This study will evaluate the longer term effectiveness of cognitive therapy (CT) versus medication treatment or placebo for prevention of recurrence of depression for 24 months after termination of continuation phase therapy.

Depression is a serious medical illness that is often difficult to diagnose and treat. It often recurs more than once in a person's lifetime. Effective treatment methods are needed to prevent the relapse in people who have had prior episodes of depression. CT is a short-term talking therapy that focuses on changing negative thinking patterns and helping patients develop coping skills to deal with their experiences. Evidence suggests that CT is effective in treating a number of psychiatric conditions, including anxiety and anger. This study will determine the effectiveness of booster sessions of CT versus antidepressant medication in preventing relapse of depression in people at risk for recurrent depression.

All participants in this double blind study will first receive 16 to 20 sessions of cognitive-behavioral therapy over 12 weeks. Participants who respond to the treatment, but do not achieve full remission of depressive symptoms, will be considered to be at risk for relapse. They will be randomly assigned to receive 10 booster sessions of one of three treatments over 8 months: cognitive-behavioral therapy, fluoxetine, or placebo. The booster sessions will take place twice monthly for the first 2 months and once monthly for the next 6 months. All participants who complete the entire 8 months of the study will be followed-up for an additional 2 years to monitor depressive relapse and psychosocial functioning.

• Drug: Fluoxetine (Prozac)
• Behavioral: Cognitive therapy (CT)
• Drug: Placebo

• Experimental: Participants will receive treatment with cognitive therapy during the continuation phase
• Experimental: Participants will receive treatment with active fluoxetine during the continuation phase
• Placebo Comparator: Patients participants will receive placebo in the continuation phase

Inclusion Criteria:

• Diagnosis of recurrent unipolar major depressive disorder
• At least 2 episodes of major depression within lifetime, including present episode
• Speaks and reads English
• Seeking cognitive therapy treatment
• At least one period of complete inter-episode recovery or a history of dysthymia prior to the onset of the presenting or past episodes

Exclusion Criteria:

• Active alcohol or other substance dependence within the 6 months prior to study entry
• Active suicidal ideation with possible intent or probable risk
• Mood disorder due to a medical condition or substance use, bipolar disorder, schizophrenia, or schizoaffective disorder
• Unable to stop mood altering medications
• Concurrent medication or exclusionary medical disorders (diabetes, head injury, stroke, cancer, multiple sclerosis) that may cause depression
• Unable to attend clinic during business hours (Monday-Thursday, 8am-5pm) twice weekly
• Unable to complete questionnaires
• Unsuccessful treatment after 8 weeks of cognitive therapy with a certified therapist
• Unsuccessful treatment after 6 weeks of 40 mg of fluoxetine (Prozac)
• Pregnant or plans to become pregnant in the next 11-12 months