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PubMed1993

Methylphenidate and desipramine in hospitalized children: I. Separate and combined effects on cognitive function.

OBJECTIVE: The separate and combined effects of methylphenidate and desipramine on cognitive function were investigated in 16 psychiatrically hospitalized children with primary, secondary, and mixed features of attention-deficit hyperactivity disorder and mood disorder. METHOD: A double-blind, placebo controlled, crossover design was used to investigate drug effects on vigilance, short-term memory, visual problem solving, and higher-order learning. RESULTS: Methylphenidate alone improved vigilance, both drugs positively affected short-term memory and visual problem solving, and combined drugs affected learning of higher-order relationships. CONCLUSIONS: Separate and combined drug effects are related to the specific cognitive domain assessed and have implications for neurotransmitter models of action.

Arousal↗
PubMed1995

Effects of methylphenidate on reward strength in boys with attention-deficit hyperactivity disorder.

OBJECTIVE: To test the hypothesis that methylphenidate reduces thresholds for reward in children with attention-deficit hyperactivity disorder (ADHD). METHOD: A double-blind crossover design was used in which 16 ADHD boys, aged 8 to 13 years, received methylphenidate on one testing occasion and placebo on another. On each occasion, subjects performed a task that required progressively greater numbers of button presses to earn a fixed monetary payoff. RESULTS: The "breaking point" above which the hyperactive child was unwilling to continue with the task was significantly higher during drug than placebo trials. CONCLUSIONS: The results support an assumption that underlies the reward system dysfunction hypothesis of ADHD, and they suggest that reward mechanisms may underlie the therapeutic effects of stimulants observed across a wide range of tasks and settings.

Adolescent↗
PubMed2001

Methylphenidate effects on task-switching performance in attention-deficit/hyperactivity disorder.

OBJECTIVE: To examine the specificity of methylphenidate effects on the processes that support the ability to rapidly and accurately coordinate the performance of multiple tasks in children with attention-deficit hyperactivity disorder (ADHD). METHOD: Twenty children with ADHD performed the task-switching paradigm while on and off medication. The paradigm involves switching between two different tasks, discriminating the value of a number presented on a computer screen and deciding how many numbers were present on the screen. The children also performed single-task control conditions. RESULTS: Analyses of variance indicated the medication selectively enhanced the children's ability to rapidly and accurately switch between tasks and to focus attention on the currently relevant response set. CONCLUSIONS: This study helps to elucidate the nature of methylphenidate effects on the cognitive processes which support the ability to coordinate the performance of multiple tasks. Medication appears to selectively enhance inhibitory processes which support task-switching.

Adolescent↗
PubMed2003

Treatment effects of methylphenidate on behavioral adjustment in children with mental retardation and ADHD.

OBJECTIVE: The effects of stimulant medication treatment were investigated in children with mental retardation (MR) and attention-deficit/hyperactivity disorder (ADHD). METHOD: Parent and teacher behavioral ratings and reports of side effects were obtained for children (N = 24, mean age = 10.9 years, SD = 2.4) during a placebo-controlled, double-blind, crossover treatment trial with 0.15 mg/kg, 0.30 mg/kg, and 0.60 mg/kg b.i.d. dosages of methylphenidate. RESULTS: The most significant improvements occurred at the 0.60 mg/kg methylphenidate dose for teacher ratings of inattention (p =.024), hyperactivity (p <.001), aggression (p <.001), and asocial behavior (p =.009). No significant improvements, relative to placebo, occurred at the 0.15 mg/kg dosage. Of interest, nearly all significant medication-related behavioral improvements were detected by teachers. However, parents were sensitive raters of side effects, noting more sleeping problems and loss of appetite at the 0.60 mg/kg dose compared with placebo. CONCLUSIONS: These results suggest that symptoms of ADHD can be treated successfully in children with ADHD/MR, and consistent with MTA study results, higher doses were most effective. Furthermore, these improvements were not accompanied by increases in symptoms such as staring, social withdrawal, or anxiety.

Attention Deficit Disorder with Hyperactivity↗
PubMed1996

Successful treatment of giggle incontinence with methylphenidate.

PURPOSE: Giggle incontinence, the second most common type of childhood enuresis unrelated to disease, is notoriously difficult to treat. However, the association of laughter or emotion precipitated alteration of muscle tone is suggestive of a functional relationship to cataplexy, a part of the narcoleptic syndrome complex that may respond to stimulant medication. MATERIALS AND METHODS: Two boys and 5 girls (mean age 10.9 years) with giggle incontinence, a positive family history of giggle incontinence (4 patients) and no evidence of urological disease were treated with methylphenidate for 1 to 5 years. RESULTS: All patients responded positively with complete cessation of enuresis to varying dose schedules of methylphenidate. CONCLUSIONS: These results suggest that giggle incontinence is a centrally mediated and likely hereditary disorder that may share a common pathophysiological basis with the narcolepsy/cataplexy syndrome.

Adolescent↗
PubMed1981

Methylphenidate in depression and states of apathy.

Methylphenidate hydrochloride (Ritalin) has been used to treat both depression and apathy. Although it can be useful for apathy, there is little reason to prefer it over a tricyclic antidepressant in the treatment of depression. Side effects and drug interactions are generally not limiting, and methylphenidate is tentatively recommended for the patient whose apathy is jeopardizing his care.

Clinical Trials as Topic↗
PubMed1984

Clinical correlates of methylphenidate blood levels.

The clinical correlates of methylphenidate blood levels in hyper-active children and normal adults were examined in five studies. Although occasional correlations between blood levels and neuroendocrine response were noted within subjects along the pharmacokinetic time profile of the drug, no significant associations were found between blood levels and clinical response in behavioral measures or laboratory tests of attention or activity. It is unlikely that routine methylphenidate blood level determinations will become a part of the routine clinical management of hyperactive children.

Adult↗
PubMed2006

Stimulant effects of 3,4-methylenedioxymethamphetamine (MDMA) 75 mg and methylphenidate 20 mg on actual driving during intoxication and withdrawal.

BACKGROUND: 3,4-methylenedioxymethamphetamine (MDMA) is currently one of the most popular drugs of abuse in Europe. Its increasing use over the last decade has led to concern regarding possible adverse effects on driving. The aims of the present study were to investigate the acute effects of MDMA on actual driving performance during the intoxication and withdrawal phase. METHODS: Eighteen recreational MDMA-users (nine males, nine females) aged 21-39 years participated in a double-blind, placebo-controlled, three-way cross-over study. MDMA 75 mg, methylphenidate 20 mg and placebo were administered on day 1 of treatment (intoxication phase). Driving tests were conducted between 3 and 5 hours post-drug. Subjects returned the following day for a repetition of the driving tests between 27 and 29 hours post-drug (withdrawal phase). On-the-road driving tests consisted of a road-tracking test and a car-following test. Its main parameters were standard deviation of lateral position (SDLP), time to speed adaptation (TSA), brake reaction time (BRT) and gain. FINDINGS: MDMA and methylphenidate significantly decreased SDLP in the road-tracking tests by about 2 cm relative to placebo on day 1 (intoxication phase). In addition, MDMA intoxication decreased performance in the car-following test as indicated by a significant rise in the 'overshoot' of the subjects' response to speed decelerations of the leading vehicle. Driving performance was not affected by treatments during withdrawal on day 2. CONCLUSION: Collectively, these data indicate that MDMA is a stimulant drug that may improve certain aspects of the driving task, such as road-tracking performance, but may reduce performance in other aspects of the driving task, such as accuracy of speed adaptation during car-following performance.

Adult↗
PubMed1979

Peer interaction in a structured communication task: comparisons of normal and hyperactive boys and of methylphenidate (Ritalin) and placebo effects.

Peer communication patterns were assessed as school-aged boys participated in a dyadic referential communication task. The responses of comparison boys were compared to those of hyperactive boys on methylphenidate (Ritalin) and on placebo in a double-blind crossover design. 2 separate systems for assessing communication were developed, a qualitative system designed to capture the "flavor" of interaction and a quantitative system focused on specific types of communicative content. Task products and completion times were also scored. The results suggest that hyperactive children, regardless of medication status, are less likely than comparison peers to (a) modulate ongoing or habitual behavior patterns in response to externally imposed shifts in role-appropriate behaviors; (b) maintain consistent, uninterrupted goal orientation; and (c) respond to subtle social learning opportunities. In this situation, methylphenidate appeared to have a greater impact on behavioral style than on competence, decreasing perceived intensity without influencing efficiency. A mild medication-induced dysphoria was also documented. Directions for future research and the need for caution in clinical interpretation are discussed.

Affect↗
PubMed1983

Children with reading disorders--II. Effects of methylphenidate in combination with reading remediation.

Sixty-six children received individual reading instruction for 18 weeks, in combination with methylphenidate (mean daily dose 44.2 mg/day) or a placebo. Assignment to medication was random and double blind. Children were re-evaluated at the end of treatment, and two and eight months later. Only occasional and weak methylphenidate effects were obtained on measures of reading performance. Highly significant improvement in some tests of mathematics was found. No treatment differences occurred at follow-up. The results do not support the hypothesis that the enhancement of attention with stimulant treatment facilitates the acquisition of reading skills in children with pure reading disorders.

Achievement↗
PubMed1985

A developmental dose-response analysis of the effects of methylphenidate on the peer interactions of attention deficit disordered boys.

Mixed dyads of 42 normal and 42 ADD boys were videotaped in free play, co-operative task, and simulated classrooms. ADD boys received placebo, 0.15 mg/kg, and 0.50 mg/kg of methylphenidate. ADD boys were more active and off task, watched peers less, and scored lower on mathematics and visual-motor tasks. Older boys interacted less, ignored peer interactions and play more frequently, were less controlling, and more compliant. In class, methylphenidate improved visual motor scores, and reduced the controlling behaviour, activity level, and off task behaviour of ADD boys. Normal peers displayed reciprocal reductions in controlling behaviour, activity level, and off task behaviour.

Age Factors↗
PubMed1986

Short term effects of methylphenidate on the cognitive, learning and academic performance of children with attention deficit disorder in the laboratory and the classroom.

Sixteen children meeting diagnostic criteria for Attention Deficit Disorder with Hyperactivity (ADD-H) were tested on methylphenidate (0.3 mg/kg) and placebo on cognitive, learning, academic and behavioral measures in a double-blind study. Assessments were carried out in the laboratory and in the children's regular classrooms. Results indicate methylphenidate-induced improvements on a majority of the measures. Drug-induced changes reflected increased output, accuracy and efficiency and improved learning acquisition. There was also evidence of increased effort and self-correcting behaviours. It is argued that reviewers have underestimated the potential of stimulants to improve the performance of ADD-H children on academic, learning and cognitive tasks.

Achievement↗
PubMed1991

A dose-response analysis of the effects of methylphenidate on the peer interactions and simulated classroom performance of ADD children with and without conduct problems.

To examine the social effects of methylphenidate, groups of 15 attention-deficit disordered boys with (ADD) and 15 ADD boys without conduct problems (ADD/CP) were paired with normal peers. ADD and ADD/CP children showed a different pattern of responses to methylphenidate. While on task behavior in ADD/CP dyads increased at 0.15 mg/kg doses, increases in ADD dyads were not observed until doses reached 0.50 mg/kg. Although controlling interaction in ADD children decreased at 0.15 mg/kg, the controlling behavior of ADD/CP children did not decline at either dose. Peers of both ADD and ADD/CP children showed reciprocal declines in controlling behavior. In both free play and cooperative task situations, 0.15 mg/kg increased social interaction in ADD boys and decreased social interaction in ADD/CP boys.

Achievement↗
PubMed1992

Methylphenidate and cognitive perseveration in hyperactive children.

Effects of methylphenidate on cognitive flexibility were investigated in 26 children with Attention Deficit Hyperactivity Disorder (ADHD), by assessing perseverative errors on the Wisconsin Card Sorting Test (WCST) and the emergence of clinical symptoms indicative of cognitive perseveration. A double-blind, placebo-control, randomized crossover design was used in which each child was assessed twice in each drug condition (placebo, 0.3 and 1.0 mg/kg). Results indicated that methylphenidate increased perseverative errors on the first assessment but decreased them on the second; clinical symptoms of perseveration occurred at both assessments. Findings suggest that MPH may reduce cognitive flexibility temporarily in some ADHD children.

Attention↗
PubMed2006

Acute neuropsychological effects of methylphenidate in stimulant drug-naïve boys with ADHD II--broader executive and non-executive domains.

BACKGROUND: Accumulating evidence supports methylphenidate-induced enhancement of neuropsychological functioning in attention deficit hyperactivity disorder (ADHD). The present study was designed to investigate the acute effects of the psychostimulant drug, methylphenidate (MPH), on neuropsychological performance in stimulant naïve boys with ADHD. METHODS: Seventy-three drug-naïve boys (age 7-15) with ADHD (combined type) completed neuropsychological tasks from the CANTAB battery under randomised, placebo controlled, double-blind conditions following an acute challenge with either placebo (n = 24), .3 (n = 25) or .6 (n = 24) mg/kg oral MPH. RESULTS: MPH did not impair performance on any task. MPH (.6 mg/kg) lengthened response latencies on a task of Spatial Recognition, shortened response times on a Reaction Time task and restored performance on a Delayed Matching to Sample visual, non-working memory task. Contrary to predictions, MPH did not enhance performance on tasks with a prominent executive component, including Go/NoGo, Spatial Working Memory, Stockings of Cambridge and Attentional Set shifting tasks. CONCLUSIONS: Acute administration of MPH to drug-naïve boys with ADHD did not impair neuropsychological performance. Acute MPH enhanced performance on some aspects of non-executive functioning. MPH-induced slowing of responding on a relatively complex Spatial Recognition memory task and quickened responding on a reaction time task requiring less cognitive resources suggests that MPH may act by improving self-regulatory ability. MPH may not exert its effects on neuropsychological functioning by enhancing executive processes.

Adolescent↗
PubMed1979

Long-term use and discontinuation of methylphenidate with hyperactive children.

The long-term effects of methylphenidate on the behavior and academic functioning of hyperactive children are described. 36 children having a positive response to methylphenidate entered a three-year follow-up study in which they were closely monitored physically, behaviorally and psychometrically. During this period 13 children spontaneously discontinued medication: there were no statistically significant differences between them and the children who continued medication in terms of age, IQ or ratings at initial interview. The greatest improvement in performance occurred in the early months of treatment, but was only partially maintained during long-term therapy and little further change occurred after medication was discontinued. The findings indicate that sustained improvement is related to factors other than continued medication, and they suggest that drug therapy should be regarded as a short-term intervention until more positive social and school behavior can be established.

Achievement↗
PubMed1987

Metaphit irreversibly inhibits [3H]threo-(+/-)-methylphenidate binding to rat striatal tissue.

Metaphit (1-[1-(3-isothiocyanatophenyl)cyclohexyl]-piperidine), a derivative of phencyclidine that contains an isothiocyanate group on the meta position of the aromatic ring, resembles its parent compound (phencyclidine) in its ability to inhibit the binding of the stimulant drug [3H]threo-(+/-)-methylphenidate to crude synaptosomal membranes from rat striatal tissue (IC50 = 1.4 and 6.2 microM for phencyclidine and Metaphit, respectively). Unlike phencyclidine, however, Metaphit appears to inhibit binding of the radiolabeled stimulant in an irreversible manner, as the degree of inhibition of binding of the stimulant does not diminish when the Metaphit-treated tissue is subjected to repeated washings before determination of the binding of [3H]threo-(+/-)-methylphenidate. This finding suggests that Metaphit may be a useful tool in the study of the molecular basis of stimulant action.

Animals↗
PubMed1975

Withdrawn, apathetic geriatric patients responsive to methylphenidate.

A double-blind randomized study showed that methylphenidate, as compared to placebo, was singularly effective in 44 withdrawn, apathetic geriatric patients. Study selection and exclusion criteria were rigidly enforced. Patients receiving methylphenidate in a dosage of 20 mg daily improved significantly over a period of six weeks as measured by results of tests for mental status, ward behavior (nursis' rating), target-symptom response, and physician's and nurses' global evaluations. For this reason and because there were no side effects, this form of antidepressant therapy should be considered in the treatment of previously unresponsive or oversedated patients.

Affective Symptoms↗