Trial Outcomes & Findings for Paroxetine/Bupropion in Suicide Attempters/Ideators With Major Depression (NCT NCT00429169)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

101 participants

Primary outcome timeframe

Measured at Baseline and Week 8

Results posted on

2018-10-30

Participant Flow

Recruitment dates were 2/2005-7/2009 with follow-up completed in January 2010.

N=101 subjects enrolled, but N=23 did not return after enrollment, so N=78 were randomized.

Participant milestones

Participant milestones
Measure	Paroxetine Participants will receive paroxetine for 8 weeks	Bupropion Participants will receive bupropion for 8 weeks
Overall Study STARTED	38	40
Overall Study COMPLETED	36	38
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Paroxetine Participants will receive paroxetine for 8 weeks	Bupropion Participants will receive bupropion for 8 weeks
Overall Study Lost to Follow-up	0	1
Overall Study Ineligibility discovered after entry	2	1

Baseline Characteristics

Paroxetine/Bupropion in Suicide Attempters/Ideators With Major Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Paroxetine n=36 Participants Participants will receive paroxetine for 8 weeks	Bupropion n=38 Participants Participants will receive bupropion for 8 weeks	Total n=74 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	36 Participants n=5 Participants	38 Participants n=7 Participants	74 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	35.2 years STANDARD_DEVIATION 12.8 • n=5 Participants	37.9 years STANDARD_DEVIATION 11.9 • n=7 Participants	36.4 years STANDARD_DEVIATION 12.7 • n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants	21 Participants n=7 Participants	42 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	17 Participants n=7 Participants	32 Participants n=5 Participants
Region of Enrollment United States	36 participants n=5 Participants	38 participants n=7 Participants	74 participants n=5 Participants

PRIMARY outcome

Timeframe: Measured at Baseline and Week 8

Population: These were the number with analyzable data

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.

Outcome measures

Outcome measures
Measure	Paroxetine n=30 Participants Participants will receive paroxetine for 8 weeks	Bupropion n=27 Participants Participants will receive bupropion for 8 weeks
Go-No go Test	-0.09 Commission errors Standard Deviation 0.8	-0.06 Commission errors Standard Deviation 0.89

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Paroxetine n=36 Participants Participants will receive paroxetine for 8 weeks	Bupropion n=38 Participants Participants will receive bupropion for 8 weeks
Scale for Suicidal Ideation Baseline	8.0 Points on Scale for Suicidal Ideation Standard Deviation 6.7 • Interval -0.57 to -0.023	9.9 Points on Scale for Suicidal Ideation Standard Deviation 7.4
Scale for Suicidal Ideation Week 8	2.3 Points on Scale for Suicidal Ideation Standard Deviation 4.5	4.7 Points on Scale for Suicidal Ideation Standard Deviation 6.6

PRIMARY outcome

Timeframe: Measured at Month 6

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

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

Outcome measures

Outcome measures
Measure	Paroxetine n=36 Participants Participants will receive paroxetine for 8 weeks	Bupropion n=38 Participants Participants will receive bupropion for 8 weeks
Occurrence of Suicidal Ideation or Acts Necessitating a Change in Treatment	4 Events	6 Events

PRIMARY outcome

Timeframe: Baseline and Week 8.

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

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

Outcome measures

Outcome measures
Measure	Paroxetine n=4 Participants Participants will receive paroxetine for 8 weeks	Bupropion n=3 Participants Participants will receive bupropion for 8 weeks
Brain Activity Measured by BOLD Signal With fMRI During a Reward Processing Task.	-0.27 percentage of change in COPE Interval -0.59 to 2.9	-0.95 percentage of change in COPE Interval -1.3 to 1.7

Adverse Events

Paroxetine

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Bupropion

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Paroxetine n=36 participants at risk Participants will receive paroxetine for 8 weeks	Bupropion n=38 participants at risk Participants will receive bupropion for 8 weeks
Hepatobiliary disorders Suicide attempt by acetaminophen overdose	2.8% 1/36 • Number of events 1	0.00% 0/38
Nervous system disorders Increased suicidal thoughts causing admission to hospital	5.6% 2/36 • Number of events 2	5.3% 2/38 • Number of events 2

Other adverse events

Adverse event data not reported

Additional Information

Michael F. Grunebaum, MD

Columbia University/NYSPI

Phone: 212-543-5842

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place