Construct validity of an attention rating scale for traumatic brain injury.

Attention deficits are nearly ubiquitous after traumatic brain injury (TBI). In the subacute phase of moderate to severe TBI, these deficits may be difficult to measure with the precision needed to predict outcomes, assess degree of recovery, and monitor treatment response. This article reports the findings of four studies, three observational and one a randomized, controlled treatment trial of methylphenidate (MP), designed to provide construct validation of the Moss Attention Rating Scale (MARS), an observational measure of attention dysfunction following TBI. One hundred seven participants with moderate to severe TBI were enrolled during treatment on an inpatient rehabilitation unit. MARS scores were provided independently by four rehabilitation disciplines (Physical, Occupational and Speech Therapies and Nursing). Results indicated that the MARS: (1) is more strongly related to concurrent measures of cognitive versus physical disability, supporting its validity as a measure of cognition, (2) is more strongly related to concurrent psychometric measures of attention versus measures thought to rely less on attention, supporting its validity as a measure of attention; and (3) predicts 1-year outcomes of TBI better than psychometric measures of attention. However, the MARS (4) was not differentially affected by MP versus placebo treatment. Results support the construct validity and utility of the MARS, with further research needed to clarify its role in treatment outcome assessment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of methylphenidate and expectancy on performance, self-evaluations, persistence, and attributions on a social task in boys with ADHD.

This study examined the effects of 0.3 mg/kg methylphenidate (MPH) and expectancy regarding medication on the performance and persistence of 137 boys with attention-deficit/hyperactivity disorder (ADHD) in a get-acquainted dyadic interaction with a peer, using a balanced-placebo design. Boys in 4 groups—administered placebo or MPH crossed with being told they received placebo or MPH—interacted with child confederates in experimental situations in which social success and failure were manipulated. In contrast with studies of academic persistence, MPH did not affect boys' task persistence or performance. Boys gave more positive self-evaluations and talked more in the success condition as compared with the failure condition. Boys attributed success to effort and ability and failure to task difficulty, and neither MPH nor expectancy affected this pattern. These findings are consistent with other studies in failing to find debilitating effects of MPH or medication expectancies on ADHD boys' attributions or self-evaluations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Delta Plots in the Study of Individual Differences: New Tools Reveal Response Inhibition Deficits in AD/HD That Are Eliminated by Methylphenidate Treatment.

The authors highlight the utility of distribution-analytical techniques in the study of individual differences and clinical disorders. Cognitive deficits associated with attention-deficit/hyperactivity disorder (AD/HD) were examined by using delta-plot analyses of performance data (reaction time and accuracy) obtained through the use of a prototypical conflict task, the Eriksen flanker task. In 20 children with AD/HD (compared with matched control participants), overall performance measures indicated a marginal performance deficit. Delta-plot analyses indicated that performance deficits associated with AD/HD involve response inhibition but not automatic response activation. In a within-subjects titration study, the response inhibition deficit was eliminated by methylphenidate treatment, but these effects were highly dose specific. The beneficial effect of methylphenidate was clarified further after correcting for inter-individual variation in sensitivity to medicine dosage. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Methylphenidate as a reinforcer for rats: Contingent delivery and intake escalation.

Methylphenidate (MPH) is one of the most widely prescribed drugs for treating attention-deficit hyperactivity disorder. Previous research suggested that MPH is a reinforcer for rats, but not all of the manipulations to show that lever pressing is controlled by the contingency to obtain MPH have been examined. In Experiment 1, responding for MPH on a progressive ratio (PR) schedule was assessed. Rats self-administered varying doses of MPH (0.056–1.0 mg/kg/infusion) on a PR schedule of reinforcement, and self-administered more MPH than saline, with maximal responding occurring at a unit dose of 0.56 mg/kg/infusion. Experiment 2 examined if there were differences in responding between contingent and noncontingent MPH (0.56 mg/kg/infusion) on a fixed ratio schedule of reinforcement. Results showed that rats responded for contingent MPH, and that responding was not maintained when MPH was delivered noncontingently. Experiment 3 examined self-administration of MPH (0.1 or 0.3 mg/kg/infusion) during long access (6 hr) compared to short access sessions (1 hr). Results showed that rats given long access to MPH showed an escalation of intake across sessions, with this escalation being more pronounced at the lower unit dose (0.1 mg/kg/infusion); in contrast, rats given short access to MPH did not show an increase in MPH self-administration across sessions at either MPH dose tested. Taken together, these results indicate that MPH is an effective intravenous reinforcer for rats and that, similar to other stimulants such as cocaine, amphetamine and methamphetamine, MPH is subject to abuse as reflected by dysregulated intake across repeated long access sessions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reinforcing and Subjective Effects of Methylphenidate: Dose and Time in Bed.

So that reinforcing and subjective effects of methylphenidate as a function of dose and level of sleepiness could be evaluated, 21 volunteers received methylphenidate (5, 10, or 20 mg) or placebo on 2 sampling days. After 4 and 8 hr time in bed (TIB), they chose their preferred capsule on 5 days. Methylphenidate was chosen more frequently after 4 hr TIB (60%) than it was after 8 hr TIB (33%). The strongest preference (68%) was seen in the 10-mg group. At 10 and 20 mg, stimulant-like subjective effects were reported. The 10-mg group was more adversely affected by the restricted bedtime and showed more pronounced drug effects with methylphenidate. These results indicate that sleepiness modulates the reinforcing and subjective effects of methylphenidate. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Discriminative-stimulus, self-reported, performance, and cardiovascular effects of atomoxetine in methylphenidate-trained humans.

Atomoxetine is marketed as a nonstimulant medication indicated for the treatment of attention-deficit/hyperactivity disorder in adults. Previous laboratory research suggests that atomoxetine has limited abuse potential but that some of its behavioral effects might overlap with traditional psychomotor stimulants like methylphenidate and d-amphetamine. A drug with this profile might be useful for the treatment of stimulant dependence. The aim of this experiment was to compare the discriminative-stimulus and self-reported effects of atomoxetine with methylphenidate, damphetamine, and triazolam in humans who had acquired a methylphenidate (30 mg) discrimination. Six healthy subjects with a recent history of nontherapeutic stimulant use were enrolled in this outpatient study. After subjects acquired the methylphenidate discrimination, a range of doses of methylphenidate (5-30 mg), atomoxetine (15-90 mg), d-amphetamine (2.5-15 mg), triazolam (0.06-0.375 mg), and placebo were tested. To more fully characterize the behavioral effects of atomoxetine, a battery of self-reported drug-effect questionnaires, a performance task, and cardiovascular assessments were also included. Methylphenidate and d-amphetamine increased drug-appropriate responding and produced typical stimulant-like effects (e.g., increased ratings of "Active, Alert, Energetic"). Atomoxetine partially substituted for methylphenidate (i.e., 33%-50%) and produced some dose-dependent, stimulant-like, subject-rated drug effects, although the magnitude of these effects was less than d-amphetamine and methylphenidate and generally did not attain statistical significance. These data suggest that the behavioral effects of atomoxetine overlap to a small degree with psychomotor stimulants and that it has low abuse potential. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Transdermal Methylphenidate, Behavioral, and Combined Treatment for Children With ADHD.

Stimulant medication and behavioral treatments are evidence-based for children with attention-deficit/hyperactivity disorder, but the combination of the 2 treatments has been understudied. In this investigation, methylphenidate (MPH) was crossed with 2 levels of behavior modification (BMOD) in a summer treatment program. Twenty-seven children with attention-deficit/hyperactivity disorder, aged 6-12, participated. Children received placebo and 3 doses of transdermal MPH (12.5 cm2, 25.0 cm2, and 37.5 cm2). BMOD was implemented on alternating weeks. Both treatments produced large and significant effects. Combined treatment was superior to either treatment alone. The effects of transdermal MPH were comparable to those found in this setting in previous studies with multiple stimulant medications and formulations. Consistent with other research, low doses of MPH--even lower than in previous studies--yielded enhanced effects in combination with behavior modification. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of Methylphenidate on Time Perception in Children With Attention-Deficit/Hyperactivity Disorder.

The effects of methylphenidate (MPH) on performance of a time-production task were studied in 17 children with attention-deficit/hyperactivity disorder who participated in 1 test session on and 1 off MPH. Participants held a response lever down for at least 10 but no longer than 14 s. Administration of MPH had no effect on the number of correct responses or on the mean duration of lever holds. MPH administration significantly decreased timing response variability, increased holds of 10- to 11-s duration, and decreased lever holds of extremely short durations. These results indicate that administration of MPH resulted in more precise timing performance without changing the mean duration of lever holds, suggesting an enhancement in working memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

含α活泼氢的哌醋甲酯衍生物在二异丙基胺锂作用下的差向异构化作用

在制备治疗滥用可卡因症的药物———(±) threo 哌醋甲酯衍生物中,发现了含α活泼氢的哌醋甲酯衍生物在二异丙基胺锂作用下的差向异构化作用,(±) erythro 哌醋甲酯经过乙酰基化、二异丙基胺锂作用关环后,生成热力学上更稳定的threo构型产物,产物构型通过1HNMR和13CNMR得到了确认,探讨了该过程的反应机理。这一发现避免了原合成路线中复杂的差向异构化和重结晶步骤,整个反应过程的产率提高了25%以上。