Serotonin transporter polymorphism (5-HTTLPR) and citalopram effectiveness and side effects in children with depression and/or anxiety disorders.
OBJECTIVE
The aim of this study was to examine the association between polymorphism in the serotonin transporter gene and citalopram effectiveness and side effects in children and adolescents with major depressive disorder (MDD) and/or anxiety disorders.


METHODS
Outpatients, aged 7- 18 years with a Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) MDD and/or anxiety disorder were treated in an 8-week open trial with 20-40 mg/day of citalopram. Subjects were genotyped with respect to short (s) versus long (l) forms of the 5-HTTLPR polymorphism of the serotonin transporter, and the relationship between genotype and outcome and side effects was assessed.


RESULTS
Subjects with 5-HTTLPR ss genotype showed a less vigorous response with regard to depressive symptoms measured by the Children's Depression Rating Scale-Revised (CDRS-R) scores over time compared to subjects with sl/ll genotypes (beta = 0.67, z = 2.02, p = 0.04). In addition, the 5-HTTLPR ss group exhibited lower rates of agitation compared to those with sl/ll genotype (6.3% vs. 32.8%, p = 0.05). Also, subjects with 5-HTTLPR ss genotype had consistently higher scores of suicidality at each week compared to the sl/ll group (beta = 0.76, z = 2.04, p = 0.04) as measured by item number 13 of the CDRS-R.


CONCLUSIONS
The 5-HTTLPR ss genotype was associated with a poorer clinical response with regard to depressive symptoms as well with fewer reports of agitation. The 5-HTTLPR polymorphism may be a genetic marker of response to citalopram in children and adolescents with depression and/or anxiety.
Kronenberg
Sefi
S
Feinberg Child Study Center, Schneider's Children's Medical Center of Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. serik@013.net.il
Apter
Alan
A
Brent
David
D
Schirman
Shella
S
Melhem
Nadine
N
Pick
Nimrod
N
Gothelf
Doron
D
Carmel
Miri
M
Frisch
Amos
A
Weizman
Abraham
A
D000293:Adolescent; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001008:Anxiety Disorders / Q000188:drug therapy*; D002648:Child; D015283:Citalopram / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011594:Psychometrics; D011595:Psychomotor Agitation / Q000209:etiology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012720:Severity of Illness Index; D013405:Suicide / Q000523:psychology; D016896:Treatment Outcome
D018687:Antidepressive Agents, Second-Generation; D050486:Serotonin Plasma Membrane Transport Proteins; D015283:Citalopram