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 journalArticle

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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 identifier: NCT00590863

Original languageEnglish (US)
Pages (from-to)105-113
Number of pages9
JournalPsychoneuroendocrinology
Volume78
DOIs
StatePublished - Apr 1 2017

Fingerprint

C-Reactive Protein
Antidepressive Agents
Outpatients
Bupropion
Depression
Citalopram
Acute-Phase Proteins
Serum Amyloid P-Component
alpha-Macroglobulins
Numbers Needed To Treat
Major Depressive Disorder
Self Report
Patient Selection
Therapeutics
Placebos
Equipment and Supplies

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

Cite this

Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial. / Jha, Manish K.; Minhajuddin, Abu; Gadad, Bharathi S.; Greer, Tracy; Grannemann, Bruce; Soyombo, Abigail; Mayes, Taryn L.; Rush, A. John; Trivedi, Madhukar H.

In: Psychoneuroendocrinology, Vol. 78, 01.04.2017, p. 105-113.

Research output: Contribution to journalArticle

Jha, Manish K. ; Minhajuddin, Abu ; Gadad, Bharathi S. ; Greer, Tracy ; Grannemann, Bruce ; Soyombo, Abigail ; Mayes, Taryn L. ; Rush, A. John ; Trivedi, Madhukar H. / Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial. In: Psychoneuroendocrinology. 2017 ; Vol. 78. pp. 105-113.
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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 identifier: NCT00590863",
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AU - Greer, Tracy

AU - Grannemann, Bruce

AU - Soyombo, Abigail

AU - Mayes, Taryn L.

AU - Rush, A. John

AU - Trivedi, Madhukar H.

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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 identifier: NCT00590863

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