Pharmacogenetics of citalopram-related side effects in children with depression and/or anxiety disorders.
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-HTR1Dβ, 5-HTR2C) and SE's was conducted. Agitation was more common in boys than girls (male:female 42.1 vs. 18.7 %, χ2= 5.61, df = 1, p = 0.018). Subjects with 5-HTR1Dβ CC genotype showed more agitation vs. both CG and GG genotypes (CC:CG:GG 71.4 vs. 33.3 vs. 18.1 %, χ2= 8.99, df = 2, p = 0.011). The 5-HTR1Dβ 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-HTR1Dβ polymorphism may be involved in citalopram-related agitation in children and adolescents treated for depression and/or anxiety.
Department of Psychological Medicine, Schneider Children's Medical Center of Israel, Petach Tikva, Israel. maya.amitai@weizmann.ac.il.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. maya.amitai@weizmann.ac.il.|The Ruhman Family Laboratory for Research on the Neurobiology of Stress, Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel. maya.amitai@weizmann.ac.il.
Maya
M
Amitai
Department of Psychiatry, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Sefi
S
Kronenberg
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|Felsenstein Medical Research Center, Petach Tikva, Israel.
Miri
M
Carmel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|Felsenstein Medical Research Center, Petach Tikva, Israel.
Elena
E
Michaelovsky
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|Felsenstein Medical Research Center, Petach Tikva, Israel.
Amos
A
Frisch
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
David
D
Brent
Department of Psychological Medicine, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Alan
A
Apter
The Ruhman Family Laboratory for Research on the Neurobiology of Stress, Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.|Department of Stress Neurobiology and Neurogenetics, Max-Planck Institute of Psychiatry, Munich, Germany.
Alon
A
Chen
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|Felsenstein Medical Research Center, Petach Tikva, Israel.|Research Unit, Geha Mental Health Center, Petach Tikva, Israel.
Abraham
A
Weizman
Department of Psychological Medicine, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Silvana
S
Fennig
D000293:Adolescent; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000235:genetics*; D002648:Child; D015283:Citalopram / Q000009:adverse effects* / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D019263:Dysthymic Disorder / Q000188:drug therapy / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D000071184:Pharmacogenomic Variants; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D012737:Sex Factors
D015283:Citalopram; D044302:Receptor, Serotonin, 5-HT1B; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D017367:Selective Serotonin Reuptake Inhibitors
Anxiety; Children and adolescents; Citalopram; Depression; Pharmacogenetics