title: Evaluation of interleukin-6 and serotonin as biomarkers to predict response to fluoxetine.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
authors.forename: Aarthi
authors.initials: A
authors.lastname: Manoharan
authors.affiliation: Department of Psychiatry, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
authors.forename: Ravi Philip
authors.initials: RP
authors.lastname: Rajkumar
authors.affiliation: Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
authors.forename: Deepak Gopal
authors.initials: DG
authors.lastname: Shewade
authors.affiliation: Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
authors.forename: Rajan
authors.initials: R
authors.lastname: Sundaram
authors.affiliation: Department of Psychiatry, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
authors.forename: Avin
authors.initials: A
authors.lastname: Muthuramalingam
authors.affiliation: Department of Clinical Pharmacology, Apollo Hospitals Enterprise Limited, Madurai, India.
authors.forename: Abialbon
authors.initials: A
authors.lastname: Paul
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012701:Serotonin / Q000097:blood*; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D053719:Tandem Mass Spectrometry; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005473:Fluoxetine; D015850:Interleukin-6; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; C036139:norfluoxetine
keywords: biomarkers; fluoxetine; interleukin-6 (IL-6); major depressive disorder (MDD); serotonin (5-HT); treatment response