Platelet-derived growth factor as an antidepressant treatment selection biomarker: Higher levels selectively predict better outcomes with bupropion-SSRI combination

Manish K. Jha, Abu Minhajuddin, Bharathi S. Gadad, Madhukar H. Trivedi

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Background: Platelet derived growth factor is integral to maintenance of blood brain barrier, increases in response to blood brain barrier disruption, and may reflect neuroinflammation. Based on previous reports of better outcomes with dopaminergic antidepressants in depressed patients with elevated inflammatory biomarkers, we hypothesize that elevated peripheral platelet derived growth factor levels can serve as a powerful biomarker for selecting dopaminergic antidepressants. Methods: Platelet derived growth factor, basic fibroblast growth factor, and granulocyte colony stimulating factor were measured as part of Bioplex Pro human cytokine 27-plex kit in participants of the Combining Medications to Enhance Depression Outcomes trial who provided baseline plasma (n = 166) and were treated with either bupropion-plus-escitalopram, escitalopram-plus-placebo, or venlafaxine-plus-mirtazapine. Differential changes in overall symptom severity and anhedonia as well as side effects were tested with a treatment-arm-by-biomarker interaction in mixed model analyses. Effect of biomarkers with significant interaction was calculated in subsequent analyses stratified by treatment arm. Results: There was a significant treatment-arm-by-platelet derived growth factor interaction for depression severity (P = .03) and anhedonia (P = .008) but not for side effects (P = .44). Higher baseline platelet derived growth factor level was associated with greater reduction in depression severity (effect size = 0.71, P = .015) and anhedonia (effect size = 0.66, P = .02) in the bupropion- selective serotonin reuptake inhibitor but not the other two treatment arms. There was no significant treatmentarm- by-biomarker interaction for both depression severity and side effects with the other two biomarkers. Conclusion: As compared with selective serotonin reuptake inhibitor monotherapy or venlafaxine-plus-mirtazapine, bupropion-plus-escitalopram selectively improves anhedonia, which in turn results in improved overall depression severity in depressed patients with elevated platelet derived growth factor levels.

Original languageEnglish (US)
Pages (from-to)919-927
Number of pages9
JournalInternational Journal of Neuropsychopharmacology
Volume20
Issue number11
DOIs
StatePublished - Nov 1 2017

Keywords

  • Antidepressant
  • Dopamine
  • Inflammation
  • Moderator
  • PDGF

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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