Paroxetine/Bupropion in Suicide Attempters/Ideators With Major Depression

This study has been terminated.
(Interim analysis showed differential treatment effects.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
New York State Psychiatric Institute
ClinicalTrials.gov Identifier:
NCT00429169
First received: January 29, 2007
Last updated: December 18, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Depression
Drug: Paroxetine
Drug: Bupropion
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Paroxetine Versus Bupropion for Suicide Ideators or Attempters With Major Depressive Disorder

Resource links provided by NLM:


Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:
  • Go-No go Test [ Time Frame: Measured at Baseline and Week 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Measured at Month 6 ] [ Designated as safety issue: Yes ]
    Suicide attempts, other suicidal behavior, or increase in suicidal thoughts that required a change in clinical treatment.


Secondary Outcome Measures:
  • Brain Activity Measured by BOLD Signal With fMRI During a Reward Processing Task. [ Time Frame: Baseline and Week 8. ] [ Designated as safety issue: No ]
    Comparison of fMRI results at baseline and after 8 weeks of antidepressant pharmacotherapy with paroxetine vs. bupropion.


Enrollment: 101
Study Start Date: June 2004
Estimated Study Completion Date: January 2013
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Paroxetine
Participants will receive paroxetine for 8 weeks
Drug: 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.
Other Name: Paxil CR
Active Comparator: Bupropion
Participants will receive bupropion for 8 weeks
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.
Other Name: Wellbutrin XL

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00429169

Locations
United States, New York
Columbia University/New York State Psychiatric Institute
New York City, New York, United States, 10032
Sponsors and Collaborators
New York State Psychiatric Institute
Investigators
Principal Investigator: Michael F. Grunebaum, MD Columbia University/New York State Psychiatric Institute
  More Information

Publications:
Responsible Party: New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT00429169     History of Changes
Other Study ID Numbers: #5933R, K23MH076049, DSIR 8KRT-AT
Study First Received: January 29, 2007
Results First Received: December 11, 2012
Last Updated: December 18, 2012
Health Authority: United States: Federal Government

Keywords provided by New York State Psychiatric Institute:
Major Depressive Disorder
MDD

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mental Disorders
Mood Disorders
Bupropion
Paroxetine
Antidepressive Agents
Antidepressive Agents, Second-Generation
Central Nervous System Agents
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Uptake Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014