Critical assessment of the methylphenidate transdermal system.

Introduction of the methylphenidate transdermal system (MTS) provides a different way of delivery for the most widely prescribed agent used to treat attention-deficit hyperactivity disorder (ADHD). The MTS delivery system provides good absorption of the active ingredient. Maximal plasma concentration of methylphenidate occurs from seven to nine hours after patch placement. Onset of action in pharmacodynamic studies has been registered at the two-hour mark after patch placement. As a result of the transdermal delivery system, the effect of first-pass metabolism is greatly diminished. Removal of the patch is associated with a biexponential decrease in methylphenidate levels. Recommended placement of the MTS is on a patient's hip, with a suggested application time of nine hours. Efficacy was demonstrated at all time points measured in ADHD, from 2-12 hours. Most adverse events reported were mild to moderate in severity; the most frequent adverse events reported were disturbances in sleep and appetite.

Dexmethylphenidate extended-release capsules for the treatment of attention deficit hyperactivity disorder.

Dexmethylphenidate is a chirally pure d-isomer of the racemic mixture of methylphenidate. The extended-release form of this compound was developed using proprietary Spheroidal Oral Drug Absorption System technology. The product is approved for the treatment of attention deficit hyperactivity disorder in individuals as young as 6 years old. It represents the first methylphenidate product approved for use in adults. The agent's delivery system is designed to provide an initial release of medication immediately after dosing, with a second release approximately 4 h later. Blood levels first peak at approximately 1.5 h, and the second peak is noted at an average of 6.5 h post-dose. Laboratory classroom studies have demonstrated clinically and statistically meaningful efficacy throughout a 12-h day. Pharmacokinetics, safety and efficacy data are reviewed.

Open-label study of dexmethylphenidate hydrochloride in children and adolescents with attention deficit hyperactivity disorder.

BACKGROUND: This pilot study examined the efficacy and duration of the effect of dexmethylphenidate (d-MPH) given once-daily in subjects with attention deficit hyperactivity disorder (ADHD). METHOD: Subjects aged 6-18 years (inclusive) with ADHD were enrolled in this 8-week, openlabel study. Outcome measures included the Conners'Teacher and Parent Rating Scales, the Attention Deficit Disorder Rating Scale (ADDRS), the Clinical Global Impression (CGI) Scale, and teacher and parent visual analog scales to estimate the duration of efficacy. d-MPH was initiated at a dose of 2.5 mg/day. The dose was flexible, based on response and tolerability, and could be increased in increments of 2.5 mg/day to a maximum daily dose of 30 mg/day. RESULTS: Twenty-two subjects (mean age, 8.7 +/- 0.4 years) were treated. Significant improvements (p <0.0001) from baseline occurred in the Conners' Teacher and Parent Rating Scales after 8 weeks. Of the evaluated subjects, 85.7% (18 of 21) showed at least a 30% improvement from baseline on the Conners' Teacher Rating Scale, and 86.4% (19 of 22) of subjects showed at least a 30% improvement from baseline on the Conners' Parent Rating Scale. Most subjects demonstrated an improvement on the ADDRS and the CGI-Improvement (CGI-I) scale. Median duration of effect was estimated at 6.2 hours (teachers) and at 7.5 hours (parents). On average, patients gained 2.4 pounds over the course of the study. CONCLUSIONS: A single daily dose of d-MPH was effective in controlling ADHD in children and was well tolerated. Future studies are needed to confirm these findings and to evaluate chronic dosing with d-MPH.

Outcome related electrophysiological subtypes of cocaine dependence.

We previously described the existence of two quantitative EEG (QEEG) subtypes of cocaine dependent males, identified at baseline, displaying differential proneness to relapse. The current study expands the population to include females and enhances the measure set to include both QEEG and somatosensory EP (SEP) features. Fifty-seven cocaine dependent adults (16 F, 41 M) were evaluated 5-14 days after last cocaine use, while in residence at a drug-free therapeutic community. The median length of stay in treatment (continued abstinence) was 25 weeks. Using a small subset of QEEG and SEP baseline features, three subtypes (CLUS) were identified. CLUS 2 (n = 25) and CLUS 3 (n = 23) replicated the published subtypes, while CLUS 1 (n = 9) was previously undescribed. Cluster membership was significantly associated with length of stay in treatment (chi 2 = 13.789, P < 0.001), but not with length of exposure to crack cocaine or to any demographic or clinical features. Seventy-eight percent of CLUS 1 and 65% of CLUS 3 left treatment < or = 25 weeks, whereas 80% of CLUS 2 remained in treatment > 25 weeks. The existence of outcome related subtypes may reflect: [1] differential neurophysiological vulnerability, "traits," predisposing individuals to cocaine addiction; or [2] differential neurosensitivity, "states," due to the effects of chronic cocaine exposure, and associated differences in treatment outcome. Using Variable Resolution Electrical Tomographic Analysis (VARETA), the mathematically most probable neuroanatomical source of the scalp recorded EEG data was localized. Computation of VARETA on the baseline Cluster profiles suggest significant differences in the underlying pathophysiology of these subtypes.