Dexmethylphenidate extended-release capsules in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: This study compared once-daily dexmethylphenidate extended release (D-MPH-ER) 20 mg/day and placebo over 12 hours in children ages 6 to 12 with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting. METHOD: All of the children were stabilized for > or =2 weeks on a total dose (nearest equivalent) MPH 40 mg/day or immediate-release D-MPH 20 mg/day before screening. After a practice day, they received 6 days of D-MPH-ER 20 mg/day or placebo at home, returning on day 7 for one dose. Subjects were evaluated at predose and postdose hours 0.5, 1, 3, 4, 5, 7, 9, 10, 11, and 12 and then crossed over to the other treatment arm using the identical protocol. The primary efficacy variable was the change from predose in Swanson, Kotkin, Agler, M-Flynn, and Pelham rating scale (SKAMP) combined score from 1 to 12 hours. Secondary efficacy variables included SKAMP combined score at 0.5 hours, SKAMP subscale scores, and math test results over 12 hours. RESULTS: Sixty-eight children were randomized, with 67 completing the study. Onset of action was indicated by a significant difference between D-MPH-ER and placebo at 0.5 hour on the SKAMP combined score (p = .001). For efficacy measures, differences from placebo were significant at all points between 0.5 and 12 hours (p < .001 top = .013). CONCLUSIONS: D-MPH-ER provided sustained improvement in attention, deportment, and academic productivity throughout the 12-hour laboratory day.

Efficacy and duration of effect of extended-release dexmethylphenidate versus placebo in schoolchildren with attention-deficit/hyperactivity disorder.

OBJECTIVE: The aim of this study was to assess changes in symptomatology of attention-deficit/ hyperactivity disorder (ADHD) with extended-release dexmethylphenidate (d-MPHER) versus placebo in a laboratory classroom setting. METHODS: This double-blind, placebo-controlled, crossover study randomized 54 children 6-12 years of age, stabilized on methylphenidate 20-40 mg/day. Patients participated in a practice day, then received 5 days of treatment with d-MPH-ER 20 mg/day or placebo. After a 1-day wash-out, they returned to the classroom and received 1 dose of their assigned treatment. Evaluations occurred predose and at postdose hours 1, 2, 4, 6, 8, 9, 10, 11, and 12. Children were then crossed over to the alternate treatment, using identical protocol. Primary efficacy variable was the Swanson, Kotkin, Agler, M-Flynn, and Pelham rating scale (SKAMP)-Combined scores, and primary analysis time point was 1 hour postdose; secondary efficacy variables over 12 hours included SKAMP-Attention and -Deportment scores and written math test results. Safety was assessed by adverse event (AE) recording following each period. Vital signs were recorded at each visit; laboratory tests were conducted at screening and final visit. RESULTS: D-MPH-ER 20 mg/day showed a significant advantage over placebo as early as 1 hour postdose on SKAMP-Combined scores (p < 0.001). When analyzing the entire sample of 54 children, d-MPH-ER maintained significant superiority over placebo from hours 1 through 12 (p-values ranged from < 0.001 to 0.046). D-MPH-ER was well tolerated, with no severe AEs reported. CONCLUSIONS: D-MPH-ER is safe and effective and improves classroom attention, deportment, and performance in children with ADHD.

Extended-release dexmethylphenidate 30 mg/d versus 20 mg/d: duration of attention, behavior, and performance benefits in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: This study aimed to compare the effects of dexmethylphenidate (D-MPH) extended-release (ER) 30 mg and D-MPH-ER 20 mg on attention, behavior, and performance in children with attention-deficit/hyperactivity disorder. METHODS: In a randomized, double-blind, 3-period-by-3-treatment, crossover study, children aged 6 to 12 years with attention-deficit/hyperactivity disorder stabilized on methylphenidate (40-60 mg/d) or D-MPH (20-30 mg/d) received D-MPH-ER 20 mg/d, 30 mg/d, and placebo for 7 days each (final dose of each treatment period administered in a laboratory classroom). Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Combined (Attention and Deportment) rating scale and Permanent Product Measure of Performance (PERMP) math test assessments were conducted at baseline and 3, 6, 9, 10, 11, and 12 hours postdose. RESULTS: A total of 165 children (94 boys; mean age, 9.6 years) were randomized (162 included in intent-to-treat analyses). Significant improvements were noted for D-MPH-ER 30 mg over D-MPH-ER 20 mg at various late time points on the SKAMP scales (Combined scores at 9, 10, 11, and 12 hours postdose; Attention scores at 10, 11, and 12 hours postdose; deportment scores at 9 and 12 hours postdose). The PERMP math test-attempted and -correct scores (change from predose) were significantly higher with D-MPH-ER 30 mg than with D-MPH-ER 20 mg at 10, 11, and 12 hours postdose. Both D-MPH-ER doses were superior to placebo at all time points. CONCLUSIONS: D-MPH-ER 30 mg was superior to D-MPH-ER 20 mg at later time points in the day, suggesting that higher doses of D-MPH-ER may be more effective later in the day.

Cardiovascular safety of stimulant medications for pediatric attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioral disorder that is often treated with stimulants such as methylphenidate and mixed amphetamine salts. Despite their efficacy and long history of use, there is concern about their potential for adverse cardiovascular effects in children and adolescents. Data from placebo-controlled and open-label extension trials published after 2000 were reviewed, and cardiovascular adverse event data were compared. Both placebo-controlled and open-label extension trials have repeatedly shown stimulant-induced increases in mean blood pressure, heart rate, and QT interval in children, adolescents, and adults. Although these increases seem relatively minor, their existence raises questions regarding whether stimulants could influence the likelihood of sudden death or other serious cardiovascular consequences, especially in patients with underlying heart problems. Moreover, questions have been raised regarding the necessity of screening patients for occult or unrecognized heart problems that are felt to be adversely affected by stimulant use. Obtaining a baseline electrocardiogram for any patient starting stimulant treatment is reasonable if access to such screening is readily available and not too costly.

Critical assessment of the methylphenidate transdermal system.

Introduction of the methylphenidate transdermal system (MTS) provides a different way of delivery for the most widely prescribed agent used to treat attention-deficit hyperactivity disorder (ADHD). The MTS delivery system provides good absorption of the active ingredient. Maximal plasma concentration of methylphenidate occurs from seven to nine hours after patch placement. Onset of action in pharmacodynamic studies has been registered at the two-hour mark after patch placement. As a result of the transdermal delivery system, the effect of first-pass metabolism is greatly diminished. Removal of the patch is associated with a biexponential decrease in methylphenidate levels. Recommended placement of the MTS is on a patient's hip, with a suggested application time of nine hours. Efficacy was demonstrated at all time points measured in ADHD, from 2-12 hours. Most adverse events reported were mild to moderate in severity; the most frequent adverse events reported were disturbances in sleep and appetite.

Psychometric properties of Darryl, a cartoon based measure to assess community violence-related PTSD in children.

OBJECTIVE: To examine the reliability and validity of Darryl, a cartoon-based measure of PTSD symptoms and a screening tool for identifying children and adolescents with a PTSD diagnosis. METHOD: Exposure to community violence, PTSD symptoms and diagnostic status were assessed in a sample of 49 children and adolescents at an urban outpatient psychiatry clinic. RESULTS: Darryl has good internal consistency for the full scale and adequate reliability for each DSM-IV PTSD symptom cluster. Darryl correlates significantly (r = 0.64, P < 0.001) with the most frequently used measure for assessing PTSD in children (CPTSD-RI). As a screening tool, Darryl has excellent sensitivity and specificity in relationship to the KID-SCID. CONCLUSIONS: In comparison to other child PTSD measures, Darryl has comparable or better psychometric properties and assesses PTSD symptoms in a more developmentally appropriate manner, especially in the domain of community violence. The value of Darryl as a screening tool remains preliminary given the limited number of diagnosed cases of PTSD in the study sample. Full scale efforts at replication are warranted.

Effectiveness of a children's home and community-based services waiver program.

OBJECTIVE: Limited alternatives exist to residential treatment or hospitalization for children with the most serious emotional disturbances. Community-based interventions are intended to offer less restrictive and expensive options than traditional treatment. One such program is New York State's Home and Community-Based Services (HCBS) Waiver Program. METHODS: From 1996 to 2002, 169 children were enrolled in the Manhattan HCBS. All spent at least one month on the wait list prior to admission to the waiver program. We used our wait list as a control group (WLC), allowing for comparison of the HCBS intervention. RESULTS: Sample consisted of 169 children between the ages of five and eighteen. The ethnic composition was 46.8% Hispanic (N = 79), 47.9% African-American (N = 81), and 5.3% Caucasian (N = 9). Average stay was 12 months in the HCBS program and 3.5 months for the WLC. Only 30% of children in the WLC were maintained in the community, while 81% of children in the HCBS were similarly maintained (P < 0.001). Also, the rate of hospitalization for the HCBS group was significantly lower (3 versus 41%; P < 0.001). There was also a trend for the WLC group to have had substantially higher rates of removal by the Administration for Children's Services (New York City's protective service agency) (8.3 versus 1.8%) and to more frequently require residential treatment (13.0 versus 8.9%). CONCLUSIONS: It would seem that the HCBS program appears to be a clinically and cost-effective method of maintaining children in their community.

Administrative issues in child psychiatry.

Administrative issues related to operating child and adolescent psychiatry programs or child mental health centers are substantially different than their adult counterpart programs. The increasing demands from managed care and other regulatory agencies make these programs difficult to operate. The smaller scale of these programs and the fewer existing programs make managing access to care more complicated. The administrators and clinicians in these programs have to be vigilant of legal responsibilities and reporting mandates that child practitioners and agencies that treat children need to abide by. In order to continue thriving, programs need to be efficient and fiscally viable. Issues such as building the continuum of care and finding the qualified personnel to staff these services are discussed in this article.

Dexmethylphenidate hydrochloride in the treatment of attention deficit hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) affects a large number of children. For decades, the stimulants have been the mainstay of pharmacological treatment for ADHD. Dexmethylphenidate (d-MPH), the d-isomer of the traditional racemic mixtures of d,l-threo-(R,R)-MPH, was recently introduced as another potential option in the stimulant class of medications. This paper reviews and summarizes the available research literature on d-MPH regarding pharmacodynamic, pharmacokinetic, chemical structure, receptor binding, toxicology, and clinical perspectives. d-MPH potentially may offer some advantages in the realms of absorption and duration of action compared with its racemic counterpart. The differences in pharmacokinetics and clinical implications of the immediate-release and extended-release forms of d-MPH are also compared and contrasted.