Mixed amphetamine salts extended-release in the treatment of adult ADHD: a randomized, controlled trial. Triple-bead mixed amphetamine salts (SPD465), a novel, enhanced extended-release amphetamine formulation for the treatment of adults with ADHD: a randomized, double-blind, multicenter, placebo-controlled study. Efficacy of a mixed amphetamine salts compound in adults with attention-deficit/hyperactivity disorder. A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD. Randomized controlled trial of brief cognitive-behavioural interventions among regular users of amphetamine. Immediate-release methylphenidate for ADHD in children with comorbid chronic multiple tic disorder. Amphetamine fails to facilitate motor performance and to enhance motor recovery among stroke patients with mild arm paresis: interim analysis and termination of a double blind, randomised, placebo-controlled trial. Efficacy of modafinil compared to dextroamphetamine for the treatment of attention deficit hyperactivity disorder in adults. Controlled stimulant treatment of ADHD and comorbid Tourette's syndrome: effects of stimulant and dose.
Attention-deficit/hyperactivity disorder (ADHD) is a serious neurobehavioral disorder of childhood onset that often persists into adolescence and adulthood. Functional impairments, underachievement, and difficult interpersonal relationships illustrate the need for effective treatment of ADHD through adulthood.
                This prospective, multisite, randomized, double-blind, placebo-controlled, parallel-group, dose-escalation study was conducted to assess the efficacy, safety, and duration of action of mixed amphetamine salts extended-release (MAS XR) in adults with ADHD, combined type. Adults > or =18 years of age were given placebo or MAS XR 20, 40, or 60 mg/day for 4 weeks. The main outcome measures were the ADHD Rating Scale and Conners' Adult ADHD Rating Scale Short Version Self-Report (CAARS-S-S).
                Two hundred fifty-five subjects were randomly assigned to treatment with MAS XR or placebo. MAS XR treatment was associated with statistically and clinically significant ADHD symptom reduction at endpoint; mean ADHD Rating Scale scores were 18.5 for the 20-mg group (P=.001), 18.4 for the 40-mg group (P<.001), and 18.5 for the 60-mg group (P<.001). Adults with severe symptoms (ADHD Rating Scale score >32 at baseline) had significantly greater symptom reduction with the highest MAS XR dose (60 mg/day), however, this dose-response relationship was determined by post-hoc analysis. The mean MAS XR effect size was 0.8. Statistically significant (P<.05) improvements in CAARS-S-S ADHD index scores occurred at 4- and 12-hours postdose for all MAS XR groups, indicating a 12-hour duration of effect. Symptoms improved within the first treatment week. Most adverse events reported were mild or moderate in intensity, and the most commonly reported adverse events were consistent with the known profile of stimulant medications. Vital signs and electrocardiograms showed no clinically significant cardiovascular changes.
                These results suggest that MAS XR is safe and effective in adults with ADHD and controlled ADHD symptoms for up to 12 hours. The efficacy and safety of triple-bead mixed amphetamine salts (MAS), an oral, once-daily, enhanced extended-release amphetamine formulation designed for a duration of action up to 16 hours, were evaluated in adults with attention-deficit/hyperactivity disorder (ADHD).
                In this phase 3, 7-week, randomized, double-blind, multicenter, placebo-controlled, parallel-group, dose-optimization study of 272 adults with ADHD (DSM-IV-TR criteria), subjects (aged 18 to 55 years) were randomly assigned to triple-bead MAS (starting dose 12.5 mg) or placebo. The primary outcome measure was change in ADHD Rating Scale-IV (ADHD-RS-IV). Secondary outcome measures included Clinical Global Impressions (CGI) scale, Time-Sensitive ADHD Symptom Scale (TASS) (measuring extended duration), Brown Attention-Deficit Disorder Scale (BADDS) (measuring executive function), Adult ADHD Impact Module (AIM-A) (measuring quality of life [QOL]), and ADHD-RS-IV hyperactivity-impulsivity and inattentiveness subscales. Adverse events (AEs), vital signs, electrocardiograms (ECGs), and laboratory data were collected. The trial was conducted from January 2005 to June 2005.
                Triple-bead MAS resulted in significantly greater improvement versus placebo in mean ADHD-RS-IV total score change (p < .0001), CGI-Improvement (p < .0001), TASS total score at 13-16 hours postdose (p = .002), BADDS total score (p < .0001), all AIM-A domains (p < or = .01), and ADHD-RS-IV subscales (p < .01), demonstrating extended duration of efficacy and improvements in executive function and QOL. The most common treatment-emergent AEs included insomnia, dry mouth, decreased appetite and weight, and headache. Most treatment-emergent AEs were mild or moderate in severity.
                Triple-bead MAS was significantly more effective than placebo in treating adult ADHD. The extended duration of action up to 16 hours and significant improvements in executive function and QOL address unique treatment needs of adults with ADHD. Treatment-emergent AEs with triple-bead MAS were consistent with amphetamine treatment.
                Copyright 2008 Physicians Postgraduate Press, Inc. We report on a controlled trial of a mixed amphetamine salts compound (Adderall, dextroamphetamine sulfate, dextro-, levoamphetamine sulfate, dextroamphetamine aspartate, levoamphetamine aspartate, and dextroamphetamine saccharate) in the treatment of adult attention-deficit/hyperactivity disorder (ADHD).
                This was a 7-week, randomized, double-blind, placebo-controlled, crossover study of Adderall in 27 well-characterized adults satisfying full DSM-IV criteria for ADHD of childhood onset and persistent symptoms into adulthood. Medication was titrated up to 30 mg twice a day. Outcome measures included the ADHD Rating Scale and the Clinical Global Impression Score. Comorbid psychiatric disorders were assessed to test for potential effects on treatment outcome.
                Treatment with Adderall at an average oral dose of 54 mg (administered in 2 daily doses) was effective and well tolerated. Drug-specific improvement in ADHD symptoms was highly significant overall (42% decrease on the ADHD Rating Scale, P<.001), and sufficiently robust to be detectable in a parallel groups comparison restricted to the first 3 weeks of the protocol (P<.001). The percentage of subjects who improved (reduction in the ADHD rating scale of > or =30%) was significantly higher with Adderall treatment than with a placebo (70% vs 7%; P =.001).
                Adderall was effective and well tolerated in the short-term treatment of adults with ADHD. More work is needed to evaluate the long-term effects of Adderall, or other amphetamine compounds, in the treatment of adults with ADHD. Previous studies have demonstrated the short-term efficacy of pharmacotherapy and behavior therapy for attention-deficit/hyperactivity disorder (ADHD), but no longer-term (i.e., >4 months) investigations have compared these 2 treatments or their combination.
                A group of 579 children with ADHD Combined Type, aged 7 to 9.9 years, were assigned to 14 months of medication management (titration followed by monthly visits); intensive behavioral treatment (parent, school, and child components, with therapist involvement gradually reduced over time); the two combined; or standard community care (treatments by community providers). Outcomes were assessed in multiple domains before and during treatment and at treatment end point (with the combined treatment and medication management groups continuing medication at all assessment points). Data were analyzed through intent-to-treat random-effects regression procedures.
                All 4 groups showed sizable reductions in symptoms over time, with significant differences among them in degrees of change. For most ADHD symptoms, children in the combined treatment and medication management groups showed significantly greater improvement than those given intensive behavioral treatment and community care. Combined and medication management treatments did not differ significantly on any direct comparisons, but in several instances (oppositional/aggressive symptoms, internalizing symptoms, teacher-rated social skills, parent-child relations, and reading achievement) combined treatment proved superior to intensive behavioral treatment and/or community care while medication management did not. Study medication strategies were superior to community care treatments, despite the fact that two thirds of community-treated subjects received medication during the study period.
                For ADHD symptoms, our carefully crafted medication management was superior to behavioral treatment and to routine community care that included medication. Our combined treatment did not yield significantly greater benefits than medication management for core ADHD symptoms, but may have provided modest advantages for non-ADHD symptom and positive functioning outcomes. To identify whether brief cognitive-behavioural interventions are feasible among regular users of amphetamine, to assess the effectiveness of intervention overall and to pilot two- and four-session interventions.
                Subjects were assigned randomly to individually receive a cognitive-behavioural intervention (n = 32) of either two or four sessions' duration or a self-help booklet (control condition; n = 32).
                Subjects were volunteers recruited from needle exchange schemes and treatment centres in Newcastle, Australia.
                Regular (at least monthly) users of amphetamine were recruited.
                Either four sessions of cognitive-behaviour therapy, consisting of a motivational interview and skills training in avoidance of high-risk situations, coping with craving and relapse prevention, or two sessions consisting of a motivational interview and discussion of skills.
                The Opiate Treatment Index was the main measure at pre-treatment and 6-month follow-up.
                There was a significant reduction in amphetamine use among the sample as a whole, with inconclusive differences between intervention subgroups. There was a moderate overall intervention effect, with the intervention group reporting over twice the reduction in daily amphetamine use as the control group. Significantly more people in the cognitive-behavioural intervention condition abstained from amphetamine at 6-month follow-up compared to the control condition.
                Brief cognitive-behavioural interventions appear feasible among regular users of amphetamine. A larger randomised controlled trial of the effectiveness of such interventions appears warranted. To examine the safety and efficacy of immediate-release methylphenidate (MPH-IR) for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children (ages 6-12 years) with Tourette's syndrome (96%) or chronic motor tic disorder (4%).
                Two cohorts of prepubertal children (N = 71) received placebo and three doses of MPH (0.1, 0.3, and 0.5 mg/kg) twice daily for 2 weeks each, under double-blind conditions as part of their involvement in a long-term observation study (1989-2004). Treatment effects were assessed with an extensive battery of parent-, teacher-, child-, and physician-completed rating scales and laboratory tasks.
                MPH-IR effectively suppressed ADHD, oppositional defiant disorder, and peer aggression behaviors. There was no evidence that MPH-IR altered the overall severity of tic disorder or obsessive-compulsive disorder behaviors. Teacher ratings indicated that MPH-IR therapy decreased tic frequency and severity.
                MPH-IR appears to be a safe and effective short-term treatment for ADHD in the majority of children with chronic tic disorder; nevertheless, the possibility of tic exacerbation in susceptible individuals warrants careful monitoring of all patients. To assess the effects of d-amphetamine on motor facilitation and recovery in stroke patients with mild arm paresis receiving the Arm Ability training.
                Thirty-one stroke patients with mild arm paresis were randomly assigned to either (a.) receiving placebo or (b.) d-amphetamine twice a week 2 hours before Arm Ability training sessions for three weeks. Main outcome measure: time needed to perform TEMPA tasks, a measure of upper extremity performance reflecting everyday life tasks. Secondary measures: aimed movements, tapping, and a 10 m walkway as well as motor performance during training sessions.
                The interim efficacy analysis of 26 stroke patients who completed the study intervention showed overall arm motor recovery both from pre to post test after 3 weeks of training and from pre test to follow-up 1 year later. No superior effect of d-amphetamine over placebo could be substantiated for either motor facilitation during training or motor recovery (post training or long-term). D-amphetamine exerted mild effects on blood pressure. Serious adverse events were not observed.
                d-Amphetamine failed to facilitate motor performance during training sessions, to promote skill acquisition with training tasks, and most importantly to enhance motor recovery among patients with mild arm paresis after stroke. Our objective was to compare the efficacy of the new wake-promoting drug modafinil to that of dextroamphetamine for the treatment of attention deficit hyperactivity disorder (ADHD) in adults. Twenty-two adults who met DSM-IV criteria for ADHD participated in a randomized, double-blind, placebo-controlled, three-phase crossover study comparing placebo, modafinil, and dextroamphetamine for the treatment of ADHD. The twice-daily study medications were titrated to doses of optimum efficacy over 4-7 days and then held constant during the rest of each 2-week treatment phase. Measures of improvement included the DSM-IV ADHD Behavior Checklist for Adults, the Controlled Oral Word Association Test (COWAT, using the letters C, F, and L version), Stroop, and Digit Span (Wechsler Adult Intelligence Scale version). For the 21 (96%) completers, the mean (+/- SD) optimum doses of modafinil and dextroamphetamine were 206.8 mg/day +/- 84.9 and 21.8 mg/day +/- 8.9, respectively. Scores on the DSM-IV ADHD Checklist (p < 0.001) were significantly improved over the placebo condition following treatment with both active medications. Performance on the COWAT (p < 0.05) reached trend levels of significance. Both medications were generally well tolerated. This preliminary study suggests that modafinil may be a viable alternative to conventional stimulants for the treatment of adults with ADHD. To determine the effects of methylphenidate (MPH) and dextroamphetamine (DEX) on tic severity in boys with attention-deficit/hyperactivity disorder (ADHD) comorbid with Tourette's syndrome.
                A 9-week, placebo-controlled, double-blind crossover using a wide range of doses was completed by 20 subjects in three cohorts.
                Relatively high doses of MPH and DEX in the first cohort produced significant increases in tic severity which were sustained on higher doses of DEX but which attenuated on MPH. Overall, 14 of 20 subjects continued stimulant treatment for 1 to 3 years, generally in combination with other psychotropics. Stimulant-associated adverse effects, including tic exacerbations, were reversible in all cases.
                A substantial minority of comorbid subjects had consistent worsening of tics on stimulants, although the majority experienced improvement in ADHD symptoms with acceptable effects on tics. MPH was better tolerated than DEX.
Amphetamines improved short-term ADHD symptom severity. MAS also increased retention in treatment. Amphetamines were associated with higher attrition due to adverse events. The short study length and the restrictive inclusion criteria limit the external validity of these findings. Furthermore, the possibility that the results of the included studies were biased was high, which could have led to an overestimation of amphetamine efficacy.