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.
"Attention Deficit/Hyperactivity Disorder (ADHD) is a common chronic psychiatric disorder, characterized by a pattern of developmentally inappropriate inattention, motor restlessness and impulsivity, which affects between 3 and 7% of school age children, according to DSM-IV criteria (American Psychiatric Association, 1994; Polanczyk et al., 2007). Prospective follow-up studies found that approximately 50% of children with ADHD show symptoms that continue into adulthood, and when left untreated, are associated with substance abuse, depression, unemployment and criminal offenses (Biederman et al., 2006; Molina et al., 2009). However, the precise neurobiological mechanisms underlying the pathophysiology of ADHD are currently unknown. "
"Furthermore, in both the clinician-rated scales, CGI-I and CGI-S, a higher proportion of patients showed improvement than in observations during the dose confirmation phase. These results are consistent with other short-term dose optimization studies evaluating efficacy of methylphenidate in adults with ADHD [2, 9, 14, 15]. The present study is of particular interest as improved symptomatic effects were observed upon dose optimization, and clinical optimization of dosing did not depend on the prior fixed MPH-LA dose in the initial phase. "
[Show abstract][Hide abstract] ABSTRACT: Background and Objectives
In the management of attention-deficit hyperactivity disorder (ADHD) in adults it is important to recognize that individual patients respond to a wide range of methylphenidate doses. Studies with methylphenidate modified release long acting (MPH-LA) in children have reported the need for treatment optimization for improved outcomes. We report the results from a post hoc analysis of a 5-week dose optimization phase from a large randomized, placebo-controlled, multicenter 40-week study (9-week double-blind dose confirmation phase, 5-week open-label dose optimization phase, and 26-week double-blind maintenance of effect phase).
Patients entering the open-label dose optimization phase initiated treatment with MPH-LA 20 mg/day; up/down titrated to their optimal dose (at which there was balance between control of symptoms and side effects) of 40, 60, or 80 mg/day in increments of 20 mg/week by week 12 or 13. Safety was assessed by monitoring the adverse events (AEs) and serious AEs. Efficacy was assessed by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, Attention-Deficit Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) and Sheehan Disability Scale (SDS) total scores.
At the end of the dose confirmation phase, similar numbers of patients were treated optimally with each of the 40, 60, and 80 mg/day doses (152, 177, and 160, respectively) for MPH-LA. Mean improvement from baseline in the dose confirmation phase in total scores of DSM-IV ADHD RS and SDS were 23.5 ± 9.90 and 9.7 ± 7.36, respectively.
Dose optimization with MPH-LA (40, 60, or 80 mg/day) improved treatment outcomes and was well-tolerated in adult ADHD patients.
Clinical Drug Investigation 07/2014; 34(9). DOI:10.1007/s40261-014-0213-2 · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Methylphenidate 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.
To evaluate the off-label use of methylphenidate and its characteristics from a database of spontaneous reports.
This 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.
In 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.
More 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.
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