Abstract
The prescription of antidepressant drugs is one of the most frequently used strategies to prevent suicide and suicidal behavior. However, some patients develop suicidal ideation at antidepressant treatment onset, a phenomenon known as treatment-emergent suicidal ideation (TESI). Few studies have explored TESI pharmacogenomics. As the Hypothalamic-Pituitary-Adrenal (HPA) axis might be implicated in suicidal behavior, we assessed the relationship between TESI and single nucleotide polymorphisms (SNPs) in the HPA axis-implicated NR3C1 (n = 7 SNPs), FKBP5 (n = 5 SNPs), AVPR1B (n = 1 SNPs), CRHR1 (n = 1 SNPs), and SKA2 (n = 1 SNPs) genes, in a sample of 3566 adult outpatients with depression for whom an antidepressant treatment was introduced. General practitioners and psychiatrists throughout France followed participants for 6 weeks after the initial prescription of tianeptine, an antidepressant molecule showing mu agonism. Suicidal ideation was assessed with item 10 of the Montgomery-Åsberg Depression Rating Scale (item dedicated to suicidal ideation) at baseline, and at week 2, 4, and 6 of treatment. Within the informative sample, 112 patients reported TESI and 384 did not. TESI was significantly associated with the TT genotype of the SNP rs6902321 in FKBP5 (OR = 1.76, 95% CI = [1.07; 2.90]; p-value = 0.03) and the GG/AG genotype of the SNP rs7208505 in SKA2 (OR = 1.85, 95% CI = [1.03;3.33]; p-value = 0.04). These associations were not significant after multiple test correction. Nevertheless, our results suggest a possible involvement of HPA axis elements in treatment-emergent suicidal ideation (TESI).
Highlights
Every year, more than 800,000 persons die by suicide in the world and the number of suicide attempts (SA) is even higher, according to the World Health Organization
3566 patients were included in the present analyses: 120 did not meet all inclusions criteria and 85 had missing data for primary variables
Sociodemographic and baseline clinical characteristics associated with treatment-emergent suicidal ideation (TESI)
Summary
More than 800,000 persons die by suicide in the world and the number of suicide attempts (SA) is even higher, according to the World Health Organization. About 90% of suicide completers have a psychiatric problems, mostly major depressive disorder (MDD)[1]. This suggests that suicidal behavior (SB) is linked to mental disorders. An international controversy began in the 1990s concerning antidepressant use and treatment emergence or worsening of suicidal ideation (TESI/TWOSI). This led to the application of a black box warning on antidepressant use by the US Food and Drug Administration (FDA)[7]. It has been estimated that if all patients with depression received antidepressants, more than one in three suicide deaths would be prevented compared with no antidepressant prescription[8].
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