Pharmacological Intervention Project (Fluoxetine)

Study Overview
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Brief Summary
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This is a large scale study involving fluoxetine (Prozac) versus a placebo in the treatment of adolescents with alcohol use disorder (AUD) and major depression (MDD). All individuals will receive treatment for 12 weeks with a followup phase lasting 9 months.

Detailed Description
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Recently, the first large-scale double-blind, placebo-controlled study of a selective serotonin reuptake inhibitor (SSRI) antidepressant in depressed adolescents was completed (Emslie et al., 1997) That study demonstrated efficacy for fluoxetine in non-AUD adolescents with major depressive disorder (MDD). Our own research group recently completed a first double-blind, placebo-controlled study of fluoxetine in adults with comorbid MDD and alcohol dependence (Cornelius et al., 1997). That study demonstrated efficacy for fluoxetine in decreasing both the depressive symptoms and the alcohol use of adult depressed alcoholics. Our own research group also recently completed a pilot study involving open label fluoxetine in adolescents with comorbid AUD and MDD. That pilot study demonstrated within-group efficacy for fluoxetine for decreasing both the drinking and the depressive symptoms of that population, and suggested that fluoxetine is a safe medication in this population (Cornelius, et al., In Press). However, to date, no double-blind, placebo-controlled study of any selective serotonin re-uptake inhibitors (SSRI) medication has been conducted in adolescents with a comorbid AUD and MDD. In this proposed study, a first large scale prospective double-blind, placebo-controlled study will be undertaken involving the SSRI medication fluoxetine versus placebo in the treatment of adolescents with an alcohol use disorder and major depression (AUD/MDD). The goals of the study include the following: 1) to compare the efficacy of the SSRI medication fluoxetine plus Treatment As Usual (TAU) to placebo plus TAU for the alcohol use and the depressive symptoms of an adolescent sample (ages 15 to 18) of subjects with comorbid diagnoses of an AUD and MDD; 2) to assess specific predictors of medication response in that study; and to perform a preliminary evaluation of the longer-term efficacy of fluoxetine in these patients, in a 9-month naturalistic follow-up period beyond the 3 month acute phase study. We hypothesize that fluoxetine plus TAU will demonstrate efficacy for decreasing both the drinking and the depressive symptoms of this population.

Official Title
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Pharmacological Intervention Project (Fluoxetine)

Conditions
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Alcoholism, Depression

Intervention / Treatment
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* Drug: fluoxetine (Prozac)
* Drug: Placebo plus Treatment As Usual


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets criteria for alcohol use disorder and major depressive disorder. Exclusion Criteria: Meets criteria for bipolar disorder, schizoaffective disorder, or schizophrenia. Hyper- or hypothyroidism, significant cardiac, neurologic, or renal impairment, and those with significant liver disease. Receiving antipsychotic or antidepressant medication in the month prior to entering the study. Use of any illicit substance abuse or dependence other than cannabis abuse (and alcohol abuse). History of intravenous drug use. Pregnancy, inability or unwillingness to use contraceptive methods. Inability to read or understand study forms Less than 15 years of age or over 18 years of age will be excluded.

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>fluoxetine plus Treatment As Usual (TAU) | Drug: fluoxetine (Prozac)<br>* fluoxetine plus Treatment As Usual (TAU); 12 weeks acute phase; plus 9 month naturalistic follow up<br>|
| Placebo Comparator: 2<br>placebo plus Treatment As Usual (TAU) | Drug: Placebo plus Treatment As Usual<br>* placebo plus Treatment as Usual; 12 weeks acute phase; plus 9 month naturalistic follow up<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alcohol Use Behaviors | Alcohol use behaviors measured by drinks per week. | Average number of drinks as recorded on the Timeline Follow-Back (subject-reported) measure daily over the 12-week acute phase. | 
| Depressive Symptoms | Beck Depression Inventory (BDI) Scores measured at Weeks 1-4, 6, 8, 10, 12. The BDI is a subject reported measure that has a minimum score of 0 and a maximum score of 63. A better outcome would consist of values near the minimum end of the scale (0) and a worse outcome would consist of values near the maximum end of the scale (63). | Average score as measured by participant's report on the Beck Depression Inventory (BDI). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fluoxetine,, adolescents,, alcohol dependence,, major depression, Alcoholism