Efficacy and Safety of Dexmethylphenidate Extended-Release Capsules in Adults with Attention-Deficit/Hyperactivity Disorder

Pediatric Psychopharmacology Research Clinic, Massachusetts General Hospital, Boston, Massachusetts 02114, and New York University School of Medicine, New York, NY, USA.
Biological Psychiatry (Impact Factor: 10.26). 06/2007; 61(12):1380-7. DOI: 10.1016/j.biopsych.2006.07.032
Source: PubMed


This multicenter, randomized, fixed-dose, double-blind, placebo-controlled study evaluated efficacy of extended-release dexmethylphenidate (d-MPH-ER) in adults with attention-deficit/hyperactivity disorder (ADHD).
Randomized adults with ADHD (n=221) received once-daily d-MPH-ER 20 mg, 30 mg, or 40 mg or placebo for 5 weeks. The primary efficacy variable was change from baseline to final visit in DSM-IV ADHD Rating Scale (ADHD-RS) total score. Secondary efficacy parameters included the proportion of patients with improvement>or=30% in ADHD-RS total score and final scores on Clinical Global Impressions-Improvement (CGI-I) scale.
Of 218 evaluable patients, 184 completed the study. All d-MPH-ER doses were significantly superior to placebo in improving ADHD-RS total scores. Placebo scores improved by 7.9; d-MPH-ER, 20 mg, improved by 13.7 (p=.006); d-MPH-ER, 30 mg, improved by 13.4 (p=.012); and d-MPH-ER, 40 mg, improved by 16.9 (p<.001). Overall distribution of CGI-I ratings at final visit was significantly better with each d-MPH-ER dosage than with placebo. There were no unexpected safety or tolerability concerns, based on experience with racemic methylphenidate (MPH) in adults and dexmethylphenidate (d-MPH) in children.
Once-daily d-MPH-ER at 20 mg, 30 mg, or 40 mg is a safe and effective treatment for adults with ADHD.

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    • "Finally, are the observed drug effects on receptor availability quantitatively different in patients with ADHD and healthy volunteers? The latter question is especially topical (Sahakian and Morein- Zamir, 2007) because methylphenidate has been reported to augment several aspects of cognition in healthy subjects (Rapoport et al., 1978, 1980; Strauss et al., 1984; Koelega, 1993; Elliott et al., 1997; Mehta et al., 2000) similar to those improved in ADHD (Mehta et al., 2004; Turner et al., 2005; Clark et al., 2007; Spencer et al., 2007). The effects of methylphenidate and related stimulant drugs in healthy individuals have been shown to be baseline-dependent; i.e. those subjects with relatively low performance levels exhibit greater benefit after the drug (Naylor et al., 1985; Rogers et al., 1999; Mehta et al., 2000; Turner et al., 2003; Clatworthy et al., 2009). "
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    • "The DRD4 gene, which produces a blunted response to dopamine (Van Tol, Wu, Guan, & Ohara, 1992), has demonstrated the most consistent association with ADHD across numerous meta-analytic studies (Faraone, Doyle, Mick, & Biederman, 2001; Loo et al., 2010; Wu, Xiao, Sun, Zou, & Zhu, 2012), and, thus, was examined in our sample of adolescents with and without ID. The dopamine transporter gene (DAT1) may be the candidate that is the most biologically plausible given that stimulant medications inhibit the dopamine transporter thereby increasing extracellular dopamine (Li & Lee, 2012; Spencer et al., 2007). Some previous studies have found an association between the DAT1 gene and ADHD (Brookes et al., 2006; Chen et al., 2003; Cook, Stein, Ellison, & Unis, 1995; Faraone et al., 2005; Loo et al., 2008, 2010; Todd et al., 2005), while others have not (Li, Sham, Owen, & He, 2006). "
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    • "ADHD is more prevalent in first degree relatives with persistent ADHD than those with childhood-limited ADHD (Faraone, Biederman, & Friedman, 2000) and the heritability of hyperactivity and inattention was estimated at 73% and 71%, respectively, in a recent meta-analysis (Nikolas & Burt, 2010). The dopamine transporter gene (DAT1; SLC6A3) is a compelling candidate gene for ADHD because stimulant medications for ADHD inhibit the dopamine (DA) transporter and increase extracellular DA (Spencer et al., 2007). The variable number of tandem repeats (VNTR) sequence in the 3¢ untranslated region (UTR) affected neural activation during working memory and response inhibition tasks using functional magnetic resonance imaging (Bertolino et al., 2008; Congdon, Constable, Lesch, & Canli, 2009). "
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