RESEARCH ON INDIVIDUAL SENSITIVITY TO BENZODIAZEPINES

目的：本研究的主要目的是通过检查BZ自我给药的个体差异来识别有药物依赖风险的焦虑症患者，并评估这种行为的特定社会心理、药理学和生物学相关性。具体目的：我们将研究：1)阿普唑仑（Alz）敏感性的个体差异是否预测自我用药行为，2)“应激激素”（如皮质醇）水平是否介导药物敏感性和/或Alz使用模式，以及3)一段时间的处方剂量是否影响患者后来如何选择使用Alz进行自我用药。方法：30名M、F焦虑症患者参加为期12周的门诊研究。患者最初将住院过夜，进行包括24小时的神经内分泌评估。监测皮质醇/ACTH血液水平和CRH刺激试验。一个自我给药程序将用于确定个体患者在“按需”服用Alz时如何选择使用它来治疗焦虑。自我用药行为将在服用安慰剂一周、服用阿普唑仑一周和同时服用安慰剂和阿普唑仑一周时进行评估。患者将根据其观察到的使用模式分为高剂量或低剂量。在自我药疗过程之后，患者将服用4周规定剂量的药物（Alz和安慰剂）。每周给予不同剂量的Alz以检查剂量-反应。将评估各组在抗焦虑作用、镇静作用、精神运动表现作用、皮质醇水平和药物喜好方面的差异。最后，患者将完成第二次自我给药程序，在此过程中，他们可以“根据需要”再次自我用药，这样我们就可以评估在处方剂量后，p.r.n.的使用模式是否发生了变化。

OBJECTIVES: The broad objectives of this study are to identify anxiety disorder patients who are at risk for drug dependence by examining individual differences in BZ self-administration and to evaluate specific psychosocial, pharmacological, and biological correlates of this behavior. SPECIFIC AIMS: We will examine: 1) whether individual differences in alprazolam (Alz) sensitivity predicts self-medication behavior, 2) whether levels of 'stress hormones" such as cortisol mediate drug sensitivity and/or patterns of Alz use, and 3) whether a period of prescribed dosing influences how patients later choose to self-medicate with Alz. METHODS: 30 M,F anxiety disorder patients will participate in this 12-week outpatient study. Patients will initially be hospitalized overnight for a neuroendocrine assessment that will include 24 hr. monitoring of cortisol/ACTH blood levels and a CRH Stimulation Test. A self- administration procedure will be used to determine how individual patients would choose to use Alz to treat anxiety when they take it "as needed." Self-medication behavior will be assessed for on-week of placebo, one week of alprazolam, and one week of concurrent access to both placebo and alprazolam. Patients will be classified as either HIGH or LOW users based on their observed patterns of use. The self-medication procedure will be followed by 4 weeks of prescribed doses of medication (Alz and placebo). A different dose of Alz will be given each week to examine dose-response. Group differences in anxiolytic effects, sedative effects, psychomotor performance effects, cortisol levels, and drug liking will be evaluated. Finally, patients will complete the second self- administration procedure in which they may again self-medicate "as needed" so that we can evaluate whether p.r.n. patterns of use have changed subsequent to the prescribed dosing.