Quetiapine for the treatment of Type A and Type B alcoholism

描述（由申请人提供）：目前批准用于治疗酒精依赖的药物并不是绝对有效的。因此，研究人员继续寻找更好的药物来治疗这种严重的疾病。一种提高药物疗效的方法是针对治疗抵抗亚群的特定药物，如Babor所述的B型酒精中毒。B型酗酒者的特点是酒精问题的早期发作，依赖性更严重，治疗反应差。相比之下，A型酗酒者的特点是问题饮酒发生较晚，酒精依赖程度较轻，与酒精相关的问题较少，对治疗的反应更好。我们进行了一项双盲、安慰剂对照的初步试验，包括61名酗酒者（32名A型和29名B型），每天服用400 mg奎替鲁胺或安慰剂。与安慰剂治疗的患者相比，在试验期间有更多的奎硫平治疗患者保持禁欲（31% vs. 6%）。在减少B型糖尿病患者的饮酒方面，奎替利显著更有效 患者在A型患者中，奎替鲁肽和安慰剂治疗的患者都显著减少了他们的饮酒量，因此没有检测到奎替鲁肽的作用。经过进一步分析，我们发现，对奎硫平产生良好反应最具预测性的特征是频繁大量饮酒，这是通过每个饮酒日的平均饮酒次数较高以及在30天内饮酒至中毒的天数较多来衡量的。试验。很可能我们的初步试验中的A型患者代表了一个不太严重的酗酒者亚组，这解释了为什么他们对安慰剂和奎替鲁胺的反应同样好。奎替鲁肽可能对频繁重度饮酒者更有效，因为它与多巴胺能和多巴胺能神经传递异常有关。非典型抗精神病药物靶向多巴胺和5-羟色胺系统，并已显示出减少患有精神疾病的酗酒者饮酒的疗效。奎替鲁是一种非典型的抗精神病药物，具有良好的副作用。拟议的5年项目旨在确认和扩展我们在双盲、安慰剂对照、13周试验中关于奎替鲁肽治疗频繁重度饮酒者的初步发现。该研究将在180名DSM-IV酒精依赖患者中比较奎替鲁肽（每日400 mg）与安慰剂，这些患者是频繁重度饮酒者，通过平均每天饮酒超过12杯并且在进入试验前30天内饮酒至中毒15天或更长时间来确定。主要假设是，与安慰剂治疗的患者相比，奎硫平治疗的患者将具有1）更多的戒酒天数和2）更少的重度饮酒天数，如通过时间轴随访测量的。将进行探索性分析，以进一步研究其他可能的奎替鲁酮/酒精亚型相互作用

DESCRIPTION (provided by applicant): Currently approved medications for the treatment of alcohol dependence are not overwhelmingly effective. Therefore, researchers continue to look for better medications to treat this serious illness. One approach to improve medication efficacy is to target specific medications for treatment resistant subpopulations such as Type B alcoholism, as described by Babor. Type B alcoholics are characterized by an early onset of alcohol problems, greater severity of dependence, and a poor treatment response. In contrast, Type A alcoholics are characterized by a later onset of problem drinking, less severe alcohol dependence, fewer alcohol-related problems, and a better response to treatment. We conducted a double-blind, placebo-controlled, pilot trial, involving 61 alcoholics (32 type A and 29 Type B) treated with quetiapine, 400 mg daily, or placebo. Significantly more quetiapine-treated patients remained abstinent during the trial, compared to placebotreated patients (31% vs. 6%). Quetiapine was significantly more effective in reducing drinking in Type B patients. In Type A patients, both the quetiapine and placebo treated patients significantly reduced their drinking so no effect of quetiapine was detected. Upon further analysis, we found that the characteristic most highly predictive of a good response to quetiapine was frequent heavy drinking as measured by a high average number of drinks per drinking day and a greater number of days of drinking to intoxication in the 30 days prior to the trial. It is likely that the Type A patients in our pilot trial represented a less severely addicted subgroup of alcoholics and this explains why they responded equally well to placebo or quetiapine. Quetiapine may be more effective in frequent heavy drinkers because of associated abnormalities of serotonergic and dopaminergic neurotransmission. Atypical antipsychotics target both the dopamine and the serotonin systems and have shown efficacy in reducing alcohol use in alcoholics with comorbid psychiatric illness. Quetiapine is an atypical antipsychotic that has a favorable side effect profile. The proposed 5-year project is intended to confirm and extend our initial findings regarding quetiapine for the treatment of frequent heavy drinkers in a double-blind, placebo-controlled, 13-week trial. The study will compare quetiapine (400 mg daily) to placebo in 180 DSM-IV alcohol dependent patients who are frequent heavy drinkers as determined by averaging more than 12 drinks per drinking day and having 15 or more days of drinking to intoxication in the thirty days prior to entering the trial. The primary hypotheses are that quetiapine-treated patients will have 1) more abstinent days from alcohol and 2) fewer heavy drinking days compared to placebo-treated patients as measured by the timeline follow back. Exploratory analyses will be conducted to further investigate other possible quetiapine / alcohol subtype interactions