Clinical and genetic correlates of suicidal ideation during antidepressant treatment in a depressed outpatient sample

Pharmacogenomics. 2011 Mar;12(3):365-77. doi: 10.2217/pgs.10.189.

Abstract

Aims: This study investigated clinical and genetic predictors of increasing suicidal ideation during antidepressant treatment.

Materials & methods: A total of 131 depressed outpatients were allocated to four antidepressants (paroxetine, venlafaxine, clomipramine or nefazodone) in a sequential step procedure until remission. Suicidality was assessed using the 10th item of the Montgomery-Asberg Depression Rating Scale (MADRS). A total of 11 candidate genes involved in different mechanisms of antidepressant action were selected for association with increasing suicidality.

Results: Increasing suicidality correlated with depression severity and higher antidepressant blood levels. Risk of increasing suicidal ideation was higher in subjects taking antidepressants other than paroxetine (odds ratio: 1.11). The strongest genetic predictor was found to be rs1360780 within the FKBP5 gene (p = 2.9 × 10(-5)), followed by 2677G>T in the ABCB1 gene. The rs130058 SNP within the 5-HTR1B gene demonstrated a differential association with increasing suicidal ideation depending on antidepressant type.

Conclusion: Increasing suicidal ideation might be an adverse effect of antidepressants. The involvement of FKBP5 indicates that dysregulation of the hypothalamic-pituitary-adrenal axis is involved in treatment increasing suicidal ideation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Adolescent
  • Adult
  • Aged
  • Antidepressive Agents / adverse effects*
  • Antidepressive Agents / blood
  • Antidepressive Agents / therapeutic use
  • Clomipramine / adverse effects
  • Clomipramine / blood
  • Clomipramine / therapeutic use
  • Cyclohexanols / adverse effects
  • Cyclohexanols / blood
  • Cyclohexanols / therapeutic use
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / genetics*
  • Depressive Disorder / psychology
  • Female
  • Genetic Association Studies
  • Humans
  • Male
  • Middle Aged
  • Paroxetine / adverse effects
  • Paroxetine / blood
  • Paroxetine / therapeutic use
  • Piperazines
  • Polymorphism, Single Nucleotide
  • Receptor, Serotonin, 5-HT1B / genetics
  • Severity of Illness Index
  • Suicidal Ideation*
  • Tacrolimus Binding Proteins / genetics*
  • Triazoles / adverse effects
  • Triazoles / blood
  • Triazoles / therapeutic use
  • Venlafaxine Hydrochloride
  • Young Adult

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antidepressive Agents
  • Cyclohexanols
  • HTR1B protein, human
  • Piperazines
  • Receptor, Serotonin, 5-HT1B
  • Triazoles
  • Paroxetine
  • nefazodone
  • Venlafaxine Hydrochloride
  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 5
  • Clomipramine