Clinical effects of a controlled trial of methylphenidate on adolescents with attention deficit disorder.

Forty-eight attention deficit disorder patients, 12 to 18 years old and without previous stimulant therapy, received a double-blind trial of methylphenidate and placebo for 3 weeks each. Stimulant treatment produced mild side effects and weight reduction. Methylphenidate significantly reduced teachers' and parents' ratings of hyperactivity, inattention, and oppositionality. In addition, patients rated themselves as clinically improved and reported elevated subjective mood during stimulant therapy. Treatment benefits were comparable for patients with and without concurrent conduct or oppositional disorder as well as those with and without past or present depressive disorders. These results support the continued effectiveness of stimulant therapy for attention deficit disorder in adolescence. However, the magnitude of clinical effectiveness reported was smaller than previously found in younger patients.

Effects of sustained-release and standard preparations of methylphenidate on attention deficit disorder.

Nineteen children with attention deficit disorder (ADD) participated in a double-blind trial consisting of four 2-week phases: sustained-release methylphenidate (MPH); standard MPH; a combination of standard and sustained-release MPH; and placebo. Pharmacological treatments were evaluated by means of parent and teacher ratings and open-ended comments, examiner ratings, and patients' performance and event-related potentials during Continuous Performance and Paired-Associate Learning Tests. Results revealed that the MPH conditions were superior to placebo and comparable to one another. Within the limited time frame of the research, the findings suggest comparable effectiveness for sustained-release and standard preparations of MPH.

Methylphenidate reduces abnormalities of stimulus classification in adolescents with attention deficit disorder.

Forty-eight adolescents with attention deficit disorder (ADD) received placebo and methylphenidate (M = 35.21 mg/day) for 3 consecutive weeks each. ADD patients who received placebo in the first phase of treatment were compared with unmedicated normal adolescents. ADD and normal adolescents did not differ in slope of reaction time as a function of memory load in a Sternberg (1969) memory task. These results may be interpreted as reflecting normal rates of memory search in ADD. However, in comparison with normal subjects, ADD subjects made disproportionately more errors to targets and lacked faster latencies of the P3b component of event-related potentials for targets than nontargets. These findings suggest abnormalities in stimulus classification. Methylphenidate did not affect ADD patients' rates of memory search, but it did reduce misclassifications of targets at high memory loads. The drug also evoked the normal pattern of slower P3b latencies for nontargets by shortening latencies for targets. Thus the stimulant reduced ADD adolescents' abnormalities in stimulus classification.

Clinical and cognitive effects of methylphenidate on children with attention deficit disorder as a function of aggression/oppositionality and age.

Children diagnosed with attention deficit disorder (ADD; n = 44), ADD plus aggression/oppositionality (ADD/O; n = 34), and as not meeting ADD criteria (NC; n = 29) received methylphenidate and placebo for 21 consecutive days each. Parents and teachers rated all groups improved under medication, but teachers reported less improvement for NC than for ADD/O children. Methylphenidate and chronological age had generally similar effects in a Sternberg task: greater accuracy and speed (especially for nontargets at low memory loads), larger P3b waves of event-related potentials, more pronounced slowing of P3b latency by memory load, and a greater trend of earlier peaks for targets than for nontargets. Both methylphenidate and maturation promoted more efficient strategies involving differentiated evaluation of targets and nontargets. These results were comparable among ADD groups.

Methylphenidate speeds evaluation processes of attention deficit disorder adolescents during a continuous performance test.

Forty-six Attention Deficit Disorder (ADD) adolescents took a Continuous Performance Test (CPT) under placebo and methylphenidate (35.33 mg/day). The task required pressing one button for targets (p = .133), and another button for nontargets. Subjects displayed a strong bias to make the more frequent negative response before completely evaluating stimuli. Consistent with this assumption, subjects responded faster (by an average of 87 ms) to nontargets than to targets. Methylphenidate increased accuracy and speeded reaction times (RTs) to targets. The drug also increased the amplitude of the P3b component of the event-related potential for nontargets and shortened the latency of P3b for both targets and nontargets. These results suggest increased capacity allocation to and faster evaluation of task stimuli. Finally, the stimulant lengthened relative motor processing time (RT-P3b latency) for nontargets, a finding implying that response processing was accomplished with the benefit of earlier completion of evaluation processes for these stimuli.

Methylphenidate does not modify the impact of response frequency or stimulus sequence on performance and event-related potentials of children with attention deficit hyperactivity disorder.

Twenty-six children with attention deficit/hyperactivity disorder (ADHD) participated in a double-blind trial consisting of 2 consecutive weeks each of placebo and methylphenidate (M = 26.92 mg/day = 0.78 mg/kg/day). As expected, stimulant therapy resulted in moderate weight loss, increased somatic complaints, and teacher and parent reports of reduced inattentiveness, aggression, and oppositionality. In both phases of the trial, patients were tested in a choice reaction time task assessing two aspects of the task that presumably affect response selection: response frequency (ratio of targets/nontargets = 25/75 vs. 50/50) and stimulus sequence (alternations vs. repetitions). Both manipulations yielded expected results on performance and event-related potentials (ERPs). Stimulant treatment increased accuracy and speed among younger children and curtailed variability of reaction time for the sample as a whole. However, methylphenidate did not affect ERPs. In combination, the results imply that the enhancement of performance by methylphenidate does not involve the demands of response selection examined in this study.

Methylphenidate slows reactions of children with attention deficit disorder during and after an error.

A Sternberg memory search task was administered under placebo and methylphenidate to 42 children with cross-situational attention deficit disorder (ADD), 31 children with cross-situational ADD plus oppositional features, and 25 patients with marginal ADD. Overall, stimulant medication enhanced accuracy and speed. In addition, patients reacted faster on correct responses not preceded by an error than on errors (especially false alarms) or on correct responses following an error. The slowness during error reactions may reflect decreased confidence or confusion during stimulus classification. This uncertainty may also lead subjects to respond with greater caution, hence more slowly, on correct responses following errors. Notably, methylphenidate increased the slowing of reactions on error trials as well as on correct reactions following an error. Stimulant medication may augment subjects' persistence when they are uncertain or confused, thereby heightening caution and promoting accuracy on succeeding trials. Consistent with previous reports of the generality of enhancement of performance by stimulant medication, the impact of methylphenidate was comparable for the three subtypes of ADD studied.

Paired-associate learning in attention-deficit/hyperactivity disorder as a function of hyperactivity-impulsivity and oppositional defiant disorder.

A paired-associate learning (PAL) test was administered to 22 community volunteers without disruptive disorders and 197 children (7.5-13.5 years-old) presenting with the inattentive and combined subtypes of attention-deficit/hyperactivity disorder (ADHD) either in combination with or without oppositional defiant disorder (ODD). Participants were screened for learning disorders. In comparison to non-ADHD participants, children with ADHD achieved worse PAL and made errors rated as more acoustically and less semantically similar to the correct paired associates. These deficits were not related to hyperactivity-impulsivity or comorbid ODD. These results suggest that ADHD children are less competent at PAL and use less efficient learning strategies than their non-ADHD peers.

Methylphenidate's effects on paired-associate learning and event-related potentials of young adults.

The effects of methylphenidate (0.3 mg/kg) on young adults paired-associate learning (PAL) of consonant-vowel-consonant (CVC) pairs and concomitant event-related potentials were assessed. The stimulant elevated mood and heart rate but did not affect PAL performance. For the first CVC, there were amplitude increases with learning for P3b at Pz, P2 at midline sites, and for a negative slow wave at Cz. For the second CVC, P3b and positive slow wave amplitude declined with learning. Increases in P3b amplitude to the first CVC were attributed to increments in stimulus meaningfulness. Decreases in P3b amplitude to the second CVC were interpreted as resulting from fewer disconfirmed expectations of feedback. The negative slow wave following the first CVC was viewed as a contingent negative variation. Methylphenidate increased parietal P3b amplitude for CVC 2, averaged over learning phases.

Effects of methylphenidate on processing negativities in patients with attention-deficit hyperactivity disorder.

This study compared the impact of methylphenidate on patients with Attention-deficit Hyperactivity Disorder (ADHD) with and without aggressive/noncompliant features in an oddball test consisting of a randomly ordered series of loud (frequent) tones, soft (rare) tones, bright (frequent) lights, and dim (rare) lights. In alternate conditions, subjects were required to respond to either the rare tones or the rare lights. These tasks were administered in a drug-free baseline session and after a counterbalanced treatment of 14 days each of methylphenidate (0.3 mg/Kg b.i.d.) and placebo (lactose b.i.d.). In comparison with placebo, methylphenidate resulted in greater accuracy and speed of reactions to targets of both modalities. The amplitude of N1 to auditory nontargets was larger when the target was a rare tone as opposed to a rare light, and this attention-related effect was increased by methylphenidate. The same differential amplitude enhancement by stimulant treatment was found for an early area measure of difference ERPs. In contrast, for N1 to visual nontargets the effect of selective attention (larger amplitude when the target was a rare light vs. a rare tone) was not significant and was not affected by stimulant medication. All these findings were comparable for the three ADHD subgroups, a result attesting to the generality of stimulant effects on information processing.