A double-blind, placebo-controlled trial of dexmethylphenidate hydrochloride and d,l-threo-methylphenidate hydrochloride in children with attention-deficit/hyperactivity disorder.
ABSTRACT To evaluate the efficacy and safety of dexmethylphenidate hydrochloride (d-MPH, Focalin) for the treatment of attention-deficit/hyperactivity disorder (ADHD) and to test an a priori hypothesis that d-MPH would have a longer duration of action than d,l-threo-methylphenidate (d,l-MPH).
This was a randomized, double-blind study conducted at 12 U.S. centers. One hundred thirty-two subjects received d-MPH (n=44), d,l-MPH (n=46), or placebo (n=42) twice daily for 4 weeks, with titration of the dose based on weekly clinic visits. The primary efficacy variable was change from baseline to last study visit on teacher-completed Swanson, Nolan, and Pelham Rating Scale (Teacher SNAP). Secondary efficacy measures included the change on parent-completed SNAP (Parent SNAP), Clinical Global Impressions Scale-Improvement (CGI-I) score, and Math Test performance. Assessments at home in late afternoon were included to test the hypothesis that d-MPH would have a longer duration of efficacy than d,l-MPH. Safety was assessed through monitoring occurrence and severity of adverse events and discontinuations related to them.
Treatment with either d-MPH (p=.0004) or d,l-MPH (p=.0042) significantly improved Teacher SNAP ratings compared with placebo. The d-MPH group showed significant improvements compared with placebo on the afternoon Parent SNAP ratings (p=.0003) and scores on the Math Test (p=.0236) obtained late in the afternoon at 6:00 p.m. Sixty-seven percent of patients showed improvement on d-MPH and 49% on d,l-MPH based on CGI-I scores. Both d-MPH and d,l-MPH were well tolerated, no patient in the d-MPH group and only two patients each in the d,l-MPH and placebo groups discontinued the study.
For the treatment of ADHD, an average titrated dose of 18.25 mg/day of d-MPH is as efficacious and safe as an average titrated dose of 32.14 mg/day of d,l-MPH. Both active treatments have large effect sizes. Thus, d-MPH and d,l-MPH appear to provide similar efficacy, and d-MPH may have longer duration of action after twice-daily dosing, but additional studies are needed to determine the statistical and clinical significance of this possibility.
- SourceAvailable from: Juliana Setyawan
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- "6 trials: Abikoff (2007) Findling (2006) Wigal (2004) Biederman (2003) Wolraich (2001) Pliszka (2000) Newcorn (2008) Dell'Agnello (2009) Martenyl (2010) Gau (2007) Kelsey (2004) Michelson (2001) Kratochvil (2011) Montoya (2009) Takahashi (2009) Block (2009) Weiss (2005) Michelson (2002) Bangs (2008) Spencer (2002) [study 1 & 2] LDX "
ABSTRACT: Abstract Objective: Systematically review and synthesise the clinical evidence of treatments for attention deficit hyperactivity disorder (ADHD) by indirectly comparing established treatments in the UK with a drug recently approved in Europe (lisdexamfetamine [LDX]). Research design and methods: Population: children and adolescents. Setting: Europe. Comparators: methylphenidate (MPH), atomoxetine (ATX), and dexamphetamine (DEX). Electronic databases and relevant conference proceedings were searched for randomised, controlled clinical trials evaluating efficacy and safety of at least one of the comparators and LDX. Quality assessments for each included trial were performed using criteria recommended by the Centre for Reviews and Dissemination. Network meta-analysis methods for dichotomous outcomes were employed to evaluate treatment efficacy. Main outcome measures: Response, as defined by either a reduction from baseline of at least 25% in the ADHD Rating Scale [ADHD-RS] total score or, separately, as assessed on the Clinical Global Impression-Improvement [CGI-I] scale, and safety (all-cause withdrawals and withdrawal due to adverse events). Results: The systematic review found 32 trials for the meta-analysis, including data on LDX, ATX, and different formulations of MPH. No trials for DEX meeting the inclusion criteria were found. Sufficient data were identified for each outcome: ADHD-RS, 16 trials; CGI-I, 20 trials; all-cause withdrawals, 28 trials; and withdrawals due to adverse events, 27 trials. The relative probability of treatment response for CGI-I (95% confidence intervals [CI]) for ATX versus LDX was 0.65 (0.53-0.78); for long acting MPH versus LDX, 0.82 (0.69-0.97); for intermediate release MPH versus LDX, 0.51 (0.40-0.65); and for short-acting MPH versus LDX, 0.62 (0.51-0.76). The relative probabilities of ADHD-RS treatment response also favoured LDX. Conclusions: For the treatment of ADHD, the synthesis of efficacy data showed statistically significant better probabilities of response with LDX than for formulations of MPH or ATX. The analysis of safety data proved inconclusive due to low event rates. These results may be limited by the studies included, which only investigated the short-term efficacy of medications in patients without comorbid disorders.Current Medical Research and Opinion 03/2014; DOI:10.1185/03007995.2014.904772 · 2.37 Impact Factor
- "— +4.1% (Findling et al., 2008; Wigal et al., 2004) — — Euphoria -3.0% (Barkley et al., 1990; Firestone et al., 1998) — — — -5.0% (Barkley et al., 1990) — Rebound — — — — +29.0% (Short et al., 2004) — *Terms used to describe emotional expression varied among studies. "
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- "Historically, informant discrepancies within controlled trials have typically been regarded as methodological nuisances that need to be ''rectified'' (e.g., Bird, Gould, & Staghezza, 1992; Piacentini, Cohen, & Cohen, 1992). Indeed, the ubiquitous presence of discrepancies has led many researchers to select one a priori measure to represent overall outcomes, deeming it a ''primary outcome measure'' (see Bowden et al., 2000; Hayward et al., 2000; Hazell & Stuart, 2003; Michelson et al., 2004; Wigal et al., 2004). In fact, when the results of a controlled trial are registered within a public database, a prerequisite for publication in journal outlets edited by members of the International Committee of Medical Journal Editors, definitions of the ''primary'' and ''secondary'' outcome measures must be included (De Angelis et al., 2004). "
ABSTRACT: In this study, the authors examined the relations among clinician ratings of treatment improvement and discrepancies between parent and blinded laboratory rater reports of child social functioning administered before and after treatment for social anxiety disorder. Participants included a clinic sample of 101 children (7-16 years old; M = 11.67, SD = 2.57; 51 girls, 81% Caucasian) receiving treatment as part of a two-site controlled trial. Overall, clinician ratings reflected lack of improvement when parents reported persistent (i.e., pre- to posttreament) social functioning deficits not reported by blinded raters. However, when blinded raters reported persistent social skill deficits not reported by parents, we did not observe the same effect on clinician ratings as we did when the direction of discrepant reports was reversed. We replicated these observations in a subset of participants (n = 81) providing parent and child pre-post reports of social anxiety symptoms. These findings have implications for the interpretations of clinical ratings as "primary outcome measures" within controlled trials.Journal of Clinical Child & Adolescent Psychology 03/2011; 40(2):281-94. DOI:10.1080/15374416.2011.546043 · 1.92 Impact Factor