EVALUATION OF A DESIPRAMINE CEILING

三项随机、双盲研究的回顾性分析， 地昔帕明在可卡因滥用治疗中公开了高地昔帕明 血浆浓度（大于200 ng./ ml.在稳定状态下）是 与非常差的药物治疗结果相关。这些耐人寻味的， 回顾性的初步数据受到样本量小的限制， 缺乏对血浆浓度的先验关注。 他们迄今 不足以指导临床护理或确定 存在. 如果确定上限，仅凭现有数据无法 确定为什么它只出现在这种疾病而不是抑郁症中，或者 测定地昔帕明血浆浓度的校正强度 有助于其在可卡因滥用者中的临床有效性。 我们建议对可能的最高限额进行第一次前瞻性评估， 可卡因滥用治疗中盐酸地昔帕明的血浆浓度 一百二十（120）名DSM-III R可卡因依赖者将 随机分配至安慰剂组（n= 40）或地昔帕明组（n= 80）。 固定 剂量（3.0 mg./ kg.）将被用来试图分发 地昔帕明受试者分为两个相等大小的组，高于和低于a 初步估计为200毫克。ml.对于天花板。 安慰剂 条件是用于1）评估是否天花板上的血浆 浓度低于安慰剂会恶化结果，正如早期观察者所建议的那样， 和2）增加随机、对照双盲研究的数量 地昔帕明治疗可卡因的有争议的竞技场中的疗效评估 虐待治疗 需要进行固定剂量的多周试验，以确定1） 本应用程序中报告的回顾性观察结果可以复制 在一项前瞻性研究中，2）血浆中 治疗后几周的浓度与 治疗的最早几周，因为本文的回顾性报告 主要关注年最初一个月的地昔帕明浓度 药物治疗.

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.