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

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

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).

Study Overview

• Status: Completed
• Conditions: Alcohol Dependence
• Intervention / Treatment: Drug: Quetiapine fumarate extended release (Quetiapine XR); Drug: Mirtazapine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Hampshire
    • Bedford, New Hampshire, United States, 03110
      • Dartmouth Medical School Department of Psychiatry's Addition Research Center
    • Hanover, New Hampshire, United States, 03755
      • Dartmouth Medical School Department of Psychiatry's Addiction Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Dartmouth-Hitchcock Medical Center
• Investigators: Principal Investigator: Mary Brunette, MD, Dartmouth-Hitchcock Medical Center

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: July 16, 2010
• First Submitted That Met QC Criteria: July 16, 2010
• First Posted (Estimate): July 20, 2010

Study Record Updates

• Last Update Posted (Actual): April 9, 2018
• Last Update Submitted That Met QC Criteria: March 12, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Anti-Anxiety Agents; Serotonin 5-HT3 Receptor Antagonists; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Adrenergic alpha-Antagonists; Adrenergic alpha-2 Receptor Antagonists; Quetiapine Fumarate; Mirtazapine
• Other Study ID Numbers: QM1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No