Fluoxetine and Bupropion to Treat Patients With Depression and Alcoholism

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00449007
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
• Enrollment: 5
• Location: 1
• Arms: 2
• Duration (Months): 58
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Depression; Alcoholism; Suicidal Behavior	Drug: fluoxetine; Drug: bupropion	Phase 4

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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)
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
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	Drug: fluoxetine; 6 months
Active Comparator: 2 bupropion -- 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	Drug: bupropion; 6 months

Outcome Measures

Primary Outcome Measures

1. Occurrence of Suicide Events Either a Suicide Death, a Suicide Attempt, or Suicidal Ideation Severe Enough to Warrant a Medical Intervention [6 months]

   patients have either a suicide death, a suicide attempt, or suicidal ideation severe enough to warrant a medical intervention. this is assessed using the Columbia Suicide History Form and a consensus conference rules on whether the event meets criteria or not. Medical interventions can include hospitalization, a change in medication (adding adjunctive meds) or an increase in frequency of visits or other methods to monitor the patient. The range is 0 and up and denotes the number of suicide events (not the number of participants and not the number of suicide attempts). Higher score is worse and predicts future suicidal behavior

Secondary Outcome Measures

1. Suicidal Ideation at 6 Months [6 month]

   Participant Score on the Scale for Suicidal Ideation will be the outcome variable. The SSI range is from 0-38 and higher score is worse and may predict suicide risk

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New York State Psychiatric Institute	New York	New York	United States	10032

Sponsors and Collaborators

• New York State Psychiatric Institute
• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT00449007
• Other Study ID Numbers: NIAAA-OQU-015630-02; P20AA015630; NIH Grant P20 AA015630-02
• First Posted: Mar 19, 2007
• Last Update Posted: Aug 4, 2021
• Last Verified: Jul 1, 2021

• Keywords provided by New York State Psychiatric Institute: Major depressive disorder; Alcohol abuse; Alcohol dependence; Suicide
• Additional relevant MeSH terms: Alcoholism; Depression; Depressive Disorder; Bupropion; Fluoxetine

Study Results

Participant Flow

Arm/Group Title	Fluoxetine	Bupropion
Arm/Group Description	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 fluoxetine: 6 months	bupropion -- 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 bupropion: 6 months
Period Title: Overall Study
STARTED	2	3
COMPLETED	2	3
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Fluoxetine	Bupropion	Total
Arm/Group Description	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 fluoxetine: 6 months	bupropion -- 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 bupropion: 6 months	Total of all reporting groups
Overall Participants	2	3	5
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 100%	3 100%	5 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.7 (3.8)	33.5 (10.6)	37.2 (12.0)
Sex: Female, Male (Count of Participants)
Female	1 50%	1 33.3%	2 40%
Male	1 50%	2 66.7%	3 60%
Region of Enrollment (participants) [Number]
United States	2 100%	3 100%	5 100%

Outcome Measures

1. Primary Outcome

Title	Occurrence of Suicide Events Either a Suicide Death, a Suicide Attempt, or Suicidal Ideation Severe Enough to Warrant a Medical Intervention
Description	patients have either a suicide death, a suicide attempt, or suicidal ideation severe enough to warrant a medical intervention. this is assessed using the Columbia Suicide History Form and a consensus conference rules on whether the event meets criteria or not. Medical interventions can include hospitalization, a change in medication (adding adjunctive meds) or an increase in frequency of visits or other methods to monitor the patient. The range is 0 and up and denotes the number of suicide events (not the number of participants and not the number of suicide attempts). Higher score is worse and predicts future suicidal behavior
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

patients randomized to one of two arms for 6 months and assessed weekly for 8 weeks and then monthly

Arm/Group Title	Fluoxetine for 6 Months	Bupropion for 6 Months
Arm/Group Description	fluoxetine -- patients randomized to one of two arms for 6 months and assessed weekly for 8 weeks and then monthly. patients receive 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 fluoxetine: 6 months	bupropion fluoxetine -- patients randomized to one of two arms for 6 months and assessed weekly for 8 weeks and then monthly. patients receive 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 : bupropion: 6 months
Measure Participants	2	3
Number [suicide events]	2	3

2. Secondary Outcome

Title	Suicidal Ideation at 6 Months
Description	Participant Score on the Scale for Suicidal Ideation will be the outcome variable. The SSI range is from 0-38 and higher score is worse and may predict suicide risk
Time Frame	6 month

Outcome Measure Data

Analysis Population Description

All 5 participants had data and calculated scores for the Scale for Suicidal Ideation during the conduct of the trial.

Arm/Group Title	Fluoxetine 6 Months of Antidepressant	Bupropion 6 Months of Antidepressant
Arm/Group Description	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 fluoxetine: 6 months	bupropion -- 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 bupropion: 6 months
Measure Participants	2	3
Mean (Standard Deviation) [units on a scale]	0.5 (0.7)	8.5 (12.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bupropion for 6 Months
	Comments	Difference between 6 months and baseline for Bupropion treated group. Due to the low number of participants, the results are unreliable.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.5
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Arm 1 Randomized to Fluoxetine		Arm 2 Randomized to Bupropion
Arm/Group Description	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 fluoxetine: 6 months		bupropion -- 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 bupropion: 6 months
All Cause Mortality
	Arm 1 Randomized to Fluoxetine		Arm 2 Randomized to Bupropion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm 1 Randomized to Fluoxetine		Arm 2 Randomized to Bupropion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Arm 1 Randomized to Fluoxetine		Arm 2 Randomized to Bupropion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/3 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.