Slow Processing Speed and Sluggish Cognitive Tempo in Pediatric Attention-Deficit/Hyperactivity Disorder: Evidence for Differentiation of Functional Correlates.

The association between slow processing speed and sluggish cognitive tempo (SCT), a phenotype described within attention-deficit/hyperactivity disorder (ADHD) samples over the past decade, remains unclear. We examined whether SCT and processing speed predict different functional correlates within children and adolescents with ADHD. Participants were 193 clinically-referred youth meeting DSM ADHD criteria without comorbid conditions (mean age = 9.9 years, SD = 2.5; age range 6-16). The incremental utility of SCT and processing speed to predict (1) adaptive functioning and (2) academic achievement, after controlling for age, sex, medication status, and ADHD symptom burden, was assessed using hierarchical multiple regressions. SCT symptoms significantly predicted adaptive functioning, accounting for 6% of the variance, but did not predict academic achievement. Processing speed did not add incrementally to the prediction of adaptive functioning, but did predict academic achievement, accounting for 4% of the variance. Results suggest that SCT and processing speed differentially predict functional abilities not accounted for by ADHD symptom burden.

Comparing Pharmacotherapies for ADHD in Adults: Evidence From Outcome-Focused Analysis of Food and Drug Administration Drug Label Registration Trials.

OBJECTIVE: We appraised whether FDA registration trials for ADHD pharmacotherapy in adults provides comparable information to inform treatment expectations. METHOD: Comparison of ADHD outcome measure patterns in ADHD pharmacotherapy FDA drug label source studies. RESULTS: Among stimulants, from fixed-dose titration data, amphetamine agents had numerically higher placebo-corrected symptom improvement and symptom effect sizes than methylphenidate agents. Symptom effect sizes were lower in the flexible dosing registration studies of atomoxetine and viloxazine. Varying responder definitions were analyzable, based on ≥30% symptom improvement and/or CGI-I improvement of "much" or "very much improved." Number of exposures needed to create these responses were lower for stimulants than for viloxazine. CONCLUSION: Heterogeneity in the design and analysis of FDA drug label source trials restricts implications for clinical practice. Research conducted using replicated designs, direct comparison of available treatments, and outcome analyses that generalize to clinical care could better inform clinical decision making.

Can Adverse Event Patterns Inform Shared Decision-Making in ADHD Treatment? A Systematic Review of Evidence From Registration Trials for FDA-Approved Treatments in Adults.

INTRODUCTION: Adult patients and clinicians are faced with several pharmacological options to manage attention-deficit/hyperactivity disorder (ADHD). If types or rates of adverse experiences vary among these options, these differences could inform the shared decision-making process. METHODS: To discern differentiating evidence-based patterns of risk, we analyzed data from FDA package labels for drugs approved to treat adult ADHD and reports from the registration trials used to create these labels. Three analyses of adverse effects were conducted: placebo-corrected occurrence at rates of 1 in 5, 10, and 20 participants, association with discontinuation, and uniqueness of occurrence within the treatment options. RESULTS: Among the 7 agents approved to treat adult ADHD, the number of types of side effects experienced during a mix of fixed and flexible-dose studies was greatest among the nonstimulant medications, but the stimulant medications had higher rates of occurrence of side effects. The minimum frequency at which all medications had adverse events was 1 in 10 participants. Overall discontinuation rates did not differ among the stimulant medications nor between stimulants and nonstimulants. DISCUSSION: To our knowledge, this is the first study to compile and compare data from all FDA registration trials for medications approved to treat adult ADHD. This article describes a process by which readily available adverse event reporting data can be used as a tool to inform shared clinical decision-making. While differences in the methodology and outcome reporting of the trials included may limit generalizability, the number of individual patients included and the completeness of the discontinuation data can be used to inform discussions with patients about the relative likelihood of adverse experiences and other patient concerns.

Treating Executive Function in Youth With Attention Deficit Hyperactivity Disorder: A Review of Pharmacological and Non-Pharmacological Interventions.

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.

Do ADHD Treatments Improve Executive Behavior Beyond Core ADHD Symptoms in Adults? Evidence From Systematic Analysis of Clinical Trials.

We sought to understand the effect of current treatments for attention deficit hyperactivity disorder (ADHD) on executive functioning deficits, which are often comorbid with ADHD, via a systematic analysis of adult ADHD treatment studies evaluating change in behavioral measures beyond the core symptoms of Diagnostic and Statistical Manual of Mental Disorders ADHD. The standardized mean difference for behavioral measures of executive functioning was determined from controlled trials of adults with ADHD and compared with effects on core ADHD symptoms. Several studies of atomoxetine revealed small to large standardized mean differences. Nonreplicated studies revealed small to medium effects for triple-bead mixed amphetamine salts, lisdexamfetamine, and forms of cognitive behavioral therapy. Proportional effect versus core ADHD symptoms ranged from 0.78 to 1.16 for atomoxetine, and from 0.65 to 1.44 across all the studies. ADHD treatments have effects on executive functioning behavior beyond core ADHD symptoms in adults. Clinicians can measure and treat this morbidity using available clinical tools.

Solriamfetol for Attention-Deficit/Hyperactivity Disorder in Adults: A Double-Blind Placebo-Controlled Pilot Study.

Objective: Some individuals with attention-deficit/hyperactivity disorder (ADHD) may not tolerate or adequately respond to currently available treatments. This study examined whether solriamfetol could have a favorable pattern of effects and tolerability as a treatment for ADHD in adults.Methods: Sixty adults with DSM-5 ADHD participated from August 2021 through January 2023 in a remotely conducted, randomized, double-blind, placebo-controlled, 6-week dose-optimization trial of 75 mg or 150 mg of solriamfetol. Measures included the Adult ADHD Investigator Symptom Rating Scale (AISRS), which was our primary outcome measure, as well as the Clinical Global Impressions scale (CGI), vital signs, the Global Assessment of Functioning (GAF), the Behavior Rating Inventory of Executive Function-Adult Form (BRIEF-A), the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI), and a modified Adult ADHD Self-Report Scale (MASRS).Results: Solriamfetol was well tolerated, with no significant effect on mean heart rate (+3.7 vs +2.2 bpm, P = .5609), systolic blood pressure (+2.4 vs +1.5 mm Hg, P = .6474), or diastolic blood pressure (+1.1 vs +1.5 mm Hg, P = .8117). There was no statistically significant treatment effect on occurrence of adverse events. Compared to individuals on placebo, individuals on solriamfetol treatment experienced adverse events at a rate of at least 10 percentage points higher in the categories of decreased appetite, headache, gastrointestinal, insomnia, increased energy, cardiovascular, and neurologic. Compared to individuals on placebo, by study endpoint, a greater proportion of individuals in the treatment group met the a priori-defined treatment response (CGI score indicating much or very much improved and AISRS score reduced ≥ 25%: 45% vs 6.9%, P = .0020); those treated with solriamfetol also had greater improvement in total AISRS scores by week 3 through week 6 (P = .0012; week 6 effect size = 1.09). Significantly more solriamfetol-treated adults than placebo-treated adults had 0.5-standard deviation improvement in T-score on the BRIEF-A Global Executive Composite (P = .0173); those treated with solriamfetol also had greater mean change in GAF score (-4.8 vs -0.3, P = .0006) and greater mean MASRS total score change (P = .0047; effect size = 1.23). Mean ESS score improved more with solriamfetol than with placebo (P = .0056), but this difference did not predict AISRS response (P = .3735). There was no significant association between solriamfetol and change in PSQI scores.Conclusions: Solriamfetol may be a novel and effective treatment for the management of ADHD in adults. Further replication in larger trials is indicated.Trial Registration: ClinicalTrials.gov identifier: NCT04839562.

Understanding the Impact of Stimulants on Sleep in ADHD: Evidence from Systematic Assessment of Sleep in Adults.

Stimulants are widely prescribed to manage attention-deficit/hyperactivity disorder (ADHD) in adults. Stimulants promote wakefulness and can produce insomnia side effects. We hypothesized that systematic studies of sleep effects would reveal patterns of sleep impairment that may be important for clinicians to monitor and manage. We conducted a review and analysis of studies that measured sleep systematically during stimulant treatment in adults. We identified nine studies that met our search criteria, including four double-blind placebo-controlled studies. All studies recorded self-report subjective sleep quality data, three studies collected actigraphy data, and three studies collected polysomnography data. One study found better subjective sleep quality under open-label treatment conditions. Both polysomnography studies found improvement in aspects of sleep patterns. Two of the actigraphy studies suggested that adults receiving stimulant treatment may have less movement during sleep, and one showed reduction in amount of sleep. Further research could inform best practices for maintaining sleep quality during stimulant treatment.

Do Treatments for Adult ADHD Improve Emotional Behavior? A Systematic Review and Analysis.

OBJECTIVE: Dysregulated emotional behavior occurs often in adults with ADHD. Analysis of clinical trials may guide clinical intervention and future research. METHOD: Controlled trials of adult ADHD measuring emotional behavior were included if another study offered a comparable analysis of the same treatment method. Standardized Mean Difference (SMD) of effects were calculated, and the size of effects for emotional and non-emotional ADHD behavior were compared. RESULTS: 13 out of 14 studies of methylphenidate, atomoxetine, and lisdexamfetamine demonstrated significant improvement in emotional behavior measures, with small to high SMDs. The proportional effect on emotional versus non-emotional behavior ranged from 46% to 110% for methylphenidate, 56% to 129% for atomoxetine, and 36% to 96% for lisdexamfetamine. CONCLUSION: Psychopharmacological treatments for ADHD are likely to improve emotional behavior, and available scales are sensitive to these effects. Studies dedicated to treatment of this domain of function can further refine clinical approaches.

Adult attention-deficit/hyperactivity disorder treatment and cardiovascular implications.

Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurobehavioral disorder afflicting adults worldwide. This article is an update on the evidence supporting medications for adult ADHD, with particular emphasis on cardiovascular implications. Relevant clinical literature was sought using PubMed searches, with an emphasis on new reports from April 2009 to April 2011. This review describes the efficacy and general tolerability of stimulant and nonstimulant medications for adults with ADHD as seen in contemporary clinical trials. Cardiovascular response to medications for ADHD is primarily seen in heart rate and blood pressure elevations, while less is known about the etiology of rare cardiovascular events or long-term sequelae. Further research is indicated to delineate clinical and functional outcomes for adults with ADHD, as well as long-term safety of medication treatment.

Improving Communication in ADHD Care: Results from In-office Linguistic Research.

UNLABELLED: IntroductionAn in-office linguistic study was conducted to help improve understanding of how to better evaluate and treat attention-deficit/hyperactivity disorder (ADHD). METHODS: Naturally occurring interactions were recorded among 7 psychiatrists and 23 patients and 8 pediatricians along with 22 patients and their parents. Participants were interviewed separately post-visit. Transcripts of interactions and interviews were analyzed using sociolinguistic techniques. RESULTS: Visits were variable in length and lacked concrete treatment plans. In the pediatric setting, children were typically excluded from dialogues, accounting for only 8% of words spoken. School was the primary metric used to evaluate symptoms. Pediatricians allayed parents' concerns about stimulant therapy by promising to prescribe the lowest possible dose, rather than discussing titrating to an optimal dose. Adults were evaluated idiosyncratically without the use of scales or tools. Stimulants were positioned as short-term "trials" without strong physician recommendations.DiscussionConversations about stimulant therapy lacked goal- and expectation-setting. Also missing from conversations was a definitive treatment plan based on the core symptoms of ADHD. Incorporating open-ended questions and tools or rating scales may result in a more effective and efficient in-office dialogue. CONCLUSION: Further research is warranted to assess the efficacy of communication strategies to enhance in-office discussions of ADHD and stimulant therapy.

Managing Sleep in Adults with ADHD: From Science to Pragmatic Approaches.

BACKGROUND: Sleep disorders and sleep problems commonly occur in adults with ADHD and add to functional impairment. Evidence-based treatments for sleep could improve function in the adult ADHD population. METHODS: A literature review was conducted to present the clinical science informing treatment of sleep in adults with ADHD. RESULTS: Six systematic prospective studies of sleep intervention in adults with ADHD were identified. Three of these, all including well-characterized ADHD patients, offered evidence for a significant effect of morning light therapy. Across the studies, preliminary evidence for melatonin, behavioral therapy, and weighted blankets were also found. IMPLICATION: Low-risk interventions such as light therapy may improve sleep in adults with ADHD, but many sleep interventions currently in use remain unstudied in the ADHD population. Considerations for evidence-informed practice and future research directions are discussed.

Post-Hoc Analyses of the Effects of Baseline Sleep Quality on SHP465 Mixed Amphetamine Salts Extended-Release Treatment Response in Adults with Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Sleep problems are common in adults with attention-deficit/hyperactivity disorder (ADHD). The presence of sleep problems at the time of presentation for ADHD treatment could impact the level of improvement in ADHD symptoms or executive function occurring with ADHD pharmacotherapy. Therefore, we examined the influence of baseline sleep quality on the effects of SHP465 mixed amphetamine salts (MAS) extended-release. METHODS: Adults (18-55 years) with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision-defined ADHD and baseline ADHD Rating Scale IV (ADHD-RS-IV) total scores ≥ 24 were randomized to once-daily SHP465 MAS (12.5-75 mg) or placebo in a 7-week, double-blind, dose-optimization study. Post-hoc analyses evaluated SHP465 MAS treatment effects on ADHD symptoms, using the ADHD-RS-IV, and executive function, using the Brown Attention-Deficit Disorder Scale (BADDS), based on baseline sleep quality as defined by Pittsburgh Sleep Quality Index (PSQI) scores [sleep quality impaired (PSQI total score > 5; PSQI component scores 2 or 3) versus not impaired (PSQI total score ≤ 5; PSQI component scores 0 or 1)]. Analyses were conducted in the intent-to-treat population. RESULTS: Of 280 enrolled participants, 272 were randomized (placebo, n = 135; SHP465 MAS, n = 137). The intent-to-treat population consisted of 268 participants (placebo, n = 132; SHP465 MAS, n = 136), and 170 participants (placebo, n = 76; SHP465 MAS, n = 94) completed the study. Treatment differences nominally favored SHP465 MAS over placebo in both sleep impairment groups regarding ADHD-RS-IV total score changes (all nominal p < 0.05), except for those with impairment defined by sleep efficiency (p = 0.2696), and regarding BADDS total score changes (all nominal p < 0.05), except for those with impairment defined by sleep duration (p = 0.1332) and sleep efficiency (p = 0.8226). There were no statistically significant differences in SHP465 MAS treatment effects between sleep impairment groups. CONCLUSIONS: Improvements in ADHD symptoms and executive function occurred with dose-optimized SHP465 MAS, regardless of baseline impairment in some aspects of sleep in adults with ADHD, with no significant differences observed as a function of sleep impairment. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier-NCT00150579.

Stimulant 'rapid metabolizers': wrong label, real phenomena.

This is a review of the empirical literature regarding what has been described anecdotally as patients who are 'rapid metabolizers' of stimulant medication. The authors propose that this is a misnomer used to describe two types of atypical pharmacokinetic patterns of response: high-dose responders, short-duration responders and two types of atypical pharmacodynamics patterns of response: patients who develop either acute or chronic tolerance. The authors propose that use of more precise terminology should facilitate both patient education and research to better understand the physiology and clinical management of atypical response patterns to stimulant treatment. Presently, the understanding of the pharmacokinetics and pharmacodynamics of psychostimulants is still quite limited. Further scientific research is needed to understand unusual patterns of pharmacological response seen in the clinic. Careful identification and precise description of these patterns would facilitate understanding the pharmacokinetics and pharmacodynamics of stimulants impacts the atypical response patterns seen in the clinic.

Clinical and functional correlates of processing speed in pediatric Attention-Deficit/Hyperactivity Disorder: a systematic review and meta-analysis.

It is well established that processing speed is negatively impacted in children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD). Unfortunately, exactly how processing speed vulnerabilities manifest in daily functioning has not been well established. To support clinical care of youth with ADHD, it is important to better understand the functional consequences and relevant outcomes associated with processing speed deficits. This systematic review and meta-analysis sought to identify the association between processing speed and clinical or functional correlates among children or adolescents diagnosed with ADHD. A total of 409 abstracts were screened, of which, 60 full-text articles were identified as potentially relevant, and 8 of these studies met inclusion criteria. Domains evaluated across these studies included reading skills, mathematics skills, written expression, anxiety, self-appraisals of competence, and adaptive functioning. Six studies reported an association between processing speed and reading skills, allowing for meta-analysis. Processing speed difficulties among youth with ADHD appear strongly associated with several clinical and functional correlates including weaker academic skills, poorer adaptive skills, increased self-reported anxiety, and overestimates of social competence. Meta-analytic results for studies reporting the association between processing speed and reading skills indicate a medium overall weighted mean effect size (r = 0.33, 95% CI = 0.28 -0.39) with minimal heterogeneity (I2 = 0.17). Clinical implications of these findings, limitations in the current knowledge base, and suggestions for future research are discussed.

Investigating Resilience to Depression in Adults With ADHD.

OBJECTIVE: ADHD is associated with elevated rates of comorbid depressive disorders, yet the nature and development of this comorbidity remain understudied. We hypothesized that a longer period of prior ADHD treatment, being less likely to engage in maladaptive cognitive/behavioral coping strategies, and less severe ADHD symptoms would predict greater likelihood of lifetime resilience to depression. METHOD: Seventy-seven adults with ADHD completed diagnostic interviews, clinician-administered symptom rating scales, a stressful life events measure, and self-report questionnaires. We used logistic regression analyses to identify factors associated with resilience to depression. RESULTS: Adults with more extensive ADHD treatment histories were more likely to be resilient to depression. Those who were less likely to report ruminative thinking patterns and cognitive-behavioral avoidance were also more resilient. Severity of current or childhood ADHD symptoms and recent negative life events did not predict resilience. CONCLUSION: Results identify protective factors that may promote the resiliency to ADHD-depression comorbidity.

The efficacy of cognitive-behavioral therapy for older adults with ADHD: a randomized controlled trial.

Older adults with ADHD exhibit significant functional impairment, yet there is little research to guide clinicians in evidence-based care of these adults. This study examined response to treatment in older adults who participated in a previous study of the efficacy of cognitive-behavioral treatment (CBT) in adult ADHD. It was hypothesized that older adults would respond less well to CBT than younger adults, given the cognitive demands of the treatment. As described in the original publication, 88 adults who met DSM-IV criteria for ADHD were randomized to receive either a manualized 12-week CBT group intervention targeting executive dysfunction or a parallel Support group. In the current study, outcomes for 26 adults, aged 50 or older, were compared with those of 55 younger adults with respect to inattentive symptoms assessed on a structured interview by a blind clinician, as well as on ratings by self and/or collateral on measures of attention, executive dysfunction, and comorbidity. Contrary to the hypothesis, older and younger adults were equally responsive to CBT on measures of attention. The older adults also responded as well to Support as to CBT on several outcome measures. The results provide preliminary evidence that CBT is an effective intervention for older adults with ADHD. The unexpected response to support highlights a possible age-specificity of effective therapeutic intervention that requires further investigation.

Are girls with ADHD at risk for eating disorders? Results from a controlled, five-year prospective study.

OBJECTIVE: To evaluate the association between attention-deficit/hyperactivity disorder (ADHD) and eating disorders in a large adolescent population of girls with and without ADHD. METHOD: We estimated the incidence of lifetime eating disorders (either anorexia or bulimia nervosa) using Cox proportional hazard survival models. Comparisons between ADHD girls with and without eating disorders were then made on measures of comorbidity, course of ADHD, and growth and puberty. RESULTS: ADHD girls were 3.6 times more likely to meet criteria for an eating disorder throughout the follow-up period compared to control females. Girls with eating disorders had significantly higher rates of major depression, anxiety disorders, and disruptive behavior disorder compared to ADHD girls without eating disorders. Girls with ADHD and eating disorders had a significantly earlier mean age at menarche than other ADHD girls. No other differences in correlates of ADHD were detected between ADHD girls with and without eating disorders. CONCLUSIONS: ADHD significantly increases the risk of eating disorders. The presence of an eating disorder in girls with ADHD heightens the risk of additional morbidity and dysfunction.

A laboratory driving simulation for assessment of driving behavior in adults with ADHD: a controlled study.

BACKGROUND: It is now estimated that attention deficit-hyperactivity disorder (ADHD) afflicts at least 4% of adults in the United States and is associated with high levels of morbidity and functional impairment. One key area of dysfunction associated with ADHD is impaired motor vehicle operation. Our goal was to examine the association between ADHD and specific driving outcomes in a sample of adults using a driving simulator. METHODS: Subjects were 20 adults with full DSM-IV ADHD and 21 controls without ADHD of equal gender distribution. However, the mean age of subjects with ADHD was somewhat older. All analyses were adjusted for age and gender. All subjects participated in a driving simulation that lasted for one hour and consisted of a short training period, a high stimulus segment and a low stimulus segment with two distinct monotonous periods. RESULTS: In the second monotonous period within the low stimulus environment, ADHD subjects were significantly more likely than controls to collide with an obstacle suddenly appearing from the periphery, adjusting for age and gender. CONCLUSION: Adults with ADHD were more likely than controls to collide with an obstacle during a driving simulation suggesting that deficits in directed attention may underlie driving impairments in this population.