Treatment of Young Adults With Comorbid AUD/MDD: A Pilot Medication Trial
Condition: Major Depressive Disorder; Alcohol Use Disorder
MeSH terms: Alcoholism; Depressive Disorder; Depression; Depressive Disorder, Major; Alcohol Drinking
Study type: Interventional
Phase: Phase 2

Summary: 
      Recent reports have shown that alcohol misuse is a particularly serious problem among the 18
      to 25 year old age group. Previous medication trials with SSRI antidepressants among young
      adults with co-occurring depressive disorders, including our own recent trials with SSRI
      medications, have produced disappointing results, especially for decreasing the level of
      alcohol consumption. Mirtazapine is a non-SSRI medication with a unique structure and
      mechanism of action. Recent study results suggest that mirtazapine is more effective than
      other antidepressants for treating non-comorbid depression. A few recent studies with
      mirtazapine have been conducted among subjects with comorbid AUD/MDD, and those studies have
      demonstrated efficacy for mirtazapine for decreasing the depressive symptoms and the alcohol
      craving of subjects with comorbid AUD/MDD. However, those studies did not measure level of
      alcohol consumption, so it is unclear whether mirtazapine decreases the level of alcohol use
      of that comorbid population. The results of our own very recent open label pilot study
      suggest robust within-group efficacy for mirtazapine for decreasing both the level of alcohol
      use and the depressive symptoms of comorbid subjects. However, that pilot study did not
      include a placebo control group, so the efficacy of mirtazapine versus placebo for decreasing
      the level of alcohol use among persons with comorbid AUD/MDD remains unclear. This 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
      both the alcohol use and depressive symptoms of young adults with comorbid AUD/MDD. If
      results (effect sizes) from the proposed study are found to be promising concerning outcome
      differences between the mirtazapine and placebo groups, then we will use those findings to
      apply for an R01 study to definitively assess the efficacy of mirtazapine for treating young
      adults with AUD/MDD.
    

Detailed description: 
      MDD and AUD are each highly prevalent among young adults, and the comorbidity of those two
      disorders occurs more often than would be expected by chance alone. The presence of this
      comorbidity is associated with increased risk for motor vehicle accidents, relapse to alcohol
      use, suicide, recurrence of depressive illness, increased morbidity, and costly
      hospitalization. Thus, the comorbidity of AUD/MDD is a highly significant public health
      problem among young adults, with considerable unmet treatment needs. Previous medication
      trials with SSRI antidepressants involving those co-occurring conditions, including our own
      recent trials with SSRI medications, have produced disappointing results, especially for
      decreasing the level of alcohol consumption. Mirtazapine is an FDA-approved medication for
      treating MDD with a unique pharmacological profile, unrelated to SSRIs. Recent study results
      suggest that mirtazapine is more effective than other antidepressants for treating
      non-comorbid depression. A few recent studies have demonstrated efficacy for mirtazapine for
      decreasing the depressive symptoms and the alcohol craving of subjects with comorbid AUD/MDD,
      but those studies did not measure level of alcohol consumption. Therefore, it is unclear
      whether mirtazapine decreases the level of alcohol use of that comorbid population. Our own
      recent pilot data suggest within-group efficacy for mirtazapine for decreasing both the
      excessive alcohol use and the depressive symptoms of persons with comorbid AD/MDD. However,
      that pilot study did not include a placebo control group, so the efficacy of mirtazapine for
      decreasing the level of alcohol use among persons with comorbid AUD/MDD remains unclear. To
      date, no double-blind, placebo-controlled study has even been conducted to assess whether
      mirtazapine decreases both the level of drinking and the depressive symptoms of young adults
      with comorbid AD/MDD. In this submission, we propose a proof of concept, double-blind,
      placebo-controlled pilot trial to provide a preliminary assessment of the efficacy of the
      medication mirtazapine vs. placebo in the treatment of young adults with co-occurring alcohol
      use disorders (AUD) and major depression (MDD). If results (effect sizes) from the proposed
      study are found to be promising concerning outcome differences between the mirtazapine and
      placebo groups, then we will use those findings to apply for an R01 study to definitively
      assess the efficacy of mirtazapine for treating young adults with AUD/MDD.
    

Intervention name(s): Mirtazapine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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.
Other intervention name(s): Remeron; Sugar Pill
Intervention MeSH terms: Mirtazapine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Major Depressive Disorder; Alcohol Use Disorder