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PubMed1996

Separate and combined effects of methylphenidate and a behavioral intervention on disruptive behavior in children with mental retardation.

We investigated the separate and combined effects of a behavioral intervention and methylphenidate (Ritalin) on disruptive behavior and task engagement in 3 children with severe to profound mental retardation. The behavioral intervention involved differential reinforcement of appropriate behavior and guided compliance. All 3 children demonstrated decreased disruptive behavior and improved task engagement in response to the response to the behavioral intervention. Two of the 3 children demonstrated similar improvement in response to methylphenidate. Although both interventions were highly effective for these 2 participants, the relative efficacy of the interventions varied between the 2 children. There was no evidence of an additive or synergistic effect of the two interventions, but the high efficacy of each intervention alone limited our ability to detect such effects.

Aggression↗
PubMed1997

A preliminary analysis of interactive effects between common classroom contingencies and methylphenidate.

To assess the drug-behavior interaction effects with an 8-year-old boy wih attention deficit hyperactivity disorder, common classroom antecedent (e.g., seating arrangement) and consequent (e.g., peer prompts) stimuli were alternated within a school day while drug conditions (methylphenidate vs. placebo) were alternated across days. The results suggested that peer attention maintained disruptive behavior when methylphenidate was absent but not when it was present.

Attention Deficit Disorder with Hyperactivity↗
PubMed2005

The effects of methylphenidate on a functional analysis of disruptive behavior: a replication and extension.

In the present investigation, a functional analysis of the disruptive behavior of a 18-year-old man who had been diagnosed with attention deficit hyperactivity disorder and moderate mental retardation was conducted, both when he was taking methylphenidate and when he was not taking the medication. The results of this functional analysis demonstrated that the participant's disruptive behaviors were reinforced by access to attention only when he was not taking methylphenidate.

Adolescent↗
PubMed1966

Some effects of methylphenidate on stimulus control of ratio avoidance behavior in the rat.

After exposure to an avoidance schedule which included a warning signal, a rat was placed on a multiple schedule in which the first component was the same as before, i.e., a single response reset the response-shock interval, delaying shock, and the second component differed only in that four bar-presses were required to postpone shock. A fixed ratio requirement of four responses (FR 4) generated behavior resembling a fixed ratio requirement of one response (FR 1) since responding was controlled by the warning signal but more shocks were received. At a dosage of 2 mg/kg, methylphenidate given intraperitoneally decreased shock frequency during FR 4 periods while FR 1 behavior was not affected; at 4 mg/kg, stimulus control of avoidance responding was impaired during both components. Results at 4 mg/kg were partially confirmed by two animals exposed to an FR 4 avoidance schedule which included a warning signal but with different parameters. Response distributions showed that methylphenidate increased response rates in the absence of the warning signal, i.e., stimulus control of ratio-avoidance behavior was impaired although the increased response rates reduced shock frequency. One hour later responses again occurred more frequently during the signal than in its absence but shocks were less frequent than during control (non-drug) periods.

Animals↗
PubMed2005

Effects of methylphenidate and morphine on delay-discount functions obtained within sessions.

Four rats responded under a "self-control" procedure designed to obtain delay-discount functions within sessions. Each session consisted of seven blocks, with seven trials within each block. Each block consisted of two initial forced-choice trials followed by five free-choice trials. On choice trials, the rats could press either of two retractable levers. A press on one lever was followed by presentation of a smaller reinforcer (a single dipper presentation of a sucrose solution); a press on the other lever was followed by presentation of a larger reinforcer (four consecutive dipper presentations). The delay associated with the smaller reinforcer always was 0 s, whereas the signaled delay associated with the larger reinforcer increased across blocks (from 0 to 50 s). Under these conditions, the percentage of choices of the larger reinforcer decreased across blocks, and relatively reliable delay-discount functions were obtained within sessions. Doses of methylphenidate (1.0 to 17.0 mg/kg) and morphine (0.3 to 17.0 mg/kg) were then administered prior to selected sessions. Typically, intermediate doses of methylphenidate shifted the discount functions to the right (increased choices of the larger reinforcer). For 2 of the rats, this effect was pronounced; for the other 2 rats, this effect occurred after the range of delays for the larger reinforcer was decreased (0 to 20 s). On the other hand, in most cases morphine produced a slight leftward shift in the discount function (decreased choices of the larger reinforcer). The present procedure appears to be a useful and efficient method to characterize drug effects on an entire delay-discount function. As with many procedures used to study self-control choices, however, sources of control other than reinforcement delay and amount may have been operating in the present study, and these sources must be considered when interpreting drug effects.

Animals↗
PubMed2006

Methylphenidate transdermal system: In attention-deficit hyperactivity disorder in children.

The methylphenidate transdermal system (MTS) patch is approved by the US FDA for use in children aged 6-12 years with attention-deficit hyperactivity disorder (ADHD). This delivery system permits sustained absorption of the drug through the skin and into the bloodstream. Methylphenidate (MPH) is a CNS agent thought to act on dopamine and noradrenaline (norepinephrine) pathways and thereby blocks the reuptake of these neurotransmitters into the presynaptic neuron. In children with ADHD, MTS patches releasing MPH doses of 10-30 mg over a 9-hour period (12.5-37.5 cm2 patch size) is steadily absorbed, with mean peak plasma concentrations of d-MPH (20-46.5 ng/mL) reached in approximately 8 hours. In well controlled trials in children with ADHD, patients administered MTS patches releasing MPH 10-30 mg over approximately 9 hours showed significantly greater improvements in their ADHD symptoms than placebo recipients. MTS patches are generally well tolerated in paediatric patients with ADHD, with treatment-emergent events being similar in nature to those reported with oral MPH. The majority of adverse events were mild to moderate in intensity.

Administration, Cutaneous↗
PubMed1978

Activity analysis of operant behavior following methylphenidate administration.

13 male Long-Evans hooded rats were tested on a CRF-50 reinforcement schedule. Total response time as well as time and total activity responses away from the bar were significantly influenced by injections of methylphenidate (1.2 mg/kg I.P.). In general, the data supported previous findings of reduced response rate to the drug. However, methylphenidate (a CNS stimulant) increased activity that was not related to bar pressing. Analysis of activity response to drug should include total time and activity as well as operant rates.

Animals↗
PubMed1979

Effects of clinical dosage levels of methylphenidate on two-flash thresholds and perceptual motor performance in hyperactive children.

Three groups (ns = 10) of children (normals, hyperactives, hyperactives on medication) were administered eight perceptual-motor tasks. The normal controls were significantly superior in performance in comparison with the hyperactives taken off methylphenidate on three tasks but only superior on one task (Digit Symbol) when compared to hyperactives on methylphenidate. The hyperactives on medication were also significantly superior to the hyperactives not on medication on the Digit Symbol task.

Attention↗
PubMed1993

Reliability of global impressions for assessing methylphenidate effects in children with attention-deficit hyperactivity disorder.

Agreement between raters using global impressions to assess methylphenidate response was analyzed for children with Attention-Deficit Hyperactivity Disorder (ADHD) undergoing double-blind, placebo-controlled, crossover methylphenidate trials. Caregivers were more likely to disagree than agree when asked to rate the children as "better, same, or worse" during each day of the trial. Over-all agreement was 42.9%, only 9.6% above what would be expected based on chance alone. Further, none of the interrater reliability coefficients (Cohen's kappa) for the individual children were statistically significant.

Attention↗
PubMedDate not supplied

A double-blind controlled study of methylphenidate treatment in closed head injury.

Closed head injuries (CHI) may produce permanent, disabling changes in cognitive functions and social behaviour. Recent clinical case reports have suggested that stimulant medications may improve neurobehavioural functioning in CHI patients. In the present study, we evaluated the effects of methylphenidate (0.3 mg/kg b.i.d.) in 12 chronic CHI patients (14 to 108 months post-injury) using a double-blind, placebo-controlled, randomized, crossover design. Outcome measures consisted of cognitive tests of attention, learning and cognitive processing speed. In addition, a rating scale was completed by a close friend or relative to assess social behaviour. No significant differences were found between drug and placebo conditions on any of the neurobehavioural measures. These data do not support the clinical use of methylphenidate in the treatment of CHI patients.

Adult↗
PubMedDate not supplied

Controlled-release methylphenidate improves attention during on-road driving by adolescents with attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with a 3- to 4-fold increase in both driving-related accidents and associated injuries. Methylphenidate (MPH) is the most commonly prescribed psychostimulant medication for ADHD. It has been demonstrated to improve performance on a driving simulator. This study investigated whether a once-daily, long-acting, osmotic, controlled-release MPH formulation improves the driving performance of ADHD adolescents while driving their own car on an actual road segment. METHODS: Twelve ADHD-diagnosed male adolescent drivers (mean age, 17.8 years) prescribed a standard dose of 1.0 mg/kg (if they were not already taking methylphenidate) of controlled-release MPH participated in this repeated-measures crossover study. On 2 separate occasions (off/on medication randomized), participants drove a standard 16-mile road course incorporating rural, highway, and urban streets. A rater, blind to medication conditions, sat in the back seat and rated impulsive (eg, "cutting off" another driver) and inattentive (eg, drove past designated turn) driving errors. RESULTS: Impulsive driving errors were observed to occur rarely under both medication and no medication conditions. Inattentive driving errors were more common and were significantly reduced while the subject was on medication (4.6 versus 7.8; P <.01). The improvement in driving performance (change in number of errors recorded) from first to second testing was positively correlated with medication dosage (r = 0.60; P <.01). CONCLUSIONS: Once-daily controlled-release MPH improves real-life driving performance of adolescent males diagnosed with ADHD. In particular, it significantly reduces driving errors arising from inattention.

Adolescent↗
PubMed1975

Brain cholesterol XVIII: EFFECt of methylphenidate (Ritalin) on [U-14C] glucose and [2-3H] acetate incorporation.

The effect of a single injection of methylphenidate (Ritalin, 4 mg/kg) on precursor ([2-3H]acetate and [U-14C]glucose) incorporation into brain cholesterol was studied. The drug caused a steady decrease in the concentration of brain cholesterol during the 24-hr period examined. Incorporation studies during this time with [U-14C]glucose indicated higher than normal incorporation for all time periods studied. The most significant incorporation increases took place 2 and 4 hr after drug injection. Experiments using [2-3H]acetate as the sterol precursor gave incorporation values which tended (not significantly) to be lower than control values at 2 and 4 h. The values after 12 hr were less than normal, while the 24-hr group indicated an increase to or slightly higher than normal values. These data suggest that the pharmacological effect of methylphenidate may be due to lowering of brain cholesterol levels directly or on some more basic metabolic process leading to a decreased level of membrane sterols.

Acetates↗
PubMed2004

Dose-proportional pharmacokinetics of a methylphenidate extended-release capsule.

OBJECTIVE: To assess the dose-proportionality of the 10 mg, 20 mg and 30 mg methylphenidate extended-release (MPH ER) capsule formulations in healthy adults. MATERIALS: Metadate CD (methylphenidate HCl, USP) extended-release capsules (10, 20 and 30 mg) were obtained from Celltech Manufacturing Inc. (Rochester, NY, USA). METHODS: This was a single-center, single-dose, fasted, randomized, open-label, 3-way crossover study with a 1-week washout period between doses, in 24 healthy male and female subjects, aged 21-40 years. MPH plasma concentration-time data were used to calculate the pharmacokinetic parameters for each treatment. The 20 mg capsule, the first FDA-approved dosage strength, was used as reference treatment. RESULTS: Twenty-three subjects completed all 3 study periods. Regardless of the dose, MPH ER capsules exhibited similar PK profiles as evidenced by a biphasic absorption profile, consisting of a sharp initial increase followed by a second increase in MPH plasma levels, all occurring at the same times. All 90% confidence intervals for the 10:20 mg and 30:20 mg dose-normalized geometric mean ratios were within the 80-125% FDA limits for bioequivalence. This was true for Cmax (maximum observed concentration), AUC(0-last) (area under the plasma concentration curve from time 0 to the last measurable time point) and AUC(0-inf) (area under the plasma concentration curve from time 0 to infinity). Adverse events were mild and the number and types of adverse events experienced by subjects did not differ among the 3 dosages. CONCLUSION: Data collected from this study demonstrate the dose proportionality of the new 10 mg and 30 mg dosage strengths of MPH ER capsules with the 20 mg capsule. The availability and predictability of these dosage strengths should facilitate dose titration of ADHD patients.

Administration, Oral↗
PubMed1975

Observations on effects of a central stimulant drug (methylphenidate) in children with hyperactive behavior.

Ninety-eight hyperactive children, ages 6 to 12 years, have been treated with methylphenidate or placebo under double-blind conditions. Only one of the 48 children receiving placebo (2%) was judged to be a drug success. Seventy-nine percent of the 94 children receiving methylphenidate were judged to be drug success at the end of the 16-week trial period. A wide range of dosage (0.2 to 1.9 mg/kg) was required for optimum drug effects. Drug failures were due either to appearance of withdrawn, apathetic behavior in the child (6 cases) or lack of evidence of drug effectiveness (14 cases). Overweight children did not respond well to medication even though milligram per kilogram dosage was equivalent to that in children who were categorized as drug successes. The most dramatic successes were seen in children who might be characterized as exhibiting "developmental hyperactivity," i.e., hyperactivity in the absence of other evidence of neurological or emotional disturbances. We conclude that a trial of stimulant drugs is clearly indicated in hyperactive children manifesting significant impairment of educational and social progress. Dosage adjustment and judgement of drug success or failure require regular reports from teachers and parents.

Birth Weight↗
PubMed1975

The influences of methylphenidate on heart rate and behavioral measures of attention in hyperactive children.

Reaction-time performance and heart-rate responses associated with attention were used to assess the hyperactive child's attentional deficit and his response to methylphenidate. Attentional deficits shown by long response latencies were reflected in heart-rate responses theoretically incompatible with sustained attention. Subjects exhibiting the greatest attentional deficit displayed the most favorable response to methylphenidate in both reaction-time performance and physiological measures. However, subjects who showed the greatest improvement in social behavior were those who showed the least improvement in reaction-time performance.

Attention↗
PubMedDate not supplied

[A pilot study of methylphenidate and parent training in the treatment of children with attention-deficit hiperactivity disorder].

OBJECTIVE: This study gives information about a parent training program and a clinical trial with a stimulant drug (methylphenidate) to reduce the symptoms of attention deficit hiperactivity disorder (ADHD) in a group of children in Venezuela. PATIENTS AND METHODS: 24 children, aged between 6 and 10 years and diagnosed as having ADHD, identified in ADHD screening days, were randomly assigned to two groups of treatment: parent training and a stimulant drug (methylphenidate). RESULTS: Both groups showed an improvement in their symptoms, to different degrees, after treatment. The differences were statistically significant, as evaluated by their parents, regarding the symptoms of inattention, hyperactivity and impulsivity. The teachers observed a significant improvement for the medication group with respect to the symptoms of hyperactivity and impulsivity, but no change in the inattention, whilst in the parent training group there was only significant difference in the ADHD index. There was no difference in the effectiveness of the two types of treatment. CONCLUSIONS: When the two programs of treatment were compared it was observed that both parent training and psychostimulant medication were effective in reducing the symptoms of ADHD. Although there was no difference in the effectiveness of the two programs, there was a tendency for medication to be more effective

Attention Deficit Disorder with Hyperactivity↗
PubMed1991

Effects of high methylphenidate doses on the cognitive performance of hyperactive children.

It has been reported that high doses of methylphenidate, required for optimal clinical efficacy in the treatment of hyperactive children impair cognitive performance. This study examines the effects of a four week placebo trial of high doses of methylphenidate on cognitive performance in hyperactive 81 children. In addition, effects of medication over more extended time (12 weeks) are examined. Dosage after 4 weeks averaged 1.78 mg/kg, and after 12 weeks 1.66 mg/kg. No significant decrements in cognitive performance were obtained on any measure which included tests of: IQ, reading, spelling, arithmetic, non-verbal reasoning, graphomotor performance, visual memory, and sustained attention. The results argue for titrating medication to obtain maximum behavioral improvement. (Tab. 2, Ref. 15.)

Attention Deficit Disorder with Hyperactivity↗
PubMed1991

Attention deficit disorder with and without hyperactivity: clinical response to three dose levels of methylphenidate.

The response of 23 children with attention deficit disorder (ADD) with hyperactivity (+H) and 17 children with ADD without hyperactivity (-H) to three doses of methylphenidate (5, 10, and 15 mg twice a day) was evaluated in a triple-blind, placebo-controlled cross-over design using parent and teacher ratings of behavior, laboratory tests of ADD symptoms, and behavioral observations during academic performance. Results indicated that the children with ADD+H were rated as having more pervasive behavioral problems at home and more pervasive and severe conduct problems at school than the children with ADD-H. Laboratory tests found the children with ADD+H to be impaired in behavioral inhibition and vigilance whereas children with ADD-H were more impaired in the consistent retrieval of verbally learned material Drug effects were noted on the parent and teacher ratings and on most laboratory measures, with all three doses typically producing significant changes but rarely differing among themselves in effectiveness. The groups were not found to differ significantly on any measures in their response to methylphenidate. However, more children with ADD-H were clinically judged as having either no clinical response (24%) or responding best to the low dose (35%) of medication. In contrast, most ADD+H (95%) children were judged to be positive responders and most were recommended to receive the moderate to high dose (71%).

Attention Deficit Disorder with Hyperactivity↗