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Sharon B Wigal,1 Tim Wigal,1 Mary Hobart,2 Jessica J Madera,3 Ross A Baker,3 Eva Kohegyi,3 Anthony McKinney,4 Timothy E Wilens5 1AVIDA Inc., Newport Beach, California, USA; 2Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, Maryland, USA; 3Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, New Jersey, USA; 4Ethismos Research, Inc, Cambridge, Massachusetts, USA; 5Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USACorrespondence: Timothy E WilensDivision of Child and Adolescent Psychiatry, Center for Addiction Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USATel +1 617-643-3481Fax +1 617-724-3742Email twilens@mgh.harvard.eduPurpose: Two phase 2 studies evaluated the efficacy and tolerability of centanafadine sustained-release (SR) for adults with attention-deficit/hyperactivity disorder (ADHD).Patients and Methods: In a phase 2a, flexible-dose, single-blind study, 41 male patients (aged 18‒55 years) with a diagnosis of ADHD (based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) were titrated with centanafadine-SR 200‒300, 400, or 500 mg/d for 2 weeks, and then were treated with the titrated dose for 2 weeks. In a phase 2b, randomized, double-blind, placebo-controlled, crossover study, 85 male and female patients (aged 18‒60 years) with a diagnosis of ADHD (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) were titrated to target doses of centanafadine-SR 400, 500, 600, or 800 mg/d over the course of 1 week, and then received their titrated dose for 3 weeks. The primary outcome in both studies was mean total ADHD Rating Scale-IV (ADHD-RS-IV) score.Results: In the phase 2a study, mean ADHD-RS-IV total score decreased by 21.41 (standard deviation 10.74) from the start of active centanafadine-SR treatment to the end of week 4 (P< 0.001). In the phase 2b study, centanafadine-SR treatment resulted in a statistically significant improvement in ADHD-RS-IV from baseline to week 3 compared with placebo (least-squares mean − 16.5 vs − 8.4; P< 0.001; effect size 0.66), with significant efficacy demonstrated as early as week 1. Centanafadine-SR was generally well tolerated at doses ≤ 400 mg. Most treatment-emergent adverse events (TEAEs) were mild or moderate; decreased appetite, headache, and nausea were the most frequently reported. In the 2 studies, 13 of 120 patients discontinued centanafadine-SR due to TEAEs; however, only 1 patient who received ≤ 400 mg discontinued due to a TEAE. No serious TEAEs were reported at any dose.Conclusion: These results support the continued development of centanafadine-SR at doses up to 400 mg/d.Keywords: ADHD Rating Scale-IV, efficacy, norepinephrine-dopamine-serotonin reuptake inhibitor, tolerability

Background: Attention-deficit/hyperactivity disorder (ADHD) and substance use disorder are often comorbid in adults. The effects of ADHD treatment on comorbid alcohol use disorder have not been extensively studied.Objective: To assess correlates of ADHD and alcohol use outcomes in ADHD with comorbid alcohol use disorders, via a post-hoc exploratory subgroup analysis of a previously conducted, randomized, double-blind, placebo-controlled study of recently abstinent adults.Methods: Adults who had ADHD and alcohol use disorders and were abstinent for 4-30 days were randomized to daily atomoxetine 25-100 mg (mean final dose = 89.9 mg) or placebo for 12 weeks. Changes in ADHD symptoms from baseline to endpoint were assessed using the ADHD Investigator Symptom Rating Scale (AISRS) total score, alcohol use by the timeline followback method, and alcohol cravings by the Obsessive Compulsive Drinking Scale.Results: Of 147 subjects receiving atomoxetine (n = 72) or placebo (n = 75) in the primary study, 80 (54%) completed 12 weeks (n = 32 atomoxetine; n = 48 placebo). Improvements in ADHD symptoms on the AISRS correlated significantly with decreases in alcohol cravings (Pearson's r = 0.28; 95% confidence interval [CI] = 0.11-0.43; p = 0.002), and the correlation was most notable with atomoxetine (r = 0.29; CI [0.04 - 0.51]; p = 0.023) rather than with placebo (r = 0.24; CI [0.00-0.46]; p = 0.055). On-treatment drinking levels correlated with AISRS scores (r = 0.12; CI [0.05 -0.19]; p = 0.001). Relapse to alcohol abuse significantly correlated with worse ADHD symptoms on 15 of 18 items of the AISRS in the placebo group (p < 0.05 for each).Conclusions: No baseline predictor (other than degree of sobriety) of alcohol use or ADHD outcomes emerged. ADHD symptom improvements correlated significantly with reductions in alcohol cravings, and relapse to alcohol abuse correlated significantly with worsening of most ADHD symptoms in the placebo group, but not in the atomoxetine group. This post-hoc subgroup analysis is of a hypothesis-generating nature, and the generalizability of the findings may be limited by exclusion of adults with common ADHD comorbidities from the base study. Further, prospective clinical trials in larger and more heterogeneous patient populations are warranted to confirm or reject these preliminary associations. TRIAL REGISTRATION (BASE STUDY): ClinicalTrials.gov identifier: NCT00190957. [ABSTRACT FROM AUTHOR]

Objective: High rates of substance-use disorders (SUD) have been found in samples of adolescents and adults with attention-deficit/hyperactivity disorder (ADHD). Predictors of SUD in children with ADHD who are at risk for the development of SUDs remain understudied. The main aims of this study were to identify clinically meaningful characteristics of children that predicted the future development of SUDs and to see whether the role of these characteristics varied by sex.Method: Subjects were children and adolescents with (n = 268; mean age ± standard deviation = 10.9 ± 3.2 years) and without (n = 229; mean age 11.9 ± 3.3 years) DSM-III-R ADHD followed prospectively and blindly over a 10-year follow-up period onto young adult years. Subjects were assessed with structured diagnostic interviews for psychopathology and SUDs.Results: Over the 10-year follow-up period, ADHD was found to be a significant predictor of any SUD (hazards ratio 1.47; 95% confidence interval 1.07-2.02; p = .01) and cigarette smoking (2.38; 1.61-3.53; p < .01). Within ADHD, comorbid conduct disorder (2.74; 1.66-4.52; p < .01) and oppositional defiant disorder (2.21; 1.40-3.51; p < .01) at baseline were also found to be significant predictors of SUDs. Similar results were found for cigarette-, alcohol-, and drug-use disorders. There were few meaningful sex interaction effects. No clinically significant associations were found for any social or family environment factors or for cognitive functioning factors (p > .05 for all comparisons).Conclusions: These results indicate that ADHD is a significant risk factor for the development of SUDs and cigarette smoking in both sexes. [ABSTRACT FROM AUTHOR]

Our objective was to compare scores on a smoking questionnaire to a diagnosis of cigarette smoking. As part of follow-ups in studies of ADHD, we assessed for cigarette smoking using structured interviews and the modified Fagerstrom Tolerance Questionnaire (mFTQ). Data were obtained from 162 subjects (mean = 19.2 yrs). ROC analysis and kappa coefficients revealed that a cutoff score of 3 on the mFTQ showed the strongest agreement with a full diagnosis of cigarette smoking (kappa = 0.68). Clinicians and researchers using the mFTQ in adolescents and young adults should consider a cutoff score of 3 to be indicative of cigarette smoking. [ABSTRACT FROM AUTHOR]

Objective: Children with attention-deficit/hyperactivity disorder often have varying needs for coverage of their symptoms throughout the day. The objectives of this study were to determine the efficacy, duration of action, and safety of methylphenidate transdermal system worn for variable times by children (ages 6-12) diagnosed with ADHD.Method: Methylphenidate dose was optimized over 5 weeks using 10-, 15-, 20-, or 30-mg patches worn for 9 hours. The efficacy of 4- and 6-hour wear times was then assessed in an Analog Classroom setting during a randomized, placebo-controlled, double-blind, three-way crossover phase. The main efficacy measures were the Swanson, Kotkin, Agler, M-Flynn, and Pelham Rating Scale deportment scale and the Permanent Product Measure of Performance math test.Results: All of the efficacy measures indicated that 4- and 6-hour wear times improved ADHD symptoms and that medication effects on the Swanson, Kotkin, Agler, M-Flynn, and Pelham Rating Scale deportment scale and Permanent Product Measure of Performance math test decreased between 2 and 4 hours after patch removal. The majority of adverse events were transient and mild to moderate in severity.Conclusions: These findings suggest that the duration of medication effect is related to the wear time of the patch and may be tailored to accommodate the schedules of patients. [ABSTRACT FROM AUTHOR]

ABSTRACT BACKGROUND: Studies of adults with attention deficit hyperactivity disorder (ADHD) show an elevated prevalence of substance use disorders (SUDs) and the substance abuse literature shows that ADHD is elevated in substance users. Some researchers postulate that stimulant treatment of ADHD increases the risk for SUD in ADHD patients but follow-up studies suggest treatment protects patients from subsequent SUDs. This report uses retrospective data to assess the impact of prior ADHD pharmacotherapy on SUDs in 206 ADHD adults (n=79 late-onset ADHD, n=127 full ADHD) grouped by lifetime history of ADHD treatment (no treatment, past treatment, current and past treatment).MethodStructured Clinical Interview for DSM-IV (SCID) data were used to establish abuse and dependence, and Drug Use Screening Inventory (DUSI) responses were used to establish prevalence of use, preference for cigarettes, alcohol and drugs of abuse, complications from use, and motivation for use (get high, change mood, sleep better). RESULTS: No differences were found in the prevalence of cigarette smoking, alcohol or drug abuse or dependence, as well as no significant differences in 1-month prevalence of any use or use more than 20 times. No differences were found in complications of drug or alcohol use across groups. Subjects with current treatment rated getting high as a motivating factor significantly more frequently than subjects in the past treatment group; this result lost significance when we included ADHD diagnostic category. CONCLUSIONS: Our results are consistent across substances and ADHD diagnoses, and support the hypothesis that pharmacotherapy does not cause subsequent SUDs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Our objective was to estimate the lifetime prevalence of psychopathology in a sample of youth with and without attention deficit hyperactivity disorder (ADHD) through young adulthood using contemporaneous diagnostic and analytic techniques. METHOD: We conducted a case-control, 10-year prospective study of ADHD youth. At baseline, we assessed consecutively referred male, Caucasian children with (n=140) and without (n=120) DSM-III-R ADHD, aged 6-18 years, ascertained from psychiatric and pediatric sources to allow for generalizability of results. At the 10-year follow-up, 112 (80%) and 105 (88%) of the ADHD and control children, respectively, were reassessed (mean age 22 years). We created the following categories of psychiatric disorders: Major Psychopathology (mood disorders and psychosis), Anxiety Disorders, Antisocial Disorders (conduct, oppositional-defiant, and antisocial personality disorder), Developmental Disorders (elimination, language, and tics disorder), and Substance Dependence Disorders (alcohol, drug, and nicotine dependence), as measured by blinded structured diagnostic interview. RESULTS: The lifetime prevalence for all categories of psychopathology were significantly greater in ADHD young adults compared to controls, with hazard ratios and 95% confidence intervals of 6.1 (3.5-10.7), 2.2 (1.5-3.2), 5.9 (3.9-8.8), 2.5 (1.7-3.6), and 2.0 (1.3-3.0), respectively, for the categories described above. CONCLUSIONS: By their young adult years, ADHD youth were at high risk for a wide range of adverse psychiatric outcomes including markedly elevated rates of antisocial, addictive, mood and anxiety disorders. These prospective findings provide further evidence for the high morbidity associated with ADHD across the life-cycle and stress the importance of early recognition of this disorder for prevention and intervention strategies. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Concerns exist that stimulant therapy of youths with attention-deficit/hyperactivity disorder (ADHD) may result in an increased risk for subsequent substance use disorders (SUD). We investigated all long-term studies in which pharmacologically treated and untreated youths with ADHD were examined for later SUD outcomes. METHODS: A search of all available prospective and retrospective studies of children, adolescents, and adults with ADHD that had information relating childhood exposure to stimulant therapy and later SUD outcome in adolescence or adulthood was conducted through PubMed supplemented with data from scientific presentations. Meta-analysis was used to evaluate the relationship between stimulant therapy and subsequent SUD in youths with ADHD in general while addressing specifically differential effects on alcohol use disorders or drug use disorders and the potential effects of covariates. RESULTS: Six studies--2 with follow-up in adolescence and 4 in young adulthood--were included and comprised 674 medicated subjects and 360 unmedicated subjects who were followed at least 4 years. The pooled estimate of the odds ratio indicated a 1.9-fold reduction in risk for SUD in youths who were treated with stimulants compared with youths who did not receive pharmacotherapy for ADHD (z = 2.1; 95% confidence interval for odds ratio [OR]: 1.1-3.6). We found similar reductions in risk for later drug and alcohol use disorders (z = 1.1). Studies that reported follow-up into adolescence showed a greater protective effect on the development of SUD (OR: 5.8) than studies that followed subjects into adulthood (OR: 1.4). Additional analyses showed that the results could not be accounted for by any single study or by publication bias. CONCLUSION: Our results suggest that stimulant therapy in childhood is associated with a reduction in the risk for subsequent drug and alcohol use disorders. [ABSTRACT FROM AUTHOR]

Objective: To assess the safety and efficacy of ABT-089, a novel α(4)β(2) neuronal nicotinic receptor partial agonist, vs. placebo in children with attention-deficit/hyperactivity disorder (ADHD).Method: Two multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of children 6 through 12 years of age were conducted. Study 1 (n = 274) assessed six treatment groups over 8 weeks: 4 once-daily (QD) ABT-089 doses (0.085-0.700 mg/kg), QD atomoxetine, and placebo. Study 2 (n = 119) assessed three treatment groups over 6 weeks: 2 QD ABT-089 doses (0.7 mg/kg, 1.4 mg/kg) and placebo. The primary efficacy variable was the investigator-administered Attention-Deficit/Hyperactivity Disorder Rating Scale-IV: Home Version (ADHD-RS-IV [HV]) Total Score. Safety was assessed by adverse event (AE) monitoring, laboratory tests, vital signs, physical examinations, and electrocardiogram measures.Results: There was no statistically significant difference between ABT-089 and placebo in mean change from baseline to final evaluation of ADHD-RS-IV (HV) Total Score or other outcome measures at any dose in either study. In Study 1, atomoxetine showed statistically significant improvement for the primary and most secondary endpoints. ABT-089 was generally safe and well tolerated, with no statistically significant difference between any ABT-089 dose and placebo in the overall incidence of any specific AE, and no clinically significant changes in other safety measures.Conclusions: ABT-089 did not show efficacy on the primary efficacy variable, the ADHD-RS-IV (HV) Total Score, or other measures of ADHD symptomatology in children with ADHD, and had a safety profile similar to placebo. These results contrast with published reports of efficacy of nicotinic modulators in adults with ADHD. [ABSTRACT FROM AUTHOR]

OBJECTIVES. Patients receiving methylphenidate for the management of attention-deficit/hyperactivity disorder are recommended to receive periodic hematologic monitoring. The objective of this study was to evaluate the long-term effects of methylphenidate treatment on blood biochemistry and hematologic values. METHODS. This study involved a detailed analysis of changes in hematologic and blood biochemistry values over the course of a 2-year study of once-daily OROS methylphenidate in otherwise healthy children aged 6 to 13 years with attention-deficit/hyperactivity disorder. Routine hematologic and blood biochemistry assessments were performed at baseline, at 6 and 12 months during study treatment, and at the end of the study. RESULTS. Of the 407 subjects enrolled in the study, 289 completed year 1, and 229 completed 21 of 24 months. No subject was excluded from entry into the study or discontinued from the study because of abnormalities of any of the blood chemistries evaluated. There were no clinically significant changes from baseline in mean values for hematologic or blood biochemistry parameters. For most values, the mean change in value over the course of the study was <5%. CONCLUSIONS. These longer-term data suggest that chronic therapy with OROS methylphenidate has no clinically significant impact on laboratory values, challenging the necessity of routine hematologic monitoring in otherwise healthy children with attention-deficit/hyperactivity disorder who are treated with methylphenidate. [ABSTRACT FROM AUTHOR]

Objective: Genes likely play a substantial role in the etiology of attention-deficit/hyperactivity disorder (ADHD). However, the genetic architecture of the disorder is unknown, and prior genome-wide association studies (GWAS) have not identified a genome-wide significant association. We have conducted a third, independent, multisite GWAS of DSM-IV-TR ADHD.Method: Families were ascertained at Massachusetts General Hospital (MGH; N = 309 trios), Washington University at St. Louis (WASH-U; N = 272 trios), and University of California at Los Angeles (UCLA; N = 156 trios). Genotyping was conducted with the Illumina Human1M or Human1M-Duo BeadChip platforms. After applying quality control filters, association with ADHD was tested with 835,136 SNPs in 735 DSM-IV ADHD trios from 732 families.Results: Our smallest p value (6.7E-07) did not reach the threshold for genome-wide statistical significance (5.0E-08), but one of the 20 most significant associations was located in a candidate gene of interest for ADHD (SLC9A9, rs9810857, p = 6.4E-6). We also conducted gene-based tests of candidate genes identified in the literature and found additional evidence of association with SLC9A9.Conclusions: We and our colleagues in the Psychiatric GWAS Consortium are working to pool together GWAS samples to establish the large data sets needed to follow-up on these results and to identify genes for ADHD and other disorders. [ABSTRACT FROM AUTHOR]

Psychostimulant misuse and use disorders are major drivers of morbidity and fatal overdose in the United States, but little is known about how differences in psychostimulant use patterns relate to Diagnostic and Statistical Manual, Diagnostic and Statistical Manual of Mental Disorders, 4th edition and Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) stimulant substance use disorder (SUD) profiles. We used nationally representative U.S. data to assess the links between polystimulant use patterns and stimulant SUD prevalence, symptom counts, and DSM-5 stimulant SUD severity. Data were from the 2015-2019 and 2020 National Survey on Drug Use and Health. Participants ( n = 282,786) were grouped by past-year psychostimulant use patterns: (a) nonmedical use of prescription stimulants (NUPS) only; (b) cocaine-only; (c) methamphetamine-only; and (d) polystimulant use. Analyses comparing groups used logistic regressions for prevalence of past-year Diagnostic and Statistical Manual of Mental Disorders, 4th edition (2015-2019 and 2020) and DSM-5 (2020 only) stimulant SUD, negative binomial regressions for stimulant SUD symptom counts, and multinomial regressions for DSM-5 stimulant SUD severity. Those with past-year methamphetamine-only or polystimulant use had significantly higher Diagnostic and Statistical Manual of Mental Disorders, 4th edition and DSM-5 prevalence rates, symptom counts, and DSM-5 severities of stimulant SUD than those with NUPS or cocaine use only. Depending on Diagnostic and Statistical Manual of Mental Disorders version, 34%-47% of those engaged in polystimulant use and 48%-54% of those with methamphetamine use only met criteria for a stimulant SUD, versus 9%-17% for NUPS-only and 16%-24% for cocaine-only. For 2020, roughly two thirds of those with methamphetamine-only use had stimulant SUD symptoms. Individuals with methamphetamine and/or polystimulant use may have different service needs than those with NUPS or cocaine use only. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Competing Interests: Conflicts of Interest: Dr. Timothy Wilens has received research funding from the National Institutes of Health through the HEAL Initiative under award number 1UG3DA050252-01 and 4UH3DA050252-02 and the Food and Drug Administration. Dr. Wilens works as a clinical consultant f or the Gavin Foundation, Bay Cove Human Services, and US Minor and Major League for Baseball. He has licensing and/or intellectual property agreements with Ironshore and White Rhino/3D Therapy LLC. Dr. James O’Connell works as a medical director for the Gavin Foundation and Bay Cove Human Services. At the time of protocol development and implementation, Adam Taylor and Lia Beltrame were employees of Bay Cove Human Services. Ronan Wilson does not have any conflicts of interest to report and is an employee of Massachusetts General Hospital.

Objective: Dramatic changes in state-level cannabis laws (CL) over the past 25 years have shifted societal beliefs throughout the United States, with unknown implications for youth. In the present study, we conducted an updated systematic review and meta-analysis examining estimated effects of medical cannabis legalization (MCL) and recreational cannabis legalization (RCL) on past-month cannabis use among US youth., Method: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, followed by a subsequent meta-analysis investigating the associations between state-level cannabis laws (ie, MCL vs non-MCL, and RCL vs non-RCL) and past-month cannabis use prevalence among US adolescents and young adults. Supplemental analyses examined age-group effects and design-related factors., Results: Our search identified 4,604 citations, 34 and 30 of which were included in qualitative and quantitative analyses, respectively. Meta-analysis of MCL studies identified no significant association between MCL and change in past-month youth cannabis use (odds ratio [OR] = 0.981, 95% CI = 0.960, 1.003). Meta-analysis of RCL studies showed significantly increased odds of past-month cannabis use (OR = 1.134, 95% CI = 1.116-1.153). Meta-analysis of more recent studies, however, showed a significantly increased odds of past-month cannabis use among both adolescents and young adults (OR = 1.089, 95% CI = 1.015,1.169, and OR = 1.221, 95% CI = 1.188,1.255, respectively)., Conclusion: Cannabis legalization has complex and heterogenous effects on youth use that may differ across law types. Our meta-analytic results showed modest positive effects of RCL on past-month cannabis use (more so in young adults than in adolescents) and minimal effects of MCL on these outcomes in US youth. Given the shift toward recreational legalization, additional focus on RCL effects is warranted., Plain Language Summary: Cannabis laws have changed dramatically throughout the United States over the past 25 years. It is important to determine if medical or recreational cannabis legalization are associated cannabis use in youth. The authors conducted a systematic review and meta-analysis to investigate the associations between state-level cannabis laws and past-month cannabis use in adolescents and young adults. The authors identified 64 articles and found that recreational cannabis laws were associated with a modest but significant higher odds of past-month cannabis use. In contrast, medical cannabis laws were not associated with past-month youth cannabis use. Analysis of more recent studies suggested a rise in cannabis use among youth. The authors conclude that further research is needed to better understand the impact of recreational cannabis legalization on youth., (Copyright © 2024 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Due to the complex interactions of psychopathology, psychosocial stressors, and risk behaviors, characterizing high-risk phenotypic groups of transitional-age youth experiencing homelessness (TAY-EH) for targeted interventions remains difficult. We aimed to uncover specific phenotypes of TAY-EH based upon psychiatric and substance use disorder (SUD) diagnoses, and to assess relationships between these phenotypes and negative outcomes including suicidality and high-risk behaviors., Methods: Participants (N = 140; 57% male, 54% Black) were individuals aged 16-25 years accessing support at a psychosocial agency in the U.S. Northeast. Data were gathered via structured assessment. Cluster analysis identified sub-groups of TAY-EH with differing diagnostic patterns. Bivariate analyses examined associations between cluster membership and target outcomes., Results: A four-cluster solution was identified. Cluster 1 (Co-occurring; N = 33) was characterized by high levels of comorbidity (i.e., major depressive disorder (MDD), SUD, and notable levels of other diagnoses). Clusters 2 (MDD alone; N = 47) and 3 (SUD alone; N = 18) were characterized by single diagnoses. Cluster 4 (None; N = 42) was characterized by low levels of psychopathology. Clusters differed significantly on several variables including suicidality, adverse childhood experiences, and social connectedness. Comorbid MDD and SUD were most strongly associated with high-risk behaviors and suicidality., Discussion and Conclusions: These results highlight the importance of diagnosis and targeted interventions for co-occurring MDD and SUD to address the crisis of early mortality and other negative outcomes among TAY-EH., Scientific Significance: This study is the first to identify specific high-risk psychiatric and psychosocial phenotypes among the highly complex group of TAY-EH based upon structured diagnostic assessments., (© 2024 The American Academy of Addiction Psychiatry (AAAP).)

Objective: Limited prospective data exist about the impact of stimulant therapy for attention-deficit hyperactivity disorder (ADHD) during adolescence on the risk for later prescription drug misuse (PDM; i.e., of benzodiazepines, opioids, and stimulants)., Methods: National longitudinal multicohort panels (baseline cohort years 2005-2017) of U.S. 12th grade students (N=11,066; ages 17 and 18 years) from the Monitoring the Future study were surveyed via self-administered questionnaires and followed up biennially during young adulthood (ages 19-24). A multivariable analysis was used to assess whether adolescents' lifetime history of stimulant therapy for ADHD was associated with subsequent PDM., Results: Overall, 9.9% of adolescents reported lifetime stimulant therapy for ADHD at ages 17 and 18. No significant differences were found in the adjusted odds of later incidence or prevalence of past-year PDM during young adulthood between adolescents with lifetime stimulant therapy and adolescents with no stimulant therapy. Over the 5-year follow-up, past-year PDM during young adulthood was most prevalent among adolescents who reported both stimulant therapy and prescription stimulant misuse (53.1%) and those who reported prescription stimulant misuse only (51.5%). Compared with adolescents in a control group without lifetime stimulant therapy or misuse, adolescents reporting prescription stimulant misuse had significantly higher adjusted odds of later incidence and prevalence of PDM during young adulthood., Conclusions: Adolescents' stimulant therapy for ADHD was not significantly associated with increased risk for later PDM during young adulthood. In contrast, adolescents' misuse of prescription stimulants strongly predicted later PDM. Monitoring adolescents for prescription stimulant misuse may help identify and mitigate the risk for future PDM., Competing Interests: Dr. Wilens reports consultant work for 3D Therapeutics; receiving book royalties from Cambridge University Press, Elsevier, and Guilford Press; having a licensing agreement with 3D Therapeutics and Ironshore; and serving as a clinical consultant to Bay Cove Human Services, Gavin House, Massachusetts General Hospital, Major and Minor League Baseball, and the National Football League. The other authors report no financial relationships with commercial interests.

Background and Objectives: While inpatient withdrawal management/acute stabilization can improve outcomes for individuals with opioid use disorder (OUD), patients often leave treatment early due to mood, tension, and cravings associated with opioid withdrawal. The aim of this study was to evaluate the feasibility and preliminary effectiveness of a novel virtual reality (VR) based intervention; 3D Therapy Thrive (3DTT)., Methods: Subjects with OUD (N = 32) were recruited from a community acute stabilization program and received up to two sessions of 3DTT. They completed questionnaires related to their overall satisfaction with the experience and side effects; as well as those related to mood, tension, and cravings., Results: There were no reported side effects and the majority of subjects (94%) reported high satisfaction with the experience. Out of 62 patients approached, 33 patients agreed to participate (53%) 33 patients completed one, and 17 of these patients (52%) completed both sessions of 3DTT, with 19 participants (58%) completing their treatment protocols. Compared to baseline, 3DTT participants reported significant reductions in depression, tension, and cravings (p's < 0.001)., Discussion and Conclusions: This pilot study supports the feasibility and preliminary effectiveness of 3DTT for improving outcomes for inpatients with OUD. Future randomized controlled trials are necessary to evaluate the efficacy of 3DTT for improving retention, reducing cravings, and improving mood and tension., Scientific Significance: This is the first study to evaluate the feasibility of a psychologically informed VR intervention in inpatients with OUD., (© 2024 The American Academy of Addiction Psychiatry (AAAP).)

Measurement based care (MBC), a practice that uses patient reported outcome measures (PROMs), is not widely used in behavioral health settings and little is known about the patient experience with MBC in safety-net settings. This study aimed to understand patient experiences completing PROMs on paper when presenting to an outpatient, behavioral health setting within a public safety-net hospital. Semi-structured interviews were conducted with 22 participants in English and Spanish. Participants were 42 years old (SD = 12.7), mostly white (36.4%) and Black (31.8%). Thematic analysis was used to analyze findings. Overall, participants were engaged with PROMs and described them as helpful for themselves and their clinicians. Participants also expressed themes focused on PROMs user-friendliness, including formatting, time to complete measures, and participant characteristics such as attention and literacy. These findings are important to consider to ensure equitable access to MBC when implemented in behavioral health in the health safety-net setting., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This national prospective multicohort study examined the relationship between US adolescents' use of stimulant therapy for attention-deficit/hyperactivity disorder (ADHD) and subsequent risk of nonmedical stimulant use (i.e., nonmedical use of prescription stimulants and cocaine use) during young adulthood, relative to nonstimulant therapy and population controls., Methods: Nationally representative multicohort panels of 11,905 US 12th-grade students were surveyed via self-administered questionnaires at baseline (age 18) and followed prospectively over six years into young adulthood (ages 19‒24)., Results: There were no statistically significant differences between adolescents who used stimulant therapy for ADHD compared to those who used only nonstimulant medications and population controls in their adjusted odds of nonmedical stimulant use incidence or prevalence during young adulthood, after adjusting for baseline covariates., Discussion: The findings offer preliminary support that adolescents who use prescription stimulant or nonstimulant medications for ADHD when clinically indicated are not at greater risk for nonmedical stimulant use during young adulthood., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Measurement-based care in behavioral health uses patient-reported outcome measures (PROMs) to screen for mental health symptoms and substance use and to assess symptom change over time. While PROMs are increasingly being integrated into electronic health record systems and administered electronically, paper-based PROMs continue to be used. It is unclear if it is feasible to administer a PROM on paper when the PROM was initially developed for electronic administration., Objective: This study aimed to examine the feasibility of patient self-administration of a 2-part substance use screener-the Tobacco, Alcohol, Prescription medications, and other Substances (TAPS)-on paper. This screener was originally developed for electronic administration. It begins with a limited number of questions and branches to either skip or reflex to additional questions based on an individual's responses. In this study, the TAPS was adapted for paper use due to barriers to electronic administration within an urgent care behavioral health clinic at an urban health safety net hospital., Methods: From August 2021 to March 2022, research staff collected deidentified paper TAPS responses and tracked TAPS completion rates and adherence to questionnaire instructions. A retrospective chart review was subsequently conducted to obtain demographic information for the patients who presented to the clinic between August 2021 and March 2022. Since the initial information collected from TAPS responses was deidentified, demographic information was not linked to the individual TAPS screeners that were tracked by research staff., Results: A total of 507 new patients were seen in the clinic with a mean age of 38.7 (SD 16.6) years. In all, 258 (50.9%) patients were male. They were predominantly Black (n=212, 41.8%), White (n=152, 30%), and non-Hispanic or non-Latino (n=403, 79.5%). Most of the patients were publicly insured (n=411, 81.1%). Among these 507 patients, 313 (61.7%) completed the TAPS screener. Of these 313 patients, 76 (24.3%) adhered to the instructions and 237 (75.7%) did not follow the instructions correctly. Of the 237 respondents who did not follow the instructions correctly, 166 (70%) answered more questions and 71 (30%) answered fewer questions than required in TAPS part 2. Among the 237 patients who did not adhere to questionnaire instructions, 44 (18.6%) responded in a way that contradicted their response in part 1 of the screener and ultimately affected their overall TAPS score., Conclusions: It was challenging for patients to adhere to questionnaire instructions when completing a substance use screener on paper that was originally developed for electronic use. When selecting PROMs for measurement-based care, it is important to consider the structure of the questionnaire and how the PROM will be administered to determine if additional support for PROM self-administration needs to be implemented., (©Joanna Kramer, Timothy E Wilens, Vinod Rao, Richard Villa, Amy M Yule. Originally published in JMIR Formative Research (https://formative.jmir.org), 25.06.2024.)

Objectives: This review aims to present recent innovations and advancements in attention-deficit/hyperactivity disorder (ADHD) care, encompassing international consensus statement, new medication formulations, digital therapeutics, and neurostimulation devices. Methods: A comprehensive literature search of relevant articles published in the past five years was conducted, emphasizing the evidence base, efficacy, safety, and practical implications of these advancements. Results: The World Federation of ADHD Consensus Statement offers an updated diagnostic and treatment framework rooted in global scientific evidence. There are several newer ADHD medication formulations, including a nonstimulant (Viloxazine extended release) and the first transdermal amphetamine patch approved to treat ADHD. These options offer some unique benefits to personalize treatment based on symptom profile, lifestyle, preferences, and response. Digital tools offer additional means to restructure environments for individuals with ADHD, reducing impairment and reliance on others. In addition, digital therapeutics enhance access, affordability, personalization, and feasibility of ADHD care, complementing or augmenting existing interventions. Trigeminal nerve stimulation emerges as a well-tolerated nonpharmacological, device-based treatment for pediatric ADHD, with initial trials indicating effect sizes comparable to nonstimulant medications. Conclusions: These innovations in ADHD care represent clinically significant new treatment options and opportunities for personalized care. Health care professionals should integrate these developments into clinical practice, mindful of individual patient and family needs and preferences. Future research should assess long-term outcomes, cost-effectiveness, and acceptability of these innovations.

Transitional age youth experiencing homelessness (TAY-EH) represent an underserved and understudied population. While an increasing number of empirical interventions have sought to address the high burden of psychopathology in this population, findings remain mixed regarding intervention effectiveness. In this systematic review of behavioral health interventions for TAY-EH, we sought to examine the structural framework in which these interventions take place and how these structures include or exclude certain populations of youth. We also examined implementation practices to identify how interventions involving youth and community stakeholders effectively engage these populations. Based on PRISMA guidelines, searches of Medline, PsycInfo, Embase, Cochrane Central, Web of Science, and ClinicalTrials.gov databases were conducted, including English language literature published before October 2022. Eligible studies reported on interventions for adolescent or young adult populations ages 13-25 years experiencing homelessness. The initial search yielded 3850 citations; 353 underwent full text review and 48 met inclusion criteria, of which there were 33 unique studies. Studies revealed a need for greater geographic distribution of empirically based interventions, as well as interventions targeting TAY-EH in rural settings. Studies varied greatly regarding their operationalizations of homelessness and their method of intervention implementation, but generally indicated a need for increased direct-street outreach in participant recruitment and improved incorporation of youth feedback into intervention design. To our knowledge, this is the first systematic review to examine the representation of various groups of TAY-EH in the literature on substance use and mental health interventions. Further intervention research engaging youth from various geographic locations and youth experiencing different forms of homelessness is needed to better address the behavioral health needs of a variety of TAY-EH., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Prevention programs that target resilience may help youth address mental health difficulties and promote well-being during public health crises., Aims: To examine the preliminary efficacy of the Resilient Youth Program (RYP)., Method: The RYP was delivered remotely from a US academic medical centre to youth in the community via a naturalistic pilot study. Data from 66 youth (ages 6-18, M age = 11.65, SD = 3.02) and their parents were collected via quality assurance procedures (May 2020 to March 2021). Pre/post-intervention child/parent-reported psychological and stress symptoms as well as well-being measures were compared via Wilcoxon signed rank tests. Child/parent-reported skills use data were collected., Results: Among child-reported outcomes, there were significant decreases in physical stress ( p = .03), anxiety ( p = .004), depressive symptoms ( p < .001) and anger ( p = .002), as well as increased life satisfaction ( p = .02). There were no significant differences in child-reported psychological stress ( p = .06) or positive affect ( p = .09). Among parent-reported child outcomes, there were significant decreases in psychological ( p < .001) and physical stress ( p = .03), anxiety ( p < .001), depressive symptoms ( p < .001), and anger ( p < .002) as well as increased positive affect ( p < .001) and life satisfaction ( p < .001). Effect sizes ranged from small to medium; 77% of youth (73% of parents) reported using RYP skills. Age and gender were not associated with outcome change., Conclusions: The RYP may help reduce psychological/stress symptoms and increase well-being among youth; further research is needed.

Background: To examine the associations between early onset of nonmedical prescription stimulant use (NPSU) and cocaine use., Methods: Nationally representative samples of high school seniors were surveyed annually. Data were collected via self-administered questionnaires in nationally representative public and private schools in the United States (1976-2020) as part of the Monitoring the Future Study. The sample consisted of 45 cohorts of 12th grade students (N = 121 909). The main outcome was lifetime, past-year, and past-month cocaine use., Results: An estimated one in every 10 (10.1%) individuals reported lifetime NPSU while 8.5% reported any cocaine use. The vast majority of youth (87.2%) initiated NPSU before cocaine among those who reported both substances. Cocaine use was most prevalent among youth who reported early onset of NPSU in 8th grade or earlier (51.7%) followed by those who reported later onset of NPSU in 12th grade (24.7%), and those who never initiated NPSU (3.7%). Binary logistic regression analysis indicated that early onset of NPSU had greater adjusted odds of cocaine use compared to those with later onset of NPSU or those who never reported NPSU. Moreover, the adjusted odds of cocaine use were higher for adolescents who initiated NPSU before or after medical use of prescription stimulants compared to those with no history of medical use or NPSU. Similar results were found for lifetime, past-year, and past-month cocaine use as a function of NPSU onset; this association was stronger among more recent cohorts., Conclusions: Early onset of NPSU appears to be a signal of increased risk of cocaine use among US adolescents. NPSU should be included in screening and early prevention strategies among secondary school students. Health professionals, school officials, and families are encouraged to monitor youth for NPSU based on the increased risk of later cocaine use and related consequences., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Drs McCabe, Schepis, Schulenberg, and Veliz report no financial relationships with commercial interests. Dr. Wilens is a consultant for 3D Therapeutics; published Straight Talk About Psychiatric Medications for Kids (Guilford Press) and co-edited ADHD in Adults and Children (Cambridge University Press), Massachusetts General Hospital Comprehensive Clinical Psychiatry (Elsevier), and Massachusetts General Hospital Psychopharmacology and Neurotherapeutics (Elsevier); is co-owner of a copyrighted diagnostic questionnaire (Before School Functioning Questionnaire, BSFQ) and has a licensing agreement with Ironshore; serves as a clinical consultant to the US Minor/Major League Baseball, Gavin House, and Bay Cove Human Services. The authors do not have any additional potential conflicts of interest to disclose.

Objective: Residential is a common treatment setting for youth with high-severity substance use disorders (SUD). This study evaluated the prevalence of psychiatric symptoms and medication for youth in residential SUD treatment., Methods: Youth in Massachusetts state licensed and funded SUD residential programs completed questionnaires assessing demographics, primary substance of use, and psychopathology symptoms (Youth Self Report [YSR]/Adult Self Report [ASR]). De-identified medication lists were provided by the programs. Descriptive statistics were used to describe the sample., Results: Among the 47 youth who participated, 51.1% were male, 72.3% white, 83% non-Hispanic, mean age 20.7 years. Opioids were the most common primary substance identified by youth (51.1%), and 75% had at least one clinically elevated subscale on the YSR/ASR. Most youth were prescribed at least one medication (89.4%) with a mean of 2.9 medications., Conclusion: Youth in SUD residential treatment frequently have clinically elevated psychiatric symptoms, and psychotropic medication was commonly prescribed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Amy Yule has received funding from the National Institutes of Health (4UH3DA050252-02 and 7R01HD092456-03), the Doris Duke Charitable Foundation’s COVID-19 Fund to Retain Clinical Scientists collaborative grant program (2021261) through support from the John Templeton Foundation (62288), and the National Center for Advancing Translational Sciences, National Institute of Health, through the Boston University Clinical and Translational Science Institute (1UL1TR001430). She also has received funding for clinical program development from the Jack Satter Foundation. She has been a consultant to the Gavin House and BayCove Human Services (clinical services), as well as the American Psychiatric Association’s Providers Clinical Support System Sub-Award. Dr. Timothy Wilens has received research funding from the National Institutes of Health through the HEAL Initiative under award number 1UG3DA050252-01 and 4UH3DA050252-02. Dr. Wilens works as a consultant for Ironshore, the Gavin Foundation, Bay Cove Human Services, the US National Football League, the US Minor and Major League for Baseball, and White Rhino/3D Therapy LLC. Dr. Wilens also serves as a co-editor for the journal Elsevier Psychiatric Clinics of North America (ADHD). In addition, he has published the book Straight Talk About Psychiatric Medications for Kids with the Guilford Press and co-edited the textbook ADHD in Adults and Children with the Cambridge University Press. Victoria Mail and Rebecca Butler have nothing to disclose.

Objective: Increasing rates of methamphetamine (METH) use, use disorders, and related overdoses are a growing public health problem. There are a lack of protocols addressing METH intoxication and withdrawal symptoms that manifest during acute withdrawal treatment resulting in inpatient management difficulties and premature discharges. This report presents a novel treatment protocol comprised of behavior-targeted and pharmacological components that aims to reduce the intensity and duration of METH intoxication and withdrawal related symptoms during early treatment, improve retention, and provide clinicians with a tool to meet this growing problem., Methods: The protocol was developed by a team of addiction physicians and other clinical staff. Clinical and administrative staff at a community acute stabilization unit were trained and the protocol was implemented with patients presenting with METH use. Pharmacological interventions, including ascorbic acid, antipsychotics, and other sedatives are discussed, as are behavior-based orders. A retrospective quality assurance examination was conducted on patient characteristics and outcomes as well as focus groups with nursing staff., Results: A total of 23 patients consecutively admitted to the unit used the protocol (100% male). Most patients (67%) displayed symptoms of METH use or withdrawal. Behavior-related interventions were used in 52% of patients, while 48% received behavior-related and pharmacological measures. Patient completion of the protocol was 83%, and the protocol's utility was supported by nursing staff., Conclusions: This retrospective evaluation of a novel METH withdrawal treatment protocol suggests feasibility, tolerability, and preliminary evidence of effectiveness, providing clinicians with a new tool that requires further study., Competing Interests: Dr. Timothy Wilens has received research funding from the National Institutes of Health through the HEAL Initiative under award number 1UG3DA050252-01 and 4UH3DA050252-02 and the Food and Drug Administration. Dr. Wilens works as a clinical consultant for the Gavin Foundation, Bay Cove Human Services, and US Minor and Major League for Baseball. He has licensing and/or intellectual property agreements with Ironshore and White Rhino/3D Therapy LLC Dr. James O’Connell works as a medical director for the Gavin Foundation and Bay Cove Human Services. At the time of protocol development and implementation, Adam Taylor and Lia Beltrame were employees of Bay Cove Human Services. Ronan Wilson does not have any conflicts of interest to report and is an employee of Massachusetts General Hospital., (Copyright © 2024 American Society of Addiction Medicine.)

Introduction: Executive function (EF) deficits are common in youth with ADHD and pose significant functional impairments. The extent and effect of interventions addressing EF in youth with ADHD remain unclear., Methods: We conducted a systematic literature review using PRISMA guidelines. Included studies were randomized controlled trials of interventions to treat EF in youth with ADHD., Results: Our search returned 136 studies representing 11,443 study participants. We identified six intervention categories: nonstimulant pharmacological ( N  = 3,576 participants), neurological ( N  = 1,935), psychological ( N  = 2,387), digital ( N  = 2,416), physiological ( N  = 680), and combination ( N  = 366). The bulk of the evidence supported pharmacological interventions as most effective in mitigating EF, followed by psychological and digital interventions., Conclusion: A breadth of treatments exists for EF in youth with ADHD. Pharmacological, psychotherapeutic, and digital interventions had the most favorable, replicable outcomes. A lack of outcome standardization across studies limited treatment comparison. More data on the persistence of intervention effects are necessary., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Timothy Wilens receives or has received grant support from NIH(NIDA). Dr. Timothy Wilens has co/edited books: Straight Talk About Psychiatric Medications for Kids (Guilford Press), ADHD in Adults and Children (Cambridge University Press), Massachusetts General Hospital Comprehensive Clinical Psychiatry (Elsevier), Massachusetts General Hospital Psychopharmacology and Neurotherapeutics (Elsevier) and Update on Pharmacotherapy of ADHD (Elsevier Press). Dr. Wilens has a licensing agreement with Ironshore (BSFQ Questionnaire) and 3D Therapy. Dr. Wilens is Chief, Division of Child and Adolescent Psychiatry and (Co) Director of the Center for Addiction Medicine at Massachusetts General Hospital. He serves as a clinical consultant to U.S. Minor/Major League Baseball, Gavin Foundation, and Bay Cove Human Services.Dr. Surman has received, in his lifetime, consulting fees from Eisai, Kayna, Ironshore, Mcneil, Neurocentria, NLS Pharma, Nutricia, Otsuka, Pfizer, Adlon/Purdue, Rhodes, Shire, Somaxon, Sunovion, Supernus, Takeda, and Teva. He has also received payments for lectures for Alcobra, Arbor, McNeil, Janssen, Janssen-Ortho, Novartis, Shire, and Reed/MGH Academy (funded by multiple companies) as well as GME CME (funded by multiple companies). Royalties have been given to Dr. Surman from Berkeley/Penguin for Fast Minds: How to Thrive If You Have ADHD (or Think You Might) and from Humana/Springer for ADHD in Adults: A Practical Guide to Evaluation and Management. Additionally, Dr. Surman has conducted clinical research at Massachusetts General Hospital supported by Abbot, Cephalon, Hilda and Preston Davis Foundation, Eli Lilly, Magceutics/Neurocentria, Jazz/Axsome, Johnson & Johnson/McNeil, Lundbeck, Merck, Nordic Naturals, Shire, and Takeda.Ms. Mira Stone, Ms. Sylvia Lanni, Ms. Amy Berger, Ms. Melis Lydston, and Mr. Ronan Wilson have no personal or financial conflicts of interest to disclose.

Introduction: Despite the benefits of measurement-based care (MBC) in the behavioral health setting, there have been difficulties in implementation and low saturation. Although barriers and facilitators to MBC implementation have been identified, research has generally only included the perspective of one stakeholder group. The current study aims to examine the similarities and differences-by stakeholder group-in the identified barriers to and facilitators of implementing MBC in the behavioral health setting., Method: A purposeful sampling approach was used to recruit and conduct interviews and focus groups with stakeholders (clinicians, clinic leaders, and administrative staff) from four behavioral health clinics at an academic medical center that is part of a larger healthcare system. The data coding process included a directed content analytic approach whereby the coding team used an iterative process to analyze deidentified transcripts starting with a codebook based on the Consolidated Framework for Implementation Research (CFIR) constructs., Results: A total of 31 clinicians, 11 clinic leaders, and 8 administrative staff participated in the interviews and focus groups. There was convergence among all stakeholder regarding which CFIR constructs were identified as barriers and facilitators, but there were differences in the specific thematic factors identified by stakeholders as barriers and facilitators within each of these implementation constructs. The barriers and facilitators that stakeholders identified within each CFIR construct were often connected to their specific role in implementing MBC., Conclusion: Collecting information on barriers and facilitators to MBC implementation from the multiple stakeholders involved in the process may enhance successful implementation of MBC given the variation between groups in identified thematic factors. Administrative staff perspectives, which have not been reported in the literature, may be of particular importance in planning for successful MBC implementation., (© 2024 Wiley Periodicals LLC.)

Objective: This study aimed to assess nationwide trends in attention-deficit hyperactivity disorder (ADHD) diagnoses and pharmacotherapy among patients with opioid use disorder and ADHD and to examine factors predicting receipt of stimulant medications among patients receiving medications for opioid use disorder (MOUDs)., Methods: A claims-based database of commercially insured patients ages 13-64 was used to conduct two analyses: an annual cross-sectional study of 387,980 patients diagnosed as having opioid use disorder (2007-2017) to estimate the prevalence of ADHD diagnoses and pharmacotherapy, and a retrospective cohort study of 158,591 patients receiving MOUDs to test, with multivariable regression, the association between patient characteristics and receipt of stimulant medication., Results: From 2007 to 2017, the prevalence of ADHD diagnoses increased from 4.6% to 15.1% and the rate of ADHD pharmacotherapy increased from 42.6% to 51.8% among patients with opioid use disorder. Among all patients receiving MOUDs, 10.5% received at least one prescription stimulant during the study period. Female sex; residence in the southern United States; and ADHD, mood, and anxiety disorder diagnoses were associated with increased likelihood of stimulant receipt. Stimulant use disorder and other substance use disorder diagnoses were associated with decreased likelihood of stimulant receipt., Conclusions: ADHD diagnoses and pharmacotherapy among patients with opioid use disorder have increased. A minority of patients with ADHD and taking MOUDs received a stimulant. Further study is needed of the benefits and risks of ADHD pharmacotherapy for patients with opioid use disorder., Competing Interests: Dr. Wilens reports receiving grant support from 3DBio Therapeutics; receiving royalties from Ironshore, Guilford Press, and Cambridge University Press; performing clinical work for Bay Cove Human Services, the Gavin Foundation, and Mass General Brigham; and serving as a consultant to Minor and Major League Baseball, the National Football League (ERM Associates), White Rhino, and 3DBio Therapeutics. Dr. Yule reports receiving funding from the Jack Satter Foundation and from Doris Duke Charitable Foundation’s COVID-19 Fund to Retain Clinical Scientists collaborative grant program, through support from the John Templeton Foundation. She reports serving as a consultant to Bay Cove Human Services, the Gavin Foundation, and the American Psychiatric Association’s Providers Clinical Support System subaward. The other authors report no financial relationships with commercial interests.

Purpose: Clinical trial data support use of medications for opioid use disorder (MOUD) in adolescents and young adults ("youth"), but qualitative data are lacking on the acceptability and importance of MOUD to youth, caregivers, and clinicians. We assessed how these stakeholders viewed the role of MOUD in treatment and recovery., Methods: We recruited youth aged from 15 to 25 years with opioid use disorder who had received buprenorphine, naltrexone, or methadone and caregivers from a primary care-based youth addiction treatment program. We also recruited clinicians with addiction expertise from social work, nursing, pediatrics, internal medicine, and psychiatry. We conducted semistructured interviews assessing special considerations for MOUD use in youth. Three coders performed inductive and deductive thematic analysis of transcripts., Results: Among 37 participants, including 15 youth (age range, 17-25 years), nine caregivers, and 13 clinicians, we identified three themes. (1) Medications support recovery in the short term: Youth described MOUD as beneficial in managing withdrawal symptoms. Notably, some youth and caregivers preferred to limit MOUD duration. (2) Medication adherence is affected by type of medication, dosing regimen, and route of administration. Participants endorsed long-acting, injectable MOUD for ease of use and youth's ability to continue engagement in "normal activities" without daily medication. (3) Caregiver involvement can support medication decisions and adherence. Youth and some clinicians described the need to assess caregiver involvement before incorporating them into treatment; caregivers and other clinicians described caregivers as critical in supporting accountability., Discussion: MOUD is evidence-based, and its provision should be developmentally responsive and youth- and family-centered, incorporating caregivers when appropriate., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: To assess whether age of onset and duration of stimulant therapy for attention-deficit/hyperactivity disorder (ADHD) are associated with cocaine, methamphetamine, and prescription stimulant misuse during adolescence., Methods: Nationally representative samples of US 10th and 12th grade students (N = 150,395) from the Monitoring the Future study were surveyed via self-administered questionnaires from 16 annual surveys (2005-2020)., Results: An estimated 8.2% of youth received stimulant therapy for ADHD during their lifetime (n = 10,937). More than one in 10 of all youth reported past-year prescription stimulant misuse (10.4%)-past-year cocaine (4.4%) and methamphetamine (2.0%) use were less prevalent. Youth who initiated early stimulant therapy for ADHD (≤9 years old) and for long duration (≥6 years) did not have significantly increased adjusted odds of cocaine or methamphetamine use relative to population controls (ie, non-ADHD and unmedicated ADHD youth). Youth who initiated late stimulant therapy for ADHD (≥10 years old) and for short duration (<1 year) had significantly higher odds of past-year cocaine or prescription stimulant misuse in adolescence than those initiating early stimulant therapy for ADHD (≤9 years old) and for long duration (≥6 years). Youth who initiated late stimulant therapy for ADHD (≥10 years) for short duration (<1 year) had significantly higher odds of past-year cocaine, methamphetamine, and prescription stimulant misuse versus population controls during adolescence. No differences in past-year cocaine, methamphetamine, and prescription stimulant misuse were found between individuals who only used non-stimulant therapy for ADHD relative to youth who initiated early stimulant therapy (≤9 years old) and for long duration (≥6 years)., Conclusions: An inverse relationship was found between years of stimulant therapy and illicit and prescription stimulant misuse. Adolescents with later initiation and/or shorter duration of stimulant treatment for ADHD should be monitored for potential illicit and prescription stimulant misuse., (© 2023 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Transitional-age youth experiencing homelessness (TAY-EH) represent a high-risk population with substantial exposure to adverse childhood experiences (ACEs) and high rates of morbidity and mortality. The current study uses a person-centered analytical approach to identify patterns of ACEs among TAY-EH and inform more nuanced characterizations of this vulnerable group. Participants were aged 16-25 years accessing support at a psychosocial agency in Boston, Massachusetts. Data were gathered via structured assessment. Hierarchical agglomerative cluster analysis identified subgroups of TAY-EH with differing ACE exposures. Within the sample of 138 TAY-EH, three unique clusters of ACE exposures were identified: two high-occurrence groups (one also endorsing sexual abuse and one not), and one lower-occurrence group. Clusters differed significantly on several variables including gender identity, sexuality, and suicidality. The ways in which trauma phenotypes inform treatment access, utilization patterns, and functional outcomes should be high-priority areas for ongoing research in TAY-EH and related marginalized youth populations.

Objective: The aim of the study is to explore the early parenting experiences among a cohort of postpartum individuals with opioid use disorder (OUD) both during and after the delivery hospitalization to identify areas of intervention to strengthen bonding and attachment., Methods: Semistructured qualitative interviews with recently pregnant people with OUD assessed parenting needs, supports, and goals in the context of the demands of addiction treatment and early motherhood. Probes explored the relationship between early parenting experiences, addiction, and recovery, as well as enabling factors and barriers to mother-infant bonding. Interviews were completed between 2019 to 2020. A constant comparative methods approach was used for codebook development and analysis., Results: Twenty-six women completed interviews a mean of 10.1 months postpartum. Twenty-four women were receiving methadone or buprenorphine treatment at delivery for OUD. Four interrelated themes emerged. Women experienced the following: (1) increased surveillance from healthcare workers who doubted their parenting ability; (2) a desire for a "normal" early parenting experience that was not disrupted by increased medical monitoring and surveillance; (3) complex and intersecting identities of being both a mother and a person in recovery; and (4) the importance of support from and advocacy by clinicians and peers to developing maternal confidence and connection., Conclusions: Interventions are needed to improve the early parenting experiences of opioid-exposed mother-infant dyads, to address the mutual mistrust between health care providers and parents, and to provide additional supports to families. Promotion of positive attachment and parental self-efficacy should be prioritized over increased surveillance and scrutiny to sustain maternal recovery trajectories into early childhood and foster family well-being., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 American Society of Addiction Medicine.)

Objectives: Some states, including Massachusetts, require automatic filing of child abuse and neglect for substance-exposed newborns, including infants exposed in-utero to clinician-prescribed medications to treat opioid use disorder (MOUD). The aim of this article is to explore effects of these mandated reporting policies on pregnant and postpartum people receiving MOUD., Methods: We used modified grounded research theory, literature findings, and constant comparative methods to extract, analyze and contextualize perinatal experiences with child protection systems (CPS) and explore the impact of the Massachusetts mandated reporting policy on healthcare experiences and OUD treatment decisions. We drew from 26 semi-structured interviews originally conducted within a parent study of perinatal MOUD use in pregnancy and the postpartum period., Results: Three themes unique to CPS reporting policies and involvement emerged. First, mothers who received MOUD during pregnancy identified mandated reporting for prenatally prescribed medication utilization as unjust and stigmatizing. Second, the stress caused by an impending CPS filing at delivery and the realities of CPS surveillance and involvement after filing were both perceived as harmful to family health and wellbeing. Finally, pregnant and postpartum individuals with OUD felt pressure to make medical decisions in a complex environment in which medical recommendations and the requirements of CPS agencies often compete., Conclusions for Practice: Uncoupling of OUD treatment decisions in the perinatal period from mandated CPS reporting at time of delivery is essential. The primary focus for families affected by OUD must shift from surveillance and stigma to evidence-based treatment and access to supportive services and resources., (© 2023. The Author(s).)

Objective: Prescription benzodiazepines are among the most commonly used and misused controlled medications. The authors aimed to examine transitions from medical use of prescription benzodiazepines to prescription benzodiazepine misuse, prescription opioid misuse, and substance use disorder symptoms during adulthood., Methods: Eleven national cohorts of U.S. 12th graders (N=26,575) were followed up from ages 18 (1976-1986) to 50 (2008-2018). Prescription benzodiazepine misuse, prescription opioid misuse, and substance use disorder symptoms were examined with prevalence estimates and multivariable logistic regression., Results: By age 35, 70.9% of respondents had not used or misused prescription benzodiazepines, 11.3% reported medical use only, 9.8% indicated both medical use and misuse, and 14.1% reported misuse only. In analyses adjusted for demographic and other characteristics, adults reporting only medical use of prescription benzodiazepines by age 35 had higher odds of later prescription benzodiazepine misuse (adjusted OR [AOR]=2.17, 95% CI=1.72-2.75) and prescription opioid misuse (AOR=1.40, 95% CI=1.05-1.86) than respondents ages 35-50 who never used prescription benzodiazepines. More frequent medical use of prescription benzodiazepines by age 35 was associated with increased risk for substance use disorder symptoms at ages 40-50. Any history of prescription benzodiazepine misuse by age 35 was associated with higher odds of later prescription benzodiazepine misuse, prescription opioid misuse, and substance use disorder symptoms, compared with no misuse., Conclusions: Prescription benzodiazepine use or misuse may signal later prescription drug misuse or substance use disorders. Medical use of prescription benzodiazepines by age 35 requires monitoring for prescription drug misuse, and any prescription benzodiazepine misuse warrants an assessment for substance use disorder., Competing Interests: Dr. Wilens has been a consultant to 3D Therapeutics, Bay Cove Human Services, Gavin Foundation, and Major and Minor League Baseball; has a licensing agreement with Ironshore for the Before School Functioning Questionnaire; and receives book royalties from Cambridge University Press, Elsevier, and Guilford Press. The other authors report no financial relationships with commercial interests.

The Helping to End Addiction Long-Term (HEAL) Prevention Cooperative (HPC) is rapidly developing 10 distinct evidence-based interventions for implementation in a variety of settings to prevent opioid misuse and opioid use disorder. One HPC objective is to compare intervention impacts on opioid misuse initiation, escalation, severity, and disorder and identify whether any HPC interventions are more effective than others for types of individuals. It provides a rare opportunity to prospectively harmonize measures across distinct outcomes studies. This paper describes the needs, opportunities, strategies, and processes that were used to harmonize HPC data. They are illustrated with a strategy to measure opioid use that spans the spectrum of opioid use experiences (termed involvement) and is composed of common "anchor items" ranging from initiation to symptoms of opioid use disorder. The limitations and opportunities anticipated from this approach to data harmonization are reviewed. Lastly, implications for future research cooperatives and the broader HEAL data ecosystem are discussed., (© 2022. Society for Prevention Research.)

Background: One mechanism to examine if major depressive disorder (MDD) is related to the development of substance use disorder (SUD) is by leveraging naturalistic data available in the electronic health record (EHR). Rules for data extraction and variable construction linked to psychometrics validating their use are needed to extract data accurately., Objective: We propose and validate a methodologic framework for using EHR variables to identify patients with MDD and non-nicotine SUD., Methods: Proxy diagnoses and index dates of MDD and/or SUD were established using billing codes, problem lists, patient-reported outcome measures, and prescriptions. Manual chart reviews were conducted for the 1-year period surrounding each index date to determine (1) if proxy diagnoses were supported by chart notes and (2) if the index dates accurately captured disorder onset., Results: The results demonstrated 100% positive predictive value for proxy diagnoses of MDD. The proxy diagnoses for SUD exhibited strong agreement (Cohen's kappa of 0.84) compared to manual chart review and 92% sensitivity, specificity, positive predictive value, and negative predictive value. Sixteen percent of patients showed inaccurate SUD index dates generated by EHR extraction with discrepancies of over 6 months compared to SUD onset identified through chart review., Conclusions: Our methodology was very effective in identifying patients with MDD with or without SUD and moderately effective in identifying SUD onset date. These findings support the use of EHR data to make proxy diagnoses of MDD with or without SUD.

Importance: The prescribing of stimulant medications for attention-deficit/hyperactivity disorder (ADHD) has increased in the US. Prescription stimulants are one of the most commonly misused controlled substances during adolescence. Despite a 10-fold increase in stimulant-related overdose deaths in the past decade, the transitions from prescription stimulants to illicit stimulants (eg, cocaine, methamphetamine) remain relatively unknown in longitudinal population-based studies., Objective: To determine the longitudinal transitions from adolescents' prescription stimulant exposure (ie, stimulant therapy for ADHD and prescription stimulant misuse [PSM]) to later cocaine and methamphetamine use during young adulthood., Design, Setting, and Participants: National longitudinal multicohort panels of US 12th grade public and private school students in the coterminous US were assessed annually (baseline cohort years 2005-2017 [between March and June]) and followed up across 3 waves over a 6-year period to 23 to 24 years of age (follow-up years 2011-2021 [between April and October])., Exposure: History of self-reported stimulant therapy for ADHD at baseline., Main Outcomes and Measures: Incidence and prevalence of past-year use of cocaine and methamphetamine during young adulthood (19-24 years of age)., Results: Among 5034 students enrolled at baseline (2589 [52.0%] female), 470 (10.2% [95% CI, 9.4%-11.2%]) reported use of stimulant therapy for ADHD, 671 (14.6% [95% CI, 13.5%-15.6%]) reported PSM only, and 3459 (75.2% [95% CI, 73.9%-76.4%]) reported neither (and served as population controls). In controlled analyses, there were no statistically significant differences between adolescents who reported stimulant therapy for ADHD at baseline compared with population controls in the adjusted odds of transitioning to later cocaine or methamphetamine initiation or use during young adulthood (19-24 years of age). In contrast, PSM during adolescence in those not treated with stimulants for ADHD had significantly higher odds of transitioning to later cocaine or methamphetamine initiation and use during young adulthood compared with population controls (adjusted odds ratio, 2.64 [95% CI, 1.54-4.55])., Conclusions and Relevance: In this multicohort study, adolescents' stimulant therapy for ADHD was not associated with increased risk of later cocaine and methamphetamine use during young adulthood. Adolescents' prescription stimulant misuse offered a signal for subsequent cocaine or methamphetamine use and warrants monitoring and screening.