Petrakis Ismene, Ralevski Elizabeth, Nich Charla, Levinson Carolyn, Carroll Kathleen, Poling James, Rounsaville Bruce
Department of Psychiatry, Yale University School of Medicine, Veterans Affairs Connecticut Healthcare System, West Haven Campus, West Haven, CT 06516, USA.
J Clin Psychopharmacol. 2007 Apr;27(2):160-5. doi: 10.1097/jcp.0b13e3180337fcb.
Although disulfiram and naltrexone have been approved by the Food and Drug Administration for the treatment of alcoholism, no medications have been approved for individuals with alcohol dependence and comorbid psychiatric disorders. In particular, the effect of these medications on alcohol use outcomes and on specific psychiatric symptoms is still unknown in patients with the most common co-occurring disorder, major depression.
Two hundred fifty-four patients with a major Axis I psychiatric disorder and comorbid alcohol dependence were treated for 12 weeks in an outpatient medication study conducted at 3 Veterans Administration outpatient clinics. Randomization included (1) open randomization to disulfiram or no disulfiram, and (2) double-blind randomization to naltrexone or placebo. This resulted in 4 groups: (1) naltrexone alone, (2) placebo alone, (3) disulfiram and naltrexone, and (4) disulfiram and placebo. Primary outcomes were measures of alcohol use. Secondary outcomes included psychiatric symptoms assessed by the Hamilton Depression Rating Scale, alcohol craving, gamma-glutamyltransferase levels, and adverse events.
One hundred thirty-nine subjects (54.7%) met the current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression. There was no relationship between the diagnosis of depression and medication treatment on alcohol use outcomes, psychiatric symptoms, or the reporting of side effects for these medications. There was a significant interaction between diagnosis, medication group, and craving, where subjects with depression on disulfram reported lower craving over time than subjects with depression on naltrexone.
The results suggest that disulfiram and naltrexone are safe pharmacotherapeutic agents for dually diagnosed individuals with depression for the treatment of alcohol use disorders.
尽管双硫仑和纳曲酮已获美国食品药品监督管理局批准用于治疗酒精中毒，但尚无药物被批准用于治疗伴有精神疾病共病的酒精依赖个体。特别是，对于最常见的共病疾病——重度抑郁症患者，这些药物对酒精使用结果和特定精神症状的影响仍不明确。
在3家退伍军人管理局门诊诊所进行的一项门诊药物研究中，对254名患有主要的轴I精神疾病且合并酒精依赖的患者进行了为期12周的治疗。随机分组包括：（1）开放随机分组至双硫仑组或非双硫仑组，以及（2）双盲随机分组至纳曲酮组或安慰剂组。这产生了4组：（1）单独使用纳曲酮，（2）单独使用安慰剂，（3）双硫仑和纳曲酮，以及（4）双硫仑和安慰剂。主要结局是酒精使用的测量指标。次要结局包括通过汉密尔顿抑郁量表评估的精神症状、酒精渴望、γ-谷氨酰转移酶水平和不良事件。
139名受试者（54.7%）符合《精神疾病诊断与统计手册》第四版中重度抑郁症的标准。抑郁症诊断与药物治疗对酒精使用结果、精神症状或这些药物副作用报告之间没有关联。在诊断、药物组和渴望之间存在显著交互作用，即服用双硫仑的抑郁症患者随着时间推移报告的渴望程度低于服用纳曲酮的抑郁症患者。
结果表明，双硫仑和纳曲酮对于同时诊断为抑郁症的酒精使用障碍患者是安全的药物治疗剂。
