• Marijuana use [ Time Frame: Measured at Weeks 1-4, 6, 8, 10, 12 and 1 year ] [ Designated as safety issue: No ]
• Depressive condition [ Time Frame: Measured at Weeks 1-4, 6, 8, 10, 12, and 1 yr. ] [ Designated as safety issue: No ]

• Marijuana use; measured at Weeks 1-4, 6, 8, 10, 12 and 52
• Depressive condition; measured at Weeks 1-4, 6, 8, 10, 12 and 52
• Effectiveness of fluoxetine for treating marijuana dependence and major depressive disorder; measured at Weeks 1-4, 6, 8, 10, 12 and 52

Adolescents who are diagnosed with major depressive disorder are often also diagnosed with marijuana dependence. Fluoxetine is an antidepressant medication currently used to treat young people who are diagnosed with major depressive disorder. The purpose of this study is to determine the effectiveness of fluoxetine in treating adolescents and young adults diagnosed with both major depressive disorder and marijuana dependence.

Marijuana dependence is the most common illicit substance use disorder in the United States. Its prevalence is highest among adolescents and young adults. Major depressive disorder is one of the most common conditions seen in marijuana dependent individuals. Fluoxetine is an antidepressant medication for treatment of major depression among adolescents and children. The purpose of this study is to determine the effectiveness of fluoxetine in treating adolescents and young people dually diagnosed with major depressive disorder and marijuana dependence.

Participants in this 12-week trial will be randomly assigned to receive either fluoxetine or placebo. Participants will initially be randomly assigned to receive either 10 mg of fluoxetine or placebo. Medication will be given in the morning. If no side effects are observed over the first two weeks of the study, medication will be increased to a daily dose of 20 mg of fluoxetine or placebo. If, at Week 4, a participant continues to demonstrate significant depressive symptoms, medication will be increased to 30 mg daily. All participants will also receive Treatment as Usual (TAU) during the acute phase of the trial, which will consist of motivation enhancement therapy (MET) and Cognitive Behavioral Therapy (CBT). Outcome measures will be obtained at screening, baseline, and weekly intervals for the first four weeks of the treatment phase; they will then be obtained biweekly for the final 8 weeks of the treatment phase. Blood will be drawn at baseline and at Weeks 4, 8, and 12 to assess the level of three liver enzymes (gamma-GTP, SGOT, and SGPT). This will provide a biochemical monitoring of drinking behavior and medication compliance. The 12-week acute phase study will be supplemented by a 9-month naturalistic follow-up phase, during which care will be transferred from the study provider to the community provider. The study will end with a 1-year follow-up evaluation.

• Depressive Disorder, Major
• Marijuana Abuse

• Drug: Fluoxetine
• Drug: Placebo

• Active Comparator: Gelatin capsules Fluoxetine 10mg, 1 capsule every a.m. Medication will be increased by one capsule, to a daily dose of fluoxetine 20mg, 2 capsules barring side effects.
• Placebo Comparator: Gelatin capsules Placebo capsules,identical to Fluoxetine capsules, 1 capsule every a.m. Medication will be increased by one capsule, to a daily dose of placebo, 2 capsules barring side effects.

Inclusion Criteria:

• DSM-IV diagnosis of current marijuana abuse or dependence, confirmed by SCID-SUD
• DSM-IV diagnosis of current major depressive disorder, confirmed by the K-SADS
• Marijuana use of at least two days within the week prior to enrollment
• Demonstrated adequate levels of depressive symptoms within the week prior to enrollment

Exclusion Criteria:

• DSM-IV diagnosis of bipolar disorder, schizoaffective disorder, or schizophrenia
• Hypo or hyperthyroidism
• Significant cardiac, neurological, or kidney impairment
• Liver disease (SGOT, SGPT, or gamma-GTP greater than 3 times the normal level)
• Use of antipsychotic or antidepressant medication in the month prior to enrollment
• DSM-IV dependence on any substance except marijuana or nicotine; alcohol dependence, or history of drug use
• History of significant medication side effects from any SSRI antidepressant
• Pregnant
• Unable to use adequate contraceptive methods for the duration of the study
• Inability to read or understand English