{"title":"<i>Correction to:</i> Machine Learning Identifies Smartwatch-Based Physiological Biomarker for Predicting Disruptive Behavior in Children: A Feasibility Study, by Romanowicz et al. <i>J Child Adolesc Psychopharmacol</i> 2023;33(9):387-392; doi: 10.1089/cap.2023.0038.","authors":"","doi":"10.1089/cap.2023.0038.correx","DOIUrl":"10.1089/cap.2023.0038.correx","url":null,"abstract":"","PeriodicalId":15277,"journal":{"name":"Journal of child and adolescent psychopharmacology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11071100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reena Thomas, Austin Sellers, Jamie L Fierstein, Mark Cavitt, Jeffrey Alvaro, Neil Goldenberg
{"title":"Suicide, Stimulants, and Selective Serotonin Reuptake Inhibitors: A Retrospective Chart Review.","authors":"Reena Thomas, Austin Sellers, Jamie L Fierstein, Mark Cavitt, Jeffrey Alvaro, Neil Goldenberg","doi":"10.1089/cap.2023.0068","DOIUrl":"10.1089/cap.2023.0068","url":null,"abstract":"<p><p><b><i>Background:</i></b> Previous studies suggest that selective serotonin reuptake inhibitors (SSRIs) may increase the risk of suicide among children and youth, although the association between suicide risk and the combination of SSRIs with other medication such as stimulants in this population remains unclear. This study explored whether the combination of SSRIs with stimulants influenced suicide risk. <b><i>Methods:</i></b> A retrospective cohort study was conducted at a single children's hospital campus-based ambulatory psychiatric clinic between September 1, 2017, and September 30, 2020. Subjects were 6-21 years of age and prescribed either stimulants or stimulants and SSRIs only. The primary outcome was suicidal thoughts and behaviors (STB), defined by documented suicidal thoughts, plans, or behaviors. Firth logistic regression evaluated associations between medication class and STB. <b><i>Results:</i></b> Among 349 patients, the prevalence of STB was 5.7% (<i>n</i> = 20). In unadjusted model, patients prescribed SSRIs and stimulants had a 2.9-fold increase of STB compared to patients prescribed stimulants only, along with increasing age, male sex, and the diagnoses of anxiety and/or depression. In the final model adjusted for each of these factors, the observed association of medication regiment with STB was attenuated (odds ratio [OR]: 1.3, confidence interval [CI]: 0.3-4.9, <i>p</i> = 0.7). The magnitude of the adjusted association between depressive diagnosis and STB was notable (OR: 3.6, CI: 1.0-12.6, <i>p</i> = 0.049). <b><i>Conclusions:</i></b> Among patients followed in a children's hospital-based ambulatory psychiatric clinic, a combination medication regimen of SSRIs and stimulants after adjusting for genetic sex, age, anxiety diagnosis, and depression diagnosis, the observed association between STB and combination stimulant and SSRI treatment was attenuated. This finding suggests that other factors, including depression, may have contributed to the association between SSRI treatment and STB. Larger, prospective studies of the relationship between combination pharmacotherapy and suicide risk are warranted to guide clinical/pharmacological decision making and to better clarify these relationships.</p>","PeriodicalId":15277,"journal":{"name":"Journal of child and adolescent psychopharmacology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sara Nooraeen, Paul E Croarkin, Jennifer R Geske, Julia Shekunov, Scott S Orth, Magdalena Romanowicz, Mark A Frye, Jennifer L Vande Voort
{"title":"High Probability of Gene-Drug Interactions Associated with Medication Side Effects in Adolescent Depression: Results from a Randomized Controlled Trial of Pharmacogenetic Testing.","authors":"Sara Nooraeen, Paul E Croarkin, Jennifer R Geske, Julia Shekunov, Scott S Orth, Magdalena Romanowicz, Mark A Frye, Jennifer L Vande Voort","doi":"10.1089/cap.2023.0043","DOIUrl":"10.1089/cap.2023.0043","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Combinatorial pharmacogenetic testing panels are widely available in clinical practice and often separate medications into columns/bins associated with low, medium, or high probability of gene-drug interactions. The objective of the Adolescent Management of Depression (AMOD) study was to determine the clinical utility of combinatorial pharmacogenetic testing in a double-blind, randomized, controlled effectiveness study by comparing patients who had genetic testing results at time of medication initiation to those that did not have results until week 8. The objective of this <i>post hoc</i> analysis was to assess and report additional outcomes with respect to significant gene-drug interactions (i.e., a medication in the high probability gene-drug interaction bin as defined by a proprietary algorithm) compared with patients taking a medication with minimal to moderate gene-drug interactions (i.e., a medication from the low or medium probability gene-drug interaction bin, respectively). <b><i>Methods:</i></b> Adolescents 13-18 years (<i>N</i> = 170) with moderate to severe major depressive disorder received pharmacogenetic testing. Symptom improvement and side effects were assessed at baseline, week 4, week 8, and 6 months. Patients were grouped into three categories based on whether the medication they were prescribed was associated with low, medium, or high risk for gene-drug interactions. Patients taking a medication from the low/medium gene-drug interaction bin were compared with patients taking a medication from the high gene-drug interaction bin. <b><i>Results:</i></b> Patients taking a medication from the high gene-drug interaction bin were more likely to endorse side effects compared with patients taking a medication in the low/medium gene-drug interaction bin at week 8 (<i>p</i> = 0.001) and 6 months (<i>p</i> < 0.0001). Depressive symptom severity scores did not differ significantly across the medication bins. <b><i>Conclusions:</i></b> This study demonstrates the utility of gene-drug interaction testing to guide medication decisions to minimize side effect burden rather than solely prioritizing the search for the most efficacious medication. (Clinical Trials Registration Identifier: NCT02286440).</p>","PeriodicalId":15277,"journal":{"name":"Journal of child and adolescent psychopharmacology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Acknowledgment of Reviewers 2023.","authors":"","doi":"10.1089/cap.2023.29252.ack","DOIUrl":"10.1089/cap.2023.29252.ack","url":null,"abstract":"","PeriodicalId":15277,"journal":{"name":"Journal of child and adolescent psychopharmacology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Salma Malik, Pragya Verma, Gualberto Ruaño, Areej Al Siaghy, Azwa Dilawar, Jeffrey R Bishop, Jeffrey R Strawn, Lisa B Namerow
{"title":"Pharmacogenetics in Child and Adolescent Psychiatry: Background and Evidence-Based Clinical Applications.","authors":"Salma Malik, Pragya Verma, Gualberto Ruaño, Areej Al Siaghy, Azwa Dilawar, Jeffrey R Bishop, Jeffrey R Strawn, Lisa B Namerow","doi":"10.1089/cap.2023.0074","DOIUrl":"10.1089/cap.2023.0074","url":null,"abstract":"<p><p>The efficacy and tolerability of psychotropic medications can vary significantly among children and adolescents, and some of this variability relates to pharmacogenetic factors. Pharmacogenetics (PGx) in child and adolescent psychiatry can potentially improve treatment outcomes and minimize adverse drug reactions. This article reviews key pharmacokinetic and pharmacodynamic genes and principles of pharmacogenetic testing and discusses the evidence base for clinical decision-making concerning PGx testing. This article reviews current guidelines from the United States Food and Drug Administration (FDA), the Clinical Pharmacogenetics Implementation Consortium (CPIC), and the Dutch Pharmacogenetics Working Group (DPWG) and explores potential future directions. This review discusses key clinical considerations for clinicians prescribing psychotropic medications in children and adolescents, focusing on antidepressants, antipsychotics, stimulants, norepinephrine reuptake inhibitors, and alpha-2 agonists. Finally, this review synthesizes the practical use of pharmacogenetic testing and clinical decision support systems.</p>","PeriodicalId":15277,"journal":{"name":"Journal of child and adolescent psychopharmacology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Duncan C Honeycutt, Thomas J Blom, Laura B Ramsey, Jeffrey R Strawn, Kaitlyn M Bruns, Jeffrey A Welge, Luis R Patino, Manpreet K Singh, Melissa P DelBello
{"title":"Pharmacogenetic Factors Influence Escitalopram Pharmacokinetics and Adverse Events in Youth with a Family History of Bipolar Disorder: A Preliminary Study.","authors":"Duncan C Honeycutt, Thomas J Blom, Laura B Ramsey, Jeffrey R Strawn, Kaitlyn M Bruns, Jeffrey A Welge, Luis R Patino, Manpreet K Singh, Melissa P DelBello","doi":"10.1089/cap.2023.0073","DOIUrl":"10.1089/cap.2023.0073","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Escitalopram is an effective and generally well-tolerated antidepressant, but children of parents with bipolar disorder (BD) may be at increased risk for adverse events associated with antidepressants, including increased irritability, restlessness, impulsivity, and manic symptoms. This risk may be influenced by polymorphisms in genes encoding cytochrome P450 enzymes (<i>CYP2C19</i> or <i>CYP2D6</i>), the serotonin transporter (<i>SLC6A4</i>), and the serotonin receptor 2A subtype (<i>HTR2A</i>). We explored whether gene-drug interactions influence the emergence of adverse events in depressed and/or anxious youth with a family history of BD. <b><i>Materials and Methods:</i></b> Children and adolescents aged 12-17 years with a first-degree relative with bipolar I disorder were treated with escitalopram and monitored for adverse effects, underwent pharmacogenetic testing, and provided serum escitalopram levels. Emergence of adverse events was determined by study clinicians, and symptoms were tracked using the Treatment-Emergent Activation and Suicidality Assessment Profile (TEASAP) and Pediatric Adverse Events Rating Scale. Clinical Pharmacogenetics Implementation Consortium guidelines were used to determine CYP2C19 and CYP2D6 phenotypes. <b><i>Results:</i></b> Slower CYP2C19 metabolizers had greater dose-normalized 24-hour area under the curve (AUC<sub>0-24</sub>; <i>p</i> = 0.025), trough concentrations (C<sub>trough</sub>; <i>p</i> = 0.013), and elimination half-lives (t<sub>1/2</sub>; <i>p</i> < 0.001). CYP2D6 phenotype was not significantly associated with any pharmacokinetic parameter. Slower CYP2D6 metabolizers had increased TEASAP akathisia (<i>p</i> = 0.015) scores. <i>HTR2A A/A</i> and <i>A/G</i> genotypes were associated with increased TEASAP \"self-injury, suicidality, and harm to others\" subscale scores (<i>p</i> = 0.017). Escitalopram maximum concentration, AUC<sub>0-24</sub>, CYP2C19 phenotype, and <i>SLC6A4</i> genotype were not associated with adverse events. <b><i>Conclusions:</i></b> CYP2C19 phenotype influences escitalopram pharmacokinetics whereas CYP2D6 phenotype does not. Slower CYP2D6 metabolism was associated with increased akathisia, and <i>HTR2A A/A</i> or <i>A/G</i> genotypes were associated with increased risk of self-harm or harm to others. Larger cohorts are needed to identify associations between genetic test results and antidepressant-associated adverse events. <b><i>Trial Registration:</i></b> ClinicalTrials.gov identifier: NCT02553161.</p>","PeriodicalId":15277,"journal":{"name":"Journal of child and adolescent psychopharmacology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stephani L Stancil, Tracy Sandritter, Jeffrey R Strawn
{"title":"Pharmacogenetics and Oxcarbazepine in Children and Adolescents: Beyond <i>HLA-B</i>*15:02.","authors":"Stephani L Stancil, Tracy Sandritter, Jeffrey R Strawn","doi":"10.1089/cap.2023.0064","DOIUrl":"10.1089/cap.2023.0064","url":null,"abstract":"<p><p><b><i>Background:</i></b> Oxcarbazepine is thought to be better-tolerated and less susceptible to drug-drug interactions than its predecessor, carbamazepine. Genetic testing for <i>HLA-B</i>*15:02 is recommended in specific populations to identify those at high risk of severe hypersensitivity reactions; however, other pharmacologic and pharmacogenetic factors that can impact drug disposition may be involved. <b><i>Methods:</i></b> We present a case of an 8-year-old boy treated with oxcarbazepine who developed drug reaction with eosinophilia and systemic symptoms (DRESS) with Stevens-Johnsons syndrome overlap and was negative for <i>HLA-B</i>*15:02. We review the extant literature related to oxcarbazepine disposition, and potential pharmacogenetic variants in aldoketoreductase 1C (<i>AKR1C</i>)2-4 that may contribute to this risk. <b><i>Results:</i></b> Genetic variability in oxcarbazepine disposition pathways may contribute to tolerability and toxicity, including the development of hypersensitivity reactions. <b><i>Conclusions:</i></b> While preemptive genetic testing for <i>HLA-B</i>*15:02 in individuals of Asian ancestry is recommended to prevent severe hypersensitivity reactions to oxcarbazepine, oxcarbazepine concentrations and <i>AKR1C</i> variation may contribute to the risk of severe adverse reactions. We provide recommendations for future study to elucidate whether these individual factors are important for reducing the risk of severe adverse events.</p>","PeriodicalId":15277,"journal":{"name":"Journal of child and adolescent psychopharmacology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Pharmacogenetic Journey in Child and Adolescent Psychopharmacology: Are We There Yet?","authors":"Lisa B Namerow, Jeffrey R Strawn","doi":"10.1089/cap.2023.29254.editorial","DOIUrl":"10.1089/cap.2023.29254.editorial","url":null,"abstract":"","PeriodicalId":15277,"journal":{"name":"Journal of child and adolescent psychopharmacology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Erica Tonti, Yee Ming Lee, Nathan Gruenke, Janie Ferren, Danielle L Stutzman
{"title":"Impact of Pharmacogenomics on Pediatric Psychotropic Medication Prescribing in an Ambulatory Care Setting.","authors":"Erica Tonti, Yee Ming Lee, Nathan Gruenke, Janie Ferren, Danielle L Stutzman","doi":"10.1089/cap.2023.0087","DOIUrl":"10.1089/cap.2023.0087","url":null,"abstract":"<p><p><b><i>Objective:</i></b> Evidence for pharmacogenomic (PGx) guided treatment in child and adolescent psychiatry is growing. This study evaluated the impact of PGx testing on psychotropic medication prescribing in an ambulatory child and adolescent psychiatry and a developmental pediatrics clinic. <b><i>Methods:</i></b> This was a single-center, retrospective, descriptive analysis of patients who underwent PGx testing between January 2015 and October 2022 at a child and adolescent psychiatry clinic or developmental pediatrics clinic. The primary outcome was the proportion of patients with at least one psychotropic medication modification made 6-month posttesting that could be attributed to CYP2C19, CYP2D6, HLA-B*15:02, or HLA-A*31:01. Secondary outcomes included reason for testing, types of therapeutic modifications made, and whether the therapeutic modifications concorded with PGx guidelines. <b><i>Results:</i></b> A total of 193 patients were analyzed. The average age was 10 ± 4 years old, 60% were male, 78% were Caucasian. Sixty-eight percent had a primary diagnosis of a neurodevelopmental disorder, namely autism spectrum disorder (51%), and attention-deficit/hyperactivity disorder (14%). The reasons for PGx testing included medication inefficacy (34%), medication intolerance (20%), and family request (19%). At the time of PGx testing, 37% of patients were taking ≥1 psychotropic medication with PGx annotation. Overall, 35 PGx-related therapeutic modifications were made in 32 (17%) patients. These included continuing current PGx medication (6.2%) and starting PGx medication (5.2%). These modifications mainly involved antidepressants. Out of these 35 PGx-related therapeutic modifications, 94% were concordant with PGx guidelines. Among 29 patients who were prescribed at least one CYP2D6 inhibitor, 25 (86%) underwent CYP2D6 phenoconversion. <b><i>Conclusions:</i></b> It is critical to apply pediatric age-specific considerations when utilizing PGx testing in child and adolescent psychiatry. PGx testing stewardship could provide a framework to guide the clinical utility of PGx in a pediatric population with mental health conditions, including neurodevelopmental disorders.</p>","PeriodicalId":15277,"journal":{"name":"Journal of child and adolescent psychopharmacology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
W Thomas Baumel, Ethan A Poweleit, Zoe Neptune, Heidi K Schroeder, Laura B Ramsey, Jeffrey Mills, Jeffrey R Strawn
{"title":"<i>Letter to the Editor:</i> The Impact of Adherence and CYP2C19 Phenotype on Escitalopram Exposure in Adolescents.","authors":"W Thomas Baumel, Ethan A Poweleit, Zoe Neptune, Heidi K Schroeder, Laura B Ramsey, Jeffrey Mills, Jeffrey R Strawn","doi":"10.1089/cap.2023.0063","DOIUrl":"10.1089/cap.2023.0063","url":null,"abstract":"","PeriodicalId":15277,"journal":{"name":"Journal of child and adolescent psychopharmacology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}