Predictive utility of autistic traits in youth with ADHD: a controlled 10-year longitudinal follow-up study.

The objective of this study was to investigate the stability and predictive utility of autistic traits (ATs) in youth with attention-deficit/hyperactivity disorder (ADHD). Participants were referred youth with and without ADHD, without a diagnosis of autism spectrum disorder, and their siblings, derived from identically designed longitudinal case-control family studies of boys and girls with ADHD. Subjects were assessed with structured diagnostic interviews and measures of social, cognitive, and educational functioning. The presence of ATs at baseline was operationalized using a unique profile of the Child Behavior Checklist (CBCL) consisting of an aggregate T score of ≥ 195 on the Withdrawn, Social, and Thought Problems subscales (CBCL-AT profile). At the follow-up, 83% of the ADHD youth with a positive AT profile at baseline continued to have a positive CBCL-AT profile. The presence of a positive CBCL-AT profile at baseline in youth with ADHD heralded a more compromised course characterized by a greater burden of psychopathology that emerged at an earlier age, along with poorer interpersonal, educational, and neurocognitive outcomes. Findings indicate a high level of persisting ATs in ADHD youth over time, as indexed through the CBCL-AT profile, and the presence of this profile prognosticates a compromised course in adult life in multiple domains of functioning.

A Novel Text Message Intervention to Improve Adherence to Stimulants in Adults With Attention Deficit/Hyperactivity Disorder.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a prevalent neurobiological disorder associated with a wide range of adverse outcomes. Although large data sets document that stimulants decrease the risks for many ADHD-associated adverse outcomes, compliance with stimulants remains very poor. The main aim of this study was to assess the effectiveness of a novel text messaging-based intervention aimed at improving the poor rate of adherence to stimulant medications in adults with ADHD. METHODS: Subjects were adults with ages 18 to 55, prescribed a stimulant medication for ADHD treatment. For comparators, we identified at a 5-to-1 ratio (age and sex matched) adult patients from the Partners HealthCare electronic medical record who had been prescribed stimulant medications over a 1-year period. We determined whether patients had timely prescription refills, defined as refilled within 37 days, using prescriptions documented in their electronic medical record. RESULTS: Our results showed that 68% of the SMS intervention group refilled their prescriptions in a timely manner. In contrast, only 34% of patients receiving treatment as usual refilled their prescriptions in a timely fashion (odds ratio, 4.04; 95% confidence interval, 2.49-6.56; P < 0.001). CONCLUSIONS: These data indicate that an innovative ADHD-centric text messaging intervention significantly improved patient engagement to treatment with stimulants in adults with ADHD. Findings provide strong support for the use of a readily accessible, inexpensive, and widely available technology to improve the poor rate of adherence to stimulant treatment in adults with ADHD. To the best of our knowledge, this study is the first digital health intervention aimed at improving adherence to stimulant medication for adults with ADHD.

Neuropsychological changes in patients with substance use disorder after completion of a one month intensive outpatient treatment program.

BACKGROUND AND OBJECTIVES: Data suggest individuals with substance use disorders (SUD) exhibit high rates of executive functioning (EF) impairment, and that EF level can predict treatment retention. The primary aim of the present study was to investigate if patients who completed a 1 month intensive outpatient program (IOP) for SUD demonstrated recovered EF. METHODS: Baseline and follow-up neurocognitive functioning was assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB) and the self-reported Behavior Rating Inventory of Executive Functioning (BRIEF-A) questionnaire. RESULTS: The final sample included 15 patients who completed the one month IOP and for whom data were available (53% male, aged 36 years ± 13.4). Despite exhibiting general improvements in EF and significant improvements in organization, subjects continued to manifest significant executive dysfunction as evaluated by self-report and computerized assessment. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Patients with SUD often manifest high levels of executive dysfunction upon entry into SUD treatment that, while improving minimally, appears to persist despite intensive outpatient treatment at 1 month. These persistent EF deficits may affect patient engagement and participation in treatment, thus necessitating SUD programs to assess and accommodate EF issues throughout treatment. (Am J Addict 2018;XX:1-7).

Factors associated with attrition in substance using patients enrolled in an intensive outpatient program.

BACKGROUND AND OBJECTIVES: Data suggest individuals with substance use disorders (SUD) have high rates of attrition from treatment and exhibit impairments on measures of executive functioning (EF). The primary aim of this pilot study was to investigate if EF is associated with attrition from a 1 month intensive outpatient program (IOP) for SUD, and examine the feasibility of implementing the project. METHODS: Baseline neurocognitive functioning was assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB) and the self-reported Behavior Rating Inventory of Executive Functioning (BRIEF-A) questionnaire. RESULTS: Thirty subjects enrolled in the pilot study: including 20 "completers" (age 39.5 ± 13.1 years) and 10 "drop-outs" who discontinued the IOP prior to completion (age 32 ± 11.1 years). IOP drop-out was associated with earlier age of substance use onset (all p-values <0.05) and male gender, as well as greater SUD, opiate use, and past week substance use. Overall a high level of executive dysfunction was found on the BRIEF-A and CANTAB assessments, and specific differences emerged between completers and drop outs. However, no statistically significant differences were found between these groups on measures of depression, anxiety, or ADHD. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Overall, findings from this pilot study suggest high levels of self-reported executive dysfunction, but EF's predictive association with drop-out was limited. Measures of addiction severity were more strongly associated with attrition, suggesting potential utility of brief motivational interventions prior to commencing an IOP may improve retention. Further investigations with larger and more diverse samples are warranted. (Am J Addict 2017;26:780-787).

Neuropsychological functioning in college students who misuse prescription stimulants.

BACKGROUND AND OBJECTIVES: Relatively little is known about the neuropsychological profiles of college students who misuse prescription stimulant medications. METHODS: Data presented are from college students aged 18-28 years who misused prescription stimulants prescribed for attention-deficit/hyperactivity disorder and controls (no prescription stimulant misuse). Students were assessed neuropsychologically using the self-report Behavioral Rating Inventory of Executive Functioning (BRIEF-A), the Cambridge Automated Neuropsychological Test and Battery (CANTAB), and other tests of cognitive functioning. The analyses included 198 controls (age 20.7 ± 2.6 years) and 100 prescription stimulant misusers (age 20.7 ± 1.7 years). RESULTS: On the BRIEF-A, misusers were more likely than controls to endorse greater dysfunction on 8 of 12 measures including Inhibition, Self Monitor, Initiation, Working Memory, and Plan/Organize, when adjusting for race and sex (all p's < .05). Similarly, when dichotomizing the BRIEF-A as abnormal (T score ≥ 65), misusers had more abnormalities on five of nine subscales, as well as all major indices (p's < .05). Misusers also performed worse on several subtests of the CANTAB and standardized cognitive battery (p's < .05). A proxy of prescription stimulant misuse frequency was positively correlated with greater executive dysfunction on the BRIEF-A. DISCUSSION AND CONCLUSIONS: These data demonstrate elevated risk for neuropsychological dysfunction among students who misuse prescription stimulants compared to non-misusing peers. The presence of ADHD contributed significantly to these cognitive findings. Students who misuse prescription stimulants should be screened for neuropsychological dysfunction. SCIENTIFIC SIGNIFICANCE: These data may better elucidate the neuropsychological profile of college-aged prescription stimulant misusers. (Am J Addict 2017;26:379-387).

Towards operationalising internal distractibility (Mind Wandering) in adults with ADHD.

OBJECTIVE: To investigate whether specific symptoms of attention deficit hyperactivity disorder (ADHD) can help identify ADHD patients with mind wandering. METHODS: Subjects were adults ages 18-55 of both sexes (n=41) who completed the Mind-Wandering Questionnaire (MWQ) and the ADHD module of the Schedule for Affective Disorders and Schizophrenia for School-Age Children Epidemiologic Version. We used Spearman's rank correlation and Pearson's χ2 analyses to examine associations between the ADHD module and the MWQ and receiver operator characteristic (ROC) analyses to evaluate the diagnostic efficiency of the ADHD module. RESULTS: Out of the three ADHD domains, the inattentive ADHD scores had the strongest association with the MWQ (total: r s=0.34, df=39, p=0.03; inattentive: r s=0.38, df=39, p=0.02; Hyperactive: r s=0.17, df=39, p=0.28). Correlation analyses between individual items on the ADHD module and the MWQ showed that two inattention items ('failure to pay attention to detail' and 'trouble following instructions') were positively associated with total scores on the MWQ (p=0.02). These two inattention items had the strongest association with the MWQ (r s=0.45, df=38, p=0.004). ROC analyses showed that the combined score of the two significant inattention items had the highest efficiency (AUC=0.71) in classifying high-level mind wanderers as defined by scores greater than the median split on the MWQ. The combined score of the two inattention items best identified high-level mind wanderers. CONCLUSION: Results suggest a way to operationalise mind wandering using the symptoms of ADHD.

A Prospective Open-Label Trial of Memantine Hydrochloride for the Treatment of Social Deficits in Intellectually Capable Adults With Autism Spectrum Disorder.

This prospective 12-week open-label trial evaluates the tolerability and efficacy of memantine hydrochloride for the treatment of core social and cognitive deficits in adults with high-functioning autism spectrum disorder (ASD). Measures for assessment of therapeutic response included the Social Responsiveness Scale-Adult Research Version (SRS-A), disorder-specific Clinical Global Impression scales, Behavior Rating Inventory of Executive Functioning-Adult Self-Report, Diagnostic Analysis of Nonverbal Accuracy Scale, and Cambridge Neuropsychological Test Automated Battery. Eighteen adults (mean age, 28 ± 9.5 years) with high-functioning ASD (SRS-A raw score, 99 ± 17) were treated with memantine (mean dose, 19.7 ± 1.2 mg/d; range, 15-20 mg), and 17 (94%) completed the trial. Treatment with memantine was associated with significant reduction on informant-rated (SRS-A, -28 ± 25; P < 0.001) and clinician-rated (Clinical Global Impression-Improvement subscale ≤2, 83%) measures of autism severity. In addition, memantine treatment was associated with significant improvement in ADHD and anxiety symptom severity. Significant improvement was noted in nonverbal communication on the Diagnostic Analysis of Nonverbal Accuracy Scale test and in executive function per self-report (Behavior Rating Inventory of Executive Functioning-Adult Self-Report Global Executive Composite, -6 ± 8.8; P < 0.015) and neuropsychological assessments (Cambridge Neuropsychological Test Automated Battery). Memantine treatment was generally well tolerated and was not associated with any serious adverse events. Treatment with memantine appears to be beneficial for the treatment of ASD and associated psychopathology and cognitive dysfunction in intellectually capable adults. Future placebo-controlled trials are warranted.

A study of the neuropsychological correlates in adults with high functioning autism spectrum disorders.

OBJECTIVE: To examine the unique neuropsychological presentation in adults with high functioning autism spectrum disorders (HF-ASD) by comparison with adults with attention deficit hyperactivity disorder (ADHD). METHODS: Adults with ASD referred to a specialty clinic (n=26) were compared to two non-ASD groups with (n=52) and without (n=52) ADHD of similar age and sex. RESULTS: No differences in IQ were found. Subjects with HF-ASD were significantly more impaired than both comparison groups in processing speed, cognitive flexibility and sight words. Subjects with HF-ASD were more impaired than controls in working memory, but not the ADHD group. CONCLUSION: These findings suggest that there may be specific neuropsychological correlates of HF-ASD differing from ADHD that could have significant implications for identifying individuals at risk for ASD.

An examination of the impact of attention-deficit hyperactivity disorder on IQ: a large controlled family-based analysis.

OBJECTIVE: Although children with attention-deficit hyperactivity disorder (ADHD) have, on average, lower intelligence quotient (IQ) scores than control subjects, the reasons for these deficits remain unknown. Because IQ is highly familial, we investigated whether children with ADHD have a decrement in IQ from expectations based on parental IQ. METHOD: Subjects were 276 children with ADHD and 239 control subjects of similar age and sex. Expected IQ was calculated based on biological parents' estimated IQ. A significant discrepancy between observed and expected estimated IQ was defined by a child scoring 15 IQ points or more lower than expected, based on parental IQ. RESULTS: Compared with control subjects, children with ADHD were significantly more likely to have lower than expected estimated IQ scores based on parental IQ, though this finding was accounted for by a small subgroup of children with ADHD who had an IQ 15 points or more lower than expected, based on parental IQ. These children were more likely to be female, have higher psychopathological, neuropsychological, educational, and interpersonal deficits, as well as higher rates of perinatal complications. CONCLUSIONS: Group differences in IQ scores between children with and without ADHD reported in the literature may be accounted for by a subgroup of children with ADHD who have a large decrement in IQ from expectations based on parental IQ. Although perinatal complications may explain these findings, more work is needed to better understand the etiology of these IQ deficits.

Examining the association between stimulant treatment and cognitive outcomes across the life cycle of adults with attention-deficit/hyperactivity disorder: a controlled cross-sectional study.

Few studies have evaluated the effects of stimulants on cognition in adults with attention-deficit/hyperactivity disorder (ADHD). We evaluated the impact of stimulant treatment on neurocognition in a cross-sectional sample of adults with ADHD. Comparisons were made between adults with ADHD who received (n = 105) and who had never received pharmacotherapy (n = 116) and 146 controls. The subjects were assessed cross-sectionally using a structured diagnostic interview and a neurocognitive battery. We modeled cognitive measures as a function of age and group status using linear regression. Treated ADHD subjects had statistically significantly better scores on measures of IQ than did untreated ones. The treated group also had better (not statistically significant) scores on neuropsychological measures. The direction of the effects of stimulant on neurocognition suggests that either good cognitive functioning may be a determinant of seeking treatment or that stimulant treatment may improve cognition in adults with ADHD. However, this does not indicate a clear causal relationship.

Using a Digital Meditation Application to Mitigate Anxiety and Sleep Problems in Children with ADHD.

Objective: ADHD affects 11% of children in the United States and is associated with significant levels of anxiety. Although the literature supports mindfulness-based interventions as a promising strategy for managing anxiety, it falls short in the feasibility of digital mindfulness interventions. Method: This study investigated the usefulness of the pediatric version of Headspace, a digital mindfulness program, for reducing stress in 18 children with ADHD. We conducted a 4-week pilot study to evaluate the Headspace digital mindfulness application for children ages 6 to 12 with ADHD. Parents completed the Beck Anxiety Inventory and the Children's Sleep Habits Questionnaire at baseline and endpoint. Results: Participants had an average age of 9.2 years and were 78% male. The Headspace intervention significantly reduced anxiety and sleep problems in children with ADHD. Conclusion: Children with ADHD and comorbid anxiety and/or sleep problems could benefit from a digitally based meditation application. (J. of Att. Dis. XXXX; XX(X) XX-XX).

Impact of executive function deficits in youth with bipolar I disorder: a controlled study.

Although psychometrically-defined executive function deficits (EFDs) and ecologically valid functional outcomes have been documented among youth with bipolar I (BP-I) disorder, little is known about their association. We hypothesized that EFDs would be associated with significant ecologically valid impairments beyond those predicted by having BP-I disorder. Youth with BP-I disorder were ascertained from psychiatric clinics and community sources. We defined EFDs as having at least two out of eight EF measures impaired from a battery of six tests. Significantly more youth with BP-I disorder had EFDs than controls (45% versus 17%). Comparisons were made between controls without EFDs (N=81), controls with EFDs (N=17), BP-I youth without EFDs (N=76), and BP-I youth with EFDs (N=62). EFDs were associated with an increased risk for placement in a special class and a decrease in academic achievement (WRAT-3 reading and arithmetic). EFDs in BP-I subjects were associated with an increased risk for speech/language disorder (as assessed in the K-SADS-E) relative to BP-I subjects without EFDs. Youth with BP-I disorder and EFDs are at high risk for significant impairments in academic functioning.

Discriminant and concurrent validity of a simplified DSM-based structured diagnostic instrument for the assessment of autism spectrum disorders in youth and young adults.

BACKGROUND: To evaluate the concurrent and discriminant validity of a brief DSM-based structured diagnostic interview for referred individuals with autism spectrum disorders (ASDs). METHODS: To test concurrent validity, we assessed the structured interview's agreement in 123 youth with the expert clinician assessment and the Social Responsiveness Scale (SRS). Discriminant validity was examined using 1563 clinic-referred youth. RESULTS: The structured diagnostic interview and SRS were highly sensitive indicators of the expert clinician assessment. Equally strong was the agreement between the structured interview and SRS. We found evidence for high specificity for the structured interview. CONCLUSIONS: A simplified DSM-based ASD structured diagnostic interview could serve as a useful diagnostic aid in the assessment of subjects with ASDs in clinical and research settings.

Can the CANTAB identify adults with attention-deficit/hyperactivity disorder? A controlled study.

We examined the diagnostic utility of the Cambridge Neuropsychological Test Automated Battery (CANTAB) for identifying adults with attention-deficit/hyperactivity disorder (ADHD). The sample consisted of clinically referred adults aged 18 to 60 years old, with (n = 474) and without (n = 163) DSM-IV diagnosis of ADHD. All subjects were administered seven subtests from the CANTAB that targeted domains of executive functioning and verbal memory. Data were analyzed to identify which CANTAB tasks would best predict ADHD status. Our results failed to show any diagnostic utility for the CANTAB in adults with ADHD, even when using the most robust tests (Affective Go/No-go [AGN] Total Commissions and [RTI] Simple Reaction Time) identified from stepwise logistic regression (forward selection; p > 0.05 for entry). However, the CANTAB was helpful in identifying executive functioning disorder (EFD) in adults with ADHD when compared with controls subjects. Even though the CANTAB lacked diagnostic utility for adults with ADHD, the findings provided further evidence that adult ADHD is strongly associated with EFD. This study represents the most comprehensive evaluation of the diagnostic utility of the CANTAB in a clinical sample of adults with ADHD.

Further evidence of low adherence to stimulant treatment in adult ADHD: an electronic medical record study examining timely renewal of a stimulant prescription.

RATIONALE: ADHD is a prevalent and morbid neurobiological disorder affecting up to 5% of adults. While stimulants have been documented to be safe and effective in adults with ADHD, uncertainties remain about adherence to these treatments. OBJECTIVES: The main aim of this article was to evaluate contemporaneous rates and correlates of adherence to stimulants in adults with ADHD using data from electronic medical records from a large healthcare organization focusing on timely renewal of an initial prescription. METHODS: Subjects were patients 18 to 44 years of age who had been prescribed a stimulant between January 1, 2015, and December 31, 2016. Prescription and sociodemographic data were extracted from the Partners HealthCare Research Patient Data Registry (RPDR). Our outcome metric was renewal of the index stimulant prescription defined as the first prescription recorded in the electronic record for the period under investigation. RESULTS: We identified 2689 patients with an index prescription for a stimulant medication. Results showed that only 42% of patients renewed their prescriptions in a timely enough fashion to be considered consistently medicated. CONCLUSIONS: Results indicate that adults with ADHD have a low rate of renewal of their initial stimulant prescription indicating poor patient engagement in their treatment for ADHD.

A novel digital health intervention to improve patient engagement to stimulants in adult ADHD in the primary care setting: Preliminary findings from an open label study.

AIMS: We piloted the effectiveness and acceptability of a novel text messaging-based (SMS) digital health intervention aimed at addressing the previously documented poor rate of patient engagement in stimulant treatment in the primary care setting. METHODS: 117 adults ages 18-55 from primary care and psychiatric practices who were prescribed a stimulant medication for ADHD treatment received the SMS intervention. Comparators were age-, race-, and sex-matched patients from the same health care organization's electronic medical record who had been prescribed stimulant medications over a similar time period. Using documented prescription records, we determined whether patients had timely prescription refills. RESULTS: Ninety-six percent (N = 112) of participants completed our a priori metric of patient engagement consisting of 37 days of the SMS program. Eighty-one percent of participants refilled their index prescriptions in a timely manner compared to only 36% of patients receiving treatment as usual (OR=7.54, 95% CI: 4.46, 12.77; p<0.001). We found no significant interaction between prescribing source (non-psychiatry vs. psychiatry) and intervention group (SMS vs. treatment as usual). CONCLUSIONS: These data suggest that an ADHD-centric, digital health intervention using text messaging significantly improves patient engagement in stimulant treatment in adults with ADHD.

Toward operationalizing deficient emotional self-regulation in newly referred adults with ADHD: A receiver operator characteristic curve analysis.

BACKGROUND: A growing body of research suggests that deficient emotional self-regulation (DESR) is common and morbid among attention-deficit/hyperactivity disorder (ADHD) patients. The main aim of the present study was to assess whether high and low levels of DESR in adult ADHD patients can be operationalized and whether they are clinically useful. METHODS: A total of 441 newly referred 18- to 55-year-old adults of both sexes with Diagnostic and Statistical Manual of Mental Disorders: Fifth Edition (DSM-5) ADHD completed self-reported rating scales. We operationalized DESR using items from the Barkley Current Behavior Scale. We used receiver operator characteristic (ROC) curves to identify the optimal cut-off on the Barkley Emotional Dysregulation (ED) Scale to categorize patients as having high- versus low-level DESR and compared demographic and clinical characteristics between the groups. RESULTS: We averaged the optimal Barkley ED Scale cut-points from the ROC curve analyses across all subscales and categorized ADHD patients as having high- (N = 191) or low-level (N = 250) DESR (total Barkley ED Scale score ≥8 or <8, respectively). Those with high-level DESR had significantly more severe symptoms of ADHD, executive dysfunction, autistic traits, levels of psychopathology, and worse quality of life compared with those with low-level DESR. There were no major differences in outcomes among medicated and unmedicated patients. CONCLUSIONS: High levels of DESR are common in adults with ADHD and when present represent a burdensome source of added morbidity and disability worthy of further clinical and scientific attention.

A literature review and meta-analysis on the effects of ADHD medications on functional outcomes.

OBJECTIVE: To conduct a systematic review and meta-analysis of literature from large databases and registries to assess the effects of ADHD medication on associated functional outcomes. STUDY DESIGN: A literature search was performed in PubMed, PsycINFO, MEDLINE, and Web of Science for articles published prior to January 2019. Sample size, age range, country of origin, medication type, number of functional events and non-events, odds ratios and hazard ratios, and means and standard deviations were extracted. Random-effects meta-analyses were conducted for 21 studies examining functional outcomes. RESULTS: 40 articles were included. The majority suggest a robust protective effect of ADHD medication treatment on mood disorders, suicidality, criminality, substance use disorders, accidents and injuries, traumatic brain injuries, motor vehicle crashes, and educational outcomes. Similarly, the meta-analyses demonstrated a protective effect of medication treatment on academic outcomes, accidents and injuries, and mood disorders. CONCLUSIONS: These findings suggest that ADHD medication treatments are associated with decreases in the risks for a wide range of ADHD-associated functional outcomes supporting efforts aimed at early diagnosis and treatment of individuals with ADHD.

An innovative SMS intervention to improve adherence to stimulants in children with ADHD: Preliminary findings.

BACKGROUND: Although large datasets document that stimulants decrease the risk for many adverse ADHD-associated outcomes, compliance with stimulants remains poor. AIMS: This study examined the effectiveness of a novel ADHD-centric text messaging-based intervention aimed to improve adherence to stimulant medications in children with ADHD. METHODS: Subjects were 87 children aged 6-12, who were prescribed a stimulant medication for ADHD treatment. Prescribers gave permission to contact their patients for participation in the study. Subjects were primarily from the primary care setting with a subsample of psychiatrically referred subjects for comparison. Age- and sex-matched comparators were identified (3:1) from the same pool of prescriber-approved subjects that did not participate. Timely prescription refills (within 37 days) were determined from prescription dates documented in patients' electronic medical record. RESULTS: Eighty-five percent of SMS intervention patients refilled their prescriptions in a timely manner compared with 62% of patients receiving treatment as usual (OR = 3.46, 95% CI: 1.82, 6.58; p < 0.001). The number needed to treat statistic was computed as five, meaning for every five patients who receive the SMS intervention, we can keep one adherent to their stimulant treatment. CONCLUSIONS: These preliminary findings support the potential utility of a readily accessible technology to improve the poor rate of adherence to stimulant treatment in children with ADHD. To the best of our knowledge, this study is the first digital health intervention aimed at improving adherence to stimulant medication for children with ADHD. These results support the need for further examination of this technology through more definitive randomized clinical trials.

A prospective open-label trial of long-acting liquid methylphenidate for the treatment of attention deficit/hyperactivity disorder in intellectually capable adults with autism spectrum disorder.

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.