Alcoholism, Depression
Conditions
Keywords
fluoxetine,, adolescents,, alcohol dependence,, major depression, Alcoholism
Brief summary
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
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.
Interventions
fluoxetine plus Treatment As Usual (TAU); 12 weeks acute phase; plus 9 month naturalistic follow up
placebo plus Treatment as Usual; 12 weeks acute phase; plus 9 month naturalistic follow up
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, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
15 Years to 20 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Depressive Symptoms | Average score as measured by participant's report on the Beck Depression Inventory (BDI). | 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). |
| Alcohol Use Behaviors | Average number of drinks as recorded on the Timeline Follow-Back (subject-reported) measure daily over the 12-week acute phase. | Alcohol use behaviors measured by drinks per week. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at the Western Psychiatric Institute and Clinic (WPIC) of the University of Pittsburgh Medical Center (UPMC). Subjects were recruited for participation in the treatment study through referrals from any of the WPIC treatment programs and by responding to newspaper, radio and bus advertisements.
Pre-assignment details
Exclusion: bipolar disorder, schizoaffective disorder, schizophrenia, hyper-or hypothyroidism, cardiac, neurological, renal impairment, significant liver disease, received antipsychotic or antidepressant medication, substance abuse or dependence, intravenous drug use, pregnancy, inability or unwillingness to use contraceptive methods, illiteracy.
Participants by arm
| Arm | Count |
|---|---|
| Fluoxetine Plus Treatment As Usual (TAU) Subjects were treated with the medication fluoxetine (15 mg to 30 mg) plus Treatment as Usual (TAU), which included Cognitive Behavioral Therapy and Motivational Enhancement Therapy (CBT/MET) psychotherapy. | 24 |
| Placebo Plus Treatment as Usual (TAU) Subjects were treated with placbo plus Treatment as Usual (TAU), which included Cognitive Behavioral Therapy and Motivational Enhancement Therapy (CBT/MET) psychotherapy. | 26 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 0 | 3 |
Baseline characteristics
| Characteristic | Placebo Plus Treatment as Usual (TAU) | Fluoxetine Plus Treatment As Usual (TAU) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 22 Participants | 47 Participants |
| Age Continuous | 19.4 years STANDARD_DEVIATION 0.91 | 19.5 years STANDARD_DEVIATION 0.94 | 19.4 years STANDARD_DEVIATION 0.92 |
| Region of Enrollment United States | 26 participants | 24 participants | 50 participants |
| Sex: Female, Male Female | 16 Participants | 12 Participants | 28 Participants |
| Sex: Female, Male Male | 10 Participants | 12 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 24 | 0 / 26 |
| serious Total, serious adverse events | 0 / 24 | 0 / 26 |
Outcome results
Primary
Alcohol Use Behaviors
Alcohol use behaviors measured by drinks per week.
Time frame: Average number of drinks as recorded on the Timeline Follow-Back (subject-reported) measure daily over the 12-week acute phase.
Population: Participants were randomized to either fluoxetine-treated or placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fluoxetine Plus Treatment As Usual (TAU) | Alcohol Use Behaviors | 1.56 standard drink (14 gr. alcohol) | Standard Deviation 1.44 |
| Placebo Plus Treatment as Usual (TAU) | Alcohol Use Behaviors | 1.73 standard drink (14 gr. alcohol) | Standard Deviation 1.61 |
Comparison: Repeated measures ANOVAp-value: 0.05ANOVA
Primary
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).
Time frame: Average score as measured by participant's report on the Beck Depression Inventory (BDI).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fluoxetine Plus Treatment As Usual (TAU) | Depressive Symptoms | 6.79 units on a scale | Standard Deviation 7.49 |
| Placebo Plus Treatment as Usual (TAU) | Depressive Symptoms | 10.46 units on a scale | Standard Deviation 10.8 |