Adult Attention-deficit/hyperactivity Disorder Rating Scale-Investigator Research Articles

Efficacy of Metadoxine Extended Release in Patients With Predominantly Inattentive Subtype Attention-Deficit/Hyperactivity Disorder

Objectives: To compare the effects of metadoxine extended release (ER) with those of placebo on inattentive (IA) versus hyperactive-impulsive (H-I) symptoms and predominantly inattentive (PI) versus combined type (CT) subtype in adults with attention-deficit/hyperactivity disorder (ADHD). Methods: This was a 1:1 randomized, double-blind, parallel-design study of metadoxine ER 1400 mg/day for 6 weeks in 120 adults with ADHD. Efficacy measures were baseline to end-of-treatment changes in Conners' Adult ADHD Rating Scale-Investigator Rated (CAARS-INV) Total ADHD Symptoms scores with adult ADHD prompts, the Test of Variables of Attention ADHD scores, and response rates (≥ 25% or ≥ 40% improvement in CAARS-INV Total ADHD Symptoms score). Results: There was a significant decrease in CAARS-INV Total ADHD Symptoms scores in patients with ADHD-PI taking metadoxine ER (40%) compared with those taking placebo (21%) (P < 0.05), while the decrease for patients with ADHD-CT was not significant (27% vs 26%). Similarly, there was a significant decrease in IA scores in patients with ADHD-PI (metadoxine ER, 50% vs placebo, 23%; P < 0.005), while the change in patients with ADHD-CT was not significant. There was no significant difference in percent decreases seen in H-I scores for patients with PI or ADHD-CT. Significantly higher response rates at both cutoffs (ie, 25% and 45% improvement) were seen in the metadoxine ER group compared with the placebo group in CAARS-INV Total ADHD Symptoms scores in patients with ADHD-PI, but not those with ADHD-CT. Test of Variables of Attention ADHD scores were significantly decreased in the metadoxine ER group compared with the placebo group for patients with ADHD-PI, but not those with ADHD-CT. Conclusion: These data suggest that metadoxine ER is selectively efficacious for treating IA symptoms in adults with ADHD-PI.

Open-label, dose-titration tolerability study of atomoxetine hydrochloride in Korean, Chinese, and Taiwanese adults with attention-deficit/hyperactivity disorder

The primary objective of this study was to assess the overall safety and tolerability of atomoxetine in Korean, Chinese, and Taiwanese adults with attention-deficit/hyperactivity disorder (ADHD). A total of 44 patients aged ≥18 years who met the Conners' Adult ADHD Diagnostic Interview for DSM-IV diagnostic criteria for ADHD were enrolled from China, Korea, and Taiwan. In this open-label, dose-escalation study, patients received atomoxetine orally once daily over a period of eight weeks, starting at 40 mg/day (one week) up to a maximum dosage of 120 mg/day. Tolerability was evaluated by rate of discontinuation due to adverse events. Safety was assessed by recording all adverse events, laboratory tests, vital signs, and electrocardiograms. ADHD symptoms were evaluated by the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) for efficacy assessment. Thirty-four patients (77.3%) completed the study. Atomoxetine was well tolerated with a discontinuation rate of 2.3% (1/44) due to adverse events. The most commonly reported adverse events were nausea, dizziness, and somnolence. The mean change from baseline to endpoint in CAARS-Inv:SV total ADHD symptom score was -12.5 (P < 0.001). A significant reduction in the CAARS-Inv:SV subscales (inattentive, hyperactive/impulsive, and ADHD index score, P < 0.001) was observed. This is the first atomoxetine clinical trial in adult patients with ADHD in China, Korea, and Taiwan. Atomoxetine was well tolerated in doses of up to 120 mg/day with no unknown safety concerns.

P-900 - Characteristics of adult patients with ADHD in europe compared with non-european adult patients with adhd participating in a large treatment study with atomoxetine

Attention deficit/hyperactivity disorder (ADHD) often presents as an impairing lifelong condition in adults, yet it is currently under-diagnosed and under-treated in many European countries. To establish the characteristics of the European (EU) adult ADHD patient relative to adult patients outside the EU (OEU). To compare the baseline characteristics of patients with ADHD in regions where adult ADHD is relatively well established (e.g., USA), with EU adult ADHD patients. Baseline data was used from the open-label acute treatment period of a multicenter, randomized, withdrawal trial of atomoxetine in adult patients with ADHD (N = 2017; EU, n = 1217; OEU, n = 800). All enrolled patients were included in the baseline analyses. The demographics for patients in the EU region and regions OEU were comparable. Patients in the EU region had a somewhat lower percentage of prior exposure to psychostimulants compared to the region OEU (32.7% versus 38.9%, p = .005). Conners’ Adult ADHD Rating Scale-Investigator Rated: Screening Version with adult ADHD prompts (18 item total, inattentive and hyperactive/impulsive subscales, and index) were comparable. The adult ADHD Quality of Life life outlook and life productivity domain scores were different between groups (p ≤ .0004). The EuroQol-5 Dimension UK and US population-based Index score, and health state score were comparable between groups. There were some subtle differences between study groups; however, overall, the adult ADHD patients were not substantially different between the EU region and regions OEU, suggesting that baseline features of ADHD in adult EU patients manifest comparable to those in patients OEU.

Efficacy and safety of the novel α4β2 neuronal nicotinic receptor partial agonist ABT-089 in adults with attention-deficit/hyperactivity disorder: a randomized, double-blind, placebo-controlled crossover study

α(4)β(2) Neuronal nicotinic receptors (NNRs) are implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). This study examined the efficacy and safety of the α(4)β(2) NNR partial agonist ABT-089 versus placebo in adults with ADHD. In this multicenter, randomized, double-blind, placebo-controlled crossover study, subjects received placebo followed by ABT-089 (2 mg once daily [QD], 5 mg QD, 15 mg QD, 40 mg QD, or 40 mg twice daily [BID]), or vice versa, in a 2 × 2 crossover design. Each treatment period was 4 weeks, separated by a 2-week washout period. The primary efficacy endpoint was the Conners' Adult ADHD Rating Scale-Investigator Rated (CAARS:Inv) total score at the end of each treatment period. Secondary outcomes based on clinician- and self-rated efficacy scales were evaluated. Of the 221 subjects enrolled, 171 met criteria for inclusion in the completers dataset for efficacy analyses. ABT-089 was superior to placebo on the CAARS:Inv total score at 40 mg QD and 40 mg BID (model-based least square mean difference from placebo: -4.33, P = 0.02; -3.02, P = 0.03, respectively). ABT-089 also demonstrated significant improvements on several secondary measures of efficacy. ABT-089 was generally safe and well tolerated. The most commonly reported adverse events (≥5%) for total ABT-089-treated subjects at rates higher than placebo were headache, upper respiratory tract infection, irritability, insomnia, and nasopharyngitis. In this phase 2 crossover study, the NNR partial agonist ABT-089, at doses of 40 mg QD and 40 mg BID, was efficacious and generally well tolerated in treatment of adults with ADHD.

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An open‐label, dose‐titration tolerability study of atomoxetine hydrochloride in Japanese adults with attention‐deficit/hyperactivity disorder

The main purpose of this first atomoxetine study in Japanese adults with attention-deficit/hyperactivity disorder (ADHD) was to investigate the tolerability of an 8-week treatment regimen. This was an open-label, dose escalation study conducted in 45 Japanese patients aged at least 18 years with DSM-IV-defined ADHD. Patients received atomoxetine orally for 8 weeks. Atomoxetine administration was started at 40 mg/day (7 days), and subsequently increased to a maximum dose of 120 mg/day. Tolerability was assessed by discontinuation rate due to adverse events. Adverse events, laboratory tests, vital signs and electrocardiograms were collected. In addition, ADHD symptoms were assessed by using the Japanese version of the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) scores. Thirty-nine patients completed the study period. Atomoxetine was well tolerated with a 6.7% (3/45) discontinuation rate due to nausea, malaise and anorexia. The most commonly reported adverse events were nausea, nasopharyngitis and headache; there were no unexpected safety concerns. No deaths or serious adverse events were reported. Mean CAARS-Inv:SV-J total ADHD symptom scores decreased in a time-dependent manner; the mean change from baseline to endpoint was -15.0 (P<0.001). This study showed that atomoxetine was well tolerated in these patients and suggested that atomoxetine at a maximum dose of 120 mg/day would be safe in Japanese ADHD patients.

Once-Daily Atomoxetine for Adult Attention-Deficit/Hyperactivity Disorder

This randomized, double-blind, placebo-controlled, 6-month trial examined the efficacy and safety of once-daily morning-dosed atomoxetine in adult patients with attention-deficit/hyperactivity disorder (ADHD) and the efficacy of atomoxetine in ameliorating symptoms through the evening hours. Patients received once-daily atomoxetine (n = 250) or placebo (n = 251) in the morning for approximately 6 months. The efficacy measures included the Adult ADHD Investigator Symptom Rating Scale (AISRS), Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version, Clinical Global Impressions-ADHD-Severity of Illness, and Adult ADHD Quality of Life Scale. Overall, 94 patients randomized to atomoxetine and 112 patients randomized to placebo completed the study. On the AISRS total score, Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version evening index total score, Clinical Global Impressions-ADHD-Severity of Illness score, and Adult ADHD Quality of Life Scale total score, atomoxetine was statistically superior to placebo at the 10-week and 6-month time points. From the visitwise analysis, the mean (SD) AISRS total scores for atomoxetine decreased from 38.2 (7.5) at baseline to 21.4 (12.3) at the 6-month end point compared with 38.6 (7.0) to 25.8 (13.2) for placebo (P = 0.035). Nausea, dry mouth, fatigue, decreased appetite, urinary hesitation, and erectile dysfunction were the treatment-emergent adverse events reported significantly more often with atomoxetine. Discontinuations due to adverse events were 17.2% and 5.6% for atomoxetine and placebo, respectively (P < 0.001). Once-daily morning-dosed atomoxetine is efficacious for treating ADHD in adults when measured 10 weeks and 6 months after initiating treatment. Atomoxetine demonstrated significant efficacy that continued into the evening. Adverse events were similar to previous trials.

Long-Term, Open-Label Safety and Efficacy of Atomoxetine in Adults With ADHD

Objective: Previously, data from 97 weeks of open-label atomoxetine treatment of adults with attention-deficit/hyperactivity disorder (ADHD) were reported. This final report of that study presents results from over 4 years of treatment. Method: Results were derived from the study of 384 patients (125 patients remaining in the open-label trial since the interim report), receiving up to 221 weeks of treatment. Primary efficacy measure was the Conners' Adult ADHD Rating Scale—Investigator Rated: Screening Version (CAARS-Inv:SV) Total ADHD Symptom score. Adverse events and vital signs were assessed. Results: CAARS-Inv:SV Total ADHD Symptom scores decreased 30.2% (p < .001) during treatment. Similar, significant decreases were noted for the secondary efficacy measures, including the Sheehan Disability Scale Total score, which improved 25.3% (p < .001). Adverse events consisted primarily of pharmacologically (noradrenergic) expected effects. Conclusions: Results of this open-label study support the long-term efficacy, safety, and tolerability of atomoxetine for the treatment of adult ADHD. (J. of Att. Dis. 2008; 12(3) 248-253)

Gender Differences in 2 Clinical Trials of Adults With Attention-Deficit/Hyperactivity Disorder

Studies show that, in childhood attention-deficit/hyperactivity disorder (ADHD), boys have the combined type with externalizing behaviors more frequently, and girls have the inattentive type with increased internalizing disorders more frequently. This study explored gender differences in adults with ADHD in 2 large, placebo-controlled, multicenter studies conducted from 2000 to 2001. Information collected included 2 measures of ADHD, multiple psychological measures, general physical symptoms, and treatment response. Thirty-four percent of the subjects were female. Women were rated as more impaired on every measure of ADHD symptoms including total Conners' Adult ADHD Rating Scale-Investigator Format (CAARS-INV), total Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS), and most subscales of both measures. More women (75%) had combined type compared with men (62%). Women showed a more complex presentation, with higher scores on the Hamilton Rating Scale for Anxiety (HAM-A) and the Hamilton Rating Scale for Depression, 17-item version (HAM-D(17)), more sleep problems, and more past DSM-IV Axis I diagnoses. Both sexes displayed substantial impairment on 3 Psychological General Well-Being Schedule factors: tension-anxiety, life satisfaction, and vitality-drive. Women experienced significantly (p = .003) greater rates of emotional dysregulation (37%) versus men (29%) as defined by a cluster of symptoms on the WRAADDS. The emotional dysregulation factor is derived by combining 3 symptoms--temper control, mood lability, and emotional overreactivity--from the Utah Criteria for ADHD in adults. These symptoms are considered associated symptoms in the DSM-IV description of ADHD. Women also experienced greater improvement (p = .011) on this symptom factor. In contrast to the results from childhood studies, women were more impaired than men on ADHD scales in our study. The higher level of emotional symptoms and more complicated presentation in women may obscure the diagnosis of ADHD. Thus, the assessments of adults with ADHD should include an exploration of the emotional dimensions of the illness.

Quality of Life Assessment in Adult Patients With Attention-deficit/Hyperactivity Disorder Treated With Atomoxetine

Attention-deficit/hyperactivity disorder (ADHD) has its onset during childhood and is estimated to affect 3% to 7% of school-aged children. Unfortunately, the disorder frequently persists into adult life. The burden of this disorder is considerable and is often characterized by academic (or occupational) impairment and dysfunction within the family and society. Despite the existence of research demonstrating the effects of ADHD on certain aspects of life, the clinical trials of treatments for this disorder have focused primarily on efficacy and safety. Atomoxetine was approved in the United States in November 2002 for the treatment of ADHD in children, adolescents, and adults. The present study uses data from a clinical trial of atomoxetine in adult patients with ADHD that incorporated a measure of health-related quality of life (the Medical Outcomes Study 36-item short-form health survey [SF-36]) as part of the overall assessment of the success of this relatively new treatment. The primary outcome measure for ADHD symptoms was the Conners Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS) ADHD total symptom score. In agreement with previous studies, adult patients with ADHD treated with atomoxetine at typical doses showed significant amelioration of ADHD symptoms, as measured on the CAARS. At baseline, the measures of overall mental health (one aspect of quality of life) of adult patients with ADHD were below the average level, as measured on the SF-36. Treatment with atomoxetine significantly improved the measures of mental health and ameliorated the ADHD symptoms. In addition, the 2 measures were correlated. These data suggest that pharmacological intervention with atomoxetine not only ameliorates ADHD symptoms in adult patients but also improves their perceived quality of life.

Long-Term, Open-Label Study of the Safety and Efficacy of Atomoxetine in Adults With Attention-Deficit/Hyperactivity Disorder

Attention-deficit/hyperactivity disorder (ADHD) is an early-onset neuropsychiatric disorder that affects 3% to 7% of school-age children and 4% of adults. Its pathophysiology is thought to involve the dopaminergic and nor-adrenergic pathways associated with attention control and impulsivity. These symptoms have largely been defined in the childhood population, but the course of the condition and expression in the adult population are not as well characterized. This is an ongoing, 3-year, open-label study consisting of adults with DSM-IV ADHD who were previously enrolled in 1 of 2 double-blind, acute-treatment studies of atomoxetine. The results of the interim analysis reported here were derived from the study of 384 patients at 31 sites who had been studied for a period of up to 97 weeks. The primary efficacy measure was the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) total ADHD symptom score. In addition, safety, adverse events, and vital sign measurements were assessed. Significant improvement was noted with atomoxetine therapy, with mean CAARS-Inv:SV total ADHD symptom scores decreasing 33.2% from 29.2 (baseline of open-label therapy) to 19.5 (endpoint of open-label therapy) (p < .001). Similar and significant decreases were noted for the secondary efficacy measures. Adverse events consisted primarily of pharmacologically (noradrenergic) expected effects, such as increases in heart rate and blood pressure and a slight decrease in weight. The results of this interim analysis of an ongoing, open-label study of adults with ADHD support the long-term efficacy, safety, and tolerability of atomoxetine for the treatment of adult ADHD.