Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, and Michael E. DeBakey VA Medical Center, Houston, TX 77030, USA.
Biol Psychiatry. 2013 Feb 1;73(3):219-24. doi: 10.1016/j.biopsych.2012.07.011. Epub 2012 Aug 18.
Disulfiram has been an effective cocaine addiction pharmacotherapy, and one of its possible mechanisms of efficacy is through copper chelation and inhibition of an enzyme involved in catecholamine metabolism, dopamine β-hydroxylase (DβH), which converts dopamine to norepinephrine. A variant in the gene encoding DβH leads to reduced DβH activity, and as such, disulfiram might not be an effective treatment of cocaine dependence for individuals with this variant. This study explored that potential matching.
Seventy-four cocaine- and opioid-codependent (DSM-V) subjects were stabilized on methadone for 2 weeks and subsequently randomized into disulfiram (250 mg/day, n = 34) and placebo groups (n = 40) for 10 weeks. We genotyped the DBH gene polymorphism, -1021C/T (rs1611115), that reduces DβH enzyme levels and evaluated its role for increasing cocaine free urines with disulfiram.
With repeated measures analysis of variance, corrected for population structure, disulfiram pharmacotherapy reduced cocaine-positive urines from 80% to 62% (p = .0001), and this disulfiram efficacy differed by DBH genotype group. Patients with the normal DβH level genotype dropped from 84% to 56% on disulfiram (p = .0001), whereas those with the low DBH level genotype showed no disulfiram effect.
This study indicates that the DBH genotype of a patient could be used to identify a subset of individuals for which disulfiram treatment might be an effective pharmacotherapy for cocaine dependence.
双硫仑已被证明是一种有效的可卡因成瘾药物治疗方法，其可能的疗效机制之一是通过螯合铜和抑制儿茶酚胺代谢中的一种酶，多巴胺β-羟化酶（DβH），从而将多巴胺转化为去甲肾上腺素。编码 DβH 的基因变异导致 DβH 活性降低，因此对于具有这种变异的个体，双硫仑可能不是治疗可卡因依赖的有效方法。本研究探讨了这种潜在的匹配关系。
74 名可卡因和阿片类药物依赖（DSM-V）患者在美沙酮稳定治疗 2 周后，随后随机分为双硫仑（250mg/天，n=34）和安慰剂组（n=40），治疗 10 周。我们对 DBH 基因多态性-1021C/T（rs1611115）进行基因分型，该基因多态性降低了 DβH 酶水平，并评估了它在增加双硫仑治疗下可卡因阴性尿液中的作用。
经过重复测量方差分析，校正了人群结构，双硫仑药物治疗将可卡因阳性尿液从 80%降低到 62%（p=0.0001），并且这种双硫仑疗效因 DBH 基因型组而异。具有正常 DβH 水平基因型的患者从双硫仑治疗的 84%降至 56%（p=0.0001），而具有低 DBH 水平基因型的患者则没有双硫仑作用。
本研究表明，患者的 DBH 基因型可用于识别双硫仑治疗可能对可卡因依赖有效的个体亚群。
