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PubMed1987

Stereoselective disposition of methylphenidate in children with attention-deficit disorder.

Six boys with attention-deficit disorder were given single doses (5 or 10 mg) of dl-threo-methylphenidate (Ritalin, Ciba-Geigy, Basel, Switzerland). Plasma samples through 8 hr were analyzed by capillary column gas chromatography with electron capture detection. Enantiomers were separated and measured as heptafluorobutyryl-1-prolyl derivatives. The method was sensitive to 0.1 ng of enantiomer per ml of plasma. The plasma levels of d-methylphenidate were at least 5-fold greater than those of the l-enantiomer in the profiles of all six children. Mean areas under the plasma level-time curves were 24.48 +/- 7.62 ng/hr/ml for d-methylphenidate and 3.77 +/- 1.04 ng/hr/ml for l-methylphenidate. There was appreciable intersubject variation in plasma level maxima and times to maximal plasma levels of each enantiomer.

Adolescent↗
PubMed1986

Components of attention, methylphenidate dosage, and blood levels in children with attention deficit disorder.

In this study we analyzed some of the cognitive components that may constitute attention deficit disorder. It consisted of a double-blind, drug-placebo study of 12 children being treated with three doses of methylphenidate and placebo. Results of an attentional test battery, teacher and parent ratings, and blood levels of methylphenidate are reported. In general, performance was best with 0.6 mg/kg of methylphenidate (the highest dose tested) and worst with placebo. It is argued that no single test provides a complete assessment of attentional deficits and that methylphenidate can improve performance by affecting the allocation of cognitive resources to a task.

Adolescent↗
PubMed1979

Effects of methylphenidate on hyperactive children's ability to sustain attention.

The purposes of this study were to investigate the attentional characteristics of hyperactive children, the relationship of subjective and objective measures of these characteristics, and the effects of methylphenidate on these measures of attention. Forty-five hyperactive children, ages 6 to 10 years, were entered into an 18-week study of the effects of methylphenidate (Ritalin) on attention. Measures included rating scales completed by teachers and parents and a vigilance task. All measures reflected significant changes during the period of investigation. Attention and behavior were significantly improved under drug conditions and significantly worsened when methylphenidate was discontinued. However, only performance on the objective measure returned to predrug levels; final off-drug parent and teacher ratings remained improved over initial reports. Parent ratings of behavior, and specifically of children's ability to attend, were unrelated to equivalent teacher ratings. Teachers' ratings of attention correlated significantly with performance on the vigilance task, discriminated between on-drug and off-drug conditions, and discriminated between children who obtained normal or near normal predrug scores on the objective measure and those who performed poorly on this measure. Methylphenidate improved attentional performance for children who had poor predrug scores on the vigilance task, but did not produce a statistically significant change on the scores of children with normal predrug performance.

Attention↗
PubMed1979

A preliminary study of the effect of pyridoxine administration in a subgroup of hyperkinetic children: a double-blind crossover comparison with methylphenidate.

A small sample of six patients with the putative "hyperkinetic syndrome" participated in a research protocol comparing administration of pyridoxine, methylphenidate, and placeboes. The children had had low whole blood serotonin levels and a history of previous responsiveness to methylphenidate. The results of the double-blind clinical evaluation showed trends suggesting that both pyridoxine and methylphenidate were more effective than placebo in suppressing the symptoms of hyperkinesis. Pyridoxine elevated whole-blood serotonin levels, methylphenidate did not. Clinical and laboratory evidence indicated that the pyridoxine effects persisted after the 3-week period when the vitamin had been given in this experimental design.

Adolescent↗
PubMed1984

Gas-chromatographic quantification of methylphenidate in plasma with use of solid-phase extraction and nitrogen-sensitive detection.

The gas-chromatographic assay for methylphenidate described here involves isolation by solid-phase extraction and quantification by thermionic nitrogen-phosphorus detection. Methylphenidate and the internal standard, ethylphenidate, are extracted from plasma by partition onto C2 reversed-phase packing. Methylphenidate and ethylphenidate are eluted, dried, derivatized with trifluoroacetic anhydride, and gas-chromatographed, with nitrogen-sensitive detection. The standard curve for the assay is linear in the range 5-100 micrograms/L. The within-run CV is less than 4%, the between-run CV less than 6%. Mean analytical recovery of methylphenidate was greater than 90%. The smallest measurable concentration is 2 micrograms/L. The sensitivity, reproducibility, and economy of this assay make it suitable for clinical monitoring and pharmacokinetic studies.

Child↗
PubMed1983

Methylphenidate hydrochloride given with or before breakfast: I. Behavioral, cognitive, and electrophysiologic effects.

Methylphenidate HCl (Ritalin) is usually given for the treatment of hyperactivity or attention deficit disorder (ADD) at 30 minutes to one hour before meals. This schedule is based on the assumption that, when taken with meals, its absorption or metabolism is altered. However, no behavioral or pharmacologic data exist to support this recommendation. Eleven patients with attention deficit disorder were tested to evaluate this hypothesis using a double-blind crossover design (methylphenidate with or before breakfast) with a placebo control condition. Parents' ratings, performance on a paired-associate learning test, and cortical auditory-evoked potentials were measured. All of these measurements showed clear differences between the placebo condition and conditions when medication was given. However, none of the measurements showed a significant difference between the conditions when methylphenidate was given with breakfast and the condition when methylphenidate was given 30 minutes before breakfast.

Analysis of Variance↗
PubMed1980

Comparison of sustained-release and standard methylphenidate in the treatment of minimal brain dysfunction.

In a randomized, double-blind study the effects of the standard form of methylphenidate (10 mg given twice daily) were compared to those of a sustained-release form of methylphenidate (20 mg given once daily) in outpatient children with minimal brain dysfunction. The study was 2 weeks in duration and involved 30 children. Psychometric tests completed by the children, as well as physician, teacher and parent questionnaires were used to measure drug effects. Comparisons between the 2 methylphenidate treatment groups showed no consistent significant changes which could be deemed clinically favorable for one group over the other nor were there significant improvements over pretreatment measurements for either group. Adverse reactions--headache, hyperactivity, restlessness were reported by 5 patients receiving the sustained-release and 2 receiving the standard methylphenidate.

Adolescent↗
PubMed1995

School observations of children with attention-deficit hyperactivity disorder and comorbid tic disorder: effects of methylphenidate treatment.

Although the findings from recent controlled studies suggest that methylphenidate is a safe and effective treatment for many children with attention-deficit hyperactivity disorder (ADHD) and comorbid tic disorder, relatively little is known about drug effects on school behavior. Thirty-four prepubertal children with ADHD and tic disorder received placebo and 3 doses of methylphenidate (0.1, 0.3, and 0.5 mg/kg) twice daily for 2 weeks each under double-blind conditions. Treatment effects were assessed using direct observations of child behavior in classroom, lunchroom, and playground settings. Treatment with methylphenidate resulted in marked reductions of hyperactive, disruptive, and aggressive behavior, which was evident even for the 0.1 mg/kg dose. There were no "nonresponders." The only observed changes in tics were a small but statistically significant increase in the frequency of motor tics (classroom, 0.1 mg/kg dose) and a tendency for fewer vocal tics (lunchroom). However, these changes in motor tic frequency were not perceived by care providers as a worsening in the severity of the child's tic disorder. Most dose-response relationships were linear, but the mean (operationally defined) minimal effective dose (MED) was 0.3 mg/kg. In summary, the findings support the conclusions that (1) methylphenidate suppresses ADHD behaviors in the classroom and aggressive behavior in all settings and that (2) a low dose may have a weak exacerbation effect on the frequency of motor tics; but, in general, the majority of youngsters do not experience clinically significant tic worsening with a MED.

Aggression↗
PubMed1975

Individual responses to methylphenidate and caffeine in children with minimal brain dysfunction.

Eight children with minimal brain dysfunction were studied for their individual responses to two stimulant medications--methylphenidate hydrochloride and caffeine citrate. Four types of behavioural responses were observed in the double-blind crossover experiment: four children responded favourably to both psychostimulants, one responded to methylphenidate alone and two responded to the placebo. The behaviour of one child deteriorated while he was taking methylphenidate and caffeine. In general, methylphenidate was superior to caffeine in diminishing hyperactive and aggressive behaviour. It is apparent that such stimulant medication exerts its therapeutic effects in these two areas primarily and would therefore be useful as one aspect of a complete treatment program for children with this syndrome.

Attention Deficit Disorder with Hyperactivity↗
PubMed1993

d-Amphetamine versus methylphenidate effects in depressed inpatients.

BACKGROUND: Both d-amphetamine and methylphenidate cause similar behavioral and subjective effects and can relieve depressive symptoms in some patients. However, the neurochemical effects of d-amphetamine and methylphenidate are distinct, and clinical experience suggests that individual depressed patients may respond dissimilarly to each stimulant. METHOD: d-Amphetamine and methylphenidate were administered sequentially to 18 DSM-III diagnosed depressed inpatients on consecutive days, and the acute effects were measured by a variety of instruments. RESULTS: Although many patients were acutely better after taking one drug or the other, as assessed by Hamilton Rating Scale for Depression and Global Visual Analogue Scale scores, relatively few responded with equal improvement to both. CONCLUSION: Acute symptomatic improvement after d-amphetamine or methylphenidate is unpredictable and can only be determined by an empirical trial on an individual basis. These data also suggest that even if one stimulant is not helpful therapeutically, another might be. The long-term benefits of selective stimulant therapy in depressed patients remain to be assessed.

Adult↗
PubMed1993

Effect of methylphenidate on brain injury-related anger.

Anger and temper outbursts can be serious clinical problems after brain injury. This study used a randomized, pretest, posttest, placebo control group, single-blind design to evaluate the therapeutic usefulness of methylphenidate to control brain-injury-related anger. The 38 subjects in the study were young adult males who had sustained serious brain injuries and who were beyond the period of rapid, spontaneous recovery. The subjects were divided into two groups, one that received 30 mg of methylphenidate per day and the placebo control group. A comparison of the drug group with the placebo group before and at the end of the six-week treatment period on all the anger outcome measures analyzed simultaneously with multivariate analysis indicated a significant drug-by-time interaction effect, F(4.33) = 5.29, p = .002, demonstrating the therapeutic effect of methylphenidate on anger. The study found that drug responders could be predicted by pretreatment level of anger with a .09 probability of misclassification. Methylphenidate also significantly reduced impairment on all of the general psychopathology outcome measures (F[3.31] = 5.42, p < .01). The drug improved memory for those subjects in the treatment response group but did not result in changes on measures of attention, nor did it have an effect on a checklist of subjective side effects, suggesting that it has minimal or absent cognitive toxicity and is likely to be tolerated well by individuals with brain injuries.

Adaptation, Psychological↗
PubMed1996

Methylphenidate toxicosis in a cat.

A 10-year-old cat with restlessness, vocalizing, and circling was examined 13 hours after it was inadvertently given a 5-mg tablet of the CNS stimulant methylphenidate hydrochloride. Physical examination findings (generalized tremors, agitation, mydriasis, tachycardia, tachypnea, and hypertension) were consistent with overstimulation of the CNS and excessive adrenergic activity resulting from methylphenidate toxicosis. Plasma methylphenidate concentration at admission (83 ng/ml) was 5 to 16 times greater than the concentration reported to provide therapeutic effect in human beings. The cat was placed in a dark, padded cage to minimize external stimuli, and supportive care consisting of fluids and diazepam were administered. Clinical signs resolved within 25 hours after ingestion of methylphenidate.

Animals↗
PubMed1997

Methylphenidate in the treatment of coma.

While there is significant morbidity and mortality involving patients in semicomatose and comatose states, the care of such patients has traditionally been limited to supportive measures. We report two cases of patients treated with methylphenidate hydrochloride: the first, a patient in a semicomatose state resulting from traumatic brain injury, and the second, a patient in a comatose state secondary to a subdural hematoma that occurred after a fall. Treatment with methylphenidate may provide neurostimulations by augmenting the activity of injured neuronal tissue within the reticular activating system, and by amplifying the net effect of the reduced number of viable neurons. Methylphenidate is a low-cost, potentially efficacious intervention for reducing the duration of comas, for preventing life-threatening and costly complications of prolonged unconsciousness, and for promoting early ambulation and recovery. Further research using more rigorous research designs to ascertain the effectiveness of methylphenidate in the treatment of patients in semicomatose and comatose states is needed.

Accidental Falls↗
PubMed1998

The effects of methylphenidate and maturation on exploratory activity in rats.

Treatment of attention-deficit hyperactivity disorder with stimulants such as methylphenidate reduces motor activity and improves performance of tasks requiring attention, learning, and memory. The present study reports the patterns of behavioral activity of rats of different ages, and the effect of methylphenidate on the behavioral activity. The behavioral activity of Wistar male rats was measured on the nine hole-board apparatus. In experiment I, the behavioral activity of rats from three age groups (4, 8 and 12 weeks old) were measured in terms of the activity time, specific exploratory behavior, diverse exploratory behavior and defecation number. The rats were re-exposed to the hole-board again every two weeks until they 14 weeks old. The younger rats showed higher activity level compared to the older rats. The activity level decreased as the rats grew older. The younger rats also showed more diverse exploratory behavior, but less specific exploratory behavior compared with the older rats. These suggested that the younger rats may be more hyperactive in nature, and less prone to focus on the specific targets. In experiment II, the methylphenidate (4 mg/kg, i.p.) injected rats showed higher activity level than the controls across the three age groups. The exploratory behavioral patterns were not significantly different among the three age groups. This suggests that the methylphenidate injection raises the motor activity level without affecting the exploratory tendency of rats.

Aging↗
PubMed1998

Response to growth hormone in attention deficit hyperactivity disorder: effects of methylphenidate and pemoline therapy.

OBJECTIVE: To determine whether treatment of attention deficit hyperactivity disorder (ADHD) with methylphenidate hydrochloride or pemoline diminishes the response to growth hormone (GH) therapy in patients with idiopathic GH deficiency (IGHD) or idiopathic short stature (ISS). METHODS: The National Cooperative Growth Study database was used to identify patients between 3 and 20 years of age with IGHD or ISS and those within these groups who were treated with methylphenidate or pemoline for ADHD. Their growth in response to GH treatment (change in height standard deviation score [SDS]) was compared with that of patients with IGHD or ISS who were not treated for ADHD, by using a stepwise multiple regression analysis. RESULTS: In the IGHD cohort, there were 184 patients who were being treated for ADHD and 2313 who were not. In the ISS cohort there were 117 patients who were being treated for ADHD and 1283 who were not. There was a higher percentage of males being treated for ADHD in both cohorts. In the IGHD cohort, the change in height SDS was positively associated with the number of years of GH treatment, parents' heights, body mass index, and GH injection schedule, and was negatively associated with height SDS at the initiation of GH therapy, age, and maximum stimulated GH level. The use of methylphenidate or pemoline had a negative effect on the change in height SDS, but the magnitude of the effect was small. Similar effects were noted in the ISS cohort, but body mass index and the use of methylphenidate or pemoline had no effect on the change in height SDS. CONCLUSIONS: Concurrent ADHD therapy is associated with a slight decrease in the change in height SDS during GH treatment in patients with IGHD but not in those with ISS. Even in IGHD, the magnitude of the effect is small and should not deter the use of such concurrent therapy.

Attention Deficit Disorder with Hyperactivity↗
PubMed1999

A fatality due to the intranasal abuse of methylphenidate (Ritalin).

A fatality in a teenager from the recreational intranasal abuse of methylphenidate (Ritalin) is reported. The prescribed use of methylphenidate (Ritalin) in the treatment of attention deficit and/or hyperactivity disorder is widespread. The intranasal abuse of methylphenidate (Ritalin) among teenagers is becoming increasingly more recognized. Previous deaths from the parenteral abuse of methylphenidate (Ritalin) have been reported. This fatality is the first reported from its intranasal abuse.

Administration, Intranasal↗
PubMed2000

Methylphenidate Abuse and Psychiatric Side Effects.

Methylphenidate is a central nervous system stimulant drug that has become the primary drug of choice in treating attention-deficit/hyperactivity disorder in children. Side effects are usually mild and are generally well tolerated by patients. Along with increases in prescribing frequency, the potential for abuse has increased. Intranasal abuse produces effects rapidly that are similar to the effects of cocaine in both onset and type. The clinical picture of stimulant abuse produces a wide array of psychiatric symptoms. There is little in the literature to differentiate methylphenidate from other stimulants when they are abused. The need for education of all involved with the use of methylphenidate is discussed to help prevent an increasing pattern of methylphenidate abuse.

Journal Article↗
PubMed1995

Carbon-11-d-threo-methylphenidate binding to dopamine transporter in baboon brain.

UNLABELLED: The more active d-enantiomer of methylphenidate (dl-threo-methyl-2-phenyl-2-(2-piperidyl)acetate, Ritalin) was labeled with 11C(t1/2:20.4 min) to characterize its binding, examine its specificity for the dopamine transporter and evaluate it as a radio-tracer for the presynaptic dopaminergic neuron. METHODS: PET studies were carried out in the baboon. The pharmacokinetics of [11C]dl-threo-methylphenidate, [11C]l-threo-MP and with its racemate ([11C]dl-threo-methylphenidate, [11C]MP). Nonradioactive methylphenidate was used to assess the reversibility and saturability of the binding. GBR 12909, 3 beta-(4-iodophenyl)tropane-2-carboxylic acid methyl ester (beta-CIT), tomoxetine and citalopram were used to assess the binding specificity. RESULTS: The ratio between radioactivity in the striatum and that in the cerebellum (ST/CB) after injection of [11C]d-threo-MP was higher than that for [11C]MP and [11C]l-threo-MP (3.3 for d-, 2.2 for racemic and 1.1 for l- in the same baboon). Most of the striatal binding of [11C]d-threo-MP was displaceable by injection of nonradioactive MP. Pretreatment with nonradioactive MP (0.5 mg/kg), GBR12909 (1.5 mg/kg) and RTI-55 (0.3 mg/kg) markedly reduced striatal but not cerebellar uptake of [11C]d-threo-MP. In all cases, the ST/CB after pretreatment was reduced by about 60% compared to 43% for [11C]MP. The ratios of distribution volumes at steady-state for the ST/CB for the three separate studies in the same baboon were reduced by about 50%, as compared with 37% for [11C]MP. In contrast, pretreatment with tomoxetine (3.0 mg/kg) or citalopram (2.0 mg/kg) did not change [11C]d-threo-MP kinetics; the ST/CB after pretreatment was similar to that for the control. CONCLUSION: These results demonstrate the saturable, reversible and specific binding of [11C]d-threo-MP to the dopamine transporter on the baboon brain, suggesting that [11C]d-threo-MP will be a useful PET tracer for the presynaptic dopaminergic neuron in living human brain.

Animals↗