Paroxetine/Bupropion in Suicide Attempters/Ideators With Major Depression

NCT00429169 | Terminated Phase 4 Results

• 3 other identifiers: #5933RK23MH076049DSIR 8KRT-AT
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 1

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.

Conditions

Depression

Keywords

Major Depressive Disorder; MDD

Outcome Measures

Primary Outcomes (4)

• 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.

  Measured at Baseline and Week 8

• 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.

  Baseline and Week 8

• 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.

  Measured at Month 6

• 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

  Baseline and Week 8.

Study Arms (2)

Paroxetine

ACTIVE COMPARATOR

Participants will receive paroxetine for 8 weeks

Drug: Paroxetine

Bupropion

ACTIVE COMPARATOR

Participants will receive bupropion for 8 weeks

Drug: Bupropion

Interventions

Paroxetine 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.

Also known as: Paxil CR

Paroxetine

Bupropion 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.

Also known as: Wellbutrin XL

Bupropion

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Columbia University/New York State Psychiatric Institute

New York, New York, 10032, United States

Location

Related Publications (2)

• 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.

  PMID: 21993207 RESULT

• 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.

  PMID: 24107760 DERIVED

MeSH Terms

Conditions

Depression; Depressive Disorder, Major

Interventions

Paroxetine; Bupropion

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Propiophenones; Ketones; Organic Chemicals

Limitations and Caveats

1. Significant dropout meant the number of subjects with analyzable data was smaller than the number enrolled. 2. An interim analysis of this pilot study showed differential treatment effects so a decision was made to stop enrollment early.

Results Point of Contact

• Title: Michael F. Grunebaum, MD
• Organization: Columbia University/NYSPI

mfg14@columbia.edu

212-543-5842

Study Officials

• Michael F. Grunebaum, MD

  Columbia University/New York State Psychiatric Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Psychiatrist

Study Record Dates

• First Submitted: January 29, 2007
• First Posted: January 31, 2007
• Study Start: June 1, 2004
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2013
• Last Updated: October 30, 2018
• Results First Posted: January 24, 2013

Record last verified: 2018-10

Locations

US (1)