Multiple secondary data analyses of TORDIA have identified important predictors of treatment response and relapse .
To up date a comparative effectiveness review ( 1980–2011 ) of treatments for adolescents whose depressive episode or disorder ( MDE/MDD ) did not respond to one or more trials of SSRI antidepressants .
Association of FKBP5 polymorphisms with suicidal events in the Treatment of Resistant Depression in Adolescents (TORDIA) study.
OBJECTIVE The authors sought to assess the relationship between c and i date genes and two clinical outcomes , namely , symptomatic improvement and the occurrence of suicidal events , in a sample of treatment-resistant depressed adolescents . METHOD A sub sample of depressed adolescents participating in the Treatment of SSRI-Resistant Depression in Adolescents ( TORDIA ) trial , 155 of whom were of European origin , were genotyped with respect to 21 polymorphisms on 12 genes that have a reported association with depression , treatment response , or suicidal events . Participants had not responded to a previous adequate trial with an antidepressant and were r and omized to receive either another selective serotonin reuptake inhibitor or venlafaxine , with or without cognitive-behavioral therapy ( CBT ) . Single-nucleotide polymorphism ( SNP ) analyses were conducted using PLINK with permutation procedures . RESULTS No relationship was observed between any polymorphism and response to treatment . The FKBP5 ( which codes for a protein causing subsensitivity of the glucocorticoid receptor ) rs1360780TT and rs3800373GG genotypes were associated with suicidal events ( N=18 ) , even after controlling for treatment effects and relevant covariates . These two SNPs were in significant linkage disequilibrium ( r=0.91 ) . CONCLUSIONS The FKBP5 genotypes associated with suicidal events in this study have been reported by others to cause the greatest degree of glucocorticoid receptor subsensitivity . These results are consistent with those of other studies linking alterations in the hypothalamic-pituitary-adrenal axis with suicidal behavior . The small number of events and lack of a placebo condition make these results preliminary . Replication with a larger sample and a placebo condition is needed to assess whether these events are related to treatment
Multiple secondary data analyses of TORDIA have identified important predictors of treatment response and relapse .
To up date a comparative effectiveness review ( 1980–2011 ) of treatments for adolescents whose depressive episode or disorder ( MDE/MDD ) did not respond to one or more trials of SSRI antidepressants .