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Pilot RCT of SSRI vs Bupropion: Effects on
Suicidal Behavior, Ideation and Mood in MDD
with Past Attempt or Current Ideation
Michael F. Grunebaum; Steven Ellis; Naihua Duan; Ainsley Burke; This poster is presented in columns for online reading.
You may also see the poster in it Pilot RCT of SSRI vs Bupropion: Effects on Suicidal Behavior, Ideation and
Mood in MDD with Past Attempt or Current Ideation
Grunebaum MF, Ellis SP, Duan N, Burke AK, Oquendo MA, Mann JJ
NYSPI/Columbia University Medical Center
ABSTRACT
Worsening SI: in Pts at 75th percentile of SSI
“Spaghetti plots” of SSI vs Time, by Tx and median split of SSI :
RCT of paroxetine (N = 36) vs bupropion (N = 38) in DSM IV MDD
towards protective effect of PXT at Wk 1: (est = 1.77, SE =
1 line = 1 patient.
with past suicide attempt or current suicidal ideation. Acute (8
0.94, df = 121.4, t = 1.89, p = .06, OR = 5.9, 95% CI = 0.94 to
weeks) and continuation treatment (up to 16 weeks). Outcomes: suicidal events and ideation; secondary outcome: non-
suicidal mood Sxs. Treatment was not associated with time to a
suicidal event. No treatment main effect or treatment x time

Non-suicidal depressive symptoms: PXT superior in Pts
interaction on suicidal ideation or non-suicidal depressive
most depressed at baseline (est = -0.46; p = 0.02)
symptoms was found. Exploratory model selection showed
modest advantages for PXT
for non-suicidal depressive
• Only predictor of SI in weeks 8-24 was SSIBL
symptoms (p = 0.02), and for suicidal ideation (p = 0.03), with
benefit increasing with baseline severity. Patients with greater
Attrition Wk 1-8 32%: 9/36 PXT and 15/38 BUP subjects did
baseline severity appeared to experience greater acute
not complete 8 weeks of randomized treatment. Overall, 29/38 improvement in suicidal ideation and non-suicidal depressive
symptoms with PXT compared to BUP.
If confirmed by future
(76%) on BUP and 24/36 (67%) on PXT did not complete 24 studies, this would favor first use of PXT or other SSRI in suicidal Scatterplots of SSI vs Time, by Tx and median split of SSI ; LOESS lines.
= 8 or less
= 9 or greater
• No differences by Tx in: time to last outcome assessment, AIM / HYPOTHESIS
adherence; side effect intensity; proportion prescribed zolpidem Compare serotonergic vs. non-serotonergic antidepressant on suicidal behavior/ideation in higher risk MDD (h/o attempt or current SI) • BZD dose (mg) 2x higher in BUP (PXT = 1.8±1.4, BUP =
Hypothesis 1: Fewer suicidal events (attempts or
3.6±2.8; U = 153.0, p = .03).
increased ideation requiring change in treatment) on PXT .
CONCLUSIONS
Hypothesis 2: Greater reduction in SI on PXT.
•RCT in this sample is feasible, can yield useful findings.
Exploratory model selection showed PXT reduced SI
more than BUP in patients with higher SSI

ELIGIBILITY: 18-75yo, MDD with HAM17≥16 plus
past suicide attempt or current SI, or both •SSI scale: “weak” vs “moderate to strong” desire to attempt
• SI threshold: HDRS-SI ≥ 2 , “wishes to be dead or suicide (item 4) is 1 point diff; no plans vs “definite plans” for
has any thoughts of possible death to self” BASELINE: No differences by group in Age, Sex, Race, Education, Employed,
suicide (item 18) is 2 point diff(Beck et al. 1979).
Inpatient, Ham17, #past MDEs, length current MDE, #past antidepressant trials, • EXCLUSIONS: bipolar, psychosis, AN/BN, SSRI/BUP
Cluster B co-morbidity, lifetime SUD, SSI, h/o past attempt •Carpenter et al. JCP 2011 meta-analysis: 1) PXT vs pbo: 2)
for other indications (e.g. anxiety), drug/EtOH Retrospective; 3) most trials excluded suicidal patients; 4)
dependence within 6m, unstable medical illness, 10 suicidal events: 2 attempts, neither w/serious injury. Tx not associated with
we stratified by prior attempt and inpatient; 5) less rating-
contraindication to either drug, non-response to 3 time to first event (log rank chi sq=0.17, df=1, p=.68).
scale based treatment emergent suicidal behavior or
SSRIs, PXT, or BUP in last 2y , pregnancy, capacity ideation in PXT-treated c/w pbo across all indications in
Suicidal Ideation: Tx x time NS (p=.27, est=0.81); Tx main effect NS (p=.07,
INTERVENTION: Triple-blind, randomized to
Limitations of our study: sample size, exploratory finding,
Exploratory Model Selection (BIC): SSI
attrition, no differential Tx effects in continuation phase.
Optional increase to PXT 50mg or BUP 450mg Tx x SSI : SE=0.14, df=59.9, t=-2.17, p=.03, est=-0.29 (-0.6 to -0.02)
ASSESSMENTS: qWk x 8 weeks ; qMo x 16 weeks
Disclosure: PXT and BUP donated by GSK to defray costs first 3 years of
study, purchased with grant thereafter. Dr. Mann support for unrelated brain
MODEL PREDICTIONS OF SUICIDAL IDEATION:
imaging studies from GSK and Novartis. Dr. Duan support from Pfizer for • STATISTICS:
unrelated health services research. GSK, Novartis and Pfizer were not involved in the design or execution of the study, had no access to the data or had any • K-M survival analysis of time to first suicidal “event” • 3.7 points lower on PXT at Wk 1 (p = 0.009)
Acknowledgments:
• GLS regression of follow-up score on Beck SSI NARSAD Young Investigator grant (mfg) and NIMH • 2.5 points lower on PXT at Wk 4 (p = 0.03)
Contact: mfg14@columbia.edu
Pilot RCT of SSRI vs Bupropion: Effects on Suicidal Behavior, Ideation and
Mood in MDD with Past Attempt or Current Ideation
Grunebaum MF, Ellis SP, Duan N, Burke AK, Oquendo MA, Mann JJ
NYSPI/Columbia University Medical Center
ABSTRACT
Worsening SI: in Pts at 75th percentile of SSI
“Spaghetti plots” of SSI vs Time, by Tx and median split of SSI :
RCT of paroxetine (N = 36) vs bupropion (N = 38) in DSM IV MDD
towards protective effect of PXT at Wk 1: (est = 1.77, SE =
1 line = 1 patient.
with past suicide attempt or current suicidal ideation. Acute (8
0.94, df = 121.4, t = 1.89, p = .06, OR = 5.9, 95% CI = 0.94 to
weeks) and continuation treatment (up to 16 weeks). Outcomes: suicidal events and ideation; secondary outcome: non-
suicidal mood Sxs. Treatment was not associated with time to a
suicidal event. No treatment main effect or treatment x time

Non-suicidal depressive symptoms: PXT superior in Pts
interaction on suicidal ideation or non-suicidal depressive
most depressed at baseline (est = -0.46; p = 0.02)
symptoms was found. Exploratory model selection showed
modest advantages for PXT
for non-suicidal depressive
• Only predictor of SI in weeks 8-24 was SSIBL
symptoms (p = 0.02), and for suicidal ideation (p = 0.03), with
benefit increasing with baseline severity. Patients with greater
Attrition Wk 1-8 32%: 9/36 PXT and 15/38 BUP subjects did
baseline severity appeared to experience greater acute
not complete 8 weeks of randomized treatment. Overall, 29/38 improvement in suicidal ideation and non-suicidal depressive
symptoms with PXT compared to BUP.
If confirmed by future
(76%) on BUP and 24/36 (67%) on PXT did not complete 24 studies, this would favor first use of PXT or other SSRI in suicidal Scatterplots of SSI vs Time, by Tx and median split of SSI ; LOESS lines.
= 8 or less
= 9 or greater
• No differences by Tx in: time to last outcome assessment, AIM / HYPOTHESIS
adherence; side effect intensity; proportion prescribed zolpidem Compare serotonergic vs. non-serotonergic antidepressant on suicidal behavior/ideation in higher risk MDD (h/o attempt or current SI) • BZD dose (mg) 2x higher in BUP (PXT = 1.8±1.4, BUP =
Hypothesis 1: Fewer suicidal events (attempts or
3.6±2.8; U = 153.0, p = .03).
increased ideation requiring change in treatment) on PXT .
CONCLUSIONS
Hypothesis 2: Greater reduction in SI on PXT.
•RCT in this sample is feasible, can yield useful findings.
Exploratory model selection showed PXT reduced SI
more than BUP in patients with higher SSI

ELIGIBILITY: 18-75yo, MDD with HAM17≥16 plus
past suicide attempt or current SI, or both •SSI scale: “weak” vs “moderate to strong” desire to attempt
• SI threshold: HDRS-SI ≥ 2 , “wishes to be dead or suicide (item 4) is 1 point diff; no plans vs “definite plans” for
has any thoughts of possible death to self” BASELINE: No differences by group in Age, Sex, Race, Education, Employed,
suicide (item 18) is 2 point diff(Beck et al. 1979).
Inpatient, Ham17, #past MDEs, length current MDE, #past antidepressant trials, • EXCLUSIONS: bipolar, psychosis, AN/BN, SSRI/BUP
Cluster B co-morbidity, lifetime SUD, SSI, h/o past attempt •Carpenter et al. JCP 2011 meta-analysis: 1) PXT vs pbo: 2)
for other indications (e.g. anxiety), drug/EtOH Retrospective; 3) most trials excluded suicidal patients; 4)
dependence within 6m, unstable medical illness, 10 suicidal events: 2 attempts, neither w/serious injury. Tx not associated with
we stratified by prior attempt and inpatient; 5) less rating-
contraindication to either drug, non-response to 3 time to first event (log rank chi sq=0.17, df=1, p=.68).
scale based treatment emergent suicidal behavior or
SSRIs, PXT, or BUP in last 2y , pregnancy, capacity ideation in PXT-treated c/w pbo across all indications in
Suicidal Ideation: Tx x time NS (p=.27, est=0.81); Tx main effect NS (p=.07,
INTERVENTION: Triple-blind, randomized to
Limitations of our study: sample size, exploratory finding,
Exploratory Model Selection (BIC): SSI
attrition, no differential Tx effects in continuation phase.
Optional increase to PXT 50mg or BUP 450mg Tx x SSI : SE=0.14, df=59.9, t=-2.17, p=.03, est=-0.29 (-0.6 to -0.02)
ASSESSMENTS: qWk x 8 weeks ; qMo x 16 weeks
Disclosure: PXT and BUP donated by GSK to defray costs first 3 years of
study, purchased with grant thereafter. Dr. Mann support for unrelated brain
MODEL PREDICTIONS OF SUICIDAL IDEATION:
imaging studies from GSK and Novartis. Dr. Duan support from Pfizer for • STATISTICS:
unrelated health services research. GSK, Novartis and Pfizer were not involved in the design or execution of the study, had no access to the data or had any • K-M survival analysis of time to first suicidal “event” • 3.7 points lower on PXT at Wk 1 (p = 0.009)
Acknowledgments:
• GLS regression of follow-up score on Beck SSI NARSAD Young Investigator grant (mfg) and NIMH • 2.5 points lower on PXT at Wk 4 (p = 0.03)
Contact: mfg14@columbia.edu
Pilot RCT of SSRI vs Bupropion: Effects on Suicidal Behavior, Ideation and
Mood in MDD with Past Attempt or Current Ideation
Grunebaum MF, Ellis SP, Duan N, Burke AK, Oquendo MA, Mann JJ
NYSPI/Columbia University Medical Center
ABSTRACT
Worsening SI: in Pts at 75th percentile of SSI
“Spaghetti plots” of SSI vs Time, by Tx and median split of SSI :
RCT of paroxetine (N = 36) vs bupropion (N = 38) in DSM IV MDD
towards protective effect of PXT at Wk 1: (est = 1.77, SE =
1 line = 1 patient.
with past suicide attempt or current suicidal ideation. Acute (8
0.94, df = 121.4, t = 1.89, p = .06, OR = 5.9, 95% CI = 0.94 to
weeks) and continuation treatment (up to 16 weeks). Outcomes: suicidal events and ideation; secondary outcome: non-
suicidal mood Sxs. Treatment was not associated with time to a
suicidal event. No treatment main effect or treatment x time

Non-suicidal depressive symptoms: PXT superior in Pts
interaction on suicidal ideation or non-suicidal depressive
most depressed at baseline (est = -0.46; p = 0.02)
symptoms was found. Exploratory model selection showed
modest advantages for PXT
for non-suicidal depressive
• Only predictor of SI in weeks 8-24 was SSIBL
symptoms (p = 0.02), and for suicidal ideation (p = 0.03), with
benefit increasing with baseline severity. Patients with greater
Attrition Wk 1-8 32%: 9/36 PXT and 15/38 BUP subjects did
baseline severity appeared to experience greater acute
not complete 8 weeks of randomized treatment. Overall, 29/38 improvement in suicidal ideation and non-suicidal depressive
symptoms with PXT compared to BUP.
If confirmed by future
(76%) on BUP and 24/36 (67%) on PXT did not complete 24 studies, this would favor first use of PXT or other SSRI in suicidal Scatterplots of SSI vs Time, by Tx and median split of SSI ; LOESS lines.
= 8 or less
= 9 or greater
• No differences by Tx in: time to last outcome assessment, AIM / HYPOTHESIS
adherence; side effect intensity; proportion prescribed zolpidem Compare serotonergic vs. non-serotonergic antidepressant on suicidal behavior/ideation in higher risk MDD (h/o attempt or current SI) • BZD dose (mg) 2x higher in BUP (PXT = 1.8±1.4, BUP =
Hypothesis 1: Fewer suicidal events (attempts or
3.6±2.8; U = 153.0, p = .03).
increased ideation requiring change in treatment) on PXT .
CONCLUSIONS
Hypothesis 2: Greater reduction in SI on PXT.
•RCT in this sample is feasible, can yield useful findings.
Exploratory model selection showed PXT reduced SI
more than BUP in patients with higher SSI

ELIGIBILITY: 18-75yo, MDD with HAM17≥16 plus
past suicide attempt or current SI, or both •SSI scale: “weak” vs “moderate to strong” desire to attempt
• SI threshold: HDRS-SI ≥ 2 , “wishes to be dead or suicide (item 4) is 1 point diff; no plans vs “definite plans” for
has any thoughts of possible death to self” BASELINE: No differences by group in Age, Sex, Race, Education, Employed,
suicide (item 18) is 2 point diff(Beck et al. 1979).
Inpatient, Ham17, #past MDEs, length current MDE, #past antidepressant trials, • EXCLUSIONS: bipolar, psychosis, AN/BN, SSRI/BUP
Cluster B co-morbidity, lifetime SUD, SSI, h/o past attempt •Carpenter et al. JCP 2011 meta-analysis: 1) PXT vs pbo: 2)
for other indications (e.g. anxiety), drug/EtOH Retrospective; 3) most trials excluded suicidal patients; 4)
dependence within 6m, unstable medical illness, 10 suicidal events: 2 attempts, neither w/serious injury. Tx not associated with
we stratified by prior attempt and inpatient; 5) less rating-
contraindication to either drug, non-response to 3 time to first event (log rank chi sq=0.17, df=1, p=.68).
scale based treatment emergent suicidal behavior or
SSRIs, PXT, or BUP in last 2y , pregnancy, capacity ideation in PXT-treated c/w pbo across all indications in
Suicidal Ideation: Tx x time NS (p=.27, est=0.81); Tx main effect NS (p=.07,
INTERVENTION: Triple-blind, randomized to
Limitations of our study: sample size, exploratory finding,
Exploratory Model Selection (BIC): SSI
attrition, no differential Tx effects in continuation phase.
Optional increase to PXT 50mg or BUP 450mg Tx x SSI : SE=0.14, df=59.9, t=-2.17, p=.03, est=-0.29 (-0.6 to -0.02)
ASSESSMENTS: qWk x 8 weeks ; qMo x 16 weeks
Disclosure: PXT and BUP donated by GSK to defray costs first 3 years of
study, purchased with grant thereafter. Dr. Mann support for unrelated brain
MODEL PREDICTIONS OF SUICIDAL IDEATION:
imaging studies from GSK and Novartis. Dr. Duan support from Pfizer for • STATISTICS:
unrelated health services research. GSK, Novartis and Pfizer were not involved in the design or execution of the study, had no access to the data or had any • K-M survival analysis of time to first suicidal “event” • 3.7 points lower on PXT at Wk 1 (p = 0.009)
Acknowledgments:
• GLS regression of follow-up score on Beck SSI NARSAD Young Investigator grant (mfg) and NIMH • 2.5 points lower on PXT at Wk 4 (p = 0.03)
Contact: mfg14@columbia.edu

Source: http://www.cmeinstitute.com/postersession/2011Session1/01Grunebaum.pdf

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