Development and validation of the ADHD Symptom and Side Effect Tracking - Baseline Scale (ASSET-BS): a novel short screening measure for ADHD in clinical populations.

OBJECTIVE: The aim was to develop and test a novel screen of adult ADHD, with a specific focus on clinical use. We designed a series of three studies to accomplish this aim. METHOD: Study One (n = 155) and Study Two (n = 591) collected data via surveys to conduct exploratory and confirmatory factor analyses, respectively. Study Three analyzed the scale's psychometrics in a clinical sample (n = 151). RESULTS: Study One and Study Two identified a 10-item scale with a two-factor structure. Study Three found good discriminant validity, sensitivity = 80.0%, specificity = 80.2%, and convergent validity with both the Brown Executive Function/Attention Scales, r (131) = .76, p < .001, and the Conner's Adult ADHD Rating Scales r (131) = .71, p < .001. CONCLUSION: The scale demonstrated effectiveness in screening for ADHD in a psychiatric outpatient population. Its results may be used to identify patients that may benefit from thorough ADHD diagnostic procedures.

A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of AR19, a Manipulation-Resistant Formulation of Amphetamine Sulfate, in Adults With Attention-Deficit/Hyperactivity Disorder.

Objective: To assess the efficacy and safety of AR19 in the treatment of attention-deficit/hyperactivity disorder (ADHD) diagnosed by DSM-5 criteria in adults from 18 through 55 years of age. AR19 is a pellets-in-capsule, immediate-release amphetamine sulfate investigational formulation with physical and chemical barriers designed to resist manipulation to deter snorting, smoking, and intravenous injection.Methods: This randomized, double-blind, placebo-controlled, fixed-dose, forced titration, multicenter trial investigated the safety and efficacy of AR19 from September 2018 to April 2019. Study participants were randomized and titrated to 20 mg or 40 mg AR19 daily or placebo. Study medication was dosed once in the morning and again 4 to 6 hours later for a period of 5 weeks. The primary efficacy measure was the total score on the Adult ADHD Investigator Symptom Rating Scale (AISRS).Results: Participants (N = 320) were randomized and received at least 1 dose of study medication. Demographics and baseline characteristics were similar across treatment groups. The least squares mean treatment differences versus placebo (97.5% CI) were -7.2 (-11.3 to -3.1) for the AR19 20-mg group and -7.3 (-11.4 to -3.2) for the AR19 40-mg group (each P < .001). The most common treatment-emergent adverse events occurring in participants in the AR19 treatment groups were insomnia, dry mouth, decreased appetite, palpitations, headache, and tachycardia and are consistent with the known safety profile of amphetamine sulfate.Conclusions: AR19 demonstrated efficacy on all endpoints and was generally well tolerated, supporting the efficacy and safety of AR19 20 mg and 40 mg in adults with ADHD.Trial Registration: ClinicalTrials.gov Identifier: NCT03659929.

Adult Attention-Deficit/Hyperactivity Disorder Diagnosis, Management, and Treatment in the DSM-5 Era.

OBJECTIVE: To increase awareness of adult attention-deficit/hyperactivity disorder (ADHD) in the primary care community and to provide guidance for the management of this condition. Despite its increasing prevalence, adult ADHD largely remains underdiagnosed and inappropriately treated in the United States. The publication of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), has provided more clear diagnostic criteria for adult ADHD, but a solid framework supporting the transition of ADHD management from pediatric to adult primary care is lacking. DATA SOURCES: We searched PubMed and MEDLINE databases (January 1, 1984-June 1, 2016) using combinations of keywords, including ADHD, adult, diagnosis, prevalence, symptoms, treatment, comorbidity, compliance, and guidelines; international treatment guidelines; and the Diagnostic Interview for Adult ADHD websites to identify relevant clinical studies, reviews, meta-analyses, guidelines, and web-based resources describing updates to the DSM. STUDY SELECTION/DATA EXTRACTION: In total, 143 citations were selected based on their relevance to adult ADHD diagnosis, treatment, major issues, and practice guidelines. RESULTS: The update on diagnostic criteria in the DSM-5 may increase the diagnosis of adult ADHD. There are critical differences between childhood and adult ADHD, and specific considerations should be taken with an adult ADHD diagnosis. Adult ADHD is primarily treated with pharmacotherapy assisted by behavior interventions. Caution should be exercised when using stimulants during pregnancy and the postpartum period. Adult ADHD patients often suffer from unemployment, financial difficulties, and an unsuccessful personal life. Adult-specific guidelines may improve adult ADHD treatment. CONCLUSIONS: The successful diagnosis and management of adult ADHD require consideration of many facets including prior medical history and comorbid conditions and use of an individualized, evidence-based treatment approach.

Supplementary guanfacine hydrochloride as a treatment of attention deficit hyperactivity disorder in adults: A double blind, placebo-controlled study.

The purpose of this study was to examine the efficacy of an extended release guanfacine hydrochloride supplement relative to a placebo supplement in adults (19-62) with ADHD and a sub-optimal response to a stimulant-only treatment program. The study's primary outcome measures were the Attention Deficit Hyperactivity Disorder Rating Scale and the Clinical Global Impression - Severity. Twenty-six adults who met criteria for attention deficit hyperactivity disorder and sub-optimal functioning were randomly assigned to supplement their existing psychostimulant treatment regimen with either a titrated dose (1-6mg) of extended release guanfacine hydrochloride or a matching placebo for a 10-week trial. The data were analyzed with standard mixed model analysis of variance procedures, and participants in both the investigational agent group and the placebo group showed statistically significant improvement in their symptoms and functioning over the course of the trial. The treatments did not differ in terms of their efficacy, safety, or tolerability. Although these results do suggest that both treatments were associated with clinical improvement, the possible impacts of socially desirable responding and regression to the mean on these results are discussed.

Atomoxetine Increased Effect over Time in Adults with Attention-Deficit/Hyperactivity Disorder Treated for up to 6 Months: Pooled Analysis of Two Double-Blind, Placebo-Controlled, Randomized Trials.

INTRODUCTION: Changes in the magnitude of efficacy throughout 26 weeks of atomoxetine treatment, along with impact of dosing, were evaluated in adults with ADHD from two randomized, double-blind, placebo-controlled studies. AIMS: Pooled placebo (n = 485) and atomoxetine (n = 518) patients, dosed 25, 40, 60, 80 (target dose), or 100 mg daily, were assessed. Change from baseline in Conners' Adult ADHD Rating Scale-Investigator Rated Scale: Screening Version (CAARS) total ADHD symptoms score and Adult ADHD Investigator Symptom Rating Scale (AISRS) total score were analyzed using mixed-model repeated measures, with least squares mean change, effect size, and response rate calculated at 1, 2, 4, 8, 12, 16, 22, and 26 weeks. RESULTS: Decreases on CAARS for atomoxetine- versus placebo-treated patients were consistently statistically significantly greater at every time point beginning at one week (P ≤ 0.006, 0.28 effect size). By 4 weeks, comparison was -13.19 compared with -8.84 (P < 0.0001, 0.45 effect size). By 26 weeks, mean change was -15.42 versus -9.71 (0.52 effect size); increase in effect size over time was most pronounced in the 80 mg group (0.82 effect size). AISRS demonstrated similar results. Atomoxetine response rate (CAARS 50% decrease) continued to increase throughout 26 weeks. CONCLUSIONS: Atomoxetine treatment in adults with ADHD was associated with small effect sizes after 4 weeks and moderate effect sizes by 6 months of treatment. The data support increased effect size and response rate over time during longer-term treatment at target dose.

A Randomized, Placebo-Controlled Trial of Guanfacine Extended Release in Adolescents With Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Despite the continuity of attention-deficit/hyperactivity disorder (ADHD) into adolescence, little is known regarding use of nonstimulants to treat ADHD in adolescents. This phase 3 trial evaluated the safety and efficacy of guanfacine extended release (GXR) in adolescents with ADHD. METHOD: This 13-week, multicenter, randomized, double-blind, placebo-controlled trial evaluated once-daily GXR (1-7 mg per day) in adolescents with ADHD aged 13 to 17 years. The primary endpoint was the change from baseline in the ADHD Rating Scale-IV (ADHD-RS-IV) total score; key secondary endpoints included scores from the Clinical Global Impressions-Severity of Illness (CGI-S), and Learning and School domain and Family domain scores from the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) at week 13. RESULTS: A total of 314 participants were randomized (GXR, n = 157; placebo, n = 157). The majority of participants received optimal doses of 3, 4, 5, or 6 mg (30 [22.9%], 26 [19.8%], 27 [20.6%], or 24 [18.3%] participants, respectively), with 46.5% of participants receiving an optimal dose above the currently approved maximum dose limit of 4 mg. Participants receiving GXR showed improvement in ADHD-RS-IV total score compared with placebo (least-squares mean score change, -24.55 [GXR] versus -18.53 [placebo]; effect size, 0.52; p <.001). More participants on GXR also showed significant improvement in CGI-S scores compared with placebo (50.6% versus 36.1%; p = .010). There was no statistically significant difference between treatments at week 13 in the 2 WFIRS-P domains. Most treatment-emergent adverse events were mild to moderate, with sedation-related events reported most commonly. CONCLUSION: GXR was associated with statistically significant improvements in ADHD symptoms in adolescents. GXR was well tolerated, with no new safety signals reported. CLINICAL TRIAL REGISTRATION INFORMATION: Dose-Optimization in Adolescents Aged 13-17 Diagnosed With Attention-Deficit/Hyperactivity Disorder (ADHD) Using Extended-Release Guanfacine HCl; http://ClinicalTrials.gov/; NCT01081132.

Chronic fatigue syndrome: 3 cases and a discussion of the natural history of attention-deficit/hyperactivity disorder.

Fatigue is commonly reported in the primary care setting; however, its cause is often unclear. This article presents 3 cases involving patients with chronic fatigue syndrome who responded poorly to treatment. After clinical evaluation, all patients were found to meet criteria for attention-deficit/hyperactivity disorder (ADHD) and underwent a standard regimen of a psychostimulant medication. After treatment with psychostimulants, the 3 patients reported improved symptoms of fatigue and pain, and cognitive and core ADHD symptoms. These cases suggest that ADHD and chronic fatigue syndrome (and possibly fibromyalgia) share a common underlying mechanism. This article presents a model suggesting that over time, ADHD (predominantly inattentive type) develops into a syndrome of chronic fatigue and pain. These cases indicate that fatigue may be an important presenting symptom of adult ADHD. These cases also suggest the need for additional research to determine the prevalence of ADHD in patients who present with fatigue, and, in those meeting criteria for ADHD, the responsiveness of fatigue to psychostimulant treatment.

Use of lisdexamfetamine dimesylate in treatment of executive functioning deficits and chronic fatigue syndrome: a double blind, placebo-controlled study.

The purpose of this study was to assess the efficacy of lisdexamfetamine dimesylate (LDX) for the treatment of executive functioning deficits in adults (ages 18-60) with chronic fatigue syndrome (CFS). The study's primary outcome measure was the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A). Secondary outcome measures were standardized assessments of fatigue, pain and global functioning. Twenty-six adults who met criteria for CFS and had clinically significant executive functioning deficits were randomly assigned to a flexible morning dose (30, 50, 70 mg/day) of either placebo or LDX for a 6-week trial. The data were analyzed with standard analysis of variance (ANOVA) procedures. Participants in the LDX group showed significantly more positive change in BRIEF-A scores (Mchange=21.38, SD=15.85) than those in the placebo group (Mchange=3.36, SD=7.26). Participants in the active group also reported significantly less fatigue and generalized pain relative to the placebo group. Although future studies with LDX should examine whether these benefits generalize to larger, more diverse samples of patients, these results suggest that LDX could be a safe and efficacious treatment for the executive functioning deficits often associated with CFS. The possibility that dopaminergic medications could play an important role addressing the symptoms of CFS is also discussed.

Delusional parasitosis in a female treated with mixed amphetamine salts: a case report and literature review.

Objectives. To explore factors underlying the onset of delusional parasitosis; a condition in which an individual has a fixed, false belief that he/she is infested with insects. Case Description. MJ is a 57-year-old female who presents with symptoms of fatigue and AD/HD. Upon treatment with extended release mixed amphetamine salts, the patient displayed symptoms of delusional parasitosis. After eventual discontinuation of this medication, her delusions resolved. Comments. In order to maintain confidentiality, all identifying information was removed. To this end, please note that MJ is a fictitious name.

Once-daily treatment with atomoxetine in adults with attention-deficit/hyperactivity disorder: a 24-week, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Atomoxetine (ATX) once daily was compared with placebo (PBO) in adults with attention-deficit/hyperactivity disorder (ADHD) at 12 and 24 weeks. METHODS: Patients were randomized to PBO (n = 234) or ATX (60-100 mg; n = 268) for 24 weeks following a 2-week on-label (40 mg for 3 days then 80 mg) or slow (40 mg for 7 days then 80 mg) titration. After 24 weeks, PBO patients were rerandomized to either ATX titration strategy. Efficacy measures included the Conners' Adult ADHD Rating Scale Total ADHD Symptoms score, Clinical Global Impression-ADHD-Severity, Montgomery-Asberg Depression Rating Scale, and State-Trait Anxiety Inventory. General and titration safety measures and tolerability were evaluated. RESULTS: Conners' Adult ADHD Rating Scale Total ADHD Symptoms score reduction was greater with ATX over PBO at 12 weeks (-14.33 vs -10.05; P < 0.001) and 24 weeks (-16.43 vs -8.65; P < 0.001; effect size, 0.57). Response (25% decrease on Conners' Adult ADHD Rating Scale Total ADHD Symptoms) was greater for ATX (68%) than PBO (42%; P < 0.001) at 24 weeks. Clinical Global Impression-ADHD-Severity improvement was greater for ATX over PBO at 8 and 24 weeks (P < 0.001; effect sizes, 0.45 and 0.46, respectively). There were no significant changes in depressive or anxiety measures for either group. Discontinuation due to an adverse event was greater for on-label versus slow titration, although the rate of patients experiencing adverse events were comparable. Common adverse events included dry mouth, nausea, and decreased appetite. CONCLUSIONS: Atomoxetine demonstrated significant improvement in ADHD symptoms at 12 and 24 weeks over PBO. Adverse events overall and for on-label or slow titration to ATX were similar and consistent with previous adult ATX studies.

Fibromylagia, chronic fatigue, and adult attention deficit hyperactivity disorder in the adult: a case study.

Adult attention deficit hyperactivity disorder (ADHD) may share common features with fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS). In an outpatient psychiatric clinic, a number of adult patients who presented primarily with symptoms of ADHD, predominately inattentive type, also reported unexplained fatigue, widespread musculoskeletal pain or a pre-existing diagnosis of CFS or FMS. As expected, ADHD pharmacotherapy usually attenuated the core ADHD symptoms of inattention, distractibility, hyperactivity, and impulsivity. Less expected was the observation that some patients also reported amelioration of pain and fatigue symptoms. The utility of ADHD medications in FMS and CFS states may be their innate arousal and enhanced filtering properties. This model supposes that FMS and CFS are central processing problems rather than peripheral disorders of muscles and joints.