Double-blind Pilot Trial of Mirtazapine for the Treatment of Co-occurring AD/MDD.

Phase 2

Completed

Conditions: Major Depressive Disorder
Alcohol Use Disorder

Interventions: Drug: Mirtazapine
Drug: Placebo

Registration Number: NCT02185131

Lead Sponsor: University of Pittsburgh

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 16

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mirtazapine	Placebo	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	Mirtazapine	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.
Placebo	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	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.

Primary Outcome Measures

Name	Time	Method
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.
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.

Secondary Outcome Measures