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心理社会，药理学和生物学相关性。具体目标：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药疗行为，2）“应激激素”（如皮质醇）的水平是否介导药物敏感性和/或Alz使用模式，以及3）处方给药期是否影响患者后来如何选择使用Alz自我药疗。方法：30例男性、女性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神经内分泌评估，包括24小时监测皮质醇/ACTH血液水平和CRH刺激试验。一个自我管理的程序将被用来确定如何个别患者会选择使用阿尔兹治疗焦虑时，他们采取“根据需要”。“自我用药行为将评估一周的安慰剂，一周的阿普唑仑，一周的安慰剂和阿普唑仑同时访问。根据观察到的使用模式，将患者分类为高或低使用者。自我药疗程序后将进行4周的处方药物（Alz和安慰剂）治疗。每周给予不同剂量的Alz，以检查剂量反应。将评价抗焦虑作用、镇静作用、精神表现作用、皮质醇水平和药物喜好的组间差异。最后，患者将完成第二次自我给药程序，在该程序中，他们可以“根据需要”再次自我给药，以便我们可以评估是否有p.r.n.在处方剂量之后，使用模式发生了变化。

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.