Paroxetine/Bupropion in Suicide Attempters/Ideators With Major Depression

NCT ID: NCT00429169

Last Updated: 2018-10-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-06-30
• Study Completion Date: 2013-01-31

Brief Summary

The primary study comparing effectiveness for suicidal ideation and/or behavior of two antidepressant medications in depressed patients who have attempted suicide or are currently experiencing suicidal thoughts has been completed.

A secondary study component using functional magnetic resonance imaging (fMRI) to investigate different medication effects on reward processing in the same sample is ongoing.

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. Selective serotonin reuptake inhibitors (SSRIs) are a type of antidepressant medication that works by increasing the amount of serotonin, a natural substance in the brain that helps maintain mental balance. The study compared the effectiveness of paroxetine, an SSRI, versus bupropion, a non-SSRI, on suicidal ideation and/or behavior in depressed patients with a past suicide attempt and/or current suicidal thoughts. Results of the completed primary study have been published (Grunebaum MF et al. Neuropsychopharmacology. 2012 Feb;37(3):697-706).

In the ongoing secondary neuro-imaging component of the study, 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.

Conditions

Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Paroxetine

Participants will receive paroxetine for 8 weeks

Group Type: ACTIVE_COMPARATOR

Paroxetine

Intervention Type: DRUG

Dosage will be 25 mg every day for 2 weeks, then 37.5 mg every day for 2 weeks, and then optional increase to 50 mg every day for the remainder of treatment.

Bupropion

Participants will receive bupropion for 8 weeks

Group Type: ACTIVE_COMPARATOR

Bupropion

Intervention Type: DRUG

Dosage will be 150 mg every day for 2 weeks, then 300 mg every day for 2 weeks, and then optional increase to 450 mg every day for the remainder of treatment.

Interventions

Paroxetine

Dosage will be 25 mg every day for 2 weeks, then 37.5 mg every day for 2 weeks, and then optional increase to 50 mg every day for the remainder of treatment.

Intervention Type: DRUG

Bupropion

Dosage will be 150 mg every day for 2 weeks, then 300 mg every day for 2 weeks, and then optional increase to 450 mg every day for the remainder of treatment.

Intervention Type: DRUG

Other Intervention Names

Paxil CR; Wellbutrin XL

Eligibility Criteria

Inclusion Criteria

• Currently suffering from a major depressive episode (unipolar only)
• History of a past suicide attempt or score greater than 2 on the Hamilton Depression Rating Scale (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.
• Patients 60 years of age and older must score at least 25 on MMSE at screening.
• Patients 60 years of age and older must have a normal ECG within the past year.

Exclusion Criteria

• Any of the following conditions: 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; already taking selective serotonin reuptake inhibitors (SSRIs) or bupropion for other indications (such as anxiety disorders)
• Primary disorder is an anxiety disorder (e.g., panic disorder, general anxiety disorder, obsessive compulsive disorder, social anxiety disorder), with secondary depression
• Drug or alcohol dependence within 6 months prior to study entry (current drug or alcohol abuse may be permitted if study officials determine that the abuse is of lesser importance than the major depressive episode)
• Systolic blood pressure greater than or equal to 140 mm Hg or diastolic blood pressure greater than or equal to 90 mm Hg
• Significant active physical illness, particularly those that may affect the brain or serotonergic system (e.g., blood dyscrasias lymphomas, hypersplenism, endocrinopathies, kidney failure, severe chronic obstructive lung disease, autonomic neuropathies, active malignancy)
• Active medical problems
• Requires antipsychotic medication
• History of hypomania or mania while taking antidepressants
• Any condition that may make the use of an SSRI or bupropion medically inadvisable
• Currently using Zyban
• Failure to respond to adequate trials of three SSRIs, paroxetine, or bupropion within 2 years prior to study entry (failure to respond to therapeutic trial defined as at least 2/3 maximal daily dose [PDR] for at least 6 weeks)
• Pregnant, breastfeeding, or plans to become pregnant during the course of study participation
• Currently on effective treatment, requires adjunctive antipsychotic or mood stabilizing medication, or is unlikely to respond to single agent treatment for depression
• Patients with ferrous metal implants in their bodies, or a history of claustrophobia that precludes MRI, will be excluded.
• Patients assessed as being unlikely to tolerate the maximum 2-week delay to start of treatment.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

New York State Psychiatric Institute

OTHER

Sponsor Role: lead

Responsible Party

Michael Grunebaum, MD

Clinical Psychiatrist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael F. Grunebaum, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University/New York State Psychiatric Institute

Locations

Columbia University/New York State Psychiatric Institute

New York, New York, United States

Countries

United States

References

Grunebaum MF, Ellis SP, Duan N, Burke AK, Oquendo MA, John Mann J. Pilot randomized clinical trial of an SSRI vs bupropion: effects on suicidal behavior, ideation, and mood in major depression. Neuropsychopharmacology. 2012 Feb;37(3):697-706. doi: 10.1038/npp.2011.247. Epub 2011 Oct 12.

Reference Type: RESULT

PMID: 21993207 (View on PubMed)

Grunebaum MF, Keilp JG, Ellis SP, Sudol K, Bauer N, Burke AK, Oquendo MA, Mann JJ. SSRI versus bupropion effects on symptom clusters in suicidal depression: post hoc analysis of a randomized clinical trial. J Clin Psychiatry. 2013 Sep;74(9):872-9. doi: 10.4088/JCP.12m08000.

Reference Type: DERIVED

PMID: 24107760 (View on PubMed)

Other Identifiers

K23MH076049

Identifier Type: NIH

Identifier Source: secondary_id

View Link

DSIR 8KRT-AT

Identifier Type: -

Identifier Source: secondary_id

#5933R

Identifier Type: -

Identifier Source: org_study_id