RESEARCH ON INDIVIDUAL SENSITIVITY TO BENZODIAZEPINES

目的：这项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示着自我用药行为，2)皮质醇等“应激激素”水平是否调节药物敏感性和/或ALZ的使用模式，以及3)一段时间的处方剂量是否影响患者以后选择使用ALZ自我用药。方法：30例男性、女性焦虑症患者参加为期12周的门诊研究。患者最初将入院过夜进行神经内分泌评估，包括24小时。监测皮质醇/促肾上腺皮质激素水平和促肾上腺皮质激素释放激素刺激试验。一个自我给药程序将被用来确定个别患者将如何选择使用ALZ来治疗焦虑，当他们“根据需要”服用时。将对服用安慰剂一周、服用阿普唑仑一周以及同时服用安慰剂和阿普唑仑一周的自我用药行为进行评估。患者将根据观察到的使用模式被归类为高使用量或低使用量。在自我用药过程之后，将进行为期4周的处方剂量的药物治疗(ALZ和安慰剂)。每周将给予不同剂量的阿尔茨海默氏剂以检查剂量反应。将评估两组在抗焦虑效果、镇静效果、精神运动表现效果、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，在该程序中，他们可以再次“根据需要”自我用药，这样我们就可以评估P.r.n。在规定的剂量之后，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.