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-â€"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.
Original language | English |
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Pages (from-to) | 365-377 |
Number of pages | 13 |
Journal | Pharmacogenomics |
Volume | 12 |
Issue number | 3 |
DOIs | |
Publication status | Published - Mar 2011 |
Externally published | Yes |
ASJC Scopus Subject Areas
- Molecular Medicine
- Genetics
- Pharmacology
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't