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PubMed1989

Comparative effects of methylphenidate on ADD girls and ADD boys.

The effects of 0.3 mg/kg methylphenidate were compared for 12 ADD boys and 12 ADD girls participating in a summer treatment program for children with behavior and/or learning problems. Previous investigations have suggested that ADD girls may differ from ADD boys in some important respects. No information exists regarding whether the effects of the most common treatment for these children, methylphenidate, has comparable effects on boys and girls. The boys and girls were matched for age and IQ. The results revealed equivalent and beneficial effects of methylphenidate for both boys and girls. Methylphenidate therefore would appear to be as useful a treatment for ADD girls as for ADD boys.

Attention Deficit Disorder with Hyperactivity↗
PubMed1990

Methylphenidate in aggressive-hyperactive boys: I. Effects on peer aggression in public school settings.

One of the least documented "known" effects of methylphenidate in hyperactive children is the suppression of peer aggression. In this study, 11 aggressive-hyperactive children received a low (0.3 mg/kg) and moderate (0.6 mg/kg) dose of methylphenidate and placebo for 2 weeks each under double-blind conditions. Children were observed in public school settings during classroom seatwork activities, lunch, and recess. Results showed that methylphenidate suppressed nonphysical aggression (p = 0.06) in the classroom, and a moderate dose decreased physical aggression (p less than 0.01) and verbal aggression (p = 0.07) on the playground. The effect on the rate of appropriate social interaction was variable. The majority of subjects exhibited either the same or higher levels of appropriate social interaction on the 0.6 mg/kg dose compared with placebo. In the classroom, both doses of methylphenidate also resulted in reduced levels of motor movement, off-task behavior, noncompliance, and disruptiveness. Teacher ratings of hyperactivity and conduct problem symptoms revealed drug effects, whereas parallel parent instruments did not.

Aggression↗
PubMed1991

Clinical effects of methylphenidate and thioridazine in intellectually subaverage children.

Thirty children with subaverage IQs and psychiatric diagnoses of attention deficit disorder and/or or conduct disorder took part in a double-blind study of placebo, methylphenidate, and thioridazine, which were given for 3 weeks each. The results showed a consistent and highly significant effect of methylphenidate in reducing teacher ratings of problem behavior. Parent ratings showed no behavioral effects for the group as a whole. An attentional model of stimulant drug response was used to divide subjects according to a cognitive maturity domain presumed to reflect selective attention. When divided according to breadth of attention, mental age, and IQ level, higher functioning subjects were found to show a generally favorable response to methylphenidate on both teacher and parent rating scales, whereas children of low functional level typically showed an adverse or indifferent response. The present data suggest that mental age and IQ may be important determinants of drug response; below a given level, there was a greatly reduced likelihood of responding positively. Clinical response to thioridazine was substantially less than the response to methylphenidate, with significant improvements confined to conduct and hyperactivity problems on teacher ratings.

Adolescent↗
PubMed1997

Children with ADHD and tic disorder and their classmates: behavioral normalization with methylphenidate.

OBJECTIVES: To examine behavioral differences between children with attention-deficit hyperactivity disorder (ADHD) and tics and their peers and the extent to which methylphenidate (0.1, 0.3, and 0.5 mg/kg) normalized the behavior of probands and indirectly influenced the behavior of peers (treatment spillover). METHOD: Thirty-four prepubertal children with ADHD and chronic tic disorder (who were participating in a double-blind, placebo-controlled methylphenidate evaluation) and their peers were observed for approximately 20 hours in the school setting (classroom seatwork activities, lunchroom, and playground). RESULTS: Children with ADHD and tics were more inattentive and more disruptive in the classroom and more aggressive in all school settings than their peers. Although treatment with methylphenidate made probands less easily distinguished from their peers (normalization), many children still scored in the deviant range for at least one ADHD behavior when receiving the 0.5-mg/kg dose. There was little evidence that peer behavior improved as a function of the proband's dose of medication. CONCLUSIONS: Although conventional doses of methylphenidate produced dramatic clinical improvement in ADHD-related behavior, complete behavioral normalization is often not attained.

Analysis of Variance↗
PubMed1999

Association of the dopamine transporter gene (DAT1) with poor methylphenidate response.

OBJECTIVE: This study attempted to relate the alleles of the D2 (DRD2), D4 (DRD4), and dopamine transporter (DAT1) genes to the behavioral outcome of methylphenidate therapy. METHOD: African-American children with attention-deficit hyperactivity disorder were treated with methylphenidate in doses not in excess of 60 mg/day. The dosage was increased until behavioral change was achieved, using a decrement in scores of less than or equal to 1 on a commonly used rating scale or until the maximum tolerated dose was achieved. Blood samples were obtained at that point, and genotypes for polymorphism at the respective genes were identified. RESULTS: Genotypes were then tested by chi 2 to assess the significance of any association with drug response. Only the dopamine transporter gene was found to be significant. Homozygosity of the 10-repeat allele was found to characterize nonresponse to methylphenidate therapy (p = .008). CONCLUSIONS: While the results suggest that alleles of the dopamine transporter gene play a role in methylphenidate response, replication in additional studies is needed.

Alleles↗
PubMed2002

Methylphenidate bioavailability in adults when an extended-release multiparticulate formulation is administered sprinkled on food or as an intact capsule.

OBJECTIVE: To determine the single-dose bioavailability of 20-mg Metadate CD (methylphenidate HCI, USP) Extended-Release Capsules sprinkled onto 1 level tablespoon (15 mL) of applesauce relative to an intact capsule under fasted conditions in healthy adults. METHOD: This was a single-center, open-label, single-dose, randomized, two-way crossover study with a 6-day washout period between doses, in healthy male and female subjects (N= 26), aged 21-40 years. Plasma concentration-time data for methylphenidate were used to calculate the pharmacokinetic parameters for each treatment. RESULTS: The pharmacokinetic profile for Metadate CD exhibited biphasic release characteristics with a sharp initial slope and a second rising portion. For Cmax (maximum observed concentration), AUC(0-infinity) (area under the plasma concentration curve from time 0 to infinity) and AUC(0-infinity) (area under the plasma concentration curve from time 0 to the last measurable time point), the geometric least squares mean ratios and 90% confidence intervals were within the 80% to 125% confidence interval for bioequivalence. Adverse events were similar to those reported for methylphenidate. CONCLUSIONS: The bioavailability of methylphenidate was not altered when Metadate CD capsules were administered by sprinkling their contents onto a small amount of applesauce.

Adult↗
PubMed2002

Anxiety and depression symptoms and response to methylphenidate in children with attention-deficit hyperactivity disorder and tic disorder.

This study examined response to methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD) and chronic multiple tic disorder. The primary goal was to determine if children with anxiety or depression symptoms showed a less favorable response to treatment. Subjects were 38 prepubertal children who participated in an 8-week, double-blind, placebo-controlled, methylphenidate crossover evaluation. Treatment effects were assessed with direct observations of child behavior in public school and clinic settings; rating scales completed by parents, teachers, and clinicians; and laboratory analogue tasks. There was little evidence (group data) that children with anxiety or depression symptoms responded in a clinically different manner to methylphenidate than youngsters who did not exhibit these symptoms, particularly in school observations of the core features of ADHD. Seeming differences between children with and without comorbid anxiety or depression symptoms and drug response are likely explained by differences in pretreatment levels of negativistic behaviors (i.e., symptoms of oppositional defiant disorder or conduct disorder). Methylphenidate appears to be effective for the management of ADHD behaviors in children with mild to moderate anxiety or depression symptoms; nevertheless, much research remains to be performed in this area.

Adolescent↗
PubMed2004

Association of norepinephrine transporter gene with methylphenidate response.

OBJECTIVE: This study aimed to explore the association between alleles of the norepinephrine transporter gene and the methylphenidate response. METHOD: Chinese Han youths with attention-deficit/hyperactivity disorder recruited in the Outpatient Department of the Institute of Mental Health from 2001 to 2004 were treated with methylphenidate in doses of 0.45 to 0.60 mg/kg per day. Behavior changes were measured by the ADHD Rating Scale-IV when optimal doses were reached. The single-nucleotide polymorphic allele of norepinephrine transporter gene G1287A was used as the genetic marker, and the genotypes were identified by restriction fragment length polymorphism analysis. RESULTS: A significant association was found between norepinephrine transporter gene G1287A genotypes and response to methylphenidate for hyperactive-impulsive subscale scores (mean score reduction was 7.15 and 6.94 for G/G and G/A genotype, respectively, and 2.13 for A/A; p = .012) but not inattentive scores. CONCLUSIONS: These findings suggest an association between the G1287A polymorphism of the norepinephrine transporter gene and variation in methylphenidate response. Further work is needed to confirm this finding and to assess its generalization to other ethnic groups.

Adolescent↗
PubMed2005

Comparison of risperidone and methylphenidate for reducing ADHD symptoms in children and adolescents with moderate mental retardation.

OBJECTIVE: To evaluate the short-term efficacy and tolerability of risperidone and methylphenidate for reducing symptoms related to attention-deficit/hyperactivity disorder (ADHD) in children and adolescents with moderate mental retardation. METHOD: In a 4-week, single-blind, parallel-group trial, 45 subjects with moderate mental retardation and ADHD were randomized to risperidone or methylphenidate and assessed using objective rating scales for efficacy (SNAP [Swanson, Nolan, and Pelham]-IV and Nisonger Child Behavior Rating Form) and side effects (Barkley's Side Effects Rating Scale and Udvalg for Kliniske Undersøgelser). RESULTS: Both groups had reduced ADHD symptoms during the trial. Repeated-measures analysis of variance yielded a significant effect for the interaction between time and group assignment in SNAP-IV Total scores (F = 3.26; p = .05), suggesting a more pronounced effect for risperidone. There was a significant weight reduction in the methylphenidate group and a weight gain in the risperidone group. CONCLUSIONS: Our findings suggest that risperidone is associated with greater reductions in ADHD Total score than methylphenidate in children with moderate mental retardation and ADHD. Comorbidity and the side effects profile might be of importance in choosing between the medications, although it is usually prudent to try stimulants before antipsychotics in such children.

Adolescent↗
PubMed2006

Methylphenidate-enhanced antidepressant response to citalopram in the elderly: a double-blind, placebo-controlled pilot trial.

OBJECTIVE: The authors evaluated the potential of methylphenidate to accelerate and enhance antidepressant response to citalopram in elderly depressed patients. METHODS: Sixteen outpatients with major depression were treated in a 10-week double-blind trial. Response was defined as a score on the Hamilton Depression Rating Scale (24-item) of less than 10. RESULTS: An accelerated response was observed by week 3 in five subjects receiving citalopram (CIT)+methylphenidate (MPH) and in none of those receiving CIT+placebo (PBO). Subjects receiving citalopram and methylphenidate showed a significant improvement in depressive symptoms compared with those on citalopram and placebo. CONCLUSION: Combined treatment with citalopram and methylphenidate appears to be a viable strategy for accelerating and enhancing antidepressant response in elderly depressed patients limited by tolerability and safety.

Aged↗
PubMed2004

Effects of methylphenidate on attention deficits after traumatic brain injury: a multidimensional, randomized, controlled trial.

OBJECTIVE: To evaluate the effects of methylphenidate on a variety of aspects of attention, ranging from laboratory-based impairment measures to caregiver ratings and work productivity, in individuals after traumatic brain injury. DESIGN: A total of 34 adults with moderate to severe traumatic brain injury and attention complaints in the postacute phase of recovery were enrolled in a 6-wk, double-blind, placebo-controlled, repeated crossover study of methylphenidate, administered in a dose of 0.3 mg/kg/dose, twice a day. A wide range of attentional measures was gathered weekly, including computerized and paper-and-pencil tests of attention, videotaped records of individual work in a distracting environment, real-time observational scoring of attentiveness in a classroom environment, and caregiver and clinician rating scales of attentiveness. Participants also attempted to guess their drug condition each week. Data from the first ten participants were used for pilot purposes, to develop attentional factors for composite scoring, and to identify attentional dimensions suggestive of a treatment effect for independent replication. The remaining 24 participants' results were used to confirm potential treatment effects seen in the pilot sample, using Wilcoxon's signed-ranks test on composite factor scores and individual variables. RESULTS: A total of 54 dependent variables were reduced to 13 composite factors and 13 remaining individual variables. Of the 13 attentional factors, five showed suggestive treatment effects in the pilot sample. Of these, three showed statistically significant treatment effects in the replication sample: speed of information processing (effect sizes, -0.06 to 0.48; P < 0.001), attentiveness during individual work tasks (effect sizes, 0.15-0.62; P = 0.01), and caregiver ratings of attention (effect sizes, 0.44-0.50; P = 0.01). Of the individual variables, four showed suggestive treatment effects in the pilot sample, but only one showed significant treatment effects in the replication sample: reaction time before errors in the Sustained Attention to Response Task (effect size, 0.20; P = 0.03). No treatment-related improvement was seen in divided attention, sustained attention, or susceptibility to distraction. None of the variables showed suggestive or definite negative treatment effects. Effect sizes for those performance measures positively affected by methylphenidate were in the small to medium range and included both impairment and activity level measures. Improvements in processing speed did not seem to come at the expense of accuracy. CONCLUSIONS: Methylphenidate, at 0.3 mg/kg/dose, given twice a day to individuals with attentional complaints after traumatic brain injury, seems to have clinically significant positive effects on speed of processing, caregiver ratings of attention, and some aspects of on-task behavior in naturalistic tasks. Further research is needed to identify the optimal dose and to extend these findings to less carefully selected individuals.

Adult↗
PubMedDate not supplied

The comparative efficacy of antecedent exercise and methylphenidate: a single-case randomized trial.

This study evaluated the comparative efficacy of antecedent exercise, methylphenidate (Ritalin), and placebo in the reduction of hyperactive behaviour in a pre-school boy. A single-case alternating treatments experimental design was employed for a total of 82 days. The dependent variable was the Conners' Abbreviated Symptom Questionnaire. Antecedent exercise failed to reduce hyperactive behaviour. Methylphenidate produced significantly less hyperactive behaviour than both placebo and antecedent exercise (P = 0.0238). Neither methylphenidate nor antecedent exercise produced notable side-effects as measured by the Monitoring of Side-Effects Scale. These data add to a sparse literature on the effects of antecedent exercise and methylphenidate amongst pre-school children.

Attention Deficit Disorder with Hyperactivity↗
PubMed2004

Methylphenidate improves working memory and set-shifting in AD/HD: relationships to baseline memory capacity.

OBJECTIVE: Catecholamine stimulant drugs are highly efficacious treatments for attention deficit/ hyperactivity disorders (AD/HD). Catecholamine modulation in humans influences performance of numerous cognitive tasks, including tests of attention and working memory (WM). Clear delineation of the effects of methylphenidate upon such cognitive functions in AD/HD would enhance understanding of the effects of drug treatment. METHOD: Here we present a double-blind, placebo-controlled study of the cognitive effects of an acute dose of methylphenidate (c. .5 mg/kg) in 14 boys aged 10.86 (+/- 1.19) years meeting criteria for DSM-IV AD/HD. Current behaviour was ascertained using Conners' teacher and parent self-report questionnaires and IQ was tested using sub-tests from WISC-III-UK. Tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were selected to assess visuo-spatial recognition memory, spatial WM, planning, visual-search and attentional-set shifting. RESULTS: Methylphenidate improved spatial WM, attentional-set shifting and visual-search task performance. Correlational analyses suggested possible relationships between WM capacity and spatial WM performance improvement. Also, poor performance on the attentional-set shifting task on placebo was associated with increased errors on the spatial WM task on placebo. CONCLUSIONS: Methylphenidate may selectively improve both underlying cognitive difficulties in tasks dependent on intact fronto-striatal structures, and clinical symptoms of AD/HD. Pre-treatment measures may have some predictive value in determining individual differences in drug response.

Adolescent↗
PubMed1990

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.

Arousal↗
PubMed2006

Comparison of monoamine and corticosterone levels 24 h following (+)methamphetamine, (+/-)3,4-methylenedioxymethamphetamine, cocaine, (+)fenfluramine or (+/-)methylphenidate administration in the neonatal rat.

We have previously shown that neonatal administration of (+/-)3,4-methylenedioxymethamphetamine and (+)fenfluramine produce deficits in spatial and path integration learning, whereas (+)methamphetamine causes deficits in spatial learning. Conversely, cocaine and (+/-)methylphenidate have no effect on either form of learning following neonatal administration. The purpose of the present study was to determine whether corticosterone and/or monoamine levels were changed following subcutaneous administration of 10 mg/kg (+)methamphetamine, (+/-)3,4-methylenedioxymethamphetamine, (+)fenfluramine, (+/-)methylphenidate or cocaine every 2 h (total of four injections) on postnatal day 11. Twenty-four hours after the first dose, plasma, striatum and hippocampus were collected. Corticosterone levels were increased in methamphetamine-, fenfluramine-, methylenedioxymethamphetamine- and methylphenidate-treated rats relative to levels in saline-treated rats, whereas cocaine-treated rats were unaffected. In the striatum and hippocampus, serotonin and 5-hydroxyindolacetic acid were reduced in animals treated with methylenedioxymethamphetamine or fenfluramine, compared with levels in saline controls. Dopamine levels were not changed by any of the drugs, although 3,4-dihydroxyphenylacetic acid was decreased following methylenedioxymethamphetamine or methamphetamine. Minimal effects were seen in neurotransmitter levels following injection of cocaine or methylphenidate. These data suggest that drugs that affect corticosterone and hippocampal serotonin are associated with both spatial learning and path integration deficits, and those that affect corticosterone and 3,4-dihydroxyphenylacetic acid are associated with spatial learning deficits only.

3,4-Methylenedioxyamphetamine↗
PubMed2002

Methylphenidate-evoked potentiation of extracellular dopamine in the brain of adolescents with premature birth: correlation with attentional deficit.

Perinatal anoxia/ischemia or premature birth increases the risk of developing attention deficit/hyperactivity disorder (ADHD). Brain imaging studies of idopathic ADHD reveal elevated dopamine transporter density in striatum of patients, predicting abnormal response to a challenge with methylphenidate in this population. We hypothesized that the severity of attention deficit in adolescents should correlate with the sensitivity to psychostimulant-evoked dopamine release. To test this hypothesis, we investigated six adolescent subjects (mean age 14.2 +/- 2.4 yr) with documented birth trauma and/or low birth weight and a diagnosis of ADHD. Using positron emission tomography (PET), we measured the relative binding of [(11)C]raclopride to dopamine receptors in striatum, first in the baseline condition and again after methylphenidate challenge at a therapeutic dose for ADHD (0.3 mg/kg, p.o.) in order to map the altered dopamine release evoked by the psychostimulant challenge. Neuropsychological measurements of impulsivity and inattention were also performed. We found a positive correlation between commission errors and the methylphenidate-evoked decrease in [(11)C]raclopride binding, thought to reflect the balance of dopamine release and reuptake. The greater the decline in the [(11)C]raclopride binding, the greater the ability of methylphenidate to block the reuptake of dopamine. As the ability to block the reuptake depends on the relative dopamine concentration, the result suggests that the impulsivity in these adolescents is associated with abnormally low extracellular dopamine concentration.

Adolescent↗
PubMed1971

Disruption of yeast membranes by methylphenidate.

Methylphenidate blocked sorbose uptake and loss by yeast spheroplasts and, at higher concentrations (30 mm), disrupted the spheroplasts. At still higher concentrations (70 mm), methylphenidate also ruptured the membranes of whole yeast cells; sorbose and materials absorbing at 280 nm were lost from the cells, and methylene blue stained them. Intracellular structures were extensively affected, as shown by electron micrographs, and were more sensitive to disruption by methylphenidate than the external membrane. N-ethylmaleimide and Ca(2+) enhanced the rupture of external membranes by methylphenidate.

Buffers↗
PubMed2005

Height, weight, IGF-I, IGFBP-3 and thyroid functions in prepubertal children with attention deficit hyperactivity disorder: effect of methylphenidate treatment.

OBJECTIVE: To investigate if there are any disease-related or methylphenidate-induced aberrations in growth parameters, growth hormone insulin-like growth factor (IGF)-I, IGFBP-3 axis and the thyroid function tests in children with attention deficit hyperactivity disorder (ADHD). METHODS: Newly diagnosed and untreated prepubertal children with ADHD were longitudinally followed before and approximately every 4 months after methylphenidate treatment for up to 16 months. Height SDS, weight SDS, BMI SDS, serum GH, IGF-I, IGFBP-3, T4, free T4, T3, and TSH were measured at each visit. RESULTS: All of the examined parameters were within normal limits for age before treatment. Methylphenidate treatment did not significantly affect SDS of height, weight, BMI, IGF-I and IGFBP-3 in the long run. Serum T4 and free T4 levels showed modest reductions within normal limits in a time-dependent manner. CONCLUSIONS: Prepubertal children with ADHD had normal height, weight, BMI, serum IGF-I and IGFBP-3 and thyroid functions. Methylphenidate treatment had no sustained effects on growth parameters, IGF-I and IGFBP-3 during the follow-up period of this study. However, it caused a mild decrease in total and free T4 which may warrant further monitoring.

Attention Deficit Disorder with Hyperactivity↗