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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.

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.

Background: Conduct Disorder (CD) is highly comorbid with Bipolar Disorder (BP) and this comorbidity is associated with high morbidity and dysfunction. We sought to better understand the clinical characteristics and familiality of comorbid BP + CD by examining children with BP with and without co-morbid CD., Methods: 357 subjects with BP were derived from two independent datasets of youth with and without BP. All subjects were evaluated with structured diagnostic interviews, the Child Behavior Checklist (CBCL), and neuropsychological testing. We stratified the sample of subjects with BP by the presence or absence of CD and compared the two groups on measures of psychopathology, school functioning, and neurocognitive functioning. First-degree relatives of subjects with BP +/- CD were compared on rates of psychopathology in relatives., Results: Subjects with BP + CD compared to BP without CD had significantly more impaired scores on the CBCL Aggressive Behavior (p < 0.001), Attention Problems (p = 0.002), Rule-Breaking Behavior (p < 0.001), Social Problems (p < 0.001), Withdrawn/Depressed clinical scales (p = 0.005), the Externalizing Problems (p < 0.001), and Total Problems composite scales(p < 0.001). Subjects with BP + CD had significantly higher rates of oppositional defiant disorder (ODD) (p = 0.002), any SUD (p < 0.001), and cigarette smoking (p = 0.001). First-degree relatives of subjects with BP + CD had significantly higher rates of CD/ODD/ASPD and cigarette smoking compared to first-degree relatives of subjects without CD., Limitations: The generalization of our findings was limited due to a largely homogeneous sample and no CD only comparison group., Conclusions: Given the deleterious outcomes associated with comorbid BP + CD, further efforts in identification and treatment are necessary., Competing Interests: Conflict 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. 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. Dr. Amy Yule currently has research funding from the National Institutes of Health (4UH3DA050252-02), 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 funding for clinical program development from the Jack Satter Foundation. She is 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. Joseph Biederman is currently receiving research support from the following sources: AACAP, Feinstein Institute for Medical Research, Genentech, Headspace Inc., NIDA, Pfizer Pharmaceuticals, Roche TCRC Inc., Sunovion Pharmaceuticals Inc., Takeda/Shire Pharmaceuticals Inc., Tris, and NIH. Dr. Biederman and his program have received royalties from a copyrighted rating scale used for ADHD diagnoses, paid by Biomarin, Bracket Global, Cogstate, Ingenix, Medavent Prophase, Shire/Takeda, Sunovion, and Theravance; these royalties were paid to the Department of Psychiatry at MGH. Through Partners Healthcare Innovation, Dr. Biederman has a partnership with MEMOTEXT to commercialize a digital health intervention to improve adherence in ADHD. Through MGH corporate licensing, Dr. Biederman has a US Patent (#14/027,676) for a non-stimulant treatment for ADHD, a US Patent (#10,245,271 B2) on a treatment of impaired cognitive flexibility, and a patent pending (#61/233,686) on a method to prevent stimulant abuse. In 2022: Dr. Biederman received honoraria from the MGH Psychiatry Academy for tuition-funded CME courses. In 2021: Dr. Biederman received an honorarium for a scientific presentation from Multi-Health Systems, and a one-time consultation for Cowen Healthcare Investments. He received honoraria from AACAP, the American Psychiatric Nurses Association, BIAL - Portela & Cª. S.A. (Portugal), Medscape Education, and MGH Psychiatry Academy for tuition-funded CME courses. In 2020: Dr. Biederman received an honorarium for a scientific presentation from Tris and from the Institute of Integrated Sciences – INI (Brazil), and research support from the Food & Drug Administration. He received honoraria from Medlearning Inc, NYU, and MGH Psychiatry Academy for tuition-funded CME courses. Dr. Janet Wozniak receives research support from PCORI, Demarest Lloyd, Jr. Foundation, and the Baszucki Brain Research Fund. In the past, Dr. Wozniak has received research support, consultation fees or speaker’s fees from Eli Lilly, Janssen, Johnson and Johnson, McNeil, Merck/Schering-Plough, the National Institute of Mental Health (NIMH) of the National Institutes of Health (NIH), Pfizer, and Shire. She is the author of the book, “Is Your Child Bipolar” published May 2008, Bantam Books. Her spouse receives royalties from UpToDate; consultation fees from Emalex, Noctrix, Disc Medicine, Avadel, HALEO, OrbiMed, and CVS; and research support from Merck, NeuroMetrix, American Regent, NIH, NIMH, the RLS Foundation, and the Baszucki Brain Research Fund. In the past, he has received honoraria, royalties, research support, consultation fees or speaker’s fees from: Otsuka, Cambridge University Press, Advance Medical, Arbor Pharmaceuticals, Axon Labs, Boehringer-Ingelheim, Cantor Colburn, Covance, Cephalon, Eli Lilly, FlexPharma, GlaxoSmithKline, Impax, Jazz Pharmaceuticals, King, Luitpold, Novartis, Neurogen, Novadel Pharma, Pfizer, Sanofi- Aventis, Sepracor, Sunovion, Takeda, UCB (Schwarz) Pharma, Wyeth, Xenoport, Zeo. Dr. Colin Burke is currently receiving funding through the American Academy of Child and Adolescent Psychiatry Physician Scientist Program in Substance Abuse Award Number 3K12DA000357-22S1 and the Louis V Gerstner Research Scholar Award. Ms. Diana Woodward, Ms. Daria Taubin, Ms. Berger, Ms. Stone, and Ms. Maura DiSalvo do not have any financial relationships to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The objective of this study was to evaluate the risk for developing a substance use disorder (SUD, alcohol or drug abuse or dependence) in individuals with high-functioning autism spectrum disorder (ASD). Subjects with high-functioning ASD were derived from consecutive referrals to a specialized ambulatory program for ASD at a major academic center from 2007 to 2016. Age-matched controls and attention-deficit hyperactivity disorder (ADHD) comparison subjects were derived from three independent studies of children and adults with and without ADHD using identical assessment methodology. Cox proportional hazard models were used to analyze the prevalence of SUD (alcohol or drug use disorder). Age of onset of SUD was analyzed with linear regression models. Our sample included 230 controls, 219 subjects with ADHD, and 230 subjects with ASD. The mean age for the ASD subjects was 20.0 ± 10.3 years. Among ASD subjects, 69% had a lifetime prevalence of ADHD, and the ASD subjects had significantly higher rates of other psychiatric psychopathology compared to ADHD and control subjects (p < 0.001) ASD subjects were at significantly decreased risk for developing a SUD compared to ADHD (hazard ratio (HR) = 0.22, p < 0.001) and control subjects (HR = 0.62, p = 0.04). The age of onset of a SUD was significantly older in ASD subjects, mean age 21.7 years, when compared to ADHD and control subjects (both p < 0.005). Individuals with ASD are at decreased risk to develop a SUD, and when they do, the onset is significantly later than ADHD and controls., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objective: Child- and adolescent-onset psychopathology is known to increase the risk for developing substance use and substance use disorders (SUDs). While pharmacotherapy is effective in treating pediatric psychiatric disorders, the impact of medication on the ultimate risk to develop SUDs in these youth remains unclear. Methods: We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) systematic review of peer-reviewed literature published on PubMed through November 2021, examining pharmacological treatments of psychiatric disorders in adolescents and young adults and their effect on substance use, misuse, and use disorder development. Results: Our search terms yielded 21 studies examining the impact of pharmacotherapy and later SUD in attention-deficit/hyperactivity disorder (ADHD), two studies on Major Depressive Disorder, and three studies on psychotic disorders. The majority of these studies reported reductions in SUD ( N  = 14 sides) followed by no effects ( N  = 10) and enhanced rates of SUD ( N  = 2). Studies in ADHD also reported that earlier-onset and longer-duration treatment was associated with the largest risk reduction for later SUD. Conclusions: Overall, pharmacological treatments for psychiatric disorders appear to mitigate the development of SUD, especially when treatment is initiated early and for longer durations. More studies on the development of SUD linked to the effects of psychotherapy alone and in combination with medication, medication initiation and duration, adequacy of treatment, non-ADHD disorders, and psychiatric comorbidity are necessary.

International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder Abstract. Background: Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance misuse and substance use disorder (SUD) in adolescence and (early) adulthood. ADHD and SUD also frequently co-occur in treatment-seeking adolescents, which complicates diagnosis and treatment and is associated with poor treatment outcomes. Research on the effect of treatment of childhood ADHD on the prevention of adolescent SUD is inconclusive, and studies on the diagnosis and treatment of adolescents with ADHD and SUD are scarce. Thus, the available evidence is generally not sufficient to justify robust treatment recommendations. Objective: The aim of the study was to obtain a consensus statement based on a combination of scientific data and clinical experience. Method: A modified Delphi study to reach consensus based upon the combination of scientific data and clinical experience with a multidisciplinary group of 55 experts from 17 countries. The experts were asked to rate a set of statements on the effect of treatment of childhood ADHD on adolescent SUD and on the screening, diagnosis, and treatment of adolescents with comorbid ADHD and SUD. Results: After 3 iterative rounds of rating and adapting 37 statements, consensus was reached on 36 of these statements representing 6 domains: general ( n = 4), risk of developing SUD ( n = 3), screening and diagnosis ( n = 7), psychosocial treatment ( n = 5), pharmacological treatment ( n = 11), and complementary treatments ( n = 7). Routine screening is recommended for ADHD in adolescent patients in substance abuse treatment and for SUD in adolescent patients with ADHD in mental healthcare settings. Long-acting stimulants are recommended as the first-line treatment of ADHD in adolescents with concurrent ADHD and SUD, and pharmacotherapy should preferably be embedded in psychosocial treatment. The only remaining no-consensus statement concerned the requirement of abstinence before starting pharmacological treatment in adolescents with ADHD and concurrent SUD. In contrast to the majority, some experts required full abstinence before starting any pharmacological treatment, some were against the use of stimulants in the treatment of these patients (independent of abstinence), while some were against the alternative use of bupropion. Conclusion: This international consensus statement can be used by clinicians and patients together in a shared decision-making process to select the best interventions and to reach optimal outcomes in adolescent patients with concurrent ADHD and SUD.

Objectives: This treatment trial is aimed at assessing the short-term tolerability and efficacy of liquid-formulation extended-release methylphenidate (MPH-ER) for the treatment of attention deficit/hyperactivity disorder (ADHD) in adults with high-functioning autism spectrum disorder (HF-ASD). Methods: A 6-week open-label trial (ClinicalTrials.gov: NCT02096952) was conducted in 15 HF-ASD adults (mean age 24.9 ± 4.6; male, 12 (80%)) suffering from moderate-severe ADHD. MPH-ER was administered based on a flexible titration schedule. Efficacy was assessed on clinician- and self-rated measures. Tolerability was assessed by documenting treatment-emergent adverse events (AEs) and other safety measures. Results: Short-term MPH-ER treatment was associated with significant improvement in ADHD severity (Adult ADHD Investigator Symptom Report Scale (AISRS) mean change (MC), -22.8 ± 8.8, P  < 0.001; Adult ADHD Self-Report Scale (ASRS) MC, -8.2 ± 15.3, P  < 0.001). Twelve (80%) participants were deemed responders, based on ≥30% reduction in AISRS score and an ADHD Clinical Global Impression-Improvement score ≤2. MPH-ER was well-tolerated (treatment-limiting AEs, 1/15; severe AEs, 1/15) at mean dose of 48.7 ± 15 mg/day. AEs were transient and experienced by 13/15 (87%) participants at mild to moderate severity. Frequently reported AEs were as typically expected (headache (53%), insomnia (33%), anxiety (33%), decreased appetite (27%)). Conclusions: Our findings suggest that MPH-ER is effective and well-tolerated in the treatment of ADHD in HF-ASD adults.

Background: Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance misuse and substance use disorder (SUD) in adolescence and (early) adulthood. ADHD and SUD also frequently co-occur in treatment-seeking adolescents, which complicates diagnosis and treatment and is associated with poor treatment outcomes. Research on the effect of treatment of childhood ADHD on the prevention of adolescent SUD is inconclusive, and studies on the diagnosis and treatment of adolescents with ADHD and SUD are scarce. Thus, the available evidence is generally not sufficient to justify robust treatment recommendations., Objective: The aim of the study was to obtain a consensus statement based on a combination of scientific data and clinical experience., Method: A modified Delphi study to reach consensus based upon the combination of scientific data and clinical experience with a multidisciplinary group of 55 experts from 17 countries. The experts were asked to rate a set of statements on the effect of treatment of childhood ADHD on adolescent SUD and on the screening, diagnosis, and treatment of adolescents with comorbid ADHD and SUD., Results: After 3 iterative rounds of rating and adapting 37 statements, consensus was reached on 36 of these statements representing 6 domains: general (n = 4), risk of developing SUD (n = 3), screening and diagnosis (n = 7), psychosocial treatment (n = 5), pharmacological treatment (n = 11), and complementary treatments (n = 7). Routine screening is recommended for ADHD in adolescent patients in substance abuse treatment and for SUD in adolescent patients with ADHD in mental healthcare settings. Long-acting stimulants are recommended as the first-line treatment of ADHD in adolescents with concurrent ADHD and SUD, and pharmacotherapy should preferably be embedded in psychosocial treatment. The only remaining no-consensus statement concerned the requirement of abstinence before starting pharmacological treatment in adolescents with ADHD and concurrent SUD. In contrast to the majority, some experts required full abstinence before starting any pharmacological treatment, some were against the use of stimulants in the treatment of these patients (independent of abstinence), while some were against the alternative use of bupropion., Conclusion: This international consensus statement can be used by clinicians and patients together in a shared decision-making process to select the best interventions and to reach optimal outcomes in adolescent patients with concurrent ADHD and SUD., (© 2020 S. Karger AG, Basel.)

Purpose/background: Interventions for attention-deficit/hyperactivity disorder (ADHD) may be inadequate for some patients. There is evidence that supplementation with L-methylfolate augments antidepressant agent effects and thus might also augment ADHD treatment effects by a common catecholaminergic mechanism., Methods: Forty-four adults with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of ADHD participated in a randomized, double-blind, placebo-controlled, 12-week trial of 15 mg of L-methylfolate in combination with osmotic-release oral system methylphenidate. Osmotic-release oral system methylphenidate was dose optimized over the first 6 weeks. We evaluated the effects on ADHD symptoms, self-report on the Behavior Rating Inventory of Executive Function of executive function, methylphenidate dosing, neuropsychological test measures, the Adult ADHD Self-report scale, emotional dysregulation, social adjustment, and work productivity, as well as moderating effects of body mass index, autoantibodies to folate receptors, and select genetic polymorphisms., Results: L-Methylfolate was well tolerated, with no significant effect over placebo except improvement from abnormal measures on the mean adaptive dimension of the ASR scale (χ = 4.36, P = 0.04). Methylphenidate dosing was significantly higher in individuals on L-methylfolate over time (χ = 7.35, P = 0.007). Exploratory analyses suggested that variation in a guanosine triphosphate cyclohydrolase gene predicted association with higher doses of methylphenidate (P < 0.001)., Conclusions: L-Methylfolate was associated with no change in efficacy on measures relevant to neuropsychiatric function in adults with ADHD, other than suggestion of reduced efficacy of methylphenidate. Further investigation would be required to confirm this effect and its mechanism and the genotype prediction of effects on dosing.

Objective: The main aim of this study was to examine the risk of exposure to parental substance use disorders (SUD; alcohol or drug abuse or dependence) on the risk for SUD in offspring with and without attention deficit hyperactivity disorder (ADHD) followed into young adult years., Methods: Subjects were derived from two longitudinal case-control studies of probands of both sexes, 6-17 years, with and without DSM-III-R ADHD and their parents. Probands were followed for ten years into young adulthood. Probands with a parental history of non-nicotine SUD were included in this analysis. Exposure to SUD was determined by active non-nicotine parental SUD while the parent was living with their child after birth. Cox proportional hazard models were used to calculate the risk of non-nicotine SUD in offspring., Results: 171 of the 404 probands reassessed at ten-year follow up had a family history of parental SUD. 102 probands were exposed to active parental SUD. The average age of our sample was 22.2 ± 3.5 years old. Exposure to maternal but not paternal SUD increased offspring risk for an alcohol use disorder in young adulthood independently of ADHD status (OR: 2.7; 95% CI: 1.1, 6.9; p = 0.04)., Conclusion: Exposure to maternal SUD increases the risk for an alcohol use disorder in offspring ten years later in young adult years irrespective of ADHD status., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Supratherapeutic doses of methylphenidate activate μ-opioid receptors, which are linked to euphoria. This study assessed whether naltrexone, a mixed μ-opioid antagonist, may attenuate the euphoric effects of stimulants, thereby minimizing their abuse potential in subjects with attention-deficit/hyperactivity disorder (ADHD)., Methods: We conducted a 6-week, double-blind, placebo-controlled, randomized clinical trial of naltrexone in adults with DSM-IV ADHD receiving open treatment with a long-acting formulation of methylphenidate (January 2013 to June 2015). Spheroidal Oral Drug Absorption System methylphenidate (SODAS-MPH) was administered twice daily, was titrated to ~1 mg/kg/d over 3 weeks, and was continued for 3 additional weeks depending on response and adverse effects. Subjects were adults with ADHD preselected for having experienced euphoria with an oral test dose of 60 mg of immediate-release methylphenidate (IR-MPH). The primary outcome measure was Question 2 (Liking a Drug Effect) on the Drug Rating Questionnaire, Subject version, which was assessed after oral test doses of 60 mg of IR-MPH were administered after the third and sixth weeks of treatment with SODAS-MPH., Results: Thirty-seven subjects who experienced stimulant-induced (mild) euphoria at a baseline visit were started in the open trial of SODAS-MPH and randomized to naltrexone 50 mg/d or placebo. Thirty-one subjects completed through week 3, and 25 completed through week 6. Naltrexone significantly diminished the euphoric effect of IR-MPH during the heightened-risk titration phase (primary outcome; first 3 weeks) (χ² = 5.07, P = .02) but not the maintenance phase (weeks 4-6) (χ² = 0.22, P = .64) of SODAS-MPH treatment., Conclusions: Preclinical findings are extended to humans showing that naltrexone may mitigate stimulant-associated euphoria. Our findings provide support for further studies combining opioid receptor antagonists with stimulants to reduce abuse potential., Trial Registration: ClinicalTrials.gov identifier: NCT01673594., (© Copyright 2018 Physicians Postgraduate Press, Inc.)

Objective: Methylphenidate activates μ-opioid receptors, which are linked to euphoria. μ-Opioid antagonists, such as naltrexone, may attenuate the euphoric effects of stimulants, thereby minimizing their abuse potential. This study assessed whether the combination of naltrexone with methylphenidate is well-tolerated while preserving the clinical benefits of stimulants in subjects with attention-deficit/hyperactivity disorder (ADHD)., Methods: We conducted a 6-week, double-blind, placebo-controlled, randomized clinical trial of naltrexone in adults with DSM-IV ADHD receiving open treatment with a long-acting formulation of methylphenidate from January 2013 to July 2015. Spheroidal Oral Drug Absorption System (SODAS) methylphenidate was administered twice daily, was titrated to approximately 1 mg/kg/d over 3 weeks, and was continued for 3 additional weeks depending on response and adverse effects. Subjects were adults with ADHD preselected for having experienced euphoria with a test dose of immediate-release methylphenidate. The primary outcome measure was the Adult ADHD Investigator Symptom Report Scale (AISRS)., Results: Thirty-seven subjects who experienced stimulant-induced (mild) euphoria at a baseline visit were started in the open trial of SODAS methylphenidate and randomly assigned to naltrexone 50 mg or placebo. Thirty-one subjects completed the study through week 3, and 25 completed through week 6. Throughout 6 weeks of blinded naltrexone and open methylphenidate treatment, the coadministration of naltrexone with methylphenidate did not interfere with the clinical effectiveness of methylphenidate for ADHD symptoms. Additionally, the combination of naltrexone and methylphenidate did not produce an increase in adverse events compared with methylphenidate alone., Conclusions: Our findings provide support for the concept of combining opioid receptor antagonists with stimulants to provide an effective stimulant formulation with less abuse potential., Trial Registration: ClinicalTrials.gov identifier: NCT01673594​., (© Copyright 2017 Physicians Postgraduate Press, Inc.)

Objective: The main aim of this study was to use familial risk analysis to examine the association between attention deficit hyperactivity disorder (ADHD) and substance use disorders (SUDs) attending to sex effects and the specificity of alcohol and drug use disorder risks., Methods: Subjects were derived from two longitudinal case-control family studies of probands aged 6-17 years with and without DSM-III-R ADHD of both sexes and their first degree relatives followed from childhood onto young adult years. Cox proportional hazard models were used to estimate rates of ADHD and SUDs (any SUD, alcohol dependence, and drug dependence). Logistic regression was used to test both co-segregation and assortative mating., Results: Our sample included 404 probands (ADHD: 112 boys and 96 girls; Control: 105 boys and 91 girls) and their 1336 relatives. SUDs in probands increased the risk for SUDs in relatives irrespective of ADHD status. The risk for dependence to drug or alcohol in relatives was non-specific. There was evidence that even in the absence of a SUD in the proband, ADHD by itself increased the risk of SUDs in relatives. Proband sex did not moderate the familial relationship between ADHD and SUDs. There was evidence of co-segregation between ADHD and SUD., Conclusions: Findings indicate that various independent pathways are involved in the transmission of SUD in ADHD and that these risks were not moderated by proband sex. ADHD children and siblings should benefit from preventive and early intervention strategies to decrease their elevated risk for developing a SUD., Competing Interests: MaryKate Martelon and Nicholas Carrellas: The authors have no conflict of interest relevant to this article to disclose., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: The nonmedical use of stimulants (misuse) in the college setting remains of utmost public health and clinical concern. The objective of this study was to evaluate comprehensively the characteristics of college students who misused stimulants, attending to rates of attention-deficit/hyperactivity disorder (ADHD), other psychopathology, and substance use disorders., Methods: The data presented are from a cross-sectional study of college students who misused prescription stimulant medications (not including cocaine or methamphetamine) and controls (college students without stimulant misuse). Between May 2010 and May 2013, college students were assessed blindly for psychopathology and substance use disorder by way of Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition (SCID-I/P) and completion of self-report questionnaires., Results: The analysis included 198 controls (mean ± SD age = 20.7 ± 2.6 years) and 100 stimulant misusers (20.7 ± 1.7 years). Misusers, when compared to controls, were more likely to endorse alcohol, drug, alcohol + drug, and any substance use disorder (all P values < .01). When a subset of stimulant misusers (n = 58) was examined, 67% had a full or subthreshold prescription stimulant use disorder. Misusers also had higher rates of conduct disorder (10% vs 3%; P = .02) and ADHD (including subthreshold cases; 27% vs 16%; P = .02) in addition to lower Global Assessment of Functioning score (P < .01). Higher rates of misuse of immediate-release—relative to extended-release—stimulants were reported., Conclusions: Our data suggest that, compared to controls, college students who misuse stimulant medications are more likely to have ADHD, conduct disorder, stimulant and other substance use disorder, and overall dysfunction.