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キーワード:
Children and adolescents, Citalopram, depression, anxiety, pharmacogenetics
要旨:
Pharmacogenetic approach to antidepressant (AD) response is a promising
avenue toward individualizing AD treatment. This is particularly
relevant in pediatric populations because of concerns about the suicide
risk of serotonin selective reuptake inhibitors (SSRIs), resulting in a
black-box warning. However, to date, no specific gene or polymorphism
has been consistently implicated as a marker of AD side effect (SE) in
the pediatric population. The aim of this study was to examine the
association between polymorphisms in genes related to the serotonergic
system and citalopram SE's in children and adolescents with major
depressive disorder (MDD)/dysthymia and/or anxiety disorders.
Outpatients (N = 87, 44 % males), aged 7-18 years with a DSM-IV-TR
diagnosis of MDD/dysthymia and/or an anxiety disorder were treated in an
8-week open trial with 20-40 mg/day of citalopram. SE's were rated using
a questionnaire devised specifically for this study. Association
analysis between known/candidate genetic variants in three genes
(5-HTR2A, 5-HTR1D beta, 5-HTR2C) and SE's was conducted. Agitation was
more common in boys than girls (male:female 42.1 vs. 18.7 %, chi (2) =
5.61, df = 1, p = 0.018). Subjects with 5-HTR1D beta CC genotype showed
more agitation vs. both CG and GG genotypes (CC:CG:GG 71.4 vs. 33.3 vs.
18.1 %, chi (2) = 8.99, df = 2, p = 0.011). The 5-HTR1D beta CC genotype
was associated with more reports of agitation. It has been suggested
that agitation may be an intermediate phenotype to suicidal behavior.
Thus, it seems that 5-HTR1D beta polymorphism may be involved in
citalopram-related agitation in children and adolescents treated for
depression and/or anxiety.
