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.

Investigation of Unusual N-(Triphenyl-λ5-phosphanylidene) Amide Fragmentation Observed upon MS/MS Collision-Induced Dissociation.

A mechanism of unusual tandem (MS/MS) fragmentation of protonated species of N-(triphenyl-λ5-phosphanylidene) derivatives, [M + H]+ to generate triphenylphosphine oxide (TPPO) within the mass spectrometer has been investigated and reported. Collision-induced dissociation of these molecules resulted in the generation of TPPO as a signature fragment. This fragment suggested the presence of a P-O bond in the structure which was contrary to the structure of the compound identified by nuclear magnetic resonance spectrometry (NMR) and single-crystal X-ray diffractometry (SXRD) techniques with a P═N bond rather than a P-O bond. In order to confirm the generation of the TPPO fragment within the mass spectrometer, 14 different N-(triphenyl-λ5-phosphanylidene) derivatives containing amide, 18O-labeled amide, thiamide, and nonacyl phosphazene derivatives were synthesized and their MS/MS behavior was studied by liquid chromatography-high-resolution mass spectrometry. Fragmentation of these amide derivatives generated TPPO/TPPS or their 18O-labeled analogues as the major fragment in almost all cases under similar MS conditions. Based on the outcome of these experiments, a plausible mechanism for such fragmentation, involving the intramolecular shifting of oxygen from carbon to phosphorus, has been proposed. DFT calculations for the protonated species at B3LYP-D3/6-31+G(d,p) further supported the proposed mechanism involving a four-membered ring, P-O-C-N, as the transition state. Details of this work are presented here.

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.

How is the medical assistance in dying (MAID) process carried out in Nova Scotia, Canada? A qualitative process model flowchart study.

OBJECTIVES: The aims of this study are: (1) to create a flowchart process model of how medical assistance in dying (MAID) occurs in Nova Scotia (NS), Canada and (2) to detail how NS healthcare professionals are involved in each stage of MAID. The research questions are: how is the MAID process carried out and which professionals are involved at which points? and which roles and activities do professionals carry out during MAID? DESIGN: Qualitative process model flowchart study with semistructured interviews. SETTING: Primary and secondary care in NS, Canada. PARTICIPANTS: Thirty-two interviewees self-selected to participate (12 physicians, 3 nurse practitioners (NP), 6 nurses, 6 pharmacists and 5 healthcare administrators and advocates). Participants were included if they conduct assessments, provide MAID, fill prescriptions, insert the intravenous lines, organise care and so on. RESULTS: The flowchart process model details five stages of how MAID occurs in NS: (1) starting the MAID process, (2) MAID assessments, (3) MAID preparation (hospital in-patient, hospital outpatient, non-hospital), (4) day of MAID and (5) post-MAID (hospital in-patient and outpatient, non-hospital, after leaving setting). Nineteen points where the process could stop or be delayed were identified. MAID differs slightly by location and multiple professionals from different organisations are involved at different points. Some physicians and NP provide MAID for free as they cannot be reimbursed or find it too difficult to be reimbursed. CONCLUSIONS: Our study adds knowledge about the MAID activities and roles of NS professionals, which are not documented in the international literature. Clinicians and pharmacists spend significant additional time to participate, raising questions about MAID's sustainability and uncompensated costs. The process model flowchart identifies where MAID can stop or be delayed, signalling where resources, training and relationship-building may need to occur. Knowing where potential delays can occur can help clinicians, administrators and policymakers in other jurisdictions improve MAID.

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.

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.

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.

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.

Development of a Control Strategy for Benzene Impurity in HPMCAS-Stabilized Spray-Dried Dispersion Drug Products Using a Science-Based and Risk-Based Approach.

PURPOSE: To develop a strategy to control benzene, an ICH Q3C Class 1 impurity that may be present in spray solvents at ppm concentration, in amorphous polymer-stabilized spray-dried dispersion (SDD) products. METHODS: Risk assessments included determining the probability for benzene concentration in primary spray solvents, the physical properties of volatiles, and the potential enrichment of benzene from solution to solid. Mechanistic understanding of benzene removal was gained through a benzene-spiked fate and tolerance (F&T) study simulating worst-case spray-drying conditions and application of diffusion models for secondary drying. RESULTS: The mass ratio of spray solution to solid presented the highest risk of benzene enrichment. With slow spray-drying kinetics, benzene was reduced about 700-fold. Under standard secondary-drying conditions to remove residual solvents, residual benzene was further removed. Using diffusion models, the maximum benzene concentration was approximated for SDDs dried to the in-process control (IPC) limit of primary solvents. CONCLUSIONS: Two critical control points were established to eliminate any risk of residual benzene reaching patients: (1) upstream control of benzene in solvents (≤10 ppm) and (2) IPC of residual solvents in polymer-stabilized SDDs.

Efficacy of guanfacine extended release assessed during the morning, afternoon, and evening using a modified Conners' Parent Rating Scale-revised: Short Form.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of once-daily guanfacine extended release (GXR) monotherapy administered either in the morning or evening, using a modified Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S) assessed three times/day in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: This multicenter, double-blind, placebo-controlled study randomized children 6-12 years of age with ADHD into three groups: GXR a.m. (GXR in the morning and placebo in the evening), GXR p.m. (placebo in the morning and GXR in the evening), or twice-daily placebo. The CPRS-R:S, administered in the morning, afternoon, and evening prior to each study visit, was a secondary measure of efficacy. RESULTS: A total of 333 subjects were included in the analysis population (GXR a.m., n=107; GXR p.m., n=114; placebo, n=112). At visit 10, last observation carried forward (LOCF), subjects receiving GXR demonstrated significantly greater improvement from baseline in the daily mean CPRS-R:S total score, as well as in each of the morning, afternoon, and evening CPRS-R:S assessments, compared with placebo, regardless of the time of GXR administration (p<0.001 vs. placebo for GXR a.m. and GXR p.m.). In addition, subjects receiving GXR showed significantly greater improvements from baseline in each subscale score (oppositional, cognitive problems/inattention, hyperactivity, and ADHD index) compared with those receiving placebo, regardless of time of administration (p<0.003 vs. placebo across all subscales for GXR a.m. and GXR p.m.). CONCLUSIONS: These results provide further support for the demonstrated efficacy of once-daily GXR in reducing ADHD symptoms, and demonstrate that response is consistent throughout the day regardless of the time of administration, with improvement seen in ratings of oppositional as well as of ADHD symptoms.

Minimally destructive sampling of type specimens of Pyropia (Bangiales, Rhodophyta) recovers complete plastid and mitochondrial genomes.

Plant species, including algae and fungi, are based on type specimens to which the name of a taxon is permanently attached. Applying a scientific name to any specimen therefore requires demonstrating correspondence between the type and that specimen. Traditionally, identifications are based on morpho-anatomical characters, but recently systematists are using DNA sequence data. These studies are flawed if the DNA is isolated from misidentified modern specimens. We propose a genome-based solution. Using 4 × 4 mm(2) of material from type specimens, we assembled 14 plastid and 15 mitochondrial genomes attributed to the red algae Pyropia perforata, Py. fucicola, and Py. kanakaensis. The chloroplast genomes were fairly conserved, but the mitochondrial genomes differed significantly among populations in content and length. Complete genomes are attainable from 19(th) and early 20(th) century type specimens; this validates the effort and cost of their curation as well as supports the practice of the type method.

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.

Clinical response and symptomatic remission in short- and long-term trials of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder.

BACKGROUND: Despite the overall high degree of response to pharmacotherapy, consensus is lacking on how to judge clinical response or define optimal treatment/remission when treating adults with attention-deficit/hyperactivity disorder (ADHD). This study examined clinical response and symptomatic remission in analyses of 2 studies of lisdexamfetamine dimesylate (LDX) in adults with ADHD. METHODS: In a 4-week, double-blind, forced-dose trial, adults with ADHD were randomized to LDX 30, 50, and 70 mg/day (mg/d) or placebo. In a second, open-label, follow-up trial, adults entering from the 4-week study were titrated to an "optimal" LDX dose (30 mg/d [n=44], 50 mg/d [n=112], and 70 mg/d [n=171]) over 4 weeks, and maintained for 11 additional months. The ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts and the Clinical Global Impressions-Improvement (CGI-I) scale assessed efficacy. Clinical response was defined, post hoc, as ≥30% reduction from baseline in ADHD-RS-IV and CGI-I rating of 1 or 2; symptomatic remission was defined as ADHD-RS-IV total score ≤18. Log rank analysis examined overall significance among the treatment groups in time to response or remission. RESULTS: Four hundred and fourteen participants in the 4-week study and 345 in the open-label, extension study were included in the efficacy populations. All LDX groups improved by ADHD-RS-IV and CGI-I scores in both studies. In the 4-week study (n=414), 69.3% responded and 45.5% achieved remission with LDX (all doses); 37.1% responded and 16.1% achieved remission with placebo; time (95% CI) to median clinical response (all LDX doses) was 15.0 (15.0, 17.0) days and to remission was 31.0 (28.0, 37.0) days (P<.0001 overall). In the open-label study, with LDX (all doses), 313 (95.7%) and 278 (85.0%) of 327 participants with evaluable maintenance-phase data met criteria for response and remission, respectively. Of participants who completed dose optimization, 75.2% remained responders and 65.7% remained in remission in the 12-month study. Overall, 285 (82.6%) and 227 (65.8%) of 345 participants were responders and remitters, respectively, at their final visits. CONCLUSION: In the long-term study, with open-label, dose-optimized LDX treatment, most adults with ADHD achieved clinical response and/or symptomatic remission; almost two-thirds maintained symptomatic remission over the remaining 11 months. TRIAL REGISTRATION: Clinical Trial Numbers: NCT00334880 and NCT01070394CLINICAL TRIAL REGISTRY: clinicaltrials.gov.

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.

Discontinuity in the transition from pediatric to adult health care for patients with attention-deficit/hyperactivity disorder.

BACKGROUND: Although attention-deficit/hyperactivity disorder (ADHD) is a chronic disorder, treatment declines dramatically in adolescence and into early adulthood. This premature termination of care is likely compounded by the difficulty many patients have switching from a pediatric to an adult provider. OBJECTIVE: To review, from the adult primary care provider perspective, the barriers to continuity of care and their implications for patients with ADHD who transition from pediatric to adult health care. DESIGN: Literature review. APPROACH: Relevant articles were identified by searches of the PubMed and EMBASE databases and by reviewing the reference lists of articles obtained from these searches. RESULTS: Health care transition for adolescents and young adults with ADHD remains a crucial area of research. The current literature reveals a number of barriers to the continuity of care, including disparities and inadequacies in ADHD education in primary care and internal medicine residencies, prohibitive prescribing practices with respect to stimulants, inadequate clinic staffing, lack of support in the college health care system, inadequate health insurance coverage, and failure to conduct transitional planning. Without improved continuity of care and adherence to medication, adolescents and young adults with ADHD are at greater risk of academic, social, and vocational difficulties, as well as behavioral problems, including substance abuse, unsafe driving, and criminal activity. CONCLUSION: If we are to adequately address the health care needs of adolescents and young adults with ADHD, we need to educate primary care providers and support additional research.

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.

Atomoxetine once daily for 24 weeks in adults with attention-deficit/hyperactivity disorder (ADHD): impact of treatment on family functioning.

OBJECTIVE: To assess the efficacy of atomoxetine (ATX) and impact of treatment on family functioning in adults with ADHD. METHODS: Adults with attention-deficit/hyperactivity disorder (ADHD) having both a spouse/partner and child were randomized to placebo (n = 234) or ATX (n = 268) for 24 weeks. Attention-deficit/hyperactivity disorder measures included the Conners Adult ADHD Rating Scale total ADHD Symptoms score and Clinical Global Impression-ADHD-Severity. Marital measures included the Dyadic Adjustment Scale and the Family Assessment Measure Dyadic Relationship Scale (FAM III). Parenting measures included the Parenting Stress Index, Alabama Parenting Questionnaire, and Parenting Sense of Competence Scale (PSCS). RESULTS: Improvement was greater with ATX over placebo at 24 weeks on the Conners Adult ADHD Rating Scale (-16.43 vs -8.65; P < 0.001, repeated measures) and Clinical Global Impression (P < 0.001, last observation carried forward). Baseline-to-end point changes in marital and parenting measures were significant but not between treatment groups. Post hoc analyses showed significant interaction of treatment and impairment for the FAM III Task Accomplishment (patient) and Role Performance (patient and spouse) items and PSCS efficacy. Further stratification by sex or presence of a child with ADHD yielded significant interaction and treatment differences for the FAM III Task Accomplishment and the FAM III and Dyadic Adjustment Scale affective expression items, PSCS total score, Alabama Parenting Questionnaire Corporal Punishment, and Parenting Stress Index attachment items. CONCLUSIONS: Atomoxetine demonstrated significant ADHD symptom reduction over 24 weeks. Although both groups demonstrated baseline-to-end point changes on many marital and parenting measure items, there were no treatment differences. Maladaptive behaviors of long-standing ADHD may benefit from both medication and behavioral-psychosocial intervention.

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.

Quantitative determination of trace levels of hydrogen peroxide in crospovidone and a pharmaceutical product using high performance liquid chromatography with coulometric detection.

A reliable and reproducible high performance liquid chromatography method with coulometric detection was developed and validated for the quantitative determination of trace-levels of hydrogen peroxide in crospovidone, a pharmaceutical excipient, and a capsule pharmaceutical product. The method conditions included: a reproducible extraction procedure to provide a concentrated extract, aqueous extraction solvent; a simple HPLC mobile phase (aqueous 50 mM ammonium acetate) compatible with the coulometric detection; a reserve-phase HPLC column that did not collapse under 100% aqueous mobile phase conditions providing sufficient retention and separation of hydrogen peroxide from interferences; and a coulometric detector with a multi-electrode array providing sensitive and selective detection. The method validation results, including those for specificity, linearity, accuracy, precision, and recovery, were acceptable for the determination of trace levels of hydrogen peroxide. The method was shown to be linear over the range of 0.6-4.5 ppm (microg/g) and 6-90 ppm (microg/g) for the pharmaceutical product and crospovidone, respectively. The described method was applied to the determination of trace levels of hydrogen peroxide in different batches of crospovidone and the corresponding pharmaceutical product batches manufactured from these batches of this excipient.