Depression, Suicidal Ideation
Conditions
Keywords
Major Depressive Disorder, MDD, Reward, BOLD signal, Suicide
Brief summary
This study uses functional magnetic resonance imaging (fMRI) to investigate the effects of two different antidepressant medications (Paxil CR versus Wellbutrin XL) on reward processing in depressed patients who have attempted suicide or are currently experiencing suicidal thoughts.
Detailed description
Major depressive disorder (MDD) is a common and serious psychiatric illness. It is among the leading causes of disability and is the psychiatric disorder most often associated with suicide. The treatment of MDD with antidepressant medication remains largely trial and error. Little empirical evidence exists to guide the treatment of MDD when suicide risk is a major factor. The study uses functional magnetic resonance imaging (fMRI) to compare the effects of paroxetine, an SSRI, versus bupropion, a non-SSRI, on brain activity in depressed patients with a past suicide attempt and/or current suicidal thoughts. Participants are randomly assigned to either paroxetine or bupropion treatment for 8 weeks, with fMRI scans involving a reward processing task at baseline and Week 8. Weekly study visits include interviews with a psychologist, self-report scales, and medication monitoring. All participants will then be offered 4 additional months of open clinical treatment. If original medication assignments prove to be ineffective, participants will have the option to switch to another medication. After completing the study, participants will be referred for ongoing treatment.
Interventions
DRUGParoxetine CR for Major Depressive Episode
Dosage will be 25mg every day for 2 weeks, then 37.5mg every day for 2 weeks, and then optional increase to 50mg every day for the remainder of treatment.
DRUGBupropion XL for Major Depressive Episode
Dosage will be 150mg every day for 2 weeks, then 300mg every day for 2 weeks, and then optional increase to 450mg every day for the remainder of treatment.
Sponsors
National Institute of Mental Health (NIMH)
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
1. Patient suffering from an episode of major depressive disorder (MDD) 2. Age range 18-65 years 3. History of a past suicide attempt or score \> 2 on HDRS item #3 (suicide) at in-person screening interview. Patients with suicidal plan or intent will only be enrolled as inpatients if independent inpatient treatment team agrees with the plan to enroll the patient. 4. Patients 60 years of age and older must score at least 25 on MMSE at screening. 5. Patients 60 years of age and older must have a normal ECG within the past year.
Exclusion criteria
1. Bipolar disorder; current psychotic symptoms; bulimia or anorexia that is current or within the past year, or current purging at least twice a week for three months; persons already taking SSRIs or bupropion for other indications (such as anxiety disorders). 2. Primary disorder is an anxiety disorder such as Panic disorder/GAD/OCD/ Social anxiety disorder, with secondary depression. 3. Drug or alcohol dependence within past six months; persons with current drug or alcohol abuse may be enrolled if this is assessed as being of lesser importance than the major depressive episode. 4. Blood pressure reading ≥ 140/90 5. Active and/or unstable medical problems including a significant risk for seizures 6. Antipsychotic medication required 7. Patients who have become hypomanic or manic on antidepressants 8. Contraindication to the use of an SSRI or bupropion, or currently using Zyban. Anorexia nervosa in remission at least one year is not an exclusion. 9. Failure to respond to adequate trials of 3 SSRIs or paroxetine 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). 10. Lacks capacity to consent 11. Pregnancy, lactation, or plans to conceive during the course of study participation. 12. Patients currently on effective treatment, who require adjunctive antipsychotic or mood stabilizing medication, or who are unlikely to respond to single agent treatment for depression will be excluded. 13. Patients with ferrous metal implants in their bodies, or a history of claustrophobia that precludes MRI, will be excluded. 14. Patients assessed as being unlikely to tolerate the maximum 2-week delay to start of treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Contrast of Parameter Estimates (COPE) | Measured at Baseline (pre-treatment) and Week 8 (post-treatment) | % change in COPE = (Post-treatment COPE - Pre-treatment COPE) / Pre-treatment COPE COPE is measured during Monetary Incentive Delay Task. Task conditions are: Reward= BOLD signal when subject wins 5 cents vs. wins 0 cents Punishment= BOLD signal when subject loses 5cents vs. loses 0 cents |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Suicidal Ideation (SSI Score) | Measured at Baseline and Week 8 | Beck Scale of Suicidal Ideation Minimum Value = 0 Maximum Value = 38 Higher score is more severe suicidal thoughts |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bupropion Participants will receive bupropion XL for 8 weeks.
Bupropion XL for Major Depressive Episode: Dosage will be 150mg every day for 2 weeks, then 300mg every day for 2 weeks, and then optional increase to 450mg every day for the remainder of treatment. | 3 |
| Paroxetine CR Participants will receive Paroxetine CR for 8 weeks.
Paroxetine CR for Major Depressive Episode: Dosage will be 25mg every day for 2 weeks, then 37.5mg every day for 2 weeks, and then optional increase to 50mg every day for the remainder of treatment. | 4 |
| Total | 7 |
Baseline characteristics
| Characteristic | Bupropion | Paroxetine CR | 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 | 4 Participants | 7 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 4 |
| other Total, other adverse events | 0 / 3 | 0 / 4 |
| serious Total, serious adverse events | 0 / 3 | 0 / 4 |
Outcome results
Primary
Percent Change in Contrast of Parameter Estimates (COPE)
% change in COPE = (Post-treatment COPE - Pre-treatment COPE) / Pre-treatment COPE COPE is measured during Monetary Incentive Delay Task. Task conditions are: Reward= BOLD signal when subject wins 5 cents vs. wins 0 cents Punishment= BOLD signal when subject loses 5cents vs. loses 0 cents
Time frame: Measured at Baseline (pre-treatment) and Week 8 (post-treatment)
Population: Major depressive disorder with suicidal thoughts or past suicide attempt.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bupropion | Percent Change in Contrast of Parameter Estimates (COPE) | ACC Reward | 0.29 Percentage change |
| Bupropion | Percent Change in Contrast of Parameter Estimates (COPE) | ACC Punishment | -1.19 Percentage change |
| Bupropion | Percent Change in Contrast of Parameter Estimates (COPE) | Amygdala Reward | -0.90 Percentage change |
| Bupropion | Percent Change in Contrast of Parameter Estimates (COPE) | Amygdala Punishment | -0.32 Percentage change |
| Paroxetine CR | Percent Change in Contrast of Parameter Estimates (COPE) | Amygdala Punishment | -0.66 Percentage change |
| Paroxetine CR | Percent Change in Contrast of Parameter Estimates (COPE) | ACC Reward | -2.12 Percentage change |
| Paroxetine CR | Percent Change in Contrast of Parameter Estimates (COPE) | Amygdala Reward | -0.87 Percentage change |
| Paroxetine CR | Percent Change in Contrast of Parameter Estimates (COPE) | ACC Punishment | -1.33 Percentage change |
Secondary
Change in Suicidal Ideation (SSI Score)
Beck Scale of Suicidal Ideation Minimum Value = 0 Maximum Value = 38 Higher score is more severe suicidal thoughts
Time frame: Measured at Baseline and Week 8
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bupropion | Change in Suicidal Ideation (SSI Score) | Baseline | 11 units on a scale | Standard Deviation 4.4 |
| Bupropion | Change in Suicidal Ideation (SSI Score) | Week 8 | 3.3 units on a scale | Standard Deviation 3.1 |
| Paroxetine CR | Change in Suicidal Ideation (SSI Score) | Baseline | 4.8 units on a scale | Standard Deviation 3.5 |
| Paroxetine CR | Change in Suicidal Ideation (SSI Score) | Week 8 | 0.3 units on a scale | Standard Deviation 0.5 |