A pilot controlled clinical trial of ABT-418, a cholinergic agonist, in the treatment of adults with attention deficit hyperactivity disorder

OBJECTIVE: Despite the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults, there is a paucity of controlled pharmacological trials. Recent reports have suggested the potential usefulness of cholinergic agents for ADHD. To this end, the authors completed a controlled study of ABT-418, a novel cholinergic activating agent, for the treatment of adults with ADHD. METHOD: This was a double-blind, placebo-controlled, randomized, crossover trial that compared a transdermal patch of ABT-418 (75 mg/day) to placebo in adults who met DSM-IV criteria for ADHD. There were two 3-week treatment periods separated by 1 week of washout. RESULTS: Of the 32 subjects enrolled in the study (88% were men; mean age = 40 years, SD = 9), 29 completed the study. At the endpoint of each active arm (last observation carried forward), a significantly higher proportion of subjects was considered improved while receiving ABT-418 than while receiving placebo (40% versus 13%). Similarly, at endpoint there was a significantly greater reduction in ADHD symptom checklist scores (28% versus 15%). Symptoms reflective of attention, and subjects with less severe ADHD, responded more robustly to ABT-418. Treatment with ABT-418 was relatively well tolerated; dizziness and nausea were the most frequently reported adverse effects. CONCLUSIONS: The results of this investigation indicate that ABT-418, a nicotinic analog, may be a potentially useful agent for the treatment of ADHD.     

An open-label study of the tolerability of mixed amphetamine salts in adults with attention-deficit/hyperactivity disorder and treated primary essential hypertension

OBJECTIVE: To evaluate the short-term tolerability of an extended-release preparation of the stimulant medication mixed amphetamine salts (MAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD) whose hypertension has been successfully treated with antihypertensive medications. METHOD: An 8-week, 2-phase, open-label study design was implemented. All adults had ADHD (DSM-IV diagnosis) and essential hypertension and were required to be normotensive (blood pressure < 135/85 mm Hg, treated) for at least 4 weeks at entry into the study. MAS XR was given for a 6-week period, titrated once each week to a target maximum dose of 60 mg/day given once daily in the morning (phase 1), and then discontinued for 2 weeks at the end of the study (phase 2). At baseline, subjects underwent a comprehensive clinical assessment, medical history, vital signs assessment, and electrocardiogram (ECG). Rating scales were used throughout the study to assess response to treatment, and blood pressure was measured manually at each study visit. The primary outcome was the effect of MAS XR on blood pressure and the development of hypertension. RESULTS: Thirteen subjects receiving antihypertensive therapy were entered and placed on MAS XR treatment and completed the trial. There were no serious adverse events. No sustained elevated blood pressure (> 140/90 mm Hg at 2 consecutive visits) was observed in the subjects treated with MAS XR. Similar rates of single episodes of hypertension were observed in phases 1 and 2. Similarly, there was no group mean increase in systolic or diastolic blood pressure or pulse during treatment with MAS XR. No clinically significant changes in the ECG were observed. During the 6-week medication phase, significant improvement was found on rating scales assessing ADHD symptoms and severity that reversed with discontinuation of MAS XR. CONCLUSION: The results of this open study suggest that adults with ADHD and controlled hypertension can be safely treated with MAS XR.     

Use of self-ratings in the assessment of symptoms of attention deficit hyperactivity disorder in adults

OBJECTIVE: The purpose of this research was to determine if adults can provide a true rating of their own childhood and current symptoms of attention deficit hyperactivity disorder (ADHD). METHOD: The authors conducted two studies. In study 1, 50 adult subjects completed a questionnaire assessing their ADHD symptoms in childhood. In addition, a parent of each subject completed a questionnaire rating the subject's childhood ADHD symptoms. In study 2, 100 adult subjects completed a questionnaire rating their own current ADHD symptoms. The subject's partner also completed a questionnaire rating the subject's current ADHD symptoms. The correlation between subject and observer ratings was measured in each study. Inattentive symptoms, hyperactive-impulsive symptoms, and total symptoms were analyzed. RESULTS: Good correlations were found between subject and observer scores in both studies. CONCLUSIONS: The diagnosis of ADHD in adults relies on an accurate recall of childhood behavior and an accurate account of current behavior. The results of this study suggest that adults can give a true account of their childhood and current symptoms of ADHD.     

Efficacy of a mixed amphetamine salts compound in adults with attention-deficit/hyperactivity disorder

BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.     

奥卡西平联合选择性5-羟色胺再摄取抑制剂治疗激越性抑郁的开放性研究

目的 观察和评价门诊32例激越性抑郁患者在应用选择性5-羟色胺再摄取抑制剂(SSRI)的基础上联合应用奥卡西平的效果与不良反应.方法 对符合抑郁症诊断标准同时伴有激越症状的32例患者在应用SSRI的基础上联合应用奥卡西平(0.3 g/片,第1、2天1片,第3天起2片,7 d内根据情况用至4～5片)治疗,观察8周,应用汉密尔顿抑郁评定量表(HAMD)、汉密尔顿焦虑评定量表(HAMA)、杨氏躁狂评定量表(YMRS)评价疗效和不良反应.结果 32例患者奥卡西平平均用量为(1020±65)mg/d.临床有效率为87.5%(28/32),痊愈率为65.6%(21/32).治疗后1周、2周、4周、8周的有效率和痊愈率分别是28.1%(9/32)与6.3%(2/32)、37.5%(12/321与12.5%(4/32)、46.9%05/32)与31.3%(10/32)、90.6%(29/32)与65.6%(21/32).患者治疗后1周、2周、4周、8周的各量表评分与治疗前比较差异均有统计学意义(P<0.05).32例患者中没有1例出现转躁狂现象.结论 奥卡西平联合SSRI治疗激越性抑郁可获得较好的疗效.     

A controlled clinical trial of bupropion for attention deficit hyperactivity disorder in adults

OBJECTIVE: Despite the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults, there is a paucity of controlled pharmacological trials demonstrating the effectiveness of compounds used in treatment, particularly nonstimulants. The authors report results from a controlled investigation to determine the anti-ADHD efficacy of bupropion in adult patients with DSM-IV ADHD. METHOD: This was a double-blind, placebo-controlled, randomized, parallel, 6-week trial comparing patients receiving sustained-release bupropion (up to 200 mg b.i.d.) (N=21) to patients receiving placebo (N=19). The authors used standardized structured psychiatric instruments for diagnosis of ADHD. To measure improvement, they used separate assessments of ADHD, depression, and anxiety symptoms at baseline and each weekly visit. RESULTS: Of the 40 subjects (55% male) enrolled in the study, 38 completed the study. Bupropion treatment was associated with a significant change in ADHD symptoms at the week-6 endpoint (42% reduction), which exceeded the effects of placebo (24% reduction). In analyses using a cutoff of 30% or better reduction to denote response, 76% of the subjects receiving bupropion improved, compared to 37% of the subjects receiving placebo. Similarly, in analyses using Clinical Global Impression scale scores, 52% of the subjects receiving bupropion reported being "much improved" to "very improved," compared to 11% of the subjects receiving placebo. CONCLUSIONS: These results indicate a clinically and statistically significant effect of bupropion in improving ADHD in adults. The results suggest a therapeutic role for bupropion in the armamentarium of agents for ADHD in adults, while further validating the continuity of pharmacological responsivity of ADHD across the lifespan.     

Comparison of two anticonvulsants in a randomized, single-blind treatment of hypomanic symptoms in patients with bipolar disorder

OBJECTIVE: Oxcarbazepine was compared to divalproex to assess clinical effectiveness of a proven agent, divalproex, against a newer, less studied agent, oxcarbazepine, in the treatment of hypomania. METHOD: Thirty patients with bipolar disorder, currently hypomanic, were randomized to receive oxcarbazepine or divalproex as add-on or monotherapy for 8 weeks. A rater blind to treatment assignment performed all symptom ratings. Hypomania and depression were rated using the Young Mania Rating Scale (YMRS) and the Inventory of Depressive Symptoms-Clinician Version (IDS-C). Random regression models were used to assess clinical symptom scores. RESULTS: There were no significant differences of YMRS or IDS-C scores between groups. Mean YMRS scores at baseline were 22.07+/-5.86 and 20.53+/-6.02 for the oxcarbazepine and the divalproex groups, respectively. Mean percent reduction from baseline to week 8 for the YMRS was 63.8% and 79.0% for oxcarbazepine and divalproex groups, respectively. Mean percent reduction from baseline to week 8 for the IDS-C was 48.7% versus 19.7% for oxcarbazepine and divalproex groups, respectively. Significant antimanic efficacy was noted for each medication. Both medications were generally well tolerated. CONCLUSION: In this pilot study, oxcarbazepine was as effective as divalproex in the treatment of hypomania. Further controlled trials are warranted.     

Twenty-four-week treatment with extended release methylphenidate improves emotional symptoms in adult ADHD

Abstract

Objectives. Treatment investigations with methylphenidate in adults with ADHD focus preferentially on the classical psychopathology: inattention, hyperactivity and impulsivity. ADHD-associated emotional symptoms, which are frequently present at least in ADHD subpopulations, were studied rarely. The vast majority of the placebo-controlled trials had observation periods between 4 and 8 weeks. To assess the medium- to long-term effects of extended release methylphenidate (MPH-ER) on emotional symptoms and other psychopathology frequently seen in ADHD patients, we conducted a large-scale, multicenter treatment study. Methods. We performed a randomised, 24-week, double-blind, placebo-controlled study in adults with ADHD. The diagnosis was made on the basis of the DSM-IV criteria, which were confirmed by clinical history and a structured psychopathological interview and the use of rating instruments. 363 patients were randomized to MPH-ER or placebo at a ratio of 2:1. The duration of the titration period was 5 weeks followed by a maintainance phase of 19 weeks. The efficacy measures were the observer rated 10-item Emotional Dysregulation Scale (EDS) derived from the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) and a self-report, six-item Emotional Lability Scale (ELS) extracted from the long version of the Conners Adult ADHD Self Report Scale (CAARS:S:L). In addition we used the SCL-90-R for the assessment of ADHD associated and comorbid psychopathology. Results. MPH-ER was statistically superior to placebo in reducing emotional symptoms as assessed by the EDS and the ELS. Obsessive-compulsive symptoms and those of problems with self-concept declined until the end of the observation period. The decline was more pronounced in MPH-ER treated individuals. The effects remained robust during the entire maintenance period until week 24. Symptoms of anxiety, depression, anger and hostility, phobia, paranoid ideations and psychoticism were not improved. Conclusions. MPH-ER appears to be an efficacious treatment for emotional symptoms with ADHD. Also obsessive-compulsive symptoms and problems with self-concept were affected positively.     

Childhood inattention and hyperactivity symptoms self-reported by adults with Asperger syndrome

BACKGROUND: Increasing public awareness of the adult manifestations of developmental neuropsychiatric disorders, like Asperger syndrome and attention deficit hyperactivity disorder (ADHD), has provoked an increasing number of persons to seek assessment for the first time in adulthood. As these disorders have their origin in childhood, instruments for retrospective evaluation of childhood behavior are needed. SAMPLING AND METHODS: In this preliminary study, 20 adults with Asperger syndrome filled in the Wender-Utah Rating Scale for ADHD to describe retrospectively their childhood behavior. RESULTS: Fourteen out of 20 adults with Asperger syndrome self-rated above the cut-off limit for ADHD. The median total score was also higher than that reported in normal populations in previous studies. When compared with 10 controls, patients with Asperger syndrome scored higher in almost all individual items. CONCLUSIONS: A high score on the Wender-Utah rating Scale for ADHD in this patient group might be a sign of true comorbidity with ADHD, an indication of overlapping features typical of both disorders, or a result of other psychiatric comorbidity originating already in childhood. Moreover, there are no data about the proper cut-off limit for ADHD in these subjects. Therefore, one should be cautious when applying this scale beyond its original context of comparison between adults with ADHD, unipolar depression and healthy controls.     

Bupropion for adults with attention-deficit hyperactivity disorder: meta-analysis of randomized, placebo-controlled trials

Aim: The aim of this study was to systematically review the efficacy, acceptability and tolerability of bupropion in comparison to placebo. Only randomized‐controlled trials were included in the meta‐analysis. Methods: MEDLINE, EMBASE, CINHL, PsycINFO and Cochrane Controlled Trials Register were searched in October 2010. Study populations comprised adults with any subtype of attention‐deficit hyperactivity disorder, attention‐deficit disorder, hyperkinetic disorder, minimal brain dysfunction, minimal cerebral dysfunction or minor cerebral dysfunction. Efficacy outcomes were pooled mean changed scores of the ADHD rating scale (ADHD‐RS) and the overall response rates. The overall discontinuation rate was considered as the measure of acceptability. Results: A total of 349 participants (n for bupropion treatment = 175) in five published randomized, controlled trials were included. Bupropion sustained‐ or extended‐release was the experimental treatment in all studies. The pooled mean changed score of the ADHD‐RS of the bupropion‐treated group was greater than that of the placebo‐treated group with a weighted mean difference (95%CI) of 5.08 (3.13–7.03). The overall response rate of the bupropion‐treated group was significantly greater than that of placebo‐treated groups with a relative risk (95%CI) of 1.67 (1.23–2.26). However, the pooled overall discontinuation rate and the pooled discontinuation rate due to adverse events were not significantly different between groups with a relative risk (95%CI) of 1.11 (0.71–1.72) and 0.87 (0.08–9.79), respectively. Conclusion: The evidence suggests that bupropion is superior to placebo and effective for the treatment of ADHD in adults. However, its acceptability and tolerability were not significantly higher than those of placebo.     

Effectiveness of symptom validity measures in identifying cognitive and behavioral symptom exaggeration in adult attention deficit hyperactivity disorder

This study examines the effectiveness of symptom validity measures to detect suspect effort in cognitive testing and invalid completion of ADHD behavior rating scales in 268 adults referred for ADHD assessment. Patients were diagnosed with ADHD based on cognitive testing, behavior rating scales, and clinical interview. Suspect effort was diagnosed by at least two of the following: failure on embedded and free-standing SVT measures, a score > 2 SD below the ADD population average on tests, failure on an ADHD behavior rating scale validity scale, or a major discrepancy between reported and observed ADHD behaviors. A total of 22% of patients engaged in symptom exaggeration. The Word Memory test immediate recall and consistency score (both 64%), TOVA omission errors (63%) and reaction time variability (54%), CAT-A infrequency scale (58%), and b Test (47%) had good sensitivity as well as at least 90% specificity. Clearly, such measures should be used to help avoid making false positive diagnoses of ADHD.      

ABT-089, a neuronal nicotinic receptor partial agonist, for the treatment of attention-deficit/hyperactivity disorder in adults: results of a pilot study.

BACKGROUND: This pilot study was designed to evaluate ABT-089, a neuronal nicotinic receptor partial agonist, as treatment for adult attention-deficit/hyperactivity disorder (ADHD). METHODS: Adults with ADHD received placebo, 2 mg, 4 mg, or 20 mg of ABT-089 for 2 weeks each in a randomized, double-blind, placebo-controlled, 4 x 4 Latin square design for a total of 8 weeks. In addition to the primary outcome, the Conner's Adult ADHD Rating Scale (CAARS), secondary rating scales, and neuropsychological and safety assessments were completed. RESULTS: A total of 11 adults with well-characterized ADHD completed this crossover study. ABT-089 b.i.d. was superior to placebo for the CAARS Total Symptom Score, which was the primary endpoint (placebo: 38.0 +/- 1.9; 2 mg b.i.d.: 32.2 +/- 1.9, one-tail p = .021; 4 mg b.i.d.: 33.2 +/- 1.9, p = .047; 20 mg b.i.d.: 33.5 +/- 1.9, p = .056). ABT-089 was also superior to placebo for the CAARS ADHD Index and Hyperactive/Impulsive scores and the Clinical Global Impression-ADHD Severity score. On the clinical efficacy endpoints, CAARS Total Symptom Score and CAARS Hyperactive/Impulsive score, a shallow inverted U-shaped dose-response curve was observed; however, the dose-response curve for attention and memory effects as measured by computerized cognitive testing seemed dose-linear. No clinically meaningful findings in safety assessments or side effect profile were observed. CONCLUSIONS: Data from this pilot study suggest that ABT-089 might be effective in treating adult ADHD and that it is well tolerated. On the basis of these promising results, larger, parallel-group ABT-089 studies of longer duration are warranted.     

Wender Utah rating scale. The short-version for the assessment of the attention-deficit hyperactivity disorder in adults

This work presents a statistical analysis of the German version of the Wender Utah rating scale (WURS) for the retrospective diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adults. Data were obtained from 703 subjects. Item selection according to item-total correlation scores, frequency, and plausibility led to a short version of the scale that includes 21 items with item-total correlations from 0.19 to 0.61. Retest reliability of the WURS-k was r=0.9.     

Validity of pilot Adult ADHD Self- Report Scale (ASRS) to Rate Adult ADHD symptoms.

BACKGROUND: The goal of this study was to validate the pilot Adult ADHD Self-Report Scale (pilot ASRS) versus standard clinician ratings on the ADHD Rating Scale (ADHD RS). METHOD: Sixty adult ADHD patients took the self-administered ADHD RS and then raters administered the standard ADHD RS. Internal consistency of symptom scores was assessed by Cronbach's alpha. Agreement of raters was established by intra-class correlation coefficients (ICCs) between scales. RESULTS: Internal consistency was high for both patient and rater-administered versions (Cronbach's alpha 0.88, 0.89, respectively). The ICC between scales for total scores was also high (0.84); ICCs for subset symptom scores were also high (both 0.83). There was acceptable agreement for individual items (% agreement: 43%-72%) and significant kappa coefficients for all items (p < 0.001). CONCLUSIONS: The pilot Adult ADHD Self-Report Scale symptom checklist is a reliable and valid scale for evaluating ADHD for adults and shows a high internal consistency and high concurrent validity with the rater-administered ADHD RS.     

Atomoxetine in the Treatment of Adults with Subthreshold and/or Late Onset Attention-Deficit Hyperactivity Disorder-Not Otherwise Specified (ADHD-NOS): A Prospective Open-Label 6-Week Study

The objective of this study was to evaluate the efficacy and tolerability of atomoxetine hydrochloride (ATX) in the treatment of adults with atypical manifestations of attention-deficit hyperactivity disorder (ADHD) (not otherwise specified [NOS]). We hypothesized that treatment with ATX will be safe and efficacious for the treatment of adults with ADHD-NOS. This was a 6-week, open-label, prospective treatment study of ATX monotherapy in 45 adult patients with ADHD-NOS assessed using standardized instruments for diagnosis and a robust oral daily dose of up to 1.2 mg/kg/day or 120 mg/day. Symptom severity was assessed with the adult ADHD Investigator Symptom Report Scale (AISRS) and Clinical Global Impression Scale. Treatment with ATX at an average daily dose of 78.7 ± 27.8 mg was associated with a statistically and clinically significant reduction in ADHD symptoms relative to baseline as assessed through the (AISRS) (−12.1 ± 8.4; P < 0.001). Using a categorical definition of response (CGI-I much or very much improved), a majority (N = 29; 64%) of subjects were rated as improved at study endpoint. Treatment with ATX was relatively well tolerated. These open-label results suggest that ATX may be safe and effective in the treatment of adults meeting criteria for ADHD-NOS and support the need for further controlled clinical trials of ATX in this population.     

Atomoxetine in adults with ADHD: two randomized, placebo-controlled studies.

BACKGRAUND: Attention-deficit/hyperactivity disorder (ADHD) has been less studied in adults than in children, and the treatment studies reported to date have been small, single-center trials. To assess the efficacy of atomoxetine, a new and highly selective inhibitor of the norepinephrine transporter, we conducted two large, multicenter treatment trials. METHODS: Two identical studies using randomized, double-blind, placebo-controlled designs and a 10-week treatment period were conducted in adults with DSM-IV-defined ADHD as assessed by clinical history and confirmed by a structured interview (study I, n = 280; study II, n = 256). The primary outcome measure was a comparison of atomoxetine and placebo using repeated measures mixed model analysis of postbaseline values of the Conners' Adult ADHD Rating Scale. RESULTS: In each study, atomoxetine was statistically superior to placebo in reducing both inattentive and hyperactive and impulsive symptoms as assessed by primary and secondary measures. Discontinuations for adverse events among atomoxetine patients were under 10% in both studies. CONCLUSION: Atomoxetine appears to be an efficacious treatment for adult ADHD. Its lack of abuse potential may be an advantage for many patients.     

Administering and evaluating the results of the adult ADHD Self-Report Scale (ASRS) in adolescents

Attention-deficit/hyperactivity disorder (ADHD) is a common condition that can be difficult to diagnose in adolescents, since symptoms may vary among patients, evolve over time, and mimic symptoms of other disorders. Various rating scales are helpful to the clinician when evaluating patients for ADHD and should be used as part of a thorough assessment. Clinicians should use both informant- and self-report rating scales to gather as much information as possible, while being aware that informants are subject to rater error and adolescents typically underreport symptoms. Rating scales can establish a baseline measure of the patient's symptom type and frequency, provide a framework for assessing symptom impairment, and aid clinicians in monitoring treatment response. The Adult ADHD Self-Report Scale (ASRS-v1.1) Symptom Checklist is a reliable self-report rating scale for adolescents as well as adults.     

A controlled study of nortriptyline in children and adolescents with attention deficit hyperactivity disorder

OBJECTIVES: To study the efficacy and tolerability of nortriptyline (NT) in the treatment of pediatric attention deficit hyperactivity disorder (ADHD). METHODOLOGY: Subjects were outpatient children and adolescents with ADHD ascertained from clinical referrals. Subjects were enrolled in a 6-week open study in which NT was titrated to 2 mg/kg/day as tolerated over 2 weeks. Using either a 30 % reduction in the ADHD rating scale or a score of 1 or 2 on the Clinical Global Impression (CGI) scale for ADHD improvement, responders to treatment were then randomized into a 3-week, controlled discontinuation phase. During this phase, subjects either continued on their current dose of NT or were tapered to placebo under double-blind conditions. Subjects were monitored for symptoms of ADHD, oppositionality, anxiety, and depression. RESULTS: Of the 35 subjects enrolled in the study, 32 completed the open phase and 23 completed the discontinuation phase. The mean dose of NT was 80 mg (1.8 mg/kg/day), resulting in a serum level of 81 ng/ml. At the conclusion of the open 6-week study, NT was related to a significant reduction in ADHD (p < 0.001) and oppositional symptoms (p < 0.001). At the conclusion of the discontinuation phase, the 12 subjects randomized to NT had significantly lower scores on the DSM-IV ADHD symptom checklist than those 11 subjects randomized to placebo (31 versus 21; t = 2.2; p < 0.04). No significant adverse events were observed, and children were noted to have weight gain during the trial. CONCLUSIONS: These data suggest that NT is effective in reducing symptoms not only of ADHD but also of oppositionality. This group of children and adolescents tolerated robust dosing of NT well, with few clinical or cardiovascular adverse events.     

A randomized, placebo-controlled trial of OROS methylphenidate in adults with attention-deficit/hyperactivity disorder.

BACKGROUND: The objective of this study was to evaluate the safety and efficacy of once-daily OROS methylphenidate (MPH) in the treatment of adults with DSM-IV attention-deficit/hyperactivity disorder (ADHD). METHODS: We conducted a randomized, 6-week, placebo-controlled, parallel-design study of OROS MPH in 141 adult subjects with DSM-IV ADHD, using standardized instruments for diagnosis. OROS MPH or placebo was initiated at 36 mg/day and titrated to optimal response, depending on efficacy and tolerability, up to 1.3 mg/kg/day. RESULTS: Treatment with OROS MPH was associated with clinically and statistically significant reductions in DSM-IV symptoms of inattention and hyperactivity/impulsivity relative to subjects treated with placebo. At endpoint, 66% of subjects (n = 44) receiving OROS MPH and 39% of subjects (n = 29) [corrected] receiving placebo attained our a priori definition of response of much or very much improved on the Clinical Global Impression-Improvement scale plus a >30% reduction in Adult ADHD Investigator System Report Scale score. OROS MPH was associated with small but statistically significant increases in systolic blood pressure (3.5 +/- 11.8 mm Hg), diastolic blood pressure (4.0 +/- 8.5 mm Hg), and heart rate (4.5 +/- 10.5 bpm). CONCLUSIONS: These results show that treatment with OROS MPH in daily doses of up to 1.3 mg/kg/day was effective in the treatment of adults with ADHD. Because of the potential for increases in blood pressure and heart rate, subjects receiving treatment with MPH should be monitored for changes in blood pressure parameters during treatment.