A Study of Quetiapine and Mirtazapine for the Treatment of Alcohol Dependency

Study Overview
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Brief Summary
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The purpose of the study is to test whether taking two medicines (quetiapine and mirtazapine) is better for helping people to decrease drinking than taking one medicine alone (quetiapine).

Detailed Description
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Alcohol dependence is a debilitating illness affecting almost 8 million people annually and for which the current FDA approved medications are only modestly effective in reducing relapse or drinking. Because alcohol dependence is such a common, devastating disease, researchers continue to search for new treatments that could be more effective and better tolerated. The development and testing of medications that target brain systems involved in alcohol dependence is of acute interest to patients, clinicians and researchers. Studies by our group in animals have suggested that medications with a combination of a weak dopamine D2 receptor antagonism, a potent norepinephrine alpha 2 receptor antagonism, and norepinephrine reuptake inhibition decrease alcohol drinking. Quetiapine is a weak D2 antagonist and a moderate alpha 2 receptor antagonist, and its primary metabolite, desalkylquetiapine, is a norepinephrine reuptake inhibitor, this medication is likely to have some ability to decrease alcohol drinking. But, when combined with mirtazapine, a potent alpha 2 antagonist, the combination should potently decrease alcohol drinking. The proposed study is based on this theoretical formulation, as well as on clinical studies of quetiapine and mirtazapine used independently. This is an open-label, sequential design study with one group of approximately 20 subjects studied under two treatment conditions; quetiapine alone and quetiapine + mirtazapine. The primary objective is to assess the efficacy of quetiapine fumarate extended-release (XR) alone vs. quetiapine fumarate XR in combination with mirtazapine in reducing the weekly percentage of days of heavy drinking (5 or more drinks per drinking day for men, 4 or more drinks per drinking day for women) in subjects meeting DSM-IV criteria for alcohol dependency. Participants will begin with quetiapine fumarate XR up to a target dose of 400 mg and will receive 16 weeks of treatment with quetiapine. At week 8 subjects will begin 9 weeks of mirtazapine added to their existing regimen of quetiapine treatment. Participants will also meet with a medical provider at each visit to encourage compliance with study medication and attending study visits, review adverse events, and set goals for reduction of drinking. Analyses will assess whether treatment with quetiapine in combination with mirtazapine reduces drinking more than treatment with quetiapine alone.

Official Title
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An Open-Label, Sequential Study of Quetiapine Fumarate Extended Release (XR) and Mirtazapine for the Treatment of Alcohol Dependency in Very Heavy Drinkers

Conditions
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Alcohol Dependence

Intervention / Treatment
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* Drug: Mirtazapine
* Drug: Quetiapine fumarate extended release (Quetiapine XR)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-64 The subject meets Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for alcohol dependence The subject is seeking treatment for alcohol dependence and desires a reduction or cessation of drinking The subject is able to verbalize understanding of the consent form, able to provide written informed consent, and able to verbalize willingness to complete study procedures? If the subject is female and of child bearing potential, she agrees to use an acceptable method of birth control. The subject is able to take oral medication, willing to adhere to the medication regimen, and willing to return for regular visits. The subject is able to understand written and oral instructions in English and able to complete the questionnaires required by the protocol. The subject has a breath alcohol concentration (BAC) equal to 0.000 on s/he signing the informed consent document.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Quetiapine fumarate extended release (Quetiapine XR)<br>Quetiapine XR 50-400mg | Drug: Quetiapine fumarate extended release (Quetiapine XR)<br>* Quetiapine fumarate extended release 50-400mg/d<br>* Other names: quetiapine XR, Seroquel XR;|
| Experimental: Quetiapine XR and Mirtazapine<br>Quetiapine XR 50-400mg + Mirtazapine 7.5-45mg | Drug: Mirtazapine<br>* mirtazapine (7.5-45mg)<br>* Other names: mirtazapine (Remeron);Drug: Quetiapine fumarate extended release (Quetiapine XR)<br>* Quetiapine fumarate extended release 50-400mg/d<br>* Other names: quetiapine XR, Seroquel XR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Very Heavy Drinking Days Per Week | The number of very heavy drinking days (8 or more drinks per drinking day for men or 6 or more drinks per drinking day for women) per week | 14 Weeks |