A randomized, placebo-controlled trial of OROS methylphenidate in adults with attention-deficit/hyperactivity disorder.
ABSTRACT 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).
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.
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).
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.
SourceAvailable from: Jürgen Wasem
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ABSTRACT: IntroductionMethylphenidate is a piperidine derivative structurally and pharmacologically similar to amphetamine. Methylphenidate is indicated for Attention Deficit Hyperactivity Disorder (ADHD) in children aged 6 years of age and over when remedial measures alone prove insufficient. In adults, its indication, except in narcolepsy, is not defined. Methylphenidate received regulatory approval almost sixty years ago with a first registration in Switzerland in October 1954.ObjectiveTo evaluate the off-label use of methylphenidate and its characteristics from a database of spontaneous reports.MethodsThis study analysed data from the French Pharmacovigilance Database of adverse drug reactions spontaneously reported by health professionals from 1985 to December 2011. Off-label use was evaluated according to age.ResultsIn the French Pharmacovigilance database, 181 cases of adverse drug reactions were reported with methylphenidate. Neuropsychiatric effects were the most frequent adverse event reported (41%) followed by cardiovascular and cutaneous side effects (14%). 143 reports concerned children (113 boys, 30 girls, mean age 10.6 ± 3.3 years) of which 46 (30%) were off-label uses. There were 38 adults (20 men, 18 women), of which 32 (88%) off-label use. In adults, methylphenidate was prescribed for depression, and this practice was associated with serious adverse events of drug dependence, overdose and suicide attempt. Overall, off-label use was detected in 43% (78/181) of all cases reported.ConclusionMore than 40% of the patients with drug reactions received methylphenidate for off-label indications. Additional long-term exposures and independent clinical studies are necessary to establish the long-term profile safety of methylphenidate.SpringerPlus 06/2014; 3:286. DOI:10.1186/2193-1801-3-286
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ABSTRACT: The relationship between attention-deficit/hyperactivity disorder (ADHD) symptoms and global clinical assessment of functionality is complex. This post-hoc analysis explores this relationship and suggests implications for patient assessment in clinical practice. Adults with ADHD on a stable lisdexamfetamine dimesylate (LDX) dose for ≥ 6 months were enrolled in a double-blind, placebo-controlled, randomized withdrawal study. Participants entered a 3-week open-label phase continuing their prior LDX dose and were then randomized to placebo or the same LDX dose for a 6-week, double-blind, randomized withdrawal phase. ADHD symptom distribution was measured by the ADHD Rating Scale IV (ADHD-RS-IV) with Adult Prompts total score reflecting DSM-IV-TR ADHD symptom criteria and severity by Clinical Global Impressions-Severity (CGI-S) ratings at study entry and at end of study. Of 123 participants enrolled in the open-label phase, 116 were included in the randomized withdrawal phase (placebo, n = 60; LDX, n = 56). As reported in a prior publication, mean (standard deviation) ADHD-RS-IV total score change from baseline (week 3) to end of study (randomized-withdrawal phase) was 16.8 (11.80) for placebo and 1.6 (8.63) for LDX. At end of study, for placebo and LDX, 5.0% and 32.1% of participants, respectively, had a CGI-S = 1, 11.7% and 35.7% had a CGI-S = 2, 11.7% and 17.9% had a CGI-S = 3, 33.3% and 7.1% had a CGI-S = 4, 35.0% and 7.1% had a CGI-S = 5, and 3.3% and 0% had a CGI-S = 6; no participants had a CGI-S = 7 (P < 0.0001). The CGI-S ratings increased (worsened) as ADHD symptom scores worsened. Post-hoc regression analysis between ADHD-RS-IV scores and CGI-S demonstrated shared variance of 47% at week 3 and 69% for both placebo and LDX at end of study. Although ADHD symptom scores demonstrate a linear relationship with global illness severity, the variance suggests that other factors not captured by symptom scales are also important in assessing patient outcomes in clinical practice. (Trial registration: ClinicalTrials.gov NCT00877487.).Postgraduate Medicine 09/2014; 126(5):31-41. DOI:10.3810/pgm.2014.09.2798 · 1.54 Impact Factor