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Pharmacogenetics of citalopram-related side effects in children with depression and/or anxiety disorders

  • Psychiatry and Preclinical Psychiatric Studies - Original Article
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Abstract

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 %, χ 2 = 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 %, χ 2 = 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.

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    Authors and Affiliations

    1. Department of Psychological Medicine, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

      Maya Amitai, Alan Apter & Silvana Fennig

    2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

      Maya Amitai, Miri Carmel, Elena Michaelovsky, Amos Frisch, Alan Apter, Abraham Weizman & Silvana Fennig

    3. The Ruhman Family Laboratory for Research on the Neurobiology of Stress, Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel

      Maya Amitai & Alon Chen

    4. Department of Psychiatry, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

      Sefi Kronenberg

    5. Felsenstein Medical Research Center, Petach Tikva, Israel

      Miri Carmel, Elena Michaelovsky, Amos Frisch & Abraham Weizman

    6. Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

      David Brent

    7. Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

      David Brent

    8. Research Unit, Geha Mental Health Center, Petach Tikva, Israel

      Abraham Weizman

    9. Department of Stress Neurobiology and Neurogenetics, Max-Planck Institute of Psychiatry, Munich, Germany

      Alon Chen

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    1. Maya Amitai
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    Correspondence to Maya Amitai.

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    M. Amitai and S. Kronenberg equally contributed to this work.

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    Amitai, M., Kronenberg, S., Carmel, M. et al. Pharmacogenetics of citalopram-related side effects in children with depression and/or anxiety disorders. J Neural Transm 123, 1347–1354 (2016). https://doi.org/10.1007/s00702-016-1585-7

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    • DOI: https://doi.org/10.1007/s00702-016-1585-7

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