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Biomedical subjects

Marc Lerner

Publications and source records attributed to Marc Lerner.

11 recordsLinked to original sources
PubMed2006

Multisite controlled study of OROS methylphenidate in the treatment of adolescents with attention-deficit/hyperactivity disorder.

BACKGROUND: Despite the persistence of attention-deficit/hyperactivity disorder (ADHD) into adolescence, little is known about the efficacy and tolerability of stimulant medications in this age group. OBJECTIVE: To report the results of a multisite controlled study among adolescents with ADHD evaluating the efficacy and tolerability of osmotic-release oral system (OROS) methylphenidate. DESIGN: Adolescents (N = 220) having a confirmed Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of ADHD underwent dose titration to identify dosages of OROS methylphenidate that improved symptoms to predefined criteria. Subjects successfully completing the dose titration phase (n = 177) (ie, tolerated and responded to treatment and adhered to the protocol) were randomized to receive 2 weeks' treatment with their individualized dosage of OROS methylphenidate (18, 36, 54, or 72 mg once daily) or placebo. Treatment effectiveness was measured using investigator, parent, and adolescent assessments of ADHD. RESULTS: A significant reduction from baseline in the investigator-rated ADHD Rating Scale, the primary efficacy measure, was found with OROS methylphenidate treatment compared with placebo. Similar findings were noted with parent- and adolescent-report measures. Based on a Clinical Global Impression improvement subscale score of much or very much improved, 52% of subjects in the OROS methylphenidate group improved compared with 31% receiving placebo. Thirty-seven percent of subjects required the maximum dosage of 72 mg/d. The incidence of drug-related adverse events was similar between the 2 study groups. CONCLUSION: In adolescents, once-daily OROS methylphenidate significantly reduced ADHD symptoms and was well tolerated using dosages up to 72 mg/d.

Administration, Oral↗
PubMed2006

Once-daily OROS methylphenidate is safe and well tolerated in adolescents with attention-deficit/hyperactivity disorder.

This 8-week, open-label extension of a double-blind study reports on safety data for 171 adolescents with attention-deficit/hyperactivity disorder (ADHD) who received once-daily OROS methylphenidate (MPH) (18-72 mg/day). Headache, anorexia, and insomnia were the most frequently reported treatment-related adverse events. The incidence of adverse events was not related to dose. OROS MPH was safe and well tolerated at doses up to 72 mg/day.

Adolescent↗
PubMed2006

Does prolonged therapy with a long-acting stimulant suppress growth in children with ADHD?

OBJECTIVE: To investigate whether prolonged therapy with a long-acting stimulant affects growth in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: One hundred seventy-eight children ages 6 to 13 years received OROS methylphenidate (OROS MPH, CONCERTA) for at least 21 months. Height and weight were measured monthly during the first year and every 3 months thereafter. RESULTS: At baseline, subjects were approximately the expected height for their age and somewhat heavier than expected. Subjects gained height steadily throughout the study and were on average 0.23 cm less than expected at month 21. Weight did not increase and BMI decreased slightly in the first 4 months. Thereafter, weight Z score and BMI Z score remained relatively constant and children were on average 1.23 kg less than expected at month 21. Previous stimulant therapy tended to be associated with a smaller decrease in Z score during the study compared with no previous stimulant therapy. Drug holidays did not significantly affect growth. CONCLUSIONS: The effects of prolonged OROS MPH therapy on growth were clinically insignificant and limited to slight decreases in weight during the first months of therapy. Drug holidays did not reduce any impact on growth and are thus of questionable utility for limiting potential effects of treatment on growth.

Attention Deficit Disorder with Hyperactivity↗
PubMed2005

ADHD treatment with once-daily OROS methylphenidate: final results from a long-term open-label study.

OBJECTIVE: Few studies have assessed effectiveness and tolerability of stimulants when used for prolonged periods in children with attention-deficit/hyperactivity disorder (ADHD). This article presents final results from an open-label, multisite study of a once-daily formulation of methylphenidate (MPH), OROS MPH. METHOD: Subjects received OROS MPH (18-54 mg initially, with adjustments based on clinical condition) for up to 24 months. Multiple measures of ADHD symptoms, vital signs, weight, height, and laboratory results were assessed throughout the study period. RESULTS: A total of 407 children enrolled in the open-label study and 229 completed the trial. Effectiveness of OROS MPH therapy was maintained throughout the study as indicated by parent and investigator assessments. There was a 26% increase in mean daily dose over the study period, with the majority of the increase occurring during year 1. In general, treatment was well tolerated, with 31 (7.6%) of subjects discontinuing because of adverse events. Minimal effects on growth in height and weight were observed during the study. No clinically significant effects on vital signs or laboratory test parameters were observed. CONCLUSIONS: : Sustained effectiveness of OROS MPH was maintained for up to 24 months with minimal effects on growth, tics, vital signs, or laboratory test values.

Adult↗
PubMed2004

Effects of once-daily osmotic-release methylphenidate on blood pressure and heart rate in children with attention-deficit/hyperactivity disorder: results from a one-year follow-up study.

OBJECTIVE: Studies of vital signs in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) receiving stimulants indicate a variable effect on blood pressure (BP) and heart rate (HR). We evaluated the longer-term effects on vital signs of once-daily osmotic-release methylphenidate (MPH, Concerta) in children with ADHD. METHODS: As part of a 1-year open-extension trial, we studied children with ADHD (aged 6-13 years; baseline assessment, n = 432) who were entered into an open-label study of osmotic-release MPH (18-54 mg) for up to 1 year. Subjects' BP and HR were recorded at monthly visits and, when applicable, analyses were by last observation carried forward. RESULTS: Compared to off-drug baseline, osmotic-release MPH was associated with minor clinical, although statistically significant, changes in systolic and diastolic blood pressure (DBP) (3.3 and 1.5 mm Hg, Ps < 0.001) and HR (3.9 bpm, P < 0.0001) at 12-month end point. There was no clear dose-response relationship. There was no tolerance to the pressor effects of osmotic-release MPH over the 1-year period. There was an inverse relationship between baseline vital signs and positive change in vital signs at end point. CONCLUSIONS: Over a 12-month period, osmotic-release MPH produced minor clinical, although statistically significant, changes in BP and HR in children with ADHD.

Administration, Oral↗
PubMed2003

Development of a new once-a-day formulation of methylphenidate for the treatment of attention-deficit/hyperactivity disorder: proof-of-concept and proof-of-product studies.

BACKGROUND: The duration of action of the immediate-release formulation of methylphenidate hydrochloride is short (3 to 4 hours), and 3 times daily dosing is thought to maximize effectiveness across a 12-hour day. The initial sustained-release formulations of methylphenidate had reduced efficacy compared with immediate-release methylphenidate and were not well accepted. Tachyphylaxis was hypothesized to account for the reduced effects, and an ascending drug delivery pattern was proposed to overcome this acute tolerance. METHODS: Children with attention-deficit/hyperactivity disorder were evaluated in a laboratory school to characterize onset and duration of the effect of a variety of methylphenidate regimens. In a proof-of-concept study, an experimental ascending profile was established by an initial bolus followed by small increasing doses of immediate-release methylphenidate in capsules administered every 30 minutes for 8 hours. Two proof-of-product studies of a new oral once-a-day formulation to deliver methylphenidate by an osmotic pump process based on OROS (ALZA Corp, Mountain View, Calif) technology (hereafter referred to "OROS-methylphenidate") were conducted: a pharmacokinetic study and a pharmacodynamic study. RESULTS: The experimental ascending profile matched the effect of the standard regimen of methylphenidate, 3 times daily. In the pharmacokinetic study, OROS-methylphenidate treatment produced a rapid rise followed by increasing plasma concentrations that peaked 7 to 9 hours after administration. In the pharmacodynamic study, OROS-methylphenidate treatment matched the 3 times daily dosing of methylphenidate for onset and duration of efficacy. CONCLUSIONS: These studies demonstrate the translation of a basic science finding (acute tolerance to clinical doses of methylphenidate) into clinical application (the selection of a new drug delivery pattern for methylphenidate). This approach produced a new product (OROS-methylphenidate or Concerta), which proved to have the predicted rapid onset (with 1-2 hours) and long duration of efficacy (10-12 hours) after a single administration in the morning.

Administration, Oral↗
PubMed2003

A pharmacokinetic/pharmacodynamic study comparing a single morning dose of adderall to twice-daily dosing in children with ADHD.

OBJECTIVE: To determine the pharmacokinetic and pharmacodynamic properties of once-daily versus twice-daily doses of Adderall. METHOD: Following a 1-week wash-out, 12 subjects with attention-deficit/hyperactivity disorder (ADHD) entered a double-blind crossover study comparing two conditions: QD (10 mg of Adderall at 7:30 a.m. and placebo at noon) or BID (10 mg of Adderall at 7:30 a.m. and at noon). At two sites, cohorts of six subjects each were assessed on two different days by a 12-hour laboratory school protocol. Plasma concentrations of d- and l-amphetamine, vital signs, teacher ratings of classroom behavior on the SKAMP, and 10-minute Math Test performance were measured repeatedly over 12 hours. An analysis of variance used center, subject-within-center, condition, and time-after-second-dose as independent variables. RESULTS: The pharmacokinetic profiles revealed similar morning concentrations of d- and l-amphetamine. However, concentrations were twice as high in the afternoon for BID as QD. The two conditions showed similar pharmacodynamic profiles in the morning, although improvement in math performance and behavior was maintained into the afternoon only in the BID condition (p <.05). CONCLUSIONS: This study suggests that twice-daily dosing of Adderall may be an effective strategy for afternoon control of attention and deportment for children with ADHD.

Administration, Oral↗
PubMed2003

A survey of voiding dysfunction in children with attention deficit-hyperactivity disorder.

PURPOSE: Physicians treating attention deficit-hyperactivity disorder (ADHD) have long had the clinical impression that these children suffer disproportionately from voiding dysfunction and incontinence. However, no data exist to confirm this suspicion. In an attempt to investigate this clinical finding, we administered a survey asking about any functional bladder symptoms to a group of children with ADHD and a control group without ADHD. MATERIALS AND METHODS: The Dysfunctional Voiding Symptom Survey (DVSS) was administered to a group of children being treated for rigorously diagnosed ADHD and a control group without ADHD. The DVSS consists of 10 questions that assess daytime incontinence, nocturnal enuresis, constipation, urgency, voiding frequency and dysuria, each scored from 0 to 4 (0-never, 1-almost never, 2-less than half the time, 3-about half the time, 4-almost every time) for a maximum total score of 40 (severest symptoms). Scores for patients and controls were compared for each question and in aggregate. Boys and girls underwent separate statistical analysis. An additional eleventh question assesses recent stressful events within the family. RESULTS: The patient group included 23 boys and 5 girls, and the control group 10 boys and 12 girls. Children with ADHD of both sexes had statistically significant higher overall DVSS scores. Boys had significant differences on several questions. Due to the small number of girls, there were no statistically significant differences on individual questions. CONCLUSIONS: Children with ADHD have significantly higher rates of incontinence, constipation, urgency, infrequent voiding, nocturnal enuresis and dysuria than those without ADHD. Further study is needed to discern the cause of this difference and develop appropriate treatment strategies.

Adolescent↗
PubMed2002

Efficacy of a new pattern of delivery of methylphenidate for the treatment of ADHD: effects on activity level in the classroom and on the playground.

OBJECTIVES: To evaluate the pharmacodynamic effects of an experimental (EXP) delivery of methylphenidate (MPH) in children with attention-deficit/hyperactivity disorder and to investigate the situational nature of effects in laboratory classroom and playground settings. METHOD: A "sipping" study methodology was used to deliver a bolus followed by small but increasing MPH doses as the EXP regimen. A randomized, double-blind crossover design was used to compare the EXP regimen to a thrice-daily (TID) regimen and a placebo (PLA) regimen. Measures of efficacy were obtained from a Motionlogger actigraph to quantify activity and from the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) rating scale to quantify two domains of behavior (attention and deportment). RESULTS: Compared with PLA, both EXP and TID delivery of MPH produced large, significant reductions in activity and inappropriate behavior in the classroom, but the two MPH regimens did not differ in onset or duration of effects across the day. The MPH effects were situationally dependent and were smaller for the playground than for the classroom settings. CONCLUSIONS: The findings of this "proof of concept" study support the efficacy of a continuous, ascending delivery of MPH. The situational effects of MPH provide support for the theory of selective effects of stimulants, dependent on the demands of the environment.

Attention Deficit Disorder with Hyperactivity↗