慰剂对照试验。在899名接受筛查的个体中，627名被诊断为正在积极饮酒的酒精依赖成年人被随机分组接受治疗，624人接受了至少1次注射。
每月肌肉注射380毫克长效纳曲酮（n = 205）或190毫克长效纳曲酮（n = 210）或等量安慰剂（n = 209），并结合12次低强度心理社会干预。
意向性治疗人群中重度饮酒日的发生率。
与安慰剂相比，380毫克长效纳曲酮使重度饮酒日的发生率降低了25%（P = .02）[校正后]，190毫克纳曲酮使发生率降低了17%（P = .07）。性别和治疗前戒酒情况在治疗结果上均与药物组存在显著交互作用，男性和治疗前已戒酒者均表现出更大的治疗效果。380毫克组因不良事件停药的比例为14.1%，190毫克组为6.7%，安慰剂组为6.7%。总体而言，各治疗组的停药率和停药时间相似。
长效纳曲酮耐受性良好，在6个月的治疗期间使寻求治疗的酒精依赖患者的重度饮酒减少。这些数据表明长效纳曲酮对酒精依赖的治疗有益。
