Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial

Manish K. Jha; Abu Minhajuddin; Bharathi S. Gadad; Tracy Greer; Bruce Grannemann; Abigail Soyombo; Taryn L. Mayes; A. John Rush; Madhukar H. Trivedi

doi:10.1016/j.psyneuen.2017.01.023

Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial

Manish K. Jha, Abu Minhajuddin, Bharathi S. Gadad, Tracy Greer, Bruce Grannemann, Abigail Soyombo, Taryn L. Mayes, A. John Rush, Madhukar H. Trivedi

Research output: Contribution to journal › Article › peer-review

142 Scopus citations

Abstract

Objective Currently, no valid measures inform treatment selection for depressed patients. Whether C-reactive protein (CRP) in particular and two other acute phase reactants (inflammatory markers) could differentiate between patients responding to either of two treatments with different mechanisms of action was assessed. Method Subjects included Combining Medications to Enhance Depression Outcomes (CO-MED) trial participants randomly assigned to either escitalopram plus placebo (SSRI monotherapy, n = 51) or bupropion plus escitalopram combination (bupropion-SSRI combination, n = 55) with baseline plasma samples. CRP, serum amyloid P component, and alpha-2-macroglobulin were measured using the Bioplex Pro™ human acute-phase 4-plex panel. We conducted mixed model analyses of depressive symptom (Quick Inventory of Depressive Symptomatology Self-Report) and side-effect burden (Frequency, Intensity, and Burden of Side-Effects Rating Scale) obtained weekly or every other week over the 12-week acute-phase of CO-MED trial to evaluate the relationship between these outcomes and baseline CRP and other acute-phase reactants. Results The treatment arms did not differ in depressive symptom or side effect outcomes. Most participants (69.8%, 74/106) had baseline CRP levels greater than 1 mg/L (indicative of systemic inflammatory activity). Higher baseline CRP levels were associated lower depression severity (correlation coefficient = −0.63) with bupropion-SSRI combination but not with SSRI monotherapy (correlation coefficient = 0.40). The overall remission rate was 41.5%. The estimated remission rate with CRP threshold based assignment (SSRI monotherapy for <1 mg/L and Bupropion-SSRI for ≥1 mg/L) was 53.1%, with a number needed to treat of 8.6. Side effect burden was unrelated to any baseline inflammatory marker. Conclusions Baseline CRP levels relate differentially to antidepressant treatment outcomes in persons with major depressive disorder. Clinicaltrials.gov

Original language	English (US)
Pages (from-to)	105-113
Number of pages	9
Journal	Psychoneuroendocrinology
Volume	78
DOIs	https://doi.org/10.1016/j.psyneuen.2017.01.023
State	Published - Apr 1 2017

Keywords

Antidepressant response
Biomarker
C-reactive protein
Depression
Inflammation

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Endocrinology
Endocrine and Autonomic Systems
Psychiatry and Mental health
Biological Psychiatry

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10.1016/j.psyneuen.2017.01.023

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title = "Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial",

abstract = "Objective Currently, no valid measures inform treatment selection for depressed patients. Whether C-reactive protein (CRP) in particular and two other acute phase reactants (inflammatory markers) could differentiate between patients responding to either of two treatments with different mechanisms of action was assessed. Method Subjects included Combining Medications to Enhance Depression Outcomes (CO-MED) trial participants randomly assigned to either escitalopram plus placebo (SSRI monotherapy, n = 51) or bupropion plus escitalopram combination (bupropion-SSRI combination, n = 55) with baseline plasma samples. CRP, serum amyloid P component, and alpha-2-macroglobulin were measured using the Bioplex Pro{\texttrademark} human acute-phase 4-plex panel. We conducted mixed model analyses of depressive symptom (Quick Inventory of Depressive Symptomatology Self-Report) and side-effect burden (Frequency, Intensity, and Burden of Side-Effects Rating Scale) obtained weekly or every other week over the 12-week acute-phase of CO-MED trial to evaluate the relationship between these outcomes and baseline CRP and other acute-phase reactants. Results The treatment arms did not differ in depressive symptom or side effect outcomes. Most participants (69.8%, 74/106) had baseline CRP levels greater than 1 mg/L (indicative of systemic inflammatory activity). Higher baseline CRP levels were associated lower depression severity (correlation coefficient = −0.63) with bupropion-SSRI combination but not with SSRI monotherapy (correlation coefficient = 0.40). The overall remission rate was 41.5%. The estimated remission rate with CRP threshold based assignment (SSRI monotherapy for <1 mg/L and Bupropion-SSRI for ≥1 mg/L) was 53.1%, with a number needed to treat of 8.6. Side effect burden was unrelated to any baseline inflammatory marker. Conclusions Baseline CRP levels relate differentially to antidepressant treatment outcomes in persons with major depressive disorder. Clinicaltrials.gov",

keywords = "Antidepressant response, Biomarker, C-reactive protein, Depression, Inflammation",

author = "Jha, {Manish K.} and Abu Minhajuddin and Gadad, {Bharathi S.} and Tracy Greer and Bruce Grannemann and Abigail Soyombo and Mayes, {Taryn L.} and Rush, {A. John} and Trivedi, {Madhukar H.}",

note = "Funding Information: CO-MED trial was funded by National Institute of Mental Health under contract N01 MH-90003 to the University of Texas Southwestern Medical Center at Dallas (Principal Investigators, M. H. Trivedi and A.J. Rush). This work was also supported in part through the Center for Depression Research and Clinical Care at UT Southwestern (Principal Investigator: Madhukar H. Trivedi, MD) and Hersh Foundation. The authors thank the clinical staff at each clinical site for their assistance with this project; all of the study participants; and Savitha Kalidas, Ph.D. for administrative support. Forest Pharmaceuticals, GlaxoSmithKline, Organon, and Wyeth Pharmaceuticals provided medications for CO-MED trial at no cost. The content of this publication does not necessarily reflect the views or policies of the U.S. Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. NIMH had no role in the drafting or review of the manuscript or in the collection or analysis of the data. Publisher Copyright: {\textcopyright} 2017 Elsevier Ltd",

year = "2017",

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day = "1",

doi = "10.1016/j.psyneuen.2017.01.023",

language = "English (US)",

volume = "78",

pages = "105--113",

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T1 - Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial

AU - Jha, Manish K.

AU - Minhajuddin, Abu

AU - Gadad, Bharathi S.

AU - Greer, Tracy

AU - Grannemann, Bruce

AU - Soyombo, Abigail

AU - Mayes, Taryn L.

AU - Rush, A. John

AU - Trivedi, Madhukar H.

N1 - Funding Information: CO-MED trial was funded by National Institute of Mental Health under contract N01 MH-90003 to the University of Texas Southwestern Medical Center at Dallas (Principal Investigators, M. H. Trivedi and A.J. Rush). This work was also supported in part through the Center for Depression Research and Clinical Care at UT Southwestern (Principal Investigator: Madhukar H. Trivedi, MD) and Hersh Foundation. The authors thank the clinical staff at each clinical site for their assistance with this project; all of the study participants; and Savitha Kalidas, Ph.D. for administrative support. Forest Pharmaceuticals, GlaxoSmithKline, Organon, and Wyeth Pharmaceuticals provided medications for CO-MED trial at no cost. The content of this publication does not necessarily reflect the views or policies of the U.S. Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. NIMH had no role in the drafting or review of the manuscript or in the collection or analysis of the data. Publisher Copyright: © 2017 Elsevier Ltd

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Objective Currently, no valid measures inform treatment selection for depressed patients. Whether C-reactive protein (CRP) in particular and two other acute phase reactants (inflammatory markers) could differentiate between patients responding to either of two treatments with different mechanisms of action was assessed. Method Subjects included Combining Medications to Enhance Depression Outcomes (CO-MED) trial participants randomly assigned to either escitalopram plus placebo (SSRI monotherapy, n = 51) or bupropion plus escitalopram combination (bupropion-SSRI combination, n = 55) with baseline plasma samples. CRP, serum amyloid P component, and alpha-2-macroglobulin were measured using the Bioplex Pro™ human acute-phase 4-plex panel. We conducted mixed model analyses of depressive symptom (Quick Inventory of Depressive Symptomatology Self-Report) and side-effect burden (Frequency, Intensity, and Burden of Side-Effects Rating Scale) obtained weekly or every other week over the 12-week acute-phase of CO-MED trial to evaluate the relationship between these outcomes and baseline CRP and other acute-phase reactants. Results The treatment arms did not differ in depressive symptom or side effect outcomes. Most participants (69.8%, 74/106) had baseline CRP levels greater than 1 mg/L (indicative of systemic inflammatory activity). Higher baseline CRP levels were associated lower depression severity (correlation coefficient = −0.63) with bupropion-SSRI combination but not with SSRI monotherapy (correlation coefficient = 0.40). The overall remission rate was 41.5%. The estimated remission rate with CRP threshold based assignment (SSRI monotherapy for <1 mg/L and Bupropion-SSRI for ≥1 mg/L) was 53.1%, with a number needed to treat of 8.6. Side effect burden was unrelated to any baseline inflammatory marker. Conclusions Baseline CRP levels relate differentially to antidepressant treatment outcomes in persons with major depressive disorder. Clinicaltrials.gov

AB - Objective Currently, no valid measures inform treatment selection for depressed patients. Whether C-reactive protein (CRP) in particular and two other acute phase reactants (inflammatory markers) could differentiate between patients responding to either of two treatments with different mechanisms of action was assessed. Method Subjects included Combining Medications to Enhance Depression Outcomes (CO-MED) trial participants randomly assigned to either escitalopram plus placebo (SSRI monotherapy, n = 51) or bupropion plus escitalopram combination (bupropion-SSRI combination, n = 55) with baseline plasma samples. CRP, serum amyloid P component, and alpha-2-macroglobulin were measured using the Bioplex Pro™ human acute-phase 4-plex panel. We conducted mixed model analyses of depressive symptom (Quick Inventory of Depressive Symptomatology Self-Report) and side-effect burden (Frequency, Intensity, and Burden of Side-Effects Rating Scale) obtained weekly or every other week over the 12-week acute-phase of CO-MED trial to evaluate the relationship between these outcomes and baseline CRP and other acute-phase reactants. Results The treatment arms did not differ in depressive symptom or side effect outcomes. Most participants (69.8%, 74/106) had baseline CRP levels greater than 1 mg/L (indicative of systemic inflammatory activity). Higher baseline CRP levels were associated lower depression severity (correlation coefficient = −0.63) with bupropion-SSRI combination but not with SSRI monotherapy (correlation coefficient = 0.40). The overall remission rate was 41.5%. The estimated remission rate with CRP threshold based assignment (SSRI monotherapy for <1 mg/L and Bupropion-SSRI for ≥1 mg/L) was 53.1%, with a number needed to treat of 8.6. Side effect burden was unrelated to any baseline inflammatory marker. Conclusions Baseline CRP levels relate differentially to antidepressant treatment outcomes in persons with major depressive disorder. Clinicaltrials.gov

KW - Antidepressant response

KW - Biomarker

KW - C-reactive protein

KW - Depression

KW - Inflammation

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Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial

Abstract

Keywords

ASJC Scopus subject areas

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