Norepinephrine-enhancing antidepressant exposure associated with reduced antiviral effect of interferon alpha on hepatitis C

Psychopharmacology (Berl). 2016 May;233(9):1689-94. doi: 10.1007/s00213-015-3956-4. Epub 2015 May 15.

Abstract

Rationale: 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.

Objectives: 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.

Keywords: Antidepressant; Cohort studies; Depression; Hepatitis C; Inflammation; Interferon alpha; Norepinephrine; S-RI; SSRI.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antidepressive Agents / therapeutic use*
  • Antiviral Agents / therapeutic use*
  • Cohort Studies
  • Depressive Disorder, Major / complications
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / psychology
  • Drug Interactions
  • Female
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / psychology*
  • Humans
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Norepinephrine / metabolism*
  • Prospective Studies
  • Ribavirin / therapeutic use
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Young Adult

Substances

  • Antidepressive Agents
  • Antiviral Agents
  • Interferon-alpha
  • Serotonin Uptake Inhibitors
  • Ribavirin
  • Norepinephrine