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.

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.

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.

4 years, 0 months.