title: An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline.
abstract: OBJECTIVE
  Major depressive disorder has been linked with inflammatory processes, but it is unclear whether individual differences in levels of inflammatory biomarkers could help match patients to treatments that are most likely to be beneficial. The authors tested the hypothesis that C-reactive protein (CRP), a commonly available marker of systemic inflammation, predicts differential response to escitalopram (a serotonin reuptake inhibitor) and nortriptyline (a norepinephrine reuptake inhibitor).
  
  
  METHODS
  The hypothesis was tested in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study, a multicenter open-label randomized clinical trial. CRP was measured with a high-sensitivity method in serum samples from 241 adult men and women with major depressive disorder randomly allocated to 12-week treatment with escitalopram (N=115) or nortriptyline (N=126). The primary outcome measure was the score on the Montgomery-Åsberg Depression Rating Scale (MADRS), administered weekly.
  
  
  RESULTS
  CRP level at baseline differentially predicted treatment outcome with the two antidepressants (CRP-drug interaction: β=3.27, 95% CI=1.65, 4.89). For patients with low levels of CRP (<1 mg/L), improvement on the MADRS score was 3 points higher with escitalopram than with nortriptyline. For patients with higher CRP levels, improvement on the MADRS score was 3 points higher with nortriptyline than with escitalopram. CRP and its interaction with medication explained more than 10% of individual-level variance in treatment outcome.
  
  
  CONCLUSIONS
  An easily accessible peripheral blood biomarker may contribute to improvement in outcomes of major depressive disorder by personalizing treatment choice.
authors.affiliation: From the Department of Psychiatry, Dalhousie University, Halifax, N.S., Canada; the Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London; the Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, U.K.; the Department of Biochemistry, King's College Hospital, London; the Department of Psychiatry, University of Bonn, Bonn, Germany; the Center for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark; Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland; University Psychiatric Clinic and the Medical Faculty, University of Ljubljana, Slovenia; the Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia; Laboratoire de Psychologie Médicale, Université Libre de Bruxelles and Psy Pluriel, Centre Européen de Psychologie Médicale, Brussels.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Uher
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Tansey
authors.forename: Tracy
authors.initials: T
authors.lastname: Dew
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Ole
authors.initials: O
authors.lastname: Mors
authors.forename: Joanna
authors.initials: J
authors.lastname: Hauser
authors.forename: Mojca Zvezdana
authors.initials: MZ
authors.lastname: Dernovsek
authors.forename: Neven
authors.initials: N
authors.lastname: Henigsberg
authors.forename: Daniel
authors.initials: D
authors.lastname: Souery
authors.forename: Anne
authors.initials: A
authors.lastname: Farmer
authors.forename: Peter
authors.initials: P
authors.lastname: McGuffin
mesh_terms: D000046:Academic Medical Centers; D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D015283:Citalopram / Q000627:therapeutic use*; D015986:Confounding Factors, Epidemiologic; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D005060:Europe; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009661:Nortriptyline / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D012107:Research Design; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D015415:Biomarkers; D015283:Citalopram; D002097:C-Reactive Protein; D009661:Nortriptyline