Evaluation of interleukin-6 and serotonin as biomarkers to predict response to fluoxetine

Hum Psychopharmacol. 2016 May;31(3):178-84. doi: 10.1002/hup.2525. Epub 2016 Mar 27.

Abstract

Objective: Only 30% of major depressive disorder (MDD) patients achieve complete remission with a serotonergic antidepressant (selective serotonin reuptake inhibitor). We investigated the potential of serotonin (5-HT) and interleukin-6 (IL-6) to serve as functional biomarkers of fluoxetine response.

Methods: Serum IL-6 and 5-HT were measured in 73 MDD patients (39 responders and 34 non-responders) pre- and 6 weeks post-treatment and in 44 normal controls with ELISA. Fluoxetine and norfluoxetine were measured using LC MS/MS.

Results: IL-6 levels were significantly higher in MDD patients when compared with controls (p < 0.01), and 5-HT levels were significantly lower in non-responders compared with controls (p = 0.0131). Pre- and post-treatment levels of both biomarkers individually and in combination did not significantly differ between responders and non-responders. Area under the receiver operating characteristics curve for the biomarkers was 0.5. Significant correlation was seen between the percentage change in IL-6 and percentage change in Hamilton Rating Scale for Depression score in responders. Fluoxetine and norfluoxetine concentrations were not significantly different in responders and non-responders, and there was no correlation between fluoxetine concentrations and percentage reduction in 5-HT from week 0 to 6.

Conclusion: 5-HT and IL-6 may not serve as useful markers of response to fluoxetine because of inconsistent results across different studies. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: biomarkers; fluoxetine; interleukin-6 (IL-6); major depressive disorder (MDD); serotonin (5-HT); treatment response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Case-Control Studies
  • Chromatography, Liquid
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / physiopathology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fluoxetine / analogs & derivatives
  • Fluoxetine / pharmacokinetics
  • Fluoxetine / therapeutic use*
  • Humans
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Selective Serotonin Reuptake Inhibitors / pharmacokinetics
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Serotonin / blood*
  • Tandem Mass Spectrometry
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers
  • Interleukin-6
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Serotonin
  • norfluoxetine