EVALUATION OF A DESIPRAMINE CEILING

三项随机双盲对照研究的回顾分析 地塞帕明在可卡因滥用治疗中披露高地塞帕明 血浆浓度(稳定状态下大于200毫微克/毫升)为 与非常糟糕的药物治疗结果有关。这些耐人寻味的 回溯性的初步数据受限于小样本量和 缺乏对血浆浓度的先验关注。到目前为止还没有 不足以指导临床护理或提供确定的上限 是存在的。如果确定了上限，仅有现有数据就不能 确定为什么它只出现在这种疾病中，而不是抑郁症中，或者 确定地塞帕明血药浓度的校正程度 有助于其在可卡因滥用者中的临床有效性。 我们建议对可能的上限进行第一次前瞻性评估 盐酸地昔帕明在可卡因滥用治疗中的血药浓度。 120名可卡因依赖者将 随机分为安慰剂组(n=40)或地塞帕明组(n=80)。一个固定的 剂量(3.0 mg/kg)。将用于尝试分发 地塞帕明受试者分为A以上和A以下的两个同等大小的组 初步估计上限为200毫克/毫升。安慰剂 条件被用来1)评估天花板上的血浆 正如早期观察家所建议的那样，浓度低于安慰剂会使结果恶化， 和2)扩大随机、控制双盲的数量 地昔帕明在有争议的可卡因领域的疗效评估 虐待治疗。 需要进行固定剂量的多周试验，以确定1) 此应用程序中报告的回溯性观察可以复制 在前瞻性研究中，以及2)血浆是否与 治疗后几周的浓度与治疗前相似 最初几周的治疗，因为这里的回顾报告 主要关注#年头一个月的地塞帕明浓度 药物疗法。

Retrospective analyses of three randomized, double-blind studies of desipramine in cocaine abuse treatment disclose that high desipramine plasma concentrations (greater than 200 ng./ml. at steady state) are associated with very poor pharmacotherapy outcome. These intriguing, retrospective, preliminary data are limited by small sample size and absence of an a priori focus on plasma concentrations. They are as yet insufficient to guide clinical care or provide certainty that a ceiling exists. If a ceiling is confirmed, the existing data alone cannot establish why it appears only in this disorder and not depression, or determine how strongly correct desipramine plasma concentrations contribute to its clinical effectiveness in cocaine abusers. We propose the first prospective evaluation of a possible ceiling of desipramine hydrochloride plasma concentration in cocaine abuse treatment. One hundred and twenty (120) DSM-lIlR cocaine dependent individuals will be randomly assigned to placebo (n=4O) or to desipramine (n=8O). A fixed dose of (3.0 mg./kg.) will be used to attempt to distribute the desipramine subjects into two equally sized groups above and below a preliminary estimate of 200 mg./ml. for the ceiling. The placebo condition is being used to 1) assess whether supra-ceiling plasma concentrations worsen outcome below placebo, as early observers suggest, and to 2) extend the number of randomized, controlled double-blind efficacy assessments in the controversial arena of desipramine for cocaine abuse treatment. Fixed dosage multi-week trials are needed to establish whether both 1) the retrospective observations reported in this application can be replicated in a prospective study, and 2) whether the relationship of plasma concentrations in later treatment weeks is similar to that presented for the earliest weeks of treatment, because the retrospective reports herein focus mainly on desipramine concentrations in the initial month of pharmacotherapy.