OBJECTIVE:Major changes in opioid prescribing have created a need to understand long-term patterns of medical prescription opioid use and its associations with substance-related consequences. This study aimed to identify trajectories of medical use of prescription opioids during middle adulthood (ages 35-60) and examine associations of such trajectories with nonmedical prescription opioid use and substance use disorder symptoms. METHODS:Twenty-seven cohorts of 31,094 adults were followed longitudinally via self-administered surveys during midlife. Latent profile analysis was used to create trajectory profiles based on frequency of medical prescription opioid use between ages 35 and 60. RESULTS:An estimated 37.3% of adults reported at least one episode of medical prescription opioid use during midlife, and four trajectories were identified: infrequent use (27.1% of all adults); multiple peaks at ages 35, 45, and 60 (3.7%); multiple peaks at ages 40 and 55 (2.9%); and frequent use at all ages (3.7%). The prevalence and adjusted odds ratio (AOR) of experiencing multiple substance use disorder symptoms were significantly higher among adults with frequent use at all ages (60.5%, AOR=2.1); multiple peaks at ages 35, 45, and 60 (51.1%, AOR=1.7); multiple peaks at ages 40 and 55 (48.9%, AOR=1.5); and infrequent use (41.1%, AOR=1.4), relative to a population control group. CONCLUSIONS:Most adults with frequent long-term medical use of prescription opioids reported multiple substance use disorder symptoms. Screening for nonmedical use and substance use disorders before prescribing opioids and ongoing monitoring for substance use disorders are critical, particularly among adults requiring frequent or long-term recurrent medical use of prescription opioids.

Background: To examine the persistence of substance use disorder (SUD) symptoms and medical use of prescription benzodiazepines and opioids in midlife (ages 40-55) as a function of SUD symptom severity at age 35. Methods: Multiple national cohorts of US adults were followed longitudinally from ages 35 to 55 in the Monitoring the Future Longitudinal Panel study. The prevalence of multiple SUD symptoms (ie, two or more SUD symptoms) and medical use of prescription benzodiazepines and opioids at ages 40-55 as a function of SUD symptom severity (0, 1, 2-3, 4-5, 6+ symptoms) at age 35 were estimated. Multivariable logistic regression models assessed the longitudinal associations between SUD symptom severity at age 35 and the odds of multiple SUD symptoms and medical use of prescription benzodiazepines and opioids at ages 40-55 using Generalized Estimating Equations analyses, controlling for relevant covariates. Outcomes: Among adults with severe SUD symptoms at age 35 (≥6 symptoms), over 80% had persistent multiple SUD symptoms and half (50%) reported medical use of prescription benzodiazepines or opioids in midlife (ie, at ages 40-55). The prevalence and adjusted odds of multiple SUD symptoms and medical use of prescription benzodiazepines or opioids at ages 40-55 increased in a stepwise fashion based on SUD symptom severity at age 35. Interpretations: Screening for SUD symptom severity is needed in midlife given the high persistence of multiple SUD symptoms. More attention is warranted to assess the balance of benefits and harms of prescribing benzodiazepines and opioids in adults with persistent and severe SUD symptom profiles.

OBJECTIVE:The objective of these analyses was to evaluate the efficacy of centanafadine for treatment of attention-deficit/hyperactivity disorder (ADHD) associated features of executive functioning and learning problems measured over 6 weeks in children and adolescents with ADHD. METHODS:Two phase 3, randomized, double-blind, placebo-controlled trials were conducted in children and adolescents with a primary diagnosis of ADHD at sites in the United States and Canada. Data presented here are from the total population of children aged 6-12 years (NCT05428033) or adolescents aged 13-17 years (NCT05257265) who received high-dose centanafadine or placebo for 6 weeks. Secondary and other efficacy endpoints assessed change from baseline in the Conners 3-Parent Short Executive Functioning and Learning Problems Content Scale T-scores and the Conners 3-Self-report Short Learning Problems Content Scale T-scores, all analyzed using a mixed-effect model for repeated measures. Clinically meaningful within-patient change and findings from a caregiver and/or adolescent self-report exit survey are also presented. RESULTS:Overall, 76.5% (367/480) of children (mean age 9.2 years, 41.7% female) and 80.8% (371/459) of adolescents (mean age 14.7 years, 40.7% female) completed their respective studies. There were clinically significant improvements with centanafadine treatment observed as early as Week 1 in the Conners 3-Parent Short Executive Functioning (T-score least squares mean change from baseline [standard error] to Week 6: children, -6.8 [1.1] vs. -11.3 [1.1], p = 0.0026 and adolescents, -8.1 [1.0] vs. -13.0 [1.0], p = 0.0003) and Learning Problems content scale T-scores when compared to placebo (children, -8.2 [1.0] vs. -2.8 [0.9], p < 0.0001 and adolescents, -8.0 [0.9] vs. -3.1 [0.9], p < 0.0001). Similar changes from baseline were observed by adolescent self-report (-6.1 [0.9] vs. -2.5 [0.9], p = 0.0023). Compared to placebo, there was a 50% and 88% greater chance of experiencing clinically meaningful within-patient change in executive functioning for children and adolescents, respectively, and a 79% and 81% chance for experiencing clinically meaningful within-patient change in learning problems, respectively. Exit survey data support findings from clinical outcome measures. CONCLUSIONS:In addition to its impact on the core symptoms of ADHD, centanafadine improved executive functioning, learning problems, and impact on daily tasks in children and adolescents with ADHD.

OBJECTIVES:To assess associations between symptomatic polysubstance use and symptom severity during adolescence and later substance use disorder (SUD) symptoms in midlife. METHODS:Multi-cohorts of nationally representative US adolescents in 12th grade (N=12,025; baseline cohort years 1976-2002) were followed longitudinally to age 55 (follow-up years 1993-2019). Poisson regression models were fitted longitudinally, accounting for repeated measures, panel attrition, and covariates. RESULTS:An estimated 8.9% (95% CI=8.3%-9.5%) of US adolescents had moderate-to-severe SUD symptoms involving multiple substances (ie, 4+ SUD symptoms for 2+ substances). The bivariate and multivariate relationships between SUD symptom severity and multiple SUDs at baseline and subsequent SUD symptoms in midlife (ages 35-55) indicated a positive near-linear association. Over two-thirds of adolescents with moderate-to-severe SUD symptoms involving multiple substances had multiple SUD symptoms in midlife (68.6%, 95% CI=63.0%-73.7%). Most adolescents with moderate-to-severe SUD symptoms of one substance and those with fewer SUD symptoms involving multiple substances (ie, 1-3 SUD symptoms for 2+ substances) persisted with multiple SUD symptoms in midlife (57.2%, 95% CI=53.2%-61.0% and 56.4%, 95% CI=51.4%-61.4%, respectively). Adolescents with moderate-to-severe SUD symptoms involving multiple substances had substantially greater odds of SUD symptoms in midlife relative to asymptomatic adolescents (aRR=2.80, 95% CI=2.49-3.15). CONCLUSIONS:Most US adolescents with symptomatic polysubstance use or moderate-to-severe SUD symptoms persisted with multiple SUD symptoms in midlife. Adolescent symptomatic polysubstance use is associated with a more severe developmental course in midlife than those with the same SUD symptom burden concentrated within a single substance, therefore, early comprehensive screening and intervention strategies are needed.

Objectives: This study examined sociodemographic and clinical factors associated with attention-deficit/hyperactivity disorder (ADHD) pharmacotherapy receipt in youth and adults with co-occurring ADHD and substance use disorder (SUD). Methods: This retrospective cohort study analyzed the TriNetX US Collaborative Network (2008–2025). Among 2,219,248 patients aged 15–65 with ADHD, 529,550 had co-occurring SUD. ADHD medication prescribing was assessed within one year of diagnosis and stratified by sociodemographic variables and SUD type. Propensity score matching was used for relative risk analyses; Cox proportional hazards models identified predictors of medication receipt. Results: Patients with ADHD and SUD were older and had more psychiatric comorbidities than those with ADHD only. CNS stimulants were prescribed less frequently in patients with SUD than in those without—amphetamines (RR: 0.73, 95% CI: 0.73–0.73) and methylphenidate (RR: 0.62, 95% CI: 0.62–0.63)—and this pattern persisted across subgroups. Nonstimulant prescribing was less affected, with higher rates among adolescents and those with stimulant, opioid, or cocaine-use disorders. Black patients experienced nearly double the SUD-associated reduction in stimulant prescribing compared with white patients. Psychotic disorders were associated with a lower hazard of receiving both medication classes, anxiety disorders with a higher hazard of either class, and mood disorders with a lower stimulant but higher nonstimulant hazard. Conclusions: Concurrent SUD was associated with lower CNS stimulant prescribing across sociodemographic and clinical factors, with disproportionate reductions among minoritized patients and those with psychiatric comorbidities, while nonstimulant prescribing was comparatively less affected. These findings underscore the need for guideline updates and structural reforms to promote equitable treatment.

Research in child and adolescent mental health stands at an inflection point: the burden of psychiatric illness is global, heterogeneous, and dynamic, whereas our evidence base often remains limited and insufficiently responsive to patient needs. To meaningfully improve outcomes for youth and families globally and at scale, innovation in child and adolescent mental health research must extend beyond developing new treatments to encompass how we design, measure, and disseminate research. Continued innovation is essential to build on the existing corpus of knowledge and to ensure that research keeps pace with real-world clinical and public health priorities.

OBJECTIVE:The authors sought to determine 1) whether receiving an initial stimulant prescription for attention deficit hyperactivity disorder (ADHD) from a provider whom a patient has never seen in person is associated with increased risk for stimulant use disorder (stimUD) or other substance use disorders (SUDs), and 2) whether receiving an initial stimulant prescription during a telehealth versus in-person appointment is associated with increased risk for stimUD or SUD. METHODS:This was a retrospective cohort study using electronic health record data from March 1, 2020, to August 25, 2023, from a not-for-profit, academically affiliated medical system in the Northeastern United States. Eligible study subjects were ≥12 years old with ADHD and initial receipt of any stimulant prescription during the study period. Exclusion criteria included a non-nicotine SUD diagnosis at the time of initial stimulant prescription. RESULTS:The sample included 7,944 patients. After adjustment for covariates, a purely telehealth-based relationship versus any in-person relationship did not significantly alter risk for SUD (adjusted odds ratio=0.85, 95% CI=0.60, 1.20) or stimUD (adjusted odds ratio=1.28, 95% CI=0.34, 4.85). A telehealth versus in-person appointment at the time of the initial stimulant prescription did not significantly alter risk for subsequent SUD (adjusted odds ratio=1.15, 95% CI=0.92, 1.44) but was associated with significantly higher risk for stimUD (adjusted odds ratio=6.18, 95% CI=1.34, 28.46). CONCLUSIONS:The results suggest that receipt of a stimulant prescription for ADHD via telehealth does not alter the risk for SUD, but receipt of an initial stimulant prescription via telehealth may signal increased risk of subsequent stimUD. The results, particularly for stimUD, require replication in other health care settings.

Introduction: Screening for unhealthy alcohol and drug use is recommended in primary care, and effective implementation requires understanding patients’ perspectives. Failure to identify and address potential differences in attitudes toward screening across demographic groups may result in care gaps, but research examining this is limited. Methods: We surveyed 977 adult patients in 9 primary care clinics that participated in a screening implementation study. The survey collected demographics and attitudes toward screening/discussion of alcohol/drug use in primary care. We described responses overall and compared across age, gender, race, and ethnicity using Chi-square/Fisher’s exact tests. Results: Mean age was 51.1 years, and the sample was 39% male, 61% female, 72% White non-Hispanic, 11% Hispanic, 10% Black non-Hispanic, and 6% other/unknown race non-Hispanic. Most participants across all demographic groups reported supportive attitudes. Comfort reporting drug use was lower among young, male, Black non-Hispanic, and Hispanic patients, and comfort with screening overall was lower among middle-aged, Black non-Hispanic, and Hispanic patients. Conclusions: Results suggest that screening/discussion of alcohol/drug use in primary care is generally highly acceptable to patients across demographic groups. Strategies are needed to increase comfort and alleviate concerns about how medical information will be used, particularly among middle-aged, Black, and Hispanic patients.

Background:Understanding attention deficit/hyperactivity disorder (ADHD) medication patterns is crucial for optimizing treatment outcomes. There are limited data on racial, ethnic, gender and socioeconomic treatment differences across longitudinal national samples. Methods:Secondary data analysis of baseline through 3rd-year follow-up (2016-2020) data from the Adolescent Brain Cognitive Development Study (ABCD) (N = 11,875). Data were collected from 21 US sites, to reflect national demographic diversity. Complete case panel included 9708 children aged 9/10 at baseline and 12/13 at 3rd-year follow up. Sociodemographic factors (sex, race, ethnicity, household income), ADHD medication use (stimulants and non-stimulants), and ADHD severity were examined. Results:By the 3rd-year follow-up, 13% of children used ADHD medications. Females were more likely to never have received medications compared to males (92% vs. 82%, odds ratio [OR] 2.34, 95% confidence interval [CI] 2.05-2.67, p < 0.001). Females exhibited lower mean ADHD severity scores, though the difference diminished over time. Asian (95% vs. 87%, OR 2.83, 95% CI 1.41-5.38, p < 0.001) and Hispanic children (90% vs. 86%, OR 1.39, 95% CI 1.17-1.64, p < 0.001) were more likely to have never received medications compared to White and non-Hispanic children. Black children were more likely to discontinue medications (9% vs. 5%, OR 1.84, 95% CI 1.45-2.33, p < 0.001) compared to White children, although this was not significant after adjusting for sociodemographic factors. Children in lower income households were more likely to have clinically significant ADHD but less likely to receive and remain on medications compared to those from higher income households. Conclusions:Significant differences exist in ADHD medication use patterns among US children based on sex, race, ethnicity, and socioeconomic status. Addressing these differences is essential to ensure equitable access to treatment.

INTRODUCTION:Overdose deaths disproportionately increased among adolescents and young adults (AYA) between 2019 and 2022, despite declining substance use. We examined the prevalence of nonfatal overdose and characteristics associated with overdose history in AYA. METHODS:AYA enrolled between 2020 and 2023 in five opioid use disorder prevention studies in child welfare, healthcare, and legal settings from six states were included in this analysis. Nonfatal overdose history, demographic, and clinical characteristics were assessed at baseline. Across studies, overdose history was assessed with slight variations in wording, but most other measures were standardized. Odds ratios (OR) of lifetime overdose were calculated with logistic regression for each risk factor with demographic control variables (age, sex, race) included as covariates, and reported separately by sample. RESULTS:Sample sizes ranged from 137 to 929 (total N = 1856). Characteristics across samples ranged from M = 16.2-26.4 years for age, and 11.7-91.9 % for female sex. For race, samples ranged from 35 % to 89.4 % White and 17.3-89.4 % Black. History of nonfatal overdose ranged from 6.6 % to 41.4 %. Statistically significant characteristics associated with overdose history in all samples included history of opioid misuse (ORs ranging from 1.98 to 6.73) and family members with a substance use problem (ORs range from 1.27 to 2.05). Frequent and early onset alcohol and cannabis use was also associated with overdose history in several samples. CONCLUSIONS:Overdose prevention interventions for AYA should include a focus on AYA who misuse opioids and families with a history of substance use problems.

Measurement-based care (MBC) is an evidence-based practice that can improve the identification of co-occurring mental health conditions and substance use disorders, as well as population differences in care in lower resource settings, through ongoing monitoring of patient-reported symptoms. The current study examined, as reported by different stakeholders prior to implementation, barriers and facilitators of implementing screening tools to monitor mental health and substance use symptoms in the outpatient behavioral health setting at a safety-net hospital. A purposeful sampling approach was used to recruit stakeholders from two outpatient clinics (child, adult) to participate in individual interviews (clinic leadership) and stakeholder-specific focus groups (clinicians and administrative staff). De-identified transcripts were coded using a directed content analytic approach guided by constructs from the Consolidated Framework for Implementation Research (CFIR). A total of 14 clinicians, 6 clinic leaders, and 4 administrative staff participated in interviews and focus groups. Results indicate stakeholder agreement on specific implementation constructs (e.g., patient needs, networks and communication) and unique perspectives influenced by the stakeholders’ day-to-day responsibilities. However, there were inconsistent responses regarding networks and communication across stakeholder groups. Clinicians only identified barriers, clinic leadership only identified facilitators, and administrative staff did not identify communication as a barrier or facilitator. Thus, when implementing MBC within a safety-net behavioral health clinic setting, cohesive communication may be perceived differently by clinicians, clinic leadership, and administrative staff and should be validated across staff roles.

Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with substance use disorder (SUD), particularly in transitional-age youth, presenting complex diagnostic and therapeutic challenges. ADHD increases the risk of developing a SUD through multiple pathways, including biological, psycho-social, and familial or genetic factors. The presence of SUD can exacerbate ADHD symptoms and reduce treatment adherence, creating a reinforcing cycle of impairment. Early and sustained ADHD treatment has been associated with reduced SUD risk and improved treatment retention. Accurate diagnosis requires comprehensive evaluation strategies that account for symptom overlap and comorbidities. Long-acting or prodrug stimulant formulations, non-stimulant pharmacotherapies, and integrated psychosocial interventions, including motivational interviewing and cognitive-behavioral therapy, play vital roles in management. Clinicians must balance the need for symptom control with diversion concerns related to central nervous system stimulants through patient education, careful medication selection, limiting or monitoring supply of medication, and secure storage recommendations. An integrated, multi-modal approach can improve outcomes and mitigate long-term risks associated with both ADHD and SUD.