DepressionPhase 4NCT00429169

Paroxetine/Bupropion in Suicide Attempters/Ideators With Major Depression

A Phase 4 study testing Paroxetine and Bupropion in people with Depression, run by New York State Psychiatric Institute at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Depression
What is being tested?: Paroxetine and Bupropion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 101 participants
Where: 1 siteUnited States
Study dates: Jun 2004to Jan 2013
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Show all 15Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Columbia University/New York State Psychiatric Institute
New York, New York, 10032

Other trials in United States

About this study

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

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

Read the 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
Being tested: Paroxetine, Bupropion
Keywords: Major Depressive Disorder, MDD
Medical subject headings: Depression, Depressive Disorder, Major

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ParoxetineDrug
Also called Paxil CR
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.
BupropionDrug
Also called Wellbutrin XL
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.

Study groups in NCT00429169
Study group	Role	What they receive
Paroxetine	Active comparator	Participants will receive paroxetine for 8 weeks Receives: Drug: Paroxetine
Bupropion	Active comparator	Participants will receive bupropion for 8 weeks Receives: Drug: Bupropion

What is being measured

The primary outcome is the main question the study is designed to answer.

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: 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.
Measured: 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: 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
Measured: Baseline and Week 8.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2004Jan 2013

First posted31 Jan 2007 (estimated)
Study startJun 2004
Primary completionJan 2010
Study completionJan 2013

Why it stopped: Interim analysis showed differential treatment effects.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for DepressionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 101 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00429169
Sponsor's protocol ID: #5933R
Other IDs: K23MH076049, DSIR 8KRT-AT
Status last verified: Oct 2018
First submitted: 29 Jan 2007
Last updated: 30 Oct 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 21993207
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.
PubMed 24107760

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Unified Protocol in Penitentiary Facilities
Depression Disorders, Anxiety
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
Not yet recruitingObservational study
Functional Impact of Psychological Symptoms in Patients With Superior Semicircular Canal Dehiscence Syndrome (SSCD): a National Cross-sectional Study
Superior Semicircular Canal Dehiscence
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
Recruiting
Cultural Adaptation of an Online Parenting Intervention to Reduce the Risk of Depression and Anxiety in Adolescents
Risk of Depression and Anxiety

All Depression trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Paroxetine Versus Bupropion for Suicide Ideators or Attempters With Major Depressive Disorder
ClinicalTrials.gov ID: NCT00429169
Acronym / sponsor ID: #5933R
Conditions: Depression
Keywords: Major Depressive Disorder, MDD
Phase: Phase 4
Study type: Interventional
Recruitment status: TerminatedReason stopped: Interim analysis showed differential treatment effects.
Enrolment: 101 participants (actual)
Lead sponsor: New York State Psychiatric InstituteUniversity, hospital or other
Collaborators: National Institute of Mental Health (NIMH)
Study start: Jun 2004
Primary completion: Jan 2010 (actual)
Study completion: Jan 2013 (actual)
First posted: 31 Jan 2007 (estimated)
Results: Posted 24 Jan 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Paroxetine	Active comparator	Drug: ParoxetineParticipants will receive paroxetine for 8 weeks
Bupropion	Active comparator	Drug: BupropionParticipants will receive bupropion for 8 weeks

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (15 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ParoxetineAlso: Paxil CRDosage 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.	Drug	Paroxetine
BupropionAlso: Wellbutrin XLDosage 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.	Drug	Bupropion

Primary outcome

Go-No go Test
Time frame: Measured at Baseline and Week 8
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
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
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.
Time frame: Baseline and Week 8.
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

Results and safety

Results posted to the registry on 24 Jan 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Paroxetine	38	36
Bupropion	40	38

Primary outcome: Go-No go Test

Time frame: Measured at Baseline and Week 8. Mean (Standard Deviation). Unit: Commission errors

Measure	Paroxetine n = 30	Bupropion n = 27
Value	-0.09 (0.8)	-0.06 (0.89)

Population analysed: These were the number with analyzable data

Primary outcome: Scale for Suicidal Ideation

Time frame: Baseline and Week 8. Mean (Standard Deviation). Unit: Points on Scale for Suicidal Ideation

Measure	Paroxetine n = 36	Bupropion n = 38
Baseline	8.0 (6.7)	9.9 (7.4)
Week 8	2.3 (4.5)	4.7 (6.6)

Paroxetine vs Bupropion: regression coefficient: -0.29 (95% CI -0.57 to -0.023), p = 0.03, Mixed Models Analysis

Population analysed: The study was powered for N=50 subjects per group based on naturalistic pilot data from our clinic. An interim data analysis showed an interaction of treatment with baseline suicidal ideation severity on follow-up ideation. After consulting with clinical colleagues, statisticians and the IRB, a decision was made to stop enrollment.

Primary outcome: Occurrence of Suicidal Ideation or Acts Necessitating a Change in Treatment

Time frame: Measured at Month 6. Number. Unit: Events

Measure	Paroxetine n = 36	Bupropion n = 38
Value	4	6

Population analysed: These were the number of subjects with analyzable data.

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

Time frame: Baseline and Week 8.. Mean (Full Range). Unit: percentage of change in COPE

Measure	Paroxetine n = 4	Bupropion n = 3
Value	-0.27 (-0.59 to 2.9)	-0.95 (-1.3 to 1.7)

Population analysed: Major depressive disorder with suicidal thoughts or past suicide attempt.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Paroxetine	3 of 36 (8.3%)	0 of 36 (0%)	Not reported
Bupropion	2 of 38 (5.3%)	0 of 38 (0%)	Not reported

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 21993207Grunebaum 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.
Derived from this study: PubMed 24107760Grunebaum 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.

Related trials for Depression

Recruiting
Unified Protocol in Penitentiary Facilities
Depression Disorders, Anxiety
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
Not yet recruitingObservational study
Functional Impact of Psychological Symptoms in Patients With Superior Semicircular Canal Dehiscence Syndrome (SSCD): a National Cross-sectional Study
Superior Semicircular Canal Dehiscence
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
Recruiting
Cultural Adaptation of an Online Parenting Intervention to Reduce the Risk of Depression and Anxiety in Adolescents
Risk of Depression and Anxiety

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Michael F. Grunebaum, MD principal investigator

Columbia University/New York State Psychiatric Institute

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Paroxetine and Bupropion in people with Depression, run by New York State Psychiatric Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jan 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Go-No go Test (time frame: Measured at Baseline and Week 8). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00429169, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2018.