Official Title: “A Randomized Controlled Study Comparing Fluoxetine With Bupropion for Impulsivity and Suicidality in Patients With Major Depressive Disorder and Comorbid Alcoholism (Abuse or Dependence)”

We will study patients with a current major depressive episode, comorbid alcoholism and a history of a past suicide attempt. All subjects with alcohol dependence will be evaluated for risk of alcohol withdrawal prior to randomization. The study will provide six months of antidepressant pharmacotherapy as well as psychotherapy focused on alcohol relapse prevention. Patients will also be encouraged to attend daily Alcoholics Anonymous meetings.

The outcome measures will be: 1) occurrence of suicide events; 2) reduction of suicidal ideation; 3) reduction in neuropsychological measures of impulsivity.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: December 2010

Suicide is a significant public health problem. Depression, alcoholism (abuse or dependence), and a prior suicide attempt are risk factors for suicide. However, little information exists to guide clinicians in the choice of antidepressant medication for patients with comorbid major depression and alcoholism who are at risk for suicidal acts.

There is evidence that selective serotonin reuptake inhibitors (SSRI) may reduce impulsive aggression, and therefore lower the risk for suicidal behavior. We will test the hypothesis that fluoxetine, an SSRI, will be associated with fewer suicide events (defined as suicidal acts or increases in suicidal ideation necessitating a change in management), decreased suicidal ideation and decreases in neuropsychological measures of impulsivity compared to bupropion. The non-serotonergic drug, bupropion will improve energy and hopelessness. We expect the two drugs to be equally efficacious in reducing global depression severity. We will compare fluoxetine with bupropion in a 6-month randomized, controlled study of major depressive disorder and comorbid alcoholism in patients who have a prior history of suicide attempt. Patients requiring alcohol detoxification will be excluded. Patients will also receive weekly psychotherapy.

We will study 42 subjects with a current major depressive episode, comorbid alcoholism and a history of a past suicide attempt (21 subjects per year) in a randomized, double-blind, controlled trial, stratified by alcoholism type (1 vs 2). All subjects with alcohol dependence will be evaluated for risk of alcohol withdrawal prior to randomization. We will include patients who have suicidal ideation. However, patients with a suicidal plan or intent will only be enrolled as inpatients if the research team and the independent treatment team on the inpatient research unit agree that this is clinically reasonable. For example, if ECT or antipsychotics are indicated, the patient will not be enrolled. The study will provide six months of antidepressant pharmacotherapy as well as psychotherapy focused on alcohol relapse prevention. Patients will also be encouraged to attend daily Alcoholics Anonymous meetings. The outcome measures will be: 1) occurrence of suicide events; 2) reduction of suicidal ideation; 3) reduction in neuropsychological measures of impulsivity.

Intervention(s) in this Clinical Trial

• Drug: fluoxetine
  • 6 months
• Drug: bupropion
  • 6 months

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • fluoxetine -- 6 months of antidepressant pharmacotherapy as well as psychotherapy focused on alcohol relapse prevention; patients will also be encouraged to attend daily Alcoholics Anonymous meetings
• Active Comparator: 2
  • buproprion -- 6 months of antidepressant pharmacotherapy as well as psychotherapy focused on alcohol relapse prevention; patients will also be encouraged to attend daily Alcoholics Anonymous meetings

Primary Measures

• occurrence of suicide events
  • Time Frame: 6 months
    Safety Issue?: Yes
• reduction of suicidal ideation
  • Time Frame: 6 months
    Safety Issue?: Yes
• reduction in neuropsychological measures of impulsivity
  • Time Frame: 6 months
    Safety Issue?: Yes

Inclusion Criteria:

• Patient suffering from a major depressive episode (unipolar only) AND alcohol dependence or abuse; Score of greater than 16 on the HDRS
• Age range 18-65 years
• History of a past suicide attempt, defined as self destructive behavior with at least some intent to die; patients with suicidal plan or intent will only be enrolled as inpatients if staff agrees it is reasonable.
• Able to tolerate cross taper to study medications

Exclusion Criteria:

• Other major psychiatric disorders such as Bipolar Disorder; schizophrenia or schizoaffective disorder, past or current psychotic symptoms; eating disorder;
• substance abuse or dependence (other than alcohol, caffeine or nicotine); persons already taking SSRIs or bupropion for other indications such as anxiety disorders.
• Primary disorder is an anxiety disorder such as Panic disorder/GAD/OCD/Social anxiety disorder, with secondary depression.
• CIWA-AR rating >10 or history of delirium tremens or seizures.
• Blood pressure >150 systolic or >90 diastolic
• Active or untreated medical problems
• Antipsychotic medication required
• History of becoming hypomanic or manic on antidepressants
• Contraindication to the use of fluoxetine or bupropion, or currently using Zyban
• Failure to respond to adequate trials of 3 SSRIs or fluoxetine or bupropion in the last 2 years (failure to respond to therapeutic trial defined as: at least 2/3 maximal
• PDR dose for at least 6 weeks)
• Lack of capacity to consent
• Pregnancy, lactation, or plans to conceive during the course of study participation

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Overall Clinical Trial Officials and Contacts

Maria A. Oquendo, MD Principal Investigator NYS Psychiatric Institute / Columbia University  

Overall Contact: Janelle Dierkins, MPH 212-543-5801 nga@rf.cpmc.columbia.edu

Information obtained from ClinicalTrials.gov on August 28, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00449007

Study ID Number: NIAAA-OQU-015630-02

ClinicalTrials.gov Identifier: NCT00449007

Health Authority: United States: Federal Government