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

Autor: Alain Malafosse, Gilles Bertschy, Nader Perroud, Rudolf Uher, Guido Bondolfi, Jean-Michel Aubry, Markus Kosel, Marianne Gex-Fabry
Rok vydání: 2011
Předmět:
Male
Clomipramine
Paroxetine/adverse effects/blood/therapeutic use
Venlafaxine
Severity of Illness Index
Piperazines
ddc:616.89
Suicidal ideation
Venlafaxine Hydrochloride
Middle Aged
Paroxetine
Antidepressive Agents
Depressive Disorder/drug therapy/genetics/psychology
Clomipramine/adverse effects/blood/therapeutic use
Receptor
Serotonin
5-HT1B
Molecular Medicine
Antidepressant
Female
medicine.symptom
Nefazodone
medicine.drug
Adult
Tacrolimus Binding Proteins/genetics
medicine.medical_specialty
ATP Binding Cassette Transporter
Subfamily B
Adolescent
Polymorphism
Single Nucleotide
P-Glycoprotein/genetics
Antidepressive Agents/adverse effects/blood/therapeutic use
Suicidal Ideation
Tacrolimus Binding Proteins
Young Adult
Internal medicine
Severity of illness
Genetics
medicine
Humans
ATP Binding Cassette Transporter
Subfamily B
Member 1
Genetic Association Studies
Aged
Pharmacology
Depressive Disorder
Cyclohexanols/adverse effects/blood/therapeutic use
Receptor
Serotonin
5-HT1B/genetics
business.industry
Odds ratio
Triazoles
Cyclohexanols
Triazoles/adverse effects/blood/therapeutic use
business
Zdroj: Pharmacogenomics, Vol. 12, No 3 (2011) pp. 365-77
ISSN: 1744-8042
1462-2416
Popis: 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. Original submitted 12 October 2010; Revision submitted 18 November 2010.
Databáze: OpenAIRE
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