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PubMed1976

Alterations in the vigilance performance of children receiving amitriptyline and methylphenidate pharmacotherapy.

The effects of amitriptyline (Elavil) and methylphenidate (Ritalin) on the vigilance of 20 hyperactive/aggressive children was investigated using an auditory version of the Continuous Performance Test (CPT). Over the course of this letter-detection task, correct detections tended to return to pretreatment levels under placebo, but were maintained at significantly improved levels under amitriptyline and methylphenidate. The relatively steep performance decrement which occurred in the placebo condition was found to be associated with a progressive increase in responses to the letter which immediately followed a target letter. Treating these 'late' responses as slow but 'correct' detections failed to eliminate the treatment effects obtained with amitriptyline and methylphenidate. It was concluded that in addition to keeping detection response latencies from increasing, the medications produced a heightened level of vigilance which resulted in an absolute increase in the number of correct detections. The facilitation of vigilance performance by amitriptyline was in apparent contradiction to reports by parents and teachers that children appeared 'drowsy' while receiving this medication. Findings of the study suggested that children's ability to process information was unaffected by the reported side effect.

Amitriptyline↗
PubMed1977

The effects of methylphenidate on various types of activity level and attention in hyperkinetic children.

The effects of methylphenidate on a number of objective measures of activity level and attention were assessed on three repeated occasions in four types of settings: free play, movie viewing, testing, and restricted play periods. Subjects were 36 boys between 5 and 12 years of age and of average intelligence. Of these, 18 were diagnosed as hyperkinetic and participated in a double-blind drug-placebo crossover design. The remaining 18 boys, matched in age and IQ with the hyperkinetic children, served as a control group and received no drugs. Results indicated that compared to placebo, methylphenidate significantly reduced wrist, ankle, locomotor, and seat movement activity in the hyperkinetic children regardless of the type of setting in which the measures were taken. Relatively fewer significant drug effects were noted on the measures of concentration or attention. While concentration to reaction time, maze performance, and a movie viewing task improved during drug treatment, the length of attention to toys in free play was not significantly improved. Parental ratings of activity level were also improved by the drug. The hyperkinetic children were also observed to increase their level of task-irrelevant activity over time while control children remained relatively stable in activity over repeated assessment. Despite the positive drug effects, clinical observations suggested that methylphenidate may have reduced the interest of some children in their environment.

Attention↗
PubMed1990

Social judgment processes in hyperactive boys: effects of methylphenidate and comparisons with normal peers.

Although there is consensus that ADHD children have serious social problems, there is little understanding of the mechanisms underlying or accompanying such problems. To examine the possibility of atypical or faulty social reasoning, we presented ADHD and normal boys with a social perception task that entailed evaluating the behaviors of unknown peers. ADHD "judges" participated under both methylphenidate and placebo conditions, and on each occasion they evaluated an unfamiliar ADHD "target" in each medication state. In contrast to placebo, methylphenidate appeared to dampen overall response rates in ADHD judges, but there was no effect on sensitivity to medication-related differences. Regardless of their own medication state, ADHD judges identified more undesirable behaviors in peers on placebo than in those taking methylphenidate. Judges with the most serious behavior problems tended to identify the greatest number of negative behaviors in peers, especially when both judge and target were unmedicated. There were no effects of target medication status on detections of positive behaviors and few differences in detection patterns of ADHD versus normal judges. Discussion focused on the need to distinguish general regulatory from specific social-cognitive processes.

Attention Deficit Disorder with Hyperactivity↗
PubMed1992

Aggression in boys with attention deficit-hyperactivity disorder: methylphenidate effects on naturalistically observed aggression, response to provocation, and social information processing.

High and low-aggressive boys with attention deficit-hyperactivity disorder (ADHD) were compared and the effects of methylphenidate were examined on measures from three domains of aggression: (1) directly observed verbal and nonverbal aggressive behaviors exhibited in the context of a day treatment program, (2) aggressive responding when provoked during a laboratory task, and (3) social information processing patterns exhibited on tasks designed to tap the putative cognitive components of aggression. The high-aggressive (HA) and low-aggressive (LA) subgroups differed significantly on observational measures of aggression and on the laboratory provocation task, but the HA group showed more deviant cognitions on only one of the numerous measures of social information processing. Regarding medication effects on the direct observation measures, methylphenidate decreased aggression for both subgroups. On the laboratory provocation task, methylphenidate had only minimal effects. Significant drug effects were obtained on only two recall social information processing measures.

Aggression↗
PubMed1979

Effects of methylphenidate (Ritalin) on selective attention in hyperactive children.

This study investigated the effect of methylphenidate (Ritalin) on the selective attention of hyperactive children designated as favorable or adverse responders to stimulant medication. Using a type II incidental learning paradigm, it was found that children in the drug condition recalled more central and less incidental stimuli than those children in the placebo condition. While no differential effects on recall were found for responder type, methylphenidate did affect the spontaneous overt labeling of central stimuli by the favorable responder group. Results were interpreted in terms of the role of methylphenidate in narrowing the focus of attention. Implications for the classification of hyperactive children as favorable and adverse responders were also discussed.

Attention↗
PubMed1996

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.

Attention Deficit Disorder with Hyperactivity↗
PubMed1991

Discriminative stimulus effects of d-amphetamine, methylphenidate, and diazepam in humans.

Eight male community volunteers, who reported current psychomotor stimulant use, were trained to discriminate between the presence and absence of orally administered d-amphetamine 30 mg. During daily experimental sessions, in which a single drug dose or placebo was tested, physiological and subjective measures were assessed and subjects indicated their discrimination by responding on an operant color-tracking procedure. During four test of acquisition sessions, discriminative responding indicated that all subjects learned the discrimination, and d-amphetamine produced physiological and subjective effects typical of psychomotor stimulants. Generalization testing then followed in which dose-response curves were determined for the following drugs: d-amphetamine (3.75, 7.5, 15 and 30 mg), diazepam (5, 10, 20 and 40 mg), and methylphenidate (7.5, 15, 30 and 60 mg). d-Amphetamine and methylphenidate produced dose-related increases in d-amphetamine-appropriate responding, whereas no dose of diazepam substituted for d-amphetamine in any subject. d-Amphetamine and methylphenidate produced a similar pattern of subjective changes, including increased ratings of euphoria and drug liking and decreased sedation. In contrast, diazepam increased subjective scales of sedation and dysphoria. These results are consistent with similar studies testing animals and humans and demonstrate the utility of human drug discrimination research as an integral component of drug abuse liability testing.

Adolescent↗
PubMed1994

Cognitive effects of milacemide and methylphenidate in healthy young adults.

Cognitive effects of the novel glycine prodrug milacemide (400 mg), the catecholaminergic agonist methylphenidate (20 mg), and placebo were evaluated in 48 healthy young adults. Throughout a 6-h drug treatment day, subjects repeatedly performed tests of target-detection vigilance, immediate and delayed verbal free recall, and Buschke Selective Reminding; total free recall and forced-choice recognition tests were administered at the end of the day. Significant improvement in both vigilance reaction time and Selective Reminding Sum Recall was observed in the methylphenidate group. Contrary to expectations, the milacemide group evidenced significant declines in both vigilance perceptual sensitivity and free-recall difference scores (delayed-immediate). Vigilance reaction times significantly decreased over repeat testing in all groups, but only the methylphenidate group differed from placebo. The reaction-time functions for milacemide and placebo were similar, suggesting arousal was not diminished under milacemide and could not account for the cognitive decrements. No significant drug effects obtained for total free recall or recognition performance. Although the glycine prodrug milacemide was ineffective as a cognitive enhancer, the involvement of the NMDA receptor in memory function reported in the literature supports continued exploration of other approaches for manipulating NMDA receptor activity.

Acetamides↗
PubMed1992

Effects of methylphenidate on response rate and measures of motor performance and reinforcement efficacy.

This experiment evaluated the effects of methylphenidate on reinforced responding in rats. In each session the subjects (rats) earned reinforcement on seven different variable-interval reinforcement schedules. The average intervals varied from 108 to 3 s and provided reinforcement rates ranging from about 30 to 1100/h. Response rate was a negatively accelerated function of reinforcement rate. Low doses of methylphenidate (1.0 and 2.0 mg/kg) increased responding maintained by the four leanest schedules, but had little effect on responding maintained by the three densest schedules. In contrast, an 8.0 mg/kg dose increased responding maintained by the three densest schedules and slightly decreased responding maintained by leaner schedules. A quantitative model of reinforced responding, referred to as the matching law or response strength equation, was fitted to the data. This equation has two parameters. On the basis of previous experiments, one was used to measure changes in reinforcement efficacy and the other was used to measure changes in motor performance. The 1.0 and 2.0 mg/kg doses changed the reinforcement parameter in the same way as did increases in deprivation and reward magnitude. The 8.0 mg/kg dose changed the motor parameter in the same was as did decreases in lever weight. It was concluded that methylphenidate increases reinforcement efficacy, and that the highest dose changed the topography of responding. The results are discussed in terms of the response strength equation, the rate dependency principle, and the question of how to interpret changes in reinforcement efficacy and motor performance.

Animals↗
PubMed2006

Drugs, sweat, and fears: a comparison of the effects of diazepam and methylphenidate on fear conditioning.

RATIONALE: Classical conditioning of a fear response involves the formation of an association between a stimulus and an emotional response and can be seen as a basic form of emotional memory. While both benzodiazepines and stimulant drugs may influence the formation of episodic memories for emotional events, their effects on fear conditioning are less clear. OBJECTIVES: This study compared the effects of diazepam with methylphenidate on fear conditioning. MATERIALS AND METHODS: In a single-session between groups design with three conditions [placebo, diazepam (10 mg), and methylphenidate (40 mg)], classical conditioning of a skin conductance response to a visual stimulus previously paired with a 100-db white noise was tested in 45 healthy volunteers. RESULTS: Diazepam blocked fear conditioning, despite responses to the unconditioned aversive stimulus and neutral control stimulus being unimpaired. Conditioning remained intact after methylphenidate. Conditioned responses were not extinguished completely by the end of the experiment, and it was not possible to draw conclusions about the effects of the drugs on extinction. CONCLUSIONS: Although diazepam has well-documented amnesic effects, it has not been found to affect implicit forms of memory like perceptual and conceptual priming. As the present study found impaired fear conditioning after diazepam, it adds weight to recent findings that emotional memories are disproportionately impaired by the benzodiazepines.

Adult↗
PubMed2002

Effects of methylphenidate on saccadic responses in patients with ADHD.

This study examined the effects of methylphenidate on different measures of saccade control, using a repeated measurement design, and the experimental and statistical control of practice effects. Twenty-seven boys with ADHD (mean age 12.6 years, range 10-15 years) were randomly assigned to two testing order conditions (first on-, second off-medication versus first off-, second on-medication) and accomplished the pro-saccadic overlap and the anti-saccadic 200-ms gap tasks (200 trials each). Methylphenidate was found to reduce pro- and anti-saccadic reaction times, error correction times, and the proportion of direction errors during the anti-saccade task. Furthermore, the drug augmented the proportions of express saccades and error corrections. Overlain practice effects were found for most of these measures. Our results suggest a weakening of the fixation, and a strengthening of the "voluntary" system of saccade control by methylphenidate.

Adolescent↗
PubMed1985

Mood response to methylphenidate and the Dexamethasone Suppression Test as predictors of treatment response to zimelidine and lithium in major depression.

Sixteen patients with a major depressive disorder underwent a Dexamethasone Suppression Test, and 15 of these patients were given intravenous methylphenidate and their mood response recorded. There was no association between the Dexamethasone Suppression Test and mood response to methylphenidate. Neither of these markers predicted clinical antidepressant response with zimelidine, although among zimelidine nonresponders, a clinical improvement upon the addition of lithium was predicted by a positive mood response to methylphenidate.

Adolescent↗
PubMed1987

Different patterns of local brain energy metabolism associated with high and low doses of methylphenidate. Relevance to its action in hyperactive children.

Rates of local cerebral glucose utilization were measured by means of the quantitative autoradiographic [14C]deoxyglucose technique in conscious rats following the acute administration of methylphenidate hydrochloride (1.25-15.0 mg/kg). Significant dose-dependent alterations in metabolic activity were found in the components of the extrapyramidal system, including the substantia nigra, subthalamic nucleus, and the entopeduncular nucleus, as well as in the lateral habenula. Significant changes were also observed in the nucleus accumbens and olfactory tubercle, but occurred only following administration of low doses of methylphenidate. Comparison of the patterns of metabolic activity observed in this study with those obtained following the administration of other psychostimulant drugs suggests possible substrates for the therapeutic action of methylphenidate in the treatment of hyperactive children.

Animals↗
PubMed1988

The effect of methylphenidate on urinary catecholamine excretion in hyperactivity: a partial replication.

Children with attention deficit disorder with hyperactivity were treated with methylphenidate HCl (0.74 +/- 0.2 mg/kg/day) for 2 weeks in an open trial to assess changes in the urinary excretion of catecholamines and behavior. The purpose of this study was to confirm earlier work that methylphenidate has a distinctly different effect on urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion as compared to earlier studies with dextroamphetamine. Results confirmed the earlier finding that methylphenidate does not significantly change urinary MHPG excretion. No significant relationship was found between behavioral change and any of the urinary catecholamines or metabolites measured.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1978

Dose-dependent biphasic alterations in the spontaneous activity of neurons in the rat neostriatum produced by d-amphetamine and methylphenidate.

A dose-response analysis was performed on D-amphetamine- and methylphenidate-induced changes in neuronal activity in the neostriatum of immobilized, phenidate-induced changes in neuronal activity in the neostriatum of immobilized, locally anesthetized rats. Whereas a marked depression of firing rate characterized the response to intraperitoneal injections of 2.5 mg/kg D-amphetamine or 10 mg/kg methylphenidate, increasing the dose (5.0--7.5 mg/kg D-amphetamine and 20--25 mg/kg methylphenidate) shifted this response pattern to a prolonged increase in activity. Both stimulant-induced increases and decreases in neostriatal activity are reversed by 2.0 mg/kg haloperidol. In contrast to the response of neostriatal neurons, the firing rate in the substantia nigra pars compacta was inhibited by both stimulants, even at doses that increased the activity of neurons in the neostriatum. The possible mechanisms underlying these drug-induced changes in firing rate are discussed along with the behavioral implications of a stimulant-induced dose-dependent shift in neostriatal unit activity.

Animals↗
PubMed1980

A pilot study of the effects of methylphenidate on the vigilance-related EEG in hyperactivity.

Seven hyperactive children underwent a reaction time (RT) test requiring prolonged (15 min) vigilance, once while receiving methylphenidate and once without medication. EEG samples taken immediately before each RT measurement were subjected to power-spectral analysis. Compared to the off-medication condition, methylphenidate reduced the RT whilst paradoxically increasing EEG alpha power relative to higher and lower frequencies in 5 out of the 7 children. On this medication, the RT increased during the course of the task, and the relative EEG alpha power increased compared to other frequencies. Off medication, RTs showed an even greater increase with prolonged vigilance, but the accompanying EEG changes were the reverse of those seen on medication. The altered EEG power spectrum on methylphenidate appears closer to that of a normal EEG, and may be related to the improvement in specific attention produced by this drug in hyperactivity.

Alpha Rhythm↗
PubMed1975

Differential effects of D- and L-amphetamine and methylphenidate on rat striatal dopamine biosynthesis.

Methylphenidate and the optical isomers of amphetamine have differential effects, in vivo and in vitro on rat striatal synaptosomal dopamine (DA) biosynthesis. Whereas the systemic administration of D- or L-amphetamine produces a dose-dependent decrease in synaptosomal DA synthesis, with ED50's of 1.1 and 3.5 mg/kg, respectively, methylphenidate, at doses which produce comparable degrees of stereotypes behavior, has no effect on this measure of DA biosynthesis. In vitro, D- and L-amphetamine exhibit a three-fold difference in ED50's (1 times 10-minus 6 M and 3 times 10-minus 6 M, respectively) with respect to both activation of striatal synpatosomal DA synthesis, and to reversal of reserpine-induced inhibition of DA synthesis. In contrast, although in vitro methylphenidate can partially activate DA synthesis, it does not overcome the reserpeine-induced inhibition. The data are discussed in terms of the possible differential mechanisms by which these two types of stimulants may exert their effects on sterotypy.

Amphetamine↗