Long Term Treatment With Zolpidem: Nightly and Intermittent Dosing

Study Overview
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Brief Summary
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We want to assess whether how and when one takes sleep medication results in similar or different outcomes with respect to symptom relief. We also want to know whether taking medication for a period of time provides continued benefit once the medication is stopped.

Detailed Description
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To date, the aggressive treatment (Tx) of chronic insomnia has been evaluated in terms of whether maintenance therapy is possible. While what constitutes maintenance therapy is a matter of debate, there are two studies which show that benzodiazepine receptor agonists (BZRAs) 1) are effective when used intermittently for up to 3 months and 2) may be used on a nightly basis for up to 6 months with no loss of efficacy. The significance of the present research is two fold. First, it will allow us to compare the two primary strategies used for long term treat of insomnia (nightly dosing vs intermittent dosing). Second, it will allow an evaluation of the possibility that extended treatment, given careful withdrawal from medication, may yield long term clinical gains. Re: Objective 1: It is widely assumed that intermittent dosing confers increased efficacy. That is, less frequent medication use will extend the duration of time for which the medication is maximally potent. An empirical assessment of this proposition is required. If incorrect, physicians and patients should be encouraged to adopt a more aggressive approach to treatment. If correct, physicians and patients should be encouraged to adopt the intermittent dosing approach to treatment. Re: Objective 2: It is widely assumed that treatment with sedatives (sleep promoting medications) constitutes only palliative care. An empirical assessment of this proposition is required. If correct, physicians and patients should be encouraged to adopt a more aggressive approach to long term treatment. If incorrect, physicians and patients should be encouraged to adopt an approach to treatment that is not currently a standard of practice: extended treatment with a clear plan to taper medication that is designed to maintain the clinical gains that occurred with medication use. We propose to evaluate the above issues in a pilot study of 40 subjects with Primary Insomnia where subjects are randomized to one of 4 conditions: QHS dosing with placebo QHS dosing with 10mg of zolpidem Intermittent dosing with 10mg of zolpidem (3-5 pills per week as needed) Monitor only condition.

Official Title
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Long Term Treatment With Zolpidem: The Relative Efficacy of Nightly (Quaque Hora Somni [QHS]) & Intermittent Dosing and the Potential for Long Term Clinical Gains After Treatment Discontinuation.

Conditions
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Insomnia, Primary Insomnia, Psychophysiologic Insomnia

Intervention / Treatment
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* Drug: Zolpidem
* Drug: Sugar Pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 25 - 55 a stable sleep/wake schedule with a preferred sleep phase between 10:00 p.m. and 8:00 a.m. Patients with Primary Insomnia will meet diagnostic criteria for Psychophysiologic Insomnia according to the International Classification of Sleep Disorders manual (ICSD). complaint of disturbed sleep must have the following characteristics: >30 minutes to fall asleep, and/or >30 minutes wake after sleep onset time, a total sleep time of no more than 6.5 hours (or a sleep efficiency of less than 85%), a problem frequency of >4 nights/ week and a problem duration >6 months. Exclusion Criteria: Unstable medical or psychiatric illness Use of medication that may cause insomnia or may be reduce the effectiveness of zolpidem (e.g. selective serotonin reuptake inhibitors(SSRI's), steroids, bronchodilators, calcium channel blockers, beta blockers, etc.) symptoms suggestive of sleep disorders other than insomnia polysomnographic data indicating sleep disorders other than insomnia Evidence of active illicit substance use or fitting criteria for alcohol abuse or dependence inadequate language comprehension pregnancy first-degree relatives with bipolar disorder or schizophrenia

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>QHS dosing with placebo (i.e. nightly dose) | Drug: Sugar Pill<br> <br> |
| Active Comparator: QHS Zolpidem<br>QHS dosing with 10mg of zolpidem (i.e. nightly dose) | Drug: Zolpidem<br>* 10 mg of Zolpidem<br>* Other names: Ambien;|
| Experimental: Intermittant Zolpidem<br>Intermittent dosing with 10mg of zolpidem (3-5 pills per week as needed | Drug: Zolpidem<br>* 10 mg of Zolpidem<br>* Other names: Ambien;|
| No Intervention: Control<br>Monitor only condition (no placebo, no drug). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep Latency (SL) | Number of subjects with any reduction in SL (time to fall asleep in minutes)at post-tx compared to baseline where mean SL = mean of daily values for one week calculated from sleep diary values. | Baseline and Post-treatment (12wks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wake After Sleep Onset (WASO) | Number of subjects with any reduction in WASO at post-tx compared to baseline where mean WASO = mean of daily values for one week calculated from sleep diary values. | Baseline and Post-Treatment (12 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sleep, Insomnia, zolpidem, Ambien, Hypnotics