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Amphetamine, but not methylphenidate, predicts antidepressant efficacy.

Several researchers have explored the possibility that acute stimulant response may predict eventual improvement after specific antidepressants. This review analyzes the relationship between stimulant response and nonspecific antidepressant response. In five studies, amphetamine responders were found to eventually improve after antidepressant treatment in 85% of the cases, while nonresponders improved in 43% of the cases. In contrast, acute methylphenidate responders and nonresponders eventually improved on antidepressants at equivalent rates. Amphetamine sensitivity appears to be a trait (possibly pharmacodynamic) that is independent of depressive illness but predictive of tricyclic responsiveness. Other evidence has suggested that amphetamine and methylphenidate cause similar behavioral and symptomatic effects through distinct mechanisms of potential clinical relevance. The most effective method for administering an amphetamine challenge and its appropriate clinical use remain unclear.

Amphetamine↗

Methylphenidate in treating poststroke depression.

The authors retrospectively studied the charts of 25 patients with poststroke depression who were treated with methylphenidate. The 13 patients (52%) who recovered completely from their depression did not differ significantly from the 12 nonresponders on demographic characteristics, location of cerebrovascular accident, and other variables. Mood usually improved within 48 hours; only 3 (12%) patients had side effects. Rapid response to treatment and lack of significant side effects indicate that methylphenidate may be a valuable treatment for poststroke depression.

Aged↗

Family abuse of methylphenidate.

Methylphenidate is often the drug of choice for pharmacologic treatment of attention deficit disorder. Cases of parental abuse of the drug have been reported. The likelihood of antisocial personality disorder appears to be greater in families of children with attention deficit disorder, which emphasizes the need for strategies to reduce the abuse of prescription methylphenidate.

Adolescent↗

Elderly depressed females as a possible subgroup of patients responsive to methylphenidate.

The records of 13 medically ill geriatric patients whose depression interfered with their participation in a hospital rehabilitation program were retrospectively reviewed. Treatment with methylphenidate at dosages ranging from 2.5 mg/day to 20 mg/day produced mild to marked improvement in 54% of the patients; the fact that 6 of the 7 responders were female may be indicative of a more responsive subgroup. Methylphenidate treatment of illness-related, nonpsychotic depression in the elderly appears to be an effective, quick-acting, and relatively safe therapeutic option.

Aged↗

Comparison of the effects of the isomers of amphetamine, methylphenidate and deoxypipradrol on the uptake of l-[3H]norepinephrine and [3H]dopamine by synaptic vesicles from rat whole brain, striatum and hypothalamus.

The ATP-Mg++-dependent uptake of [3H]dopamine and l-[3H]norepinephrine into purified synaptic vesicles of whole rat brain, rat striatum and rat hypothalamus was inhibited 10-fold more effectively by S-(+)-amphetamine as compared to its corresponding (R-(-)-enantiomer. In contrast, S-(+)-deoxypipradrol and its R-(-)-enantiomer were approximately equipotent inhibitors of 3H-amine uptake into these synaptic vesicular preparations. The 1R:2R-methylphenidate was twice as potent as its 1R:2S-enantiomer as an inhibitor of 3H-catecholamine uptake. These data suggest that the receptor sites on the amine pumps present in the membranes of all three vesicular preparations are similar in so far as they are all sensitive to the stereochemical configuration around the alpha-carbon of amphetamine but are not sensitive to the stereochemical configuration around the analogous carbon of deoxypipradrol and methylphenidate. These observations are the reverse of those previously observed for the phenethylamine pumps present in peripheral and central neuronal membranes.

Amphetamine↗

Clinical experience with methylphenidate.

The indications for the use of methylphenidate in 250 children are reviewed, and the effect of the drug is examined. Concentration was improved or hyperactive behaviour diminished in 89% of the children with normal intelligence and with no gross physical defect, in 72% of the children with cerebral palsy, and 68% of the children with subnormal intelligence. In children with emotional disturbance, response to methylphenidate was seldom satisfactory. Significant side-effects occurred infrequently and only 2 children lost weight during the period of medication.

Adolescent↗

(14C)Methylphenidate hydrochloride. Studies on disposition in rat brain.

Studies with [14C]methylphenidate-HCl were carried out in rats administered the drug intravenously or intraperitoneally. Levels of total radioactivity and parent drug were measured in plasma, brain, and certain brain regions up to 6 hr after dosing. The intravenous route of administration was characterized by rapid entry into brain; during the first half hour, brain levels were 3- to 6-fold higher than those obtained by the intraperitoneal route. At later time periods, brain and plasma concentration for both routes were comparable, and the decline of drug concentrations in brain paralleled that in plasma. No significant variance was found in regional distribution of drug in brain. Whereas the major fraction of circulating drug consisted of metabolites, predominantly unchanged drug was found in brain. After intravenous injection of [14C]ritalinic acid (the major metabolite of methylphenidate), no substantial concentrations were found in brain.

Animals↗

Comparison of the effects of chlorpromazine, dextroamphetamine and methylphenidate on the behaviour and intellectual functioning of hyperactive children.

Chlorpromazine, dextroamphetamine and methylphenidate were significantly superior to placebo in producing overall improvement in the behaviour of hyperactive children. Chlorpromazine was effective for the majority of the children, but reduced only hyperactivity, having no demonstrable effect on distractibility, aggressivity or excitability. Both stimulants produced more goal-oriented behaviour and reduced distractibility. Methylphenidate was the most effective of the drugs in prpducing exceptional improvement. All three active drugs had to be discontinued in a few of the children because of side effects. Not all hyperactive children were benefited by the drugs.No background variables (with the exception of mother-child relationship) were found in the present studies to predict favourable response to the drugs.Methylphenidate became our drug of choice for this group of hyperactive children.

Child↗

A comparative study of the efficacy of ACTH4-9 analog, methylphenidate, and placebo on attention deficit disorder with hyperkinesis.

The present study compared the behavioral performance of 30 children with attention deficit disorder with hyperkinesis (HK) on electrophysiological, biochemical, behavioral, and psychometric measurements. HK children were partitioned into cells of 10 and were then treated with placebo, methylphenidate, and adrenocorticotropic hormone fractions (ACTH4-9 analog), respectively, in a double-blind randomized cell sequence according to body weight. The results revealed that HK children on methylphenidate manifested a significantly greater vasomotor reactivity, behavioral improvement, and learning receptivity than did HK children taking ACTH4-9 analog and/or placebo. Future research implications with ACTH4-9 and HK children are discussed.

Adrenocorticotropic Hormone↗

Attention deficit disorder and the effect of methylphenidate on attention, behavioral, and cardiovascular functioning.

The effect of a 0.3 mg/kg dose of methylphenidate on attentional, behavioral, and cardiovascular measures in boys with attention deficit disorder (ADD) was examined. The results of double-blind clinical trials demonstrated a significant improvement in sustained attention and impulse control, as well as in ratings of social behavior by both teachers and parents. Consistent with previous research, cardiovascular functioning did not significantly increase as a function of methylphenidate. Due to the large intraindividual variability in cardiovascular response, careful monitoring of each patient's response is recommended.

Attention↗

Teacher response to the methylphenidate (ritalin) versus placebo status of hyperactive boys in the classroom.

The effects of children's medication status on teacher behaviors were studied in a classroom setting. Teacher behaviors toward hyperactive boys on methylphenidate were compared to those toward hyperactive boys on placebo, as well as those toward normal comparison peers. A medication crossover design was used within the hyperactive group, and the teacher had no knowledge of diagnoses or medication condition. Across 4 different classroom experiments, the teacher was more intense and controlling toward hyperactive boys on placebo than toward the other 2 groups. No differences emerged between the comparison and medicated hyperactive groups, suggesting that methylphenidate served to "normalize" teacher-pupil interactions. Teacher behaviors toward individual boys were also moderately to strongly related to teacher global impressions of these youngsters, as indexed by qualitative rating scales. Discussion focuses on the social ramifications of medication and the need for broader monitoring of treatment outcomes.

Attention↗

Optimal dosages of methylphenidate for improving the learning and behavior of hyperactive children.

The effects of methylphenidate dosages were assessed in 42 hyperactive children who were tested off drug at the beginning and end of an 18-week study and 2 weeks after initiation of various dosages. Initial methylphenidate doses of 0.2 mg/kg were increased biweekly until 0.8 mg/kg was reached or the child showed adverse personality or physiologic effects. Measures included an objective test of the ability to sustain attention and behavioral ratings completed by parents and teachers. Data were analyzed separately for groups attaining low, moderate, and high maximum doses (0.4, 0.6, and 0.8 mg/kg, respectively). For all dosage groups behavior and attention improved with increased dosage, and the best scores were associated with the highest drug levels. In contrast to previous reports, differences in optimal dosage levels for behavior and cognitive performance were not seen. This discrepancy may result from the lack of individual titration based on tolerance in earlier reports.

Attention↗

Methylphenidate-induced hallucinosis: case histories and possible mechanisms of action.

Published reports of toxic hallucinosis during treatment with methylphenidate are rare. Two cases are described and it is suggested that methylphenidate-induced hallucinosis is more common than has been appreciated. Symptoms may be understood in terms of dose-related effects at pre- and postsynaptic receptors. Two other hypotheses that may clarify underlying mechanisms of action that produce toxic effects relate to (1) noradrenergic facilitation transmission of information in the visual pathway, and (2) interactions among brain monoamine systems.

Brain Chemistry↗

The effects of methylphenidate on the soft neurological signs of hyperactive children.

The neurological examination of many hyperactive children reveals the presence of abnormal neurological signs. Of 40 hyperactive children who had three or more neurological abnormalities on an initial neurological evaluation, 29 (72.5%) showed marked improvement or complete resolution of the neurological signs following treatment with methylphenidate hydrochloride (Ritalin) for 60 days. The administration of placebo did not change appreciably the neurological status of 20 hyperactive children. Improvement in behavior, which was ascertained by the use of Conners' Abbreviated Teacher Rating Scale, did not always correspond with resolution of the abnormal neurological signs. This finding suggests that methylphenidate affects behavioral and motoric functions separately and independently. Repeat neurological assessment, looking for resolution of abnormal neurological signs, should be included as part of the follow-up medical examination in treated hyperactive children. Coupled with other objective and subjective test information, improvement of the neurological status provides supportive evidence of overall improvement in the hyperactive child who is receiving drug therapy.

Child↗

Effect of long-term treatment of hyperactive children with methylphenidate.

SUMMARY: Three groups of hyperactive children were compared by various measures of outcome 5 years after initial evaluation: 24 who were treated with methylphenidate for 3 to 5 years during the follow-up period, 22 treated with chlorpromazine for 18 months to 5 years, and 20 who had received no medication during the follow-up period. The three groups were matched with respect to age, IQ, socioeconomic class and sex. No statistically significant differences were found between the three groups on the following measures of outcome: emotional adjustment, delinquency, Wechsler Intelligence Scale for Children, Bender Gestalt visual-motor test and academic performance (as measured by number of grades failed). Initially there was a significant difference between the three groups on ratings of hyperactivity and family diagnosis. Hyperactivity scores decreased significantly over the 5 years; family diagnosis ratings changed little. Analysis of covariance for these two measures showed no difference in degree of improvement between the three groups. Our impression was that methylphenidate was helpful in making hyperactive children more manageable at home and at school, but did not significantly affect their outcome after 5 years of treatment.

Child↗

Methylphenidate's effects on paired-associate learning and event-related potentials of young adults.

The effects of methylphenidate (0.3 mg/kg) on young adults paired-associate learning (PAL) of consonant-vowel-consonant (CVC) pairs and concomitant event-related potentials were assessed. The stimulant elevated mood and heart rate but did not affect PAL performance. For the first CVC, there were amplitude increases with learning for P3b at Pz, P2 at midline sites, and for a negative slow wave at Cz. For the second CVC, P3b and positive slow wave amplitude declined with learning. Increases in P3b amplitude to the first CVC were attributed to increments in stimulus meaningfulness. Decreases in P3b amplitude to the second CVC were interpreted as resulting from fewer disconfirmed expectations of feedback. The negative slow wave following the first CVC was viewed as a contingent negative variation. Methylphenidate increased parietal P3b amplitude for CVC 2, averaged over learning phases.

Adolescent↗

Growth of hyperkinetic children taking methylphenidate, dextroamphetamine, or imipramine/desipramine.

One hundred children with the hyperkinetic syndrome or minimal brain dysfunction syndrome were treated with medication: 60 with methylphenidate (Ritalin), 24 with dextroamphetamine (Dexedrine), and 16 with either imipramine or desipramine. The duration of treatment was for a minimum of two years, and averaged five years, with an average follow-up of six years from the onset of treatment. Their weight and height had been measured prior to treatment, and these and subsequent measurements were converted to percentiles, using the tables of norms of the Iowa City study. Initially there was a diminution in expected weight, but not height, but after a few years the growth in weight and height was found to be greater than predicted from the norms to a statistically significant degree. Gains in weight and height were greater for those whose medication had been stopped prior to the final measurements than for those still taking medication; but these differences did not reach statistical significance. No correlations were found between dosage level and changes in weight and height percentiles. It is concluded that there is no stunting of growth from the long-term use of methylphenidate, dextroamphetamine, or imipramine/desipramine in children. Any slowing of growth when treatment is first started is compensated for later on, both while the patient is still taking the medication, and after discontinuing it.

Adolescent↗

[Talc pulmonary granulomatosis caused by intravenous administration of methylphenidate].

A 57-year-old man was admitted with fever and a dry cough in 1985. He had used methylphenidate intravenously for 3 years. A chest X-ray film on admission showed diffuse micronodular shadows and massive lesions in the lower lung fields bilaterally. Pulmonary granulomatosis was diagnosed histologically, but the etiology remained unclear. In 1993, the patient was readmitted because of symptom exacerbation. The micronodular shadows had extended and the bilateral, massive lesions had enlarged. Transbronchial lung biopsy revealed granulomas with crystallized foreign bodies. Electron microscopy confirmed that the foreign bodies consisted of magnesium and silicon, suggesting talc. Talc granulomatosis caused by intravenous administration of methylphenidate was subsequently diagnosed. The symptoms improved with conservative treatment, and no signs of reexacerbation have appeared.

Central Nervous System Stimulants↗