Quetiapine for the treatment of Type A and Type B alcoholism

描述（由申请人提供）：目前批准的治疗酒精依赖的药物并非绝对有效。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。如Babor所述，提高药物疗效的一种方法是针对治疗耐药亚群（如B型酒精中毒）的特定药物。B型酗酒者的特点是酒精问题发作早，依赖程度高，治疗效果差。相比之下，A型酗酒者的特点是饮酒问题发作较晚，酒精依赖程度较低，酒精相关问题较少，对治疗的反应较好。我们进行了一项双盲、安慰剂对照、试点试验，涉及61名酗酒者（32名a型和29名B型），每日使用喹硫平400mg或安慰剂治疗。与安慰剂治疗的患者相比，接受喹硫平治疗的患者在试验期间保持戒断的比例明显更高（31%对6%）。喹硫平在减少B型患者饮酒方面明显更有效

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