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.

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.

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.

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.

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.

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.

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.

Logistics modelling: improving resource management and public information strategies in Florida.

One of the most time-sensitive and logistically-challenging emergency response operations today is to provide mass prophylaxis to every man, woman and child in a community within 48 hours of a bioterrorism attack. To meet this challenge, federal, state and local public health departments in the USA have joined forces to develop, test and execute large-scale bioterrorism response plans. This preparedness and response effort is funded through the US Centers for Disease Control and Prevention's Cities Readiness Initiative, a programme dedicated to providing oral antibiotics to an entire population within 48 hours of a weaponised inhalation anthrax attack. This paper will demonstrate how the State of Florida used a logistics modelling tool to improve its CRI mass prophylaxis plans. Special focus will be on how logistics modelling strengthened Florida's resource management policies and validated its public information strategies.