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Paroxetine/Bupropion in Suicide Attempters/Ideators With Major Depression

Primary Purpose

Depression

Status

Terminated

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Paroxetine

Bupropion

About this trial

This is an interventional treatment trial for Depression focused on measuring Major Depressive Disorder, MDD

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Columbia University/New York State Psychiatric Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Paroxetine

Bupropion

Arm Description

Participants will receive paroxetine for 8 weeks

Participants will receive bupropion for 8 weeks

Outcomes

Primary Outcome Measures

Go-No go Test

Change in neuropsychological measure of impulsivity. Computer-based task involving induction of a dominant response tendency and testing of the subject's ability to withhold responding to less frequent non-target stimuli.

Scale for Suicidal Ideation

The clinician-rated Beck Scale for Suicidal Ideation (SSI) (Beck et al 1979)was used weekly for 8 weeks. It has 19 items scaled 0 (least severe) to 2 (most severe) and total score is the sum, ranging 0 to 38 (Beck et al 1979). Items measure frequency, intensity, and attitudes toward suicidal thoughts, feelings of control over them, and suicide plans. Mean score in 90 inpatients hospitalized for suicidal ideation was 9.4±8.4, versus 4.4±5.8 in outpatients as cited in the study by Beck et al, 1979.

Occurrence of Suicidal Ideation or Acts Necessitating a Change in Treatment

Suicide attempts, other suicidal behavior, or increase in suicidal thoughts that required a change in clinical treatment.

Brain Activity Measured by BOLD Signal With fMRI During a Reward Processing Task.

Comparison of fMRI results at baseline and after 8 weeks of antidepressant pharmacotherapy with paroxetine vs. bupropion. Percent change in contrast of parameter estimates (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 5 cents vs. loses 0 cents

Secondary Outcome Measures

Full Information

NCT ID

NCT00429169

First Posted

January 29, 2007

Last Updated

October 3, 2018

Sponsor

New York State Psychiatric Institute

Collaborators

National Institute of Mental Health (NIMH)

1. Study Identification

Unique Protocol Identification Number

NCT00429169

Brief Title

Paroxetine/Bupropion in Suicide Attempters/Ideators With Major Depression

Official Title

Paroxetine Versus Bupropion for Suicide Ideators or Attempters With Major Depressive Disorder

Study Type

Interventional

2. Study Status

Record Verification Date

October 2018

Overall Recruitment Status

Terminated

Why Stopped

Interim analysis showed differential treatment effects.

Study Start Date

June 2004 (undefined)

Primary Completion Date

January 2010 (Actual)

Study Completion Date

January 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

New York State Psychiatric Institute

Collaborators

National Institute of Mental Health (NIMH)

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Depression

Keywords

Major Depressive Disorder, MDD

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

101 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Paroxetine

Arm Type

Active Comparator

Arm Description

Participants will receive paroxetine for 8 weeks

Arm Title

Bupropion

Arm Type

Active Comparator

Arm Description

Participants will receive bupropion for 8 weeks

Intervention Type

Drug

Intervention Name(s)

Paroxetine

Other Intervention Name(s)

Paxil CR

Intervention Description

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

Intervention Name(s)

Bupropion

Other Intervention Name(s)

Wellbutrin XL

Intervention Description

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.

Primary Outcome Measure Information:

Title

Go-No go Test

Description

Time Frame

Measured at Baseline and Week 8

Title

Scale for Suicidal Ideation

Description

Time Frame

Baseline and Week 8

Title

Occurrence of Suicidal Ideation or Acts Necessitating a Change in Treatment

Description

Suicide attempts, other suicidal behavior, or increase in suicidal thoughts that required a change in clinical treatment.

Time Frame

Measured at Month 6

Title

Brain Activity Measured by BOLD Signal With fMRI During a Reward Processing Task.

Description

Time Frame

Baseline and Week 8.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael F. Grunebaum, MD

Organizational Affiliation

Columbia University/New York State Psychiatric Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Columbia University/New York State Psychiatric Institute

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

21993207

Citation

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.

Results Reference

result

PubMed Identifier

24107760

Citation

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.

Results Reference

derived

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Paroxetine/Bupropion in Suicide Attempters/Ideators With Major Depression

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