Alcohol Use Disorder, Major Depressive Disorder
Conditions
Keywords
Major Depressive Disorder, Alcohol Use Disorder
Brief summary
Mirtazapine is a non-SSRI (selective serotonin reuptake inhibitor) medication with a unique structure and mechanism of action. Recent study results suggest that mirtazapine may be more effective and faster acting than other antidepressants. Levels of alcohol use have been shown to be associated with levels of depressive symptoms among comorbid populations. Our own recent open label pilot study suggested robust within-group efficacy for mirtazapine for decreasing both the drinking and the depressive symptoms of persons with co-occurring alcohol dependence/major depressive disorder (AD/MDD). However, no placebo control group was employed in that study, so between-group efficacy versus placebo could not be assessed. The current grant submission proposes to conduct a first double-blind, placebo-controlled study to evaluate the efficacy of mirtazapine versus placebo for decreasing the alcohol use and depressive symptoms of persons with comorbid AD/MDD. If the results of this proposed double-blind pilot trial are promising, then the effect sizes found in this proposed study will be used to help design an adequately-powered R01 treatment trial to definitively test the efficacy of mirtazapine in this comorbid population.
Detailed description
Alcohol dependence (AD) and Major Depressive Disorder (MDD) are among the most frequent psychiatric disorders in the general population, and the co-occurrence of those disorders represents a significant public health problem. Levels of alcohol use have been shown to be associated with levels of depressive symptoms among comorbid populations. Previous medication trials with SSRI antidepressants in this comorbid population have produced disappointing results. Mirtazapine is a non-SSRI medication with a unique structure and mechanism of action. Recent study results suggest that mirtazapine may be more effective and faster acting than other antidepressants. Our own recent open label pilot study suggested robust within-group efficacy for mirtazapine for decreasing both the drinking and the depressive symptoms of AD/MDD subjects. However, no placebo control group was employed in that study, so between-group efficacy versus placebo could not be assessed. The current grant submission proposes to conduct a first double-blind, placebo-controlled pilot study to provide a preliminary assessment of the efficacy of mirtazapine versus placebo for decreasing the alcohol use and depressive symptoms of persons with comorbid AD/MDD. If the results of this proposed double-blind pilot study are promising, then the effect sizes found in this proposed study will be used to help design an adequately-powered R01 treatment trial to definitively test the efficacy of mirtazapine versus placebo in this comorbid population.
Interventions
DRUGMirtazapine
Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.
DRUGPlacebo
Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects.
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
University of Pittsburgh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* DSM-IV-TR diagnosis of current alcohol dependence, confirmed by the Mini International Neuropsychiatric Interview (MINI) * DSM-IV-TR diagnosis of current major depressive disorder, confirmed by the Mini International Neuropsychiatric Interview (MINI)
Exclusion criteria
* Any person who meets criteria for alcohol-induced depression * Any psychotic disorder bipolar disorder, mental retardation, impaired cognitive functioning, or use of any psychotropic medication in the previous month * Current Diagnostic and Statistical Manual (DSM-IV) criteria for dependence on substances other than alcohol, cannabis, nicotine, or caffeine * Significant neurological conditions or medical conditions * Persistent elevation of liver function enzymes indicating active liver disease (elevated t. bilirubin or elevation to three-time normal range of liver enzymes, SGOT, SGPT, or g-GTP) * The presence of renal function impairment defined as serum creatinine \>2x upper limit of normal * Pregnancy, inability or unwillingness to use contraceptive methods * Use of any antidepressant medication in the prior two months, or any lifetime use of mirtazapine * Inability to read or understand study forms and agree to informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drinks Per Drinking Day | 12 Weeks | Level of drinking, as indicated by the number of drinks per day as recorded on the Timeline Follow-Back calendar. |
| Level of Depressive Symptoms | 12 Weeks | Level of depressive symptoms, as indicated by the score on the Beck Depression Inventory. The Beck Depression Inventory II scoring range is as follows: 0-13 minimal depressive symptoms, 14-19 mild depressive symptoms, 20-28 moderate depressive symptoms and 29-63 severe depressive symptoms. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mirtazapine Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.
Mirtazapine: Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.
Placebo: Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects. | 7 |
| Placebo Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects.
Mirtazapine: Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.
Placebo: Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects. | 9 |
| Total | 16 |
Baseline characteristics
| Characteristic | Mirtazapine | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 45.2 Years STANDARD_DEVIATION 5.9 | 37.4 Years STANDARD_DEVIATION 9.8 | 41.3 Years STANDARD_DEVIATION 8.8 |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 0 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 8 |
Outcome results
Primary
Drinks Per Drinking Day
Level of drinking, as indicated by the number of drinks per day as recorded on the Timeline Follow-Back calendar.
Time frame: 12 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirtazapine | Drinks Per Drinking Day | 3.5 Drinks per drinking day | Standard Deviation 1.6 |
| Placebo | Drinks Per Drinking Day | 4.4 Drinks per drinking day | Standard Deviation 1.5 |
Primary
Level of Depressive Symptoms
Level of depressive symptoms, as indicated by the score on the Beck Depression Inventory. The Beck Depression Inventory II scoring range is as follows: 0-13 minimal depressive symptoms, 14-19 mild depressive symptoms, 20-28 moderate depressive symptoms and 29-63 severe depressive symptoms.
Time frame: 12 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirtazapine | Level of Depressive Symptoms | 27.6 Units on a scale | Standard Deviation 7.7 |
| Placebo | Level of Depressive Symptoms | 26.1 Units on a scale | Standard Deviation 11.7 |