Abstract
In pediatric patients, the selective serotonin reuptake inhibitors (SSRIs) escitalopram and citalopram (es/citalopram) are commonly prescribed for anxiety and depressive disorders. However, pharmacogenetic studies examining CYP2C19 metabolizer status and es/citalopram treatment outcomes have largely focused on adults. We report a retrospective study of electronic medical record data from 263 youth < 19 years of age with anxiety and/or depressive disorders prescribed escitalopram or citalopram who underwent routine clinical CYP2C19 genotyping. Slower CYP2C19 metabolizers experienced more untoward effects than faster metabolizers (p = 0.015), including activation symptoms (p = 0.029) and had more rapid weight gain (p = 0.018). A larger proportion of slower metabolizers discontinued treatment with es/citalopram than normal metabolizers (p = 0.007). Meanwhile, faster metabolizers responded more quickly to es/citalopram (p = 0.005) and trended toward less time spent in subsequent hospitalizations (p = 0.06). These results highlight a disparity in treatment outcomes with es/citalopram treatment in youth with anxiety and/or depressive disorders when standardized dosing strategies were used without consideration of CYP2C19 metabolizer status. Larger, prospective trials are warranted to assess whether tailored dosing of es/citalopram based on CYP2C19 metabolizer status improves treatment outcomes in this patient population.
Highlights
Up to 10% of children and adolescents in the United States may have an anxiety or depressive disorder (Merikangas et al, 2010)
Of the 248 inpatient pediatric patients with anxiety and/or depressive disorders assessed for tolerability, 95.6% (n = 237/248) had at least one side effect while prescribed es/citalopram (Table 3)
CYP2C19 metabolizer status was associated with the total number of side effects experienced, with Poor metabolizers (PMs) having the most and ultrarapid metabolizer (UM) having the fewest side effects (Figure 1A)
Summary
Up to 10% of children and adolescents in the United States may have an anxiety or depressive disorder (Merikangas et al, 2010). Psychiatric disorders are among the most expensive conditions to treat in pediatric patients (Soni, 2015) and approximately 1 in 10 pediatric hospitalizations is related to a primary psychiatric disorder (Bardach et al, 2014). These disorders are commonly treated with selective serotonin reuptake inhibitors (SSRIs); treatment response is variable. In pediatric patients with anxiety and depressive disorders, SSRIs decrease symptoms, restore functioning and improve quality of life (Strawn et al, 2015, 2018; Cipriani et al, 2016; Locher et al, 2017; Dobson et al, 2019). With about 5% of patients experiencing intolerable side effects that lead them to discontinue treatment (Wagner et al, 2004, 2006; Goodman et al, 2005; Isolan et al, 2007; Emslie et al, 2009)
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