title: Norepinephrine-enhancing antidepressant exposure associated with reduced antiviral effect of interferon alpha on hepatitis C.
abstract: BACKGROUND
  Major depressive disorder is a common consequence of exposure to the pro-inflammatory cytokine interferon alpha, which is treated effectively with antidepressant medication. Antidepressant mode of action may conflict with interferon alpha's mechanism in treating hepatitis C however.
  
  
  OBJECTIVE
  The purpose of this study is to prospectively explore, in a large naturalistic cohort, whether antidepressant exposure influenced end of treatment response of hepatitis C to interferon alpha.
  
  
  METHODS
  Two hundred thirty-nine patients infected with chronic hepatitis C and due to receive treatment were recruited. All participants initiated peg-interferon-2-alpha 180 μg weekly sub-cutaneously plus oral ribavirin 800-1200 mg daily. Participants were assessed for DSM-IV major depression at baseline and four weekly during treatment.
  
  
  RESULTS
  32.6 % of the cohort was exposed to an antidepressant (serotonin-reuptake inhibitor: other categorised antidepressants 49:29). At baseline, 3.8 % had major depression and 55.2 % developed major depression during interferon alpha treatment. Exposure to an antidepressant not classified as a serotonin-reuptake inhibitor, of which all were norepinephrine-enhancing (OR 0.15, 95 % CI 0.04-0.60) and having a past history of psychiatric disorder (OR 4.41, 95 % CI 1.39-13.96) independently reduced the likelihood of end of treatment response. Serotonin-reuptake inhibitor exposure did not influence end of treatment response (OR 1.21, 95 % CI 0.35-4.19), neither did major depression at baseline (OR 2.31, 95 % CI 0.55-9.60) or during treatment (OR 0.69, 95 % CI 0.36-1.33).
  
  
  CONCLUSIONS
  Our findings support a lack of conflict of therapeutic mechanism of serotonin-reuptake inhibitor antidepressants with interferon alpha in treating hepatitis C, which may include inflammatory influence. This appears not to be true for norepinephrine-enhancing antidepressant types and warrants investigation using more direct methods.
authors.affiliation: Sussex Partnership NHS Foundation Trust, Brighton, UK.|School of Psychology, University of Sussex, Brighton, UK.
authors.forename: Renata
authors.initials: R
authors.lastname: Fialho
authors.affiliation: Brighton and Sussex Medical School, Falmer, Brighton, Sussex, BN1 9PH, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Burridge
authors.affiliation: Faculty of Psychology and Educational Sciences, University of Coimbra, Coimbra, Portugal.
authors.forename: Marco
authors.initials: M
authors.lastname: Pereira
authors.affiliation: Digestive Diseases Centre, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK.
authors.forename: Majella
authors.initials: M
authors.lastname: Keller
authors.affiliation: Digestive Diseases Centre, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK.
authors.forename: Alexandra
authors.initials: A
authors.lastname: File
authors.affiliation: Digestive Diseases Centre, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Tibble
authors.affiliation: Sussex Partnership NHS Foundation Trust, Brighton, UK. Richard.whale@brighton.ac.uk.|Brighton and Sussex Medical School, Falmer, Brighton, Sussex, BN1 9PH, UK. Richard.whale@brighton.ac.uk.
authors.forename: Richard
authors.initials: R
authors.lastname: Whale
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D003865:Major Depressive Disorder / Q000150:complications / Q000188:drug therapy / Q000523:psychology; D004347:Drug Interactions; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000523:psychology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*; D011446:Prospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D000998:Antiviral Agents; D016898:Interferon-alpha; D009638:Norepinephrine; D012254:Ribavirin; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Antidepressant; Cohort studies; Depression; Hepatitis C; Inflammation; Interferon alpha; Norepinephrine; S-RI; SSRI