Pharmacogenetics of Sertraline Tolerability and Response in Pediatric Anxiety and Depressive Disorders

Poweleit, Ethan A.; Aldrich, Stacey L.; Martin, Lisa J.; Hahn, David; Strawn, Jeffrey R.; Ramsey, Laura B.

doi:10.1089/cap.2019.0017

Cited by 34 publications

(26 citation statements)

References 62 publications

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“…Sertraline dose extrapolations based on pharmacokinetic parameters among CYP2C19 phenotypes suggest a 50% dose reduction may be needed for poor metabolizers [121]. A recent study found that the number of CYP2C19 no function alleles influenced the rate of titration of sertraline in a retrospective cohort of children and adolescents with anxiety and depressive disorders [122]. While the relationship between CYP2C19 increased or no function alleles and sertraline exposure and response is still being elucidated [123,124], the increased function CYP2C19*17 allele has not been observed to greatly affect sertraline plasma concentrations [27].…”

Section: Pharmacogenomicsmentioning

confidence: 99%

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PharmGKB summary: sertraline pathway, pharmacokinetics

Huddart

Hicks

Ramsey

et al. 2020

Pharmacogenetics and Genomics

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Section: Pharmacogenomicsmentioning

confidence: 99%

“…Patients that are homozygous for the 5HTTLPR long allele in SLC6A4 have shown an improved response to sertraline compared to patients with one or two copies of the short allele [122,127,128]. However, not all studies have observed this effect [129,130].…”

Section: Pharmacogenomicsmentioning

confidence: 99%

PharmGKB summary: sertraline pathway, pharmacokinetics

Huddart

Hicks

Ramsey

et al. 2020

Pharmacogenetics and Genomics

Self Cite

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“…Evidence supporting the use of widespread PGx testing of children has not been reported, but rather, reports of specific medications or classes have suggested some benefit of PGx testing for children 119–123. If evidence continues to accumulate for different pediatric medications, it is likely that this will be used to support the use of preemptive PGx testing in children along with data documenting the increasing use of medications in children.…”

Section: Weighing the Benefits And Risks Of Pgx Testing In Childrenmentioning

confidence: 99%

<p>Pharmacogenomic Testing In Pediatrics: Navigating The Ethical, Social, And Legal Challenges</p>

Haga

2019

PGPM

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For the past several years, the implementation of pharmacogenetic (PGx) testing has become widespread in several centers and clinical practice settings. PGx testing may be ordered at the point-of-care when treatment is needed or in advance of treatment for future use. The potential benefits of PGx testing are not limited to adult patients, as children are increasingly using medications more often and at earlier ages. This review provides some background on the use of PGx testing in children as well as mothers (prenatally and post-natally) and discusses the challenges, benefits, and the ethical, legal, and social implications of providing PGx testing to children.

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“…In CYP2C19 poor metabolizers, CPIC recommends a dose reduction of 50% for citalopram, escitalopram, and sertraline because elevated medication concentrations have been observed (e.g., citalopram/escitalopram) or more side effects have been reported (e.g., sertraline). These recommendations are based on data from adults, but pediatric data are increasingly reported [ 17 , 19 , 20 , 21 ] and will be assessed in the update of the CPIC SSRI guideline, expected to be published in late 2021 or early 2022.…”

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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Pharmacogenetics of Sertraline Tolerability and Response in Pediatric Anxiety and Depressive Disorders

Cited by 34 publications

References 62 publications

PharmGKB summary: sertraline pathway, pharmacokinetics

PharmGKB summary: sertraline pathway, pharmacokinetics

<p>Pharmacogenomic Testing In Pediatrics: Navigating The Ethical, Social, And Legal Challenges</p>

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

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