Escitalopram in Adolescents With Generalized Anxiety Disorder

Mills, Jeffrey A.; Schroeder, Heidi K.; Mossman, Sarah A.; Varney, Sara T.; Ramsey, Laura B.; Poweleit, Ethan A.; Desta, Zeruesenay; Cecil, Kim M.; DelBello, Melissa P.

doi:10.4088/jcp.20m13396

Cited by 66 publications

(65 citation statements)

References 30 publications

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“…In this sample, youth who were homozygous for the G allele of the HTR2A gene (consistent with lower expression) did not respond as well as those patients who had at least one A allele. Finally, adolescents who were homozygous short for the promoter region of the serotonin transporter polymorphism, SLC6A4, had reduced magnitude and trajectory of response compared with those who were had a long allele (Strawn et al, 2019). In this study, slower CYP2C19 metabolism was associated with greater escitalopram exposure and reduced clearance; the latter was also associated with escitalopram tolerability (Tulisiak et al, 2019).…”

Section: Predicting Treatment Response In Pediatric Anxiety Disordersmentioning

confidence: 61%

“…However, it is noteworthy that nearly one third of anxious youth who are treated with medication in the United States begin treatment with a non-SSRI medication (Bushnell et al, 2018). To date, sertraline (Rynn, Siqueland, & Rickels, 2001;Walkup et al, 2008), fluoxetine (Beidel et al, 2007;Birmaher et al, 2003;Clark et al, 2005), escitalopram (Strawn et al,2019), fluvoxamine (The Research Unit on Pediatric Psychopharmacology Anxiety Study Group, 2001), and paroxetine (Wagner et al, 2004) have been evaluated in pediatric anxiety disorders. These individual clinical trials are reviewed in detail elsewhere, and their primary findings are shown in Table 3.…”

Section: Ssris In Pediatric Anxiety Disordersmentioning

confidence: 99%

“…In youth with anxiety and/or depressive disorders who were naturalistically treated with escitalopram or citalopram, slower CYP2C19 metabolizers experienced more side effects than faster metabolizers (p = .015), including activation symptoms (p = 0.029) and had more rapid weight gain (p = .018) (Aldrich et al, 2019). In a prospective trial of adolescents with GAD who were treated with escitalopram (forced-flexible titration), slower CYP2C19 metabolizers had greater and faster improvement (Strawn et al, 2019). In this sample, youth who were homozygous for the G allele of the HTR2A gene (consistent with lower expression) did not respond as well as those patients who had at least one A allele.…”

Section: Predicting Treatment Response In Pediatric Anxiety Disordersmentioning

confidence: 99%

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Research Review: Pediatric anxiety disorders – what have we learnt in the last 10 years?

Strawn

Peris³

et al. 2020

Child Psychology Psychiatry

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Background Anxiety disorders first emerge during the critical developmental periods of childhood and adolescence. This review synthesizes recent findings on the prevalence, risk factors, and course of the anxiety disorders; and their neurobiology and treatment. Methods For this review, searches were conducted using PubMed, PsycINFO, and http://clinicaltrials.gov. Findings related to the epidemiology, neurobiology, risk factors, and treatment of pediatric anxiety disorders were then summarized. Findings Anxiety disorders are high prevalence, and early‐onset conditions associated with multiple risk factors including early inhibited temperament, environment stress, and structural and functional abnormalities in the prefrontal‐amygdala circuitry as well as the default mode and salience networks. The anxiety disorders are effectively treated with cognitive behavioral therapy (CBT), selective serotonin reuptake inhibitors (SSRIs), and serotonin–norepinephrine reuptake inhibitors (SNRIs). Conclusions Anxiety disorders are high prevalence, early‐onset conditions associated with a distinct neurobiological fingerprint, and are consistently responsive to treatment. Questions remain regarding who is at risk of developing anxiety disorders as well as the way in which neurobiology predicts treatment response.

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Section: Predicting Treatment Response In Pediatric Anxiety Disordersmentioning

confidence: 61%

Section: Ssris In Pediatric Anxiety Disordersmentioning

confidence: 99%

Section: Predicting Treatment Response In Pediatric Anxiety Disordersmentioning

confidence: 99%

See 1 more Smart Citation

Research Review: Pediatric anxiety disorders – what have we learnt in the last 10 years?

Strawn

Peris³

et al. 2020

Child Psychology Psychiatry

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“…The predicted phenotypes are the focus of functional studies, which evaluate the impact of allelic variation on SSRI pharmacokinetics and clinical outcomes, including efficacy and tolerability. For example, we previously demonstrated that CYP2C19 metabolizer status impacts the outcomes with escitalopram/citalopram in youth with anxiety and depressive disorders [ 17 , 18 ]. Slower metabolizers were more likely to discontinue treatment compared to normal metabolizers, and were more likely to experience significant side effects, including weight gain and activation.…”

Section: Introductionmentioning

confidence: 99%

The Impact of Marijuana on Antidepressant Treatment in Adolescents: Clinical and Pharmacologic Considerations

Vaughn

Poweleit

Sarangdhar

et al. 2021

JPM

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The neuropharmacology of marijuana, including its effects on selective serotonin reuptake inhibitor (SSRI)/antidepressant metabolism and the subsequent response and tolerability in youth, has received limited attention. We sought to (1) review clinically relevant pharmacokinetic (PK) and pharmacodynamic (PD) interactions between cannabinoids and selected SSRIs, (2) use PK models to examine the impact of cannabinoids on SSRI exposure (area under curve (AUC)) and maximum concentration (CMAX) in adolescents, and (3) examine the frequency of adverse events reported when SSRIs and cannabinoids are used concomitantly. Cannabinoid metabolism, interactions with SSRIs, impact on relevant PK/PD pathways and known drug–drug interactions were reviewed. Then, the impact of tetrahydrocannabinol (THC) and cannabidiol (CBD) on exposure (AUC24) and CMAX for escitalopram and sertraline was modeled using pediatric PK data. Using data from the Food and Drug Administration Adverse Events Reporting System (FAERS), the relationship between CBD and CYP2C19-metabolized SSRIs and side effects was examined. Cannabis and CBD inhibit cytochrome activity, alter serotonergic transmission, and modulate SSRI response. In PK models, CBD and/or THC increases sertraline and es/citalopram concentrations in adolescents, and coadministration of CBD and CYP2C19-metabolized SSRIs increases the risk of cough, diarrhea, dizziness, and fatigue. Given the significant SSRI–cannabinoid interactions, clinicians should discuss THC and CBD use in youth prescribed SSRIs and be aware of the impact of initiating, stopping, or decreasing cannabinoid use as this may significantly affect es/citalopram and sertraline exposure.

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“…Given the current approach to dosing SSRIs and increasing evidence linking variation in SSRI exposure and differences in efficacy and tolerability, TDM may have increasing utility in child and adolescent psychiatry. TDM offers the opportunity to leverage individual variability of antidepressant pharmacokinetics to: 1) shed light on non-response and partial response (Sakolsky et al, 2011); 2) understand drugdrug interactions (Vaughn et al, 2021); 3) evaluate adherence (Fekete et al, 2020); and 4) understand the impact of genetic and developmental variation in pharmacokinetic genes (Strawn et al, 2020c). With these considerations in mind, this Perspective introduces clinicians to TDM principles and illustrates TDM applications in child and adolescent psychiatry.…”

Section: Introductionmentioning

confidence: 99%

Pediatric Therapeutic Drug Monitoring for Selective Serotonin Reuptake Inhibitors

2021

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Therapeutic drug monitoring (TDM) is uncommon in child and adolescent psychiatry, particularly for selective serotonin reuptake inhibitors (SSRIs)—the first-line pharmacologic treatments for depressive and anxiety disorders. However, TDM in children and adolescents offers the opportunity to leverage individual variability of antidepressant pharmacokinetics to shed light on non-response and partial response, understand drug-drug interactions, evaluate adherence, and characterize the impact of genetic and developmental variation in pharmacokinetic genes. This perspective aims to educate clinicians about TDM principles and examines evolving uses of TDM in SSRI-treated youths and their early applications in clinical practice, as well as barriers to TDM in pediatric patients. First, the impact of pharmacokinetic genes on SSRI pharmacokinetics in youths could be used to predict tolerability and response for some SSRIs (e.g., escitalopram). Second, plasma concentrations are significantly influenced by adherence, which may relate to decreased efficacy. Third, pharmacometric analyses reveal interactions with proton pump inhibitors, oral contraceptives, cannabinoids, and SSRIs in youths. Rapid developments in TDM and associated modeling have enhanced the understanding of variation in SSRI pharmacokinetics, although the treatment of anxiety and depressive disorders with SSRIs in youths often remains a trial-and-error process.

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Escitalopram in Adolescents With Generalized Anxiety Disorder

Cited by 66 publications

References 30 publications

Research Review: Pediatric anxiety disorders – what have we learnt in the last 10 years?

Research Review: Pediatric anxiety disorders – what have we learnt in the last 10 years?

The Impact of Marijuana on Antidepressant Treatment in Adolescents: Clinical and Pharmacologic Considerations

Pediatric Therapeutic Drug Monitoring for Selective Serotonin Reuptake Inhibitors

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