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
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
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Adolescent
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Adult
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Aged
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Antidepressive Agents / adverse effects*
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Antidepressive Agents / blood
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Antidepressive Agents / therapeutic use
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Clomipramine / adverse effects
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Clomipramine / blood
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Clomipramine / therapeutic use
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Cyclohexanols / adverse effects
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Cyclohexanols / blood
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Cyclohexanols / therapeutic use
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Depressive Disorder / drug therapy*
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Depressive Disorder / genetics*
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Depressive Disorder / psychology
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Female
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Genetic Association Studies
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Humans
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Male
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Middle Aged
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Paroxetine / adverse effects
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Paroxetine / blood
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Paroxetine / therapeutic use
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Piperazines
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Polymorphism, Single Nucleotide
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Receptor, Serotonin, 5-HT1B / genetics
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Severity of Illness Index
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Suicidal Ideation*
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Tacrolimus Binding Proteins / genetics*
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Triazoles / adverse effects
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Triazoles / blood
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Triazoles / therapeutic use
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Venlafaxine Hydrochloride
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Young Adult
Substances
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ABCB1 protein, human
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Antidepressive Agents
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Cyclohexanols
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HTR1B protein, human
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Piperazines
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Receptor, Serotonin, 5-HT1B
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Triazoles
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Paroxetine
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nefazodone
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Venlafaxine Hydrochloride
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Tacrolimus Binding Proteins
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tacrolimus binding protein 5
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Clomipramine