The acknowledged drugs of choice for the pharmacological treatment of insomnia are the benzodiazepine receptor agonist hypnotics (BzRA). Studies show that at therapeutic doses, used over the short-term, the abuse liability of BzRAs is relatively low and their efficacy outweighs their minimal risks. However, an increasing number of patients use BzRAs nightly for longer periods of time than is currently indicated (i.e. 4 weeks) and, minimal data on the long-term abuse liability and efficacy of these drugs exist. This project, using both prospective and retrospective methods, will address questions about the long-term abuse liability and efficacy of the BzRAs. The questions being raised are: What is the abuse liability and efficacy of hypnotics currently being used chronically and what is the prospective abuse liability and efficacy of hypnotics used chronically? Zolpidem is the chosen standard for this project as it is the most frequently prescribed BzRA and also arguably the BzRA with the best short-term efficacy and safety profile. The focus of the first question is clinical; it is about the long-term abuse liability and efficacy of BzRAs, specifically zolpidem, as it is currently being prescribed and about the type of patients who receive this drug. The second question addresses the issue of whether a standard BzRA can be prescribed efficaciously and safely for the long-term to patients with primary insomnia. Over the first 4 years of this 5 year project a total 240 insomniacs will be entered into this study to yield 60 insomniacs who have been using zolpidem chronically (>6 months) and 180 who have never used a prescribed hypnotic. The 60 chronic-current zolpidem users will be followed for approximately 1 month. The 180 treatment-naive insomniacs will be randomly assigned to a placebo or zolpidem group and followed for 12 months. In the first month (all groups) and long-term (the two prospective groups), assessments for dependence, including probes for both physical and behavioral dependence, hypnotic efficacy, next-day residual effects, and markers of """"""""hyperarousal' as predictors of dependence risk, will be conducted. Drug self administration will be used to assess behavioral dependence, standard polysomnography (PSG), withdrawal symptom checklists, urinary catecholamine and cortisol levels and Multiple Sleep Latency Testing for physical dependence, and PSG and self-reports for hypnotic efficacy.
