Disclosures: Strawn reports receiving research support from the NIH, as well as Allergan, Neuronetics and Otsuka; receiving material support from and provided consultation to Myriad Genetics; providing consultation to the FDA and Intracellular Therapeutics; receiving royalties from Springer for the publication of two texts; receiving research support from the Yung Family Foundation; and serving as an author for UpToDate and an associate editor for Current Psychiatry. Please see the study for all other authors’ relevant financial disclosures.
August 28, 2020
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Escitalopram may reduce adolescent anxiety

Disclosures: Strawn reports receiving research support from the NIH, as well as Allergan, Neuronetics and Otsuka; receiving material support from and provided consultation to Myriad Genetics; providing consultation to the FDA and Intracellular Therapeutics; receiving royalties from Springer for the publication of two texts; receiving research support from the Yung Family Foundation; and serving as an author for UpToDate and an associate editor for Current Psychiatry. Please see the study for all other authors’ relevant financial disclosures.
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Escitalopram treatment was linked to reduced anxiety symptoms among adolescents, according to results of a double-blind, randomized, placebo-controlled study published in Journal of Clinical Psychiatry.

Pharmacogenetics variables effected the magnitude and trajectory of improvement, researchers found.

“While [selective serotonin reuptake inhibitors] represent the first-line pharmacotherapy for anxious youth, including those with [generalized anxiety disorder], predicting treatment response is difficult,” Jeffrey R. Strawn, MD, of the department of psychiatry at University of Cincinnati College of Medicine, and colleagues wrote. “SSRI-related improvement varies considerably from patient to patient, often resulting in a trial-and-error process of medication selection and dosing. An additional shortcoming of SSRI treatment in pediatric anxiety disorders is the limited availability of data to aid clinicians in determining which patients will respond.”

In a prior study, the Child/Adolescent Anxiety Multimodal Study, researchers compared sertraline, sertraline plus cognitive behavioral therapy, CBT and placebo and found that youth with severe anxiety needed both CBT and an SSRI; however, youth with lower baseline anxiety levels and those without social anxiety disorder more often experienced remission with all treatments. Further, other studies were able to uncover clinical and demographic factors associated with SSRI or SSRI plus CBT response among youth with anxiety, yet examinations of biological factors and SSRI response remain rare among youth and extremely scarce in pediatric anxiety disorders.

In the current study, Strawn and colleagues aimed to determine the tolerability and efficacy of escitalopram, the S-enantiomer of citalopram, among adolescents with generalized anxiety disorder according to DSM-IV-TR, as well as the genetic and phenotypic effects on response. They treated 26 patients with forced titration to 15 mg/d, then flexible titration to 20 mg/d, of escitalopram and 25 with placebo for 8 weeks. Change in scores on Clinical Global Impressions (CGI) scales and the Pediatric Anxiety Rating Scale (PARS), as well as vital signs and adverse events, served as the outcomes. They determined plasma escitalopram and desmethylcitalopram area under the curve over a period of 24 hours and maximum concentration and compared results across cytochrome P450 2C19 (CYP2C19) phenotypes.

Results showed superiority of escitalopram compared with placebo for mean baseline-to-endpoint change in (P = .005) and CGI scores. Moreover, increasing CYP2C19 metabolism was linked to reductions in escitalopram maximum concentration (P = .07) and area under the curve for 24 hours (P < .05). Both patients who received escitalopram and placebo exhibited similar vital signs, correct QT interval and adverse events.

“This study has many implications for clinicians treating adolescents with [generalized anxiety disorder] and provides preliminary answers to important questions: Is escitalopram effective in treating you with anxiety?” Strawn and colleagues wrote. “How quickly will patients respond? Does CYP2C19 metabolism affect escitalopram pharmacokinetics in youth?

“Finally, the answers to these questions, although incomplete, provide a scaffold for larger studies of pharmacodynamic and pharmacokinetic predictors of treatment response and studies that leverage variability in exposure to inform medication dosing and selection,” they added.