{"title":"Psychedelic Treatments in Adolescent Psychopharmacology: Considering Safety, Ethics, and Scientific Rigor.","authors":"Isabella Sutherland, Ming-Fen Ho, Paul E Croarkin","doi":"10.1089/cap.2024.0082","DOIUrl":"https://doi.org/10.1089/cap.2024.0082","url":null,"abstract":"<p><p>Interest in psychedelic therapies for adults is rapidly growing, with substances like 3,4-methylenedioxymethamphetamine for posttraumatic stress disorder, psilocybin for treatment-resistant depression, and lysergic acid diethylamide for generalized anxiety disorder showing promise. However, research on these therapies in children and adolescents is limited, with no recent trials. Despite this lack of scientific exploration, adolescents may still experiment with these substances for both recreational and therapeutic purposes as accessibility continues to increase. This raises significant concerns, as adolescents are a vulnerable population requiring heightened caution and safety measures. Therefore, we advocate for structured, safe, and well-controlled exploration of psychedelic therapies in adolescents.</p>","PeriodicalId":15277,"journal":{"name":"Journal of child and adolescent psychopharmacology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931912","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}
Jennifer Vermilion, Nicole Walsh, Matthew Tae, Alyssa Peechatka, Jason Kahn, Jessica Ragnio, Emily Stone, Jonathan W Mink
{"title":"Biofeedback-Based Videogame May Improve Rage Attacks in Tourette Syndrome.","authors":"Jennifer Vermilion, Nicole Walsh, Matthew Tae, Alyssa Peechatka, Jason Kahn, Jessica Ragnio, Emily Stone, Jonathan W Mink","doi":"10.1089/cap.2024.0084","DOIUrl":"https://doi.org/10.1089/cap.2024.0084","url":null,"abstract":"<p><p><b><i>Background:</i></b> Approximately 20%-40% of individuals with Tourette syndrome (TS) have rage attacks (RAs), which are recurrent, explosive behavioral outbursts that can cause significant functional impairment. Despite the impact of RA in TS, there has been limited research on treatment, and most studies have focused on pharmacologic interventions. Nonpharmacologic interventions have the potential to improve symptoms with fewer side effects. <i>Mightier,</i> a video game-based biofeedback therapy, may help teach emotional regulation through heart rate control and has the potential to improve RA in youth with TS. <b><i>Objective:</i></b> To evaluate the feasibility and acceptability of <i>Mightier</i> as a therapeutic intervention for RA in youth with TS. <b><i>Methods:</i></b> Subjects aged 6-12 years old with a diagnosis of TS and RA were enrolled between October 2021 and May 2022 into a 20-week single-arm trial. Feasibility was assessed by the rate of enrollment, screen failures, and retention and device engagement. We also evaluated efficacy by assessing rage severity (Clinical Global Impressions of Rage), Rage Outbursts and Anger Rating Scale (ROARS) and overall aggression severity (Modified Overt Aggression Scale [MOAS]) pre- and postintervention. CGI-Improvement (CGI-I) was completed postintervention. <b><i>Results:</i></b> We enrolled 11 participants. The study was feasible based on enrollment rate (one participant every 2.5 months), screen failures (<i>n</i> = 1), and retention rate (91%). Mean weekly play time was 38 (SD 18) minutes/week. No adverse effects were reported. Median rage severity scores improved across all assessment measures. All participants reported overall improvement on the post-intervention CGI-I. <b><i>Conclusions:</i></b> This <i>Mightier</i> study was feasible in terms of recruitment and retention. Participants with TS and RA used the device often and engaged with the device throughout the 12-week intervention period. Rage severity overall improved across the various outcome measures, and all participants had at least some improvement by parent report. Mightier may be a helpful tool for reducing rage severity in children with RA and TS.</p>","PeriodicalId":15277,"journal":{"name":"Journal of child and adolescent psychopharmacology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931951","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}
Jeffrey R Strawn, Jeffrey A Mills, Zoe A Neptune, Alyssa Burgei, Heidi K Schroeder, Lisa J Martin, Jenni Farrow, Ethan A Poweleit, Laura B Ramsey
{"title":"Electronically Monitored Antidepressant Adherence in Adolescents with Anxiety Disorders: A Pilot Study.","authors":"Jeffrey R Strawn, Jeffrey A Mills, Zoe A Neptune, Alyssa Burgei, Heidi K Schroeder, Lisa J Martin, Jenni Farrow, Ethan A Poweleit, Laura B Ramsey","doi":"10.1089/cap.2024.0102","DOIUrl":"10.1089/cap.2024.0102","url":null,"abstract":"<p><p><b><i>Background:</i></b> Antidepressant medication adherence patterns are inconsistent in adolescents with anxiety and related disorders, and the clinical and demographic features predicting adherence are poorly understood. <b><i>Methods:</i></b> In an ongoing single-site prospective trial involving adolescents (aged 12-17) with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition anxiety disorders treated with escitalopram, adherence was measured for 12 weeks using electronic monitoring caps. Adherence patterns were examined using qualitative and unsupervised clustering approaches, and predictors of adherence were evaluated using logistic regression, with demographic (age, sex, and race) and clinical variables (e.g., anxiety severity [Pediatric Anxiety Rating Scale], irritability [Affective Reactivity Index], depressive symptoms [Children's Depression Rating Scale]). <b><i>Results:</i></b> Among adolescents (<i>N</i> = 33) aged 14.5 ± 1.8 years (64% female), four adherence patterns were identified: persistent adherence, intermittent adherence, early adherence-late nonadherence, and nonadherence. In a logistic model of a 5-day moving average measure of adherence, social anxiety disorder (<i>β</i> = -0.68 ± 0.19, <i>p</i> = 0.002) and separation anxiety disorder (<i>β</i> = -0.61 ± 0.18, <i>p</i> < 0.001) were associated with lower adherence. In contrast, panic disorder, attention-deficit/hyperactivity disorder, generalized anxiety disorder, and depressive symptoms were not associated with adherence. Baseline anxiety severity was linked to lower adherence (<i>β</i> = -0.199 ± 0.05, <i>p</i> < 0.001). Older age also reduced adherence (<i>β</i> = -0.342 ± 0.05, <i>p</i> < 0.001), with each additional year of age increasing time spent nonadherent by 5% (<i>p</i> < 0.001). Being female (<i>β</i> = 0.451 ± 0.17, <i>p</i> = 0.011) and expecting treatment to be efficacious (<i>β</i> = 0.092 ± 0.04, <i>p</i> = 0.011) increased adherence, while greater irritability was associated with nonadherence (<i>β</i> = -0.075 ± 0.03, <i>p</i> = 0.006). <b><i>Conclusions:</i></b> Antidepressant adherence is variable, with distinct patterns, and those with social and separation anxiety disorders were less likely to be adherent. Factors such as older age, severe anxiety, and greater irritability predicted lower adherence, while being female and expecting treatment efficacy were associated with better adherence. Interventions that address specific symptoms or enhance treatment expectations may improve adherence.</p>","PeriodicalId":15277,"journal":{"name":"Journal of child and adolescent psychopharmacology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882120","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":"A Rare Case of Dose-Dependent Priapism in a Child with Autism Treated with Aripiprazole and Risperidone.","authors":"Mehri Durak, Ümit Işık","doi":"10.1089/cap.2024.0134","DOIUrl":"https://doi.org/10.1089/cap.2024.0134","url":null,"abstract":"","PeriodicalId":15277,"journal":{"name":"Journal of child and adolescent psychopharmacology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876875","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}
Greta A Bushnell, Daniel B Horton, Mark Olfson, Hillary Samples, Elizabeth A Suarez, Diane P Calello
{"title":"Current Utilization of Bupropion Treatment in Children, Young Adults, and Adults in the United States.","authors":"Greta A Bushnell, Daniel B Horton, Mark Olfson, Hillary Samples, Elizabeth A Suarez, Diane P Calello","doi":"10.1089/cap.2024.0111","DOIUrl":"10.1089/cap.2024.0111","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> While available for decades, the use of bupropion has increased in recent years. To provide an updated review on the use of bupropion, this article aimed to describe bupropion prescription details, potential indication, and treatment duration in children, young adults, and adults starting bupropion treatment. <b><i>Methods:</i></b> Individuals aged 6-64 newly initiating bupropion hydrochloride treatment were identified from commercial claims data (MarketScan, 1/1/2016-12/31/2022). New bupropion use was defined as at least 1 year without any prior bupropion dispensed prescription. Potential indications for bupropion treatment were identified from inpatient/outpatient records (ICD-10-CM diagnoses) in the 30 days prior to bupropion initiation. All analyses were stratified by age: children (6-17 years), young adults (18-29 years), and adults (30-64 years) and treatment duration up to 1 year was estimated with Kaplan-Meier estimation. <b><i>Results:</i></b> The study sample included 39,833 children, 177,710 young adults, and 548,557 adults newly initiating bupropion treatment. Bupropion extended-release 24-hour 150 mg was the most common (62%) formulation and dose at initiation. Depression was the most prevalent potential indication (children = 57%, young adults = 47%, adults = 36%) and attention-deficit/hyperactivity disorder (ADHD) was the next most common potential indication in children (25%) and young adults (12%); tobacco cessation and weight loss also identified as potential indications. Twenty-two percent of bupropion initiators were on concurrent selective serotonin reuptake inhibitor treatment. In children, suicidal ideation (16.3%), poisoning (5.9%), and anorexia or bulimia nervosa (2.2%) were relatively common diagnoses prior to bupropion initiation. Overall, 39%-45% remained on bupropion treatment for at least 6 months, with variation by potential indication. <b><i>Conclusion:</i></b> The antidepressant bupropion is prescribed to children, young adults, and adults for a variety of indications in the United States, with depression and ADHD the most common indications in children. As the prescribing of bupropion becomes more widespread, additional safety and effectiveness data will be necessary to inform prescribing decisions, particularly in populations with unknown efficacy.</p>","PeriodicalId":15277,"journal":{"name":"Journal of child and adolescent psychopharmacology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869387","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}
Robyn P Thom, Danielle Renzi, Meredith Pecukonis, Jennifer Mullett, Caitlin Ravichandran, Christopher J McDougle
{"title":"A Prospective Open-Label Trial of Buspirone for the Treatment of Anxiety in Williams Syndrome.","authors":"Robyn P Thom, Danielle Renzi, Meredith Pecukonis, Jennifer Mullett, Caitlin Ravichandran, Christopher J McDougle","doi":"10.1089/cap.2024.0124","DOIUrl":"https://doi.org/10.1089/cap.2024.0124","url":null,"abstract":"<p><p><b><i>Study Design:</i></b> Prospective open-label trial. <b><i>Objectives:</i></b> The objective of this study was to determine whether buspirone showed preliminary evidence of effectiveness, safety, and tolerability in individuals with Williams syndrome (WS). <b><i>Methods:</i></b> This is a 16-week, prospective, flexibly dosed, open-label trial of buspirone in 20 individuals with WS aged 5-65 years. The primary outcome measure was the Pediatric Anxiety Rating Scale (PARS). <b><i>Results:</i></b> Buspirone use (mean dose, 22.6 mg per day) was associated with a reduction in anxiety severity, with Cohen's <i>d</i> estimate of -4.02 for the PARS. All 18 participants who completed the study received the Clinical Global Impression-Improvement subscale score for anxiety of \"much improved\" or \"very much improved.\" No serious or severe adverse events occurred during the trial, and no participants discontinued the study due to adverse events. <b><i>Conclusion:</i></b> Buspirone was safe and well tolerated. It was also associated with a reduction in anxiety severity. Given these findings, a double-blind, placebo-controlled study of buspirone in WS is warranted.</p>","PeriodicalId":15277,"journal":{"name":"Journal of child and adolescent psychopharmacology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836630","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}
Walker S McKinney, Lauren M Schmitt, Lisa A De Stefano, Lauren Ethridge, Jordan E Norris, Paul S Horn, Shelby Dauterman, Hilary Rosselot, Ernest V Pedapati, Debra L Reisinger, Kelli C Dominick, Rebecca C Shaffer, Danielle Chin, Nicole R Friedman, Michael Hong, John A Sweeney, Craig Erickson
{"title":"Results from a Double-Blind, Randomized, Placebo-Controlled, Single-Dose, Crossover Trial of Lovastatin or Minocycline in Fragile X Syndrome.","authors":"Walker S McKinney, Lauren M Schmitt, Lisa A De Stefano, Lauren Ethridge, Jordan E Norris, Paul S Horn, Shelby Dauterman, Hilary Rosselot, Ernest V Pedapati, Debra L Reisinger, Kelli C Dominick, Rebecca C Shaffer, Danielle Chin, Nicole R Friedman, Michael Hong, John A Sweeney, Craig Erickson","doi":"10.1089/cap.2024.0103","DOIUrl":"10.1089/cap.2024.0103","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Treatment studies in <i>FMR1</i> knockout rodent models have found that minocycline and lovastatin each improve synaptic, neurological, and behavioral functioning, and open-label chronic dosing studies in human patients with fragile X syndrome (FXS) have demonstrated modest clinical improvements. Findings from blinded studies are mixed, and there is a limited understanding of electrophysiological target engagement that would facilitate cross-species translational studies. Smaller-scale, acute (e.g., single-dose) drug studies may speed treatment identification by detecting subtle electrophysiological and behavioral changes. <b><i>Materials and Methods:</i></b> Twenty-nine participants with FXS (31% female) ages 15-45 years completed a randomized, double-blind, crossover study in which they received a single oral dose of 40 mg of lovastatin, 270 mg of minocycline, or placebo, with a 2-week washout period between dosing visits. Participants completed a comprehensive neuropsychological battery and three EEG paradigms (resting state; auditory chirp; auditory habituation) before and 4 hours after dosing. <b><i>Results:</i></b> No serious adverse events were reported, and both drugs were well-tolerated. Compared with placebo, there were no overall treatment effects for any outcomes, including EEG, but several modest drug responses varied as a function of sex and age. Lovastatin treatment was associated with improved spatial awareness in older participants and females compared with minocycline and placebo. <b><i>Discussion:</i></b> We show that single-dose drug studies are highly feasible in FXS and that patients with FXS can complete a range of EEG and behavioral tasks, many of which have been shown to be reliable and may therefore be sensitive to subtle drug target engagement. <b><i>Conclusions:</i></b> Acute single doses of lovastatin or minocycline did not lead to changes in electrophysiological or performance-based measures. This may be due to the limited effects of these drugs in human patients or limited acute effects relative to chronic dosing. However, the study design was further validated for use in neurodevelopmental populations.</p>","PeriodicalId":15277,"journal":{"name":"Journal of child and adolescent psychopharmacology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800900","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}
Can Beser, Genevieve Davis, Megan O'Connell, Adam Ali
{"title":"Agitation Management in a 5-Year-Old Boy with X Chromosome-Linked Monoamine Oxidase-A and Monoamine Oxidase-B Deficiency.","authors":"Can Beser, Genevieve Davis, Megan O'Connell, Adam Ali","doi":"10.1089/cap.2024.0074","DOIUrl":"https://doi.org/10.1089/cap.2024.0074","url":null,"abstract":"","PeriodicalId":15277,"journal":{"name":"Journal of child and adolescent psychopharmacology","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780212","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}
William V Bobo, Katherine M Moore, Hannah K Betcher, Alyssa M Larish, Cynthis M Stoppel, Jennifer L VandeVoort, Mohit Chauhan, Arjun P Athreya, Ardesheer Talati
{"title":"The Association of Antidepressants in Late Pregnancy with Postpartum Hemorrhage: Systematic Review of Controlled Observational Studies.","authors":"William V Bobo, Katherine M Moore, Hannah K Betcher, Alyssa M Larish, Cynthis M Stoppel, Jennifer L VandeVoort, Mohit Chauhan, Arjun P Athreya, Ardesheer Talati","doi":"10.1089/cap.2024.0085","DOIUrl":"10.1089/cap.2024.0085","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Despite advances in obstetric care, postpartum hemorrhage (PPH) is a leading cause of maternal mortality worldwide. Prior reviews of studies published through 2016 suggest an association of antidepressant use during late pregnancy and increased risk of PPH. However, a causal link between prenatal antidepressants and PPH remains controversial. <b><i>Objectives:</i></b> This systematic literature review aimed to synthesize the empirical evidence on the association of antidepressant exposure in late pregnancy with the risk of PPH, including studies published before and after 2016. <b><i>Methods:</i></b> A systematic literature search was conducted using PubMed, OVID Medline, EMBASE, SCOPUS, PsycINFO, and CINAHL from inception to September 9, 2023. Original, peer-reviewed studies (published in English) that reported on the frequency or risk of PPH in women with evidence of antidepressant use during pregnancy and included at least one control group were included. <b><i>Results:</i></b> Twenty studies (eight published after 2016) met inclusion criteria, most of which focused on the risks of PPH associated with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). The main findings from the individual studies were mixed, but the majority documented statistically significant associations of PPH with late prenatal exposure, especially for exposures occurring within 30 days of delivery, compared with unexposed deliveries. Fourteen studies addressed underlying antidepressant indications or their correlates. Few studies focused on prenatal antidepressants and the risk of well-defined severe PPH or on antidepressant dose changes and general PPH risk. None examined competing risks of antidepressant discontinuation on mental health outcomes. <b><i>Conclusions:</i></b> Late pregnancy exposure to antidepressants may be a minor risk factor for PPH, but it is unclear to what extent reported associations are causal in nature, as opposed to correlational (effects related to nonpharmacological factors including maternal indication). For patients needing antidepressants during pregnancy, current evidence does not favor routinely discontinuing antidepressants specifically to reduce the risk of PPH.</p>","PeriodicalId":15277,"journal":{"name":"Journal of child and adolescent psychopharmacology","volume":" ","pages":"428-446"},"PeriodicalIF":1.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501147","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}
Jeffrey R Bishop, Chuan Zhou, Andrea Gaedigk, Beth Krone, Rick Kittles, Edwin H Cook, Jeffrey H Newcorn, Mark A Stein
{"title":"Dopamine Transporter and <i>CYP2D6</i> Gene Relationships with Attention-Deficit/Hyperactivity Disorder Treatment Response in the Methylphenidate and Atomoxetine Crossover Study.","authors":"Jeffrey R Bishop, Chuan Zhou, Andrea Gaedigk, Beth Krone, Rick Kittles, Edwin H Cook, Jeffrey H Newcorn, Mark A Stein","doi":"10.1089/cap.2024.0069","DOIUrl":"10.1089/cap.2024.0069","url":null,"abstract":"<p><p><b><i>Background:</i></b> Few biological or clinical predictors guide medication selection and/or dosing for attention-deficit/hyperactivity disorder (ADHD). Accumulating data suggest that genetic factors may contribute to clinically relevant pharmacodynamic (e.g., dopamine transporter-<i>SLC6A3</i> also commonly known as <i>DAT1</i>) or pharmacokinetic (e.g., the drug metabolizing enzyme Cytochrome P450 2D6 <i>CYP2D6</i>) effects of methylphenidate (stimulant) and atomoxetine (non-stimulant), which are commonly prescribed medications. This is the first study of youth with ADHD exposed to both medications examining the clinical relevance of genetic variation on treatment response. <b><i>Methods:</i></b> Genetic variations in <i>DAT1</i> and <i>CYP2D6</i> were examined to determine how they modified time relationships with changes in ADHD symptoms over a 4-week period in 199 youth participating in a double-blind crossover study following a stepped titration dose optimization protocol. <b><i>Results:</i></b> Our results identified trends in the modification effect from CYP2D6 phenotype and the time-response relationship between ADHD total symptoms for both medications (atomoxetine [ATX]: <i>p</i> = 0.058, Methylphenidate [MPH]: <i>p</i> = 0.044). There was also a trend for the <i>DAT1</i> 3' untranslated region (UTR) variable number of tandem repeat (VNTR) genotype to modify dose relationships with ADHD-RS total scores for atomoxetine (<i>p</i> = 0.029). Participants with <i>DAT1</i> 9/10 repeat genotypes had a more rapid dose-response to ATX compared to 10/10, while those with 9/9 genotypes did not respond as doses were increased. Regardless of genotype, ADHD symptoms and doses were similar across CYP2D6 metabolizer groups after 4 weeks of treatment. <b><i>Conclusions:</i></b> Most children with ADHD who were CYP2D6 normal metabolizers or had <i>DAT1</i> 10/10 or 9/10 genotypes responded well to both medications. While we observed some statistically significant effects of <i>CYP2D6</i> and <i>DAT1</i> with treatment response over time, our data indicate that genotyping for clinical purposes may have limited utility to guide treatment decisions for ATX or MPH because both medications were generally effective in the studied cohort after 3 weeks of titration to higher doses. The potential <i>DAT1</i> association with ATX treatment is a novel finding, consistent with prior reports suggesting an association of the <i>DAT1</i> in 9/9 genotypes with lower responsive rates to treatment at low and moderate doses.</p>","PeriodicalId":15277,"journal":{"name":"Journal of child and adolescent psychopharmacology","volume":" ","pages":"458-469"},"PeriodicalIF":1.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466420","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}