A Study of Quetiapine and Mirtazapine for the Treatment of Alcohol Dependency
Study Details
Study Description
Brief Summary
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 Design
Arms and Interventions
| 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:
|
| Experimental: Quetiapine XR and Mirtazapine Quetiapine XR 50-400mg + Mirtazapine 7.5-45mg |
Drug: Mirtazapine
mirtazapine (7.5-45mg)
Other Names:
Drug: Quetiapine fumarate extended release (Quetiapine XR)
Quetiapine fumarate extended release 50-400mg/d
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Very Heavy Drinking Days Per Week [14 Weeks]
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
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Dartmouth Medical School Department of Psychiatry's Addition Research Center | Bedford | New Hampshire | United States | 03110 |
| 2 | Dartmouth Medical School Department of Psychiatry's Addiction Research Center | Hanover | New Hampshire | United States | 03755 |
Sponsors and Collaborators
- Dartmouth-Hitchcock Medical Center
Investigators
- Principal Investigator: Mary Brunette, MD, Dartmouth-Hitchcock Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- QM1
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Entire Study Population |
|---|---|
| Arm/Group Description | Quetiapine fumarate extended release (Quetiapine XR): Quetiapine fumarate extended release 50-400mg/d first for 7 weeks; then Quetiapine XR plus mirtazapine: Quetiapine fumarate extended release (50-400mg) plus mirtazapine (7.5-45mg) for 7 weeks. |
| Period Title: Quetiapine XR Monotherapy | |
| STARTED | 20 |
| COMPLETED | 16 |
| NOT COMPLETED | 4 |
| Period Title: Quetiapine XR Monotherapy | |
| STARTED | 16 |
| COMPLETED | 11 |
| NOT COMPLETED | 5 |
Baseline Characteristics
| Arm/Group Title | Entire Study Population |
|---|---|
| Arm/Group Description | Quetiapine fumarate extended release (Quetiapine XR): Quetiapine fumarate extended release 50-400mg/d first for 7 weeks; then Quetiapine XR and mirtazapine: Quetiapine fumarate extended release (50-400mg) and mirtazapine (7.5-45mg) for 7 weeks. |
| Overall Participants | 20 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
48.1
(10.1)
|
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
20
100%
|
| >=65 years |
0
0%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
6
30%
|
| Male |
14
70%
|
| Region of Enrollment (participants) [Number] | |
| United States |
20
100%
|
Outcome Measures
| Title | Number of Very Heavy Drinking Days Per Week |
|---|---|
| Description | 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 |
| Time Frame | 14 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Analysis Population only consists of participants that completed both phases of the study. |
| Arm/Group Title | Quetiapine Fumarate Extended Release (Quetiapine XR) | Quetiapine XR Plus Mirtazapine |
|---|---|---|
| Arm/Group Description | Quetiapine XR 50-400mg Quetiapine fumarate extended release (Quetiapine XR): Quetiapine fumarate extended release 50-400mg/d | Quetiapine XR 50-400mg + Mirtazapine 7.5-45mg Quetiapine XR plus mirtazapine: Quetiapine fumarate extended release (50-400mg) plus mirtazapine (7.5-45mg) |
| Measure Participants | 11 | 11 |
| Mean (Standard Deviation) [days] |
2.1
(2.8)
|
1.3
(2.4)
|
Adverse Events
| Time Frame | Adverse events were collected throughout both periods of the study and included a 30 day follow-up call made after study participation ended to assess for additional events.. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | This study included two phases (quetiapine XR monotherapy and quetipapine XR andmirtazapine). An adverse event was attributed to a given phase if it began during that phase. | |||
| Arm/Group Title | Quetiapine Fumarate Extended Release (Quetiapine XR) | Quetiapine XR andMirtazapine | ||
| Arm/Group Description | Quetiapine XR 50-400mg Quetiapine fumarate extended release (Quetiapine XR): Quetiapine fumarate extended release 50-400mg/d | Quetiapine XR 50-400mg + Mirtazapine 7.5-45mg Quetiapine XR and mirtazapine: Quetiapine fumarate extended release (50-400mg) and mirtazapine (7.5-45mg) | ||
All Cause Mortality |
||||
| Quetiapine Fumarate Extended Release (Quetiapine XR) | Quetiapine XR andMirtazapine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Quetiapine Fumarate Extended Release (Quetiapine XR) | Quetiapine XR andMirtazapine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/20 (0%) | 0/16 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Quetiapine Fumarate Extended Release (Quetiapine XR) | Quetiapine XR andMirtazapine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 20/20 (100%) | 14/16 (87.5%) | ||
| Cardiac disorders | ||||
| Prolonged QTC | 0/20 (0%) | 0 | 1/16 (6.3%) | 1 |
| Eye disorders | ||||
| Blurred Vision | 1/20 (5%) | 1 | 0/16 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Dry Mouth | 7/20 (35%) | 7 | 2/16 (12.5%) | 2 |
| Gastrointestinal Problems | 9/20 (45%) | 12 | 4/16 (25%) | 7 |
| General disorders | ||||
| Fatigue | 5/20 (25%) | 6 | 3/16 (18.8%) | 4 |
| Foggy Thinking | 3/20 (15%) | 4 | 3/16 (18.8%) | 4 |
| Sweats | 1/20 (5%) | 1 | 2/16 (12.5%) | 2 |
| Fever | 1/20 (5%) | 1 | 0/16 (0%) | 0 |
| Swelling | 1/20 (5%) | 2 | 0/16 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Injury | 2/20 (10%) | 5 | 1/16 (6.3%) | 1 |
| Investigations | ||||
| Increase Triglycerides | 0/20 (0%) | 0 | 2/16 (12.5%) | 2 |
| Metabolism and nutrition disorders | ||||
| Weight Gain | 1/20 (5%) | 1 | 2/16 (12.5%) | 2 |
| Appetite Increased | 1/20 (5%) | 1 | 0/16 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Muscoloskeletal Disorder | 3/20 (15%) | 4 | 7/16 (43.8%) | 10 |
| Nervous system disorders | ||||
| Dizzy | 6/20 (30%) | 6 | 1/16 (6.3%) | 1 |
| Headache | 4/20 (20%) | 4 | 3/16 (18.8%) | 4 |
| Insomnia | 3/20 (15%) | 4 | 2/16 (12.5%) | 3 |
| Neurologic Disorder | 4/20 (20%) | 5 | 3/16 (18.8%) | 3 |
| Somnolence | 8/20 (40%) | 9 | 6/16 (37.5%) | 6 |
| Psychiatric disorders | ||||
| Unusual Dream Activity | 3/20 (15%) | 3 | 1/16 (6.3%) | 1 |
| Irritated | 2/20 (10%) | 2 | 1/16 (6.3%) | 1 |
| Miscellaneous Sleep Disorder | 2/20 (10%) | 2 | 1/16 (6.3%) | 1 |
| Psychiatric Symptoms | 2/20 (10%) | 4 | 2/16 (12.5%) | 2 |
| Libido Descreased | 1/20 (5%) | 1 | 0/16 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Nose Bleeds | 2/20 (10%) | 3 | 0/16 (0%) | 0 |
| Upper Respiratory Symptoms | 3/20 (15%) | 6 | 0/16 (0%) | 0 |
| Decreased Smoking | 1/20 (5%) | 1 | 0/16 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Dermatological Condition | 2/20 (10%) | 2 | 1/16 (6.3%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Mary Brunette, MD |
|---|---|
| Organization | Geisel School of Medicine At Dartmouth |
| Phone | 603-271-7642 |
| mary.brunette@dartmouth.edu |
- QM1