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

• Amount of alcohol consumed [ Time Frame: 14 Weeks ] [ Designated as safety issue: No ]
  The primary endpoint is a statistically significant reduction in the weekly percentage of heavy drinking days during Weeks 10-14 (quetiapine + mirtazapine) compared to Weeks 3-7 (quetiapine monotherapy).
  
  

• Anxiety [ Time Frame: 14 Weeks ] [ Designated as safety issue: No ]
  A statistically significant reduction in the Hamilton Anxiety Scale scores at Weeks 10-14 (quetiapine + mirtazapine) compared to Weeks 3-7 (quetiapine monotherapy).
  
  
• Depression [ Time Frame: 14 Weeks ] [ Designated as safety issue: Yes ]
  A statistically significant reduction in the Montgomery-Asburg Depression Rating Scale scores at Weeks 10-14 (quetiapine + mirtazapine) compared to Weeks 3-7 (quetiapine monotherapy).
  
  
• Craving [ Time Frame: 14 Weeks ] [ Designated as safety issue: No ]
  A statistically significant reduction in the Penn Alcohol Craving Scale scores at Weeks 10-14 (quetiapine + mirtazapine) compared to Weeks 3-7 (quetiapine monotherapy).
  
  
• Sleep [ Time Frame: 14 Weeks ] [ Designated as safety issue: No ]
  A statistically significant reduction of scores on multiple measures of sleep at Weeks 10-14 (quetiapine + mirtazapine) compared to Weeks 3-7 (quetiapine monotherapy).
  
  
• Safety and tolerability [ Time Frame: 14 Weeks ] [ Designated as safety issue: Yes ]
  Assessments of adverse events throughout the study, including: akathisia, parkinsonism, hyperlipidemia, elevated glucose levels, and decreased absolute neutrophil count.
  
  

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.