Alcoholism, Depression, Suicidal Behavior
Conditions
Keywords
Major depressive disorder, Alcohol abuse, Alcohol dependence, Suicide
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.
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.
Interventions
DRUGfluoxetine
6 months
DRUGbupropion
6 months
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fluoxetine 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 | 2 |
| Bupropion 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 | 3 |
| Total | 5 |
Baseline characteristics
| Characteristic | Bupropion | Fluoxetine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 2 Participants | 5 Participants |
| Age, Continuous | 33.5 years STANDARD_DEVIATION 10.6 | 49.7 years STANDARD_DEVIATION 3.8 | 37.2 years STANDARD_DEVIATION 12 |
| Region of Enrollment United States | 3 participants | 2 participants | 5 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 2 | 0 / 3 |
| serious Total, serious adverse events | 0 / 2 | 0 / 3 |
Outcome results
Primary
Occurrence of Suicide Events Either a Suicide Death, a Suicide Attempt, or Suicidal Ideation Severe Enough to Warrant a Medical Intervention
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
Population: patients randomized to one of two arms for 6 months and assessed weekly for 8 weeks and then monthly
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fluoxetine for 6 Months | Occurrence of Suicide Events Either a Suicide Death, a Suicide Attempt, or Suicidal Ideation Severe Enough to Warrant a Medical Intervention | 2 suicide events |
| Bupropion for 6 Months | Occurrence of Suicide Events Either a Suicide Death, a Suicide Attempt, or Suicidal Ideation Severe Enough to Warrant a Medical Intervention | 3 suicide events |
Secondary
Suicidal Ideation at 6 Months
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
Population: All 5 participants had data and calculated scores for the Scale for Suicidal Ideation during the conduct of the trial.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fluoxetine for 6 Months | Suicidal Ideation at 6 Months | 0.5 units on a scale | Standard Deviation 0.7 |
| Bupropion for 6 Months | Suicidal Ideation at 6 Months | 8.5 units on a scale | Standard Deviation 12 |
Comparison: Difference between 6 months and baseline for Bupropion treated group.~Due to the low number of participants, the results are unreliable.p-value: 1Wilcoxon (Mann-Whitney)