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Methylphenidate eliminated mutism in a catatonic schizophrenic after Amytal had failed. Response permitted an adequate clinical evaluation and temporary resumption of eating, self-care and sociability. This suggests that methylphenidate has a useful role in the clinical evaluation of the mute patient who fails to respond to Amytal and that 2 psychopharmacological varieties of catatonic mutism may exist.
The effects of the stimulant drugs, d-amphetamine and methylphenidate, upon the motor activity of male and female off-spring of pregnant rats, treated on gestation day 15 with the antimitotic agent methylazoxymethanol (MAM, 25 mg/kg) were studied in four experiments. Cortical and striatal hypoplasia induced by prenatal administration of MAM resulted in increased concentrations of catecholamines in those regions. Administration of d-amphetamine and methylphenidate caused significant increases in motor activity; this effect was markedly potentiated in the MAM-treated rats, both the male and female off-spring. Thus, the locomotion and total activity parameters showed similar, but not identical, drastic increases in behaviour induced by the stimulant drugs as a result of the prenatal MAM treatment whereas for the rearing parameter a lesser potentiation by the MAM treatment was observed. This potentiation of the excitatory effects of the stimulant compounds upon the behavioural parameters is interpreted in terms of a relative increase in the density of catecholaminergic terminals in the forebrain regions of the central nervous system. The present results are discussed with regard to the utility of prenatal MAM treatment as a possible animal model for certain neurological disorders.
Observations of nursery behavior and tests of cognitive style and motor impulsivity were carried out with 28 hyperactive preschool children of normal intelligence and 26 matched control children. The hyperactive group was also observed and tested on methylphenidate and placebo. Methylphenidate was found to reduce hyperactivity at home, but it did not improve nursery behavior or psychological functioning. Unwanted side effects made the drug less useful at this age than in older hyperactive children.
The electroencephalogram in three patients with Jakob-Creutzfeldt disease showed two separate abnormalities-namely, progressive background suppression and periodic generalized synchronous triphasic sharp wave complexes which evolve to a uniform morphology and periodicity. The abnormalities, when found in the EEG of a patient in middle-age with a dementing illness, should not be confused with other periodic electroencephalographic phenomena. Since the neuropathological abnormalities of Jakob-Creutzfeldt disease are non-specific, the electroencephalogram is essential for the recognition of this disorder, although serial recordings may be necessary to establish the diagnosis. Modification of the electroencephalographic abnormalities occurs with afferent stimuli and with methylphenidate or diazepam, suggesting that the phenomenon of background suppression is independent of the presence of the periodic complexes. Modification of clinical activity with methylphenidate suggests that some degree of reversibility of function exists in this inexorably fatal disorder. Further detailed studies of the electroencephalogram in cases of Jakob-Creutzfeldt disease are indicated.
The aim of this review is to compare the experimental evidence obtained from in vitro studies on the effect of amphetamine and methylphenidate on dopamine transmission with the results obtained in animal models of attention deficit hyperactivity disorder (ADHD). This comparison can extend the knowledge on the mechanism of action of the drugs used in the therapy of ADHD and provide insight into the etiology of ADHD. In particular, we considered the results obtained from in vitro methods, such as synaptosomes, cells in culture, and slices and from in vivo animal models of ADHD, such as spontaneous hypertensive rats (SHR) and the Naples high-excitability (NHE) rat lines. The different experimental approaches produce consonant results and suggest that in SHR rats, in contrast to Wistar Kyoto rats (WKY), amphetamine and depolarization by high K+ might release different pools of dopamine-containing vesicles. The pool depleted by amphetamine might represent dopamine that is stored in large dense core vesicles, whereas dopamine released by high K+ might be contained in small synaptic vesicles (SSV). The sustained dopamine transmission observed in the nucleus accumbens of SHR but not WKY rats can be supported by an elevated synthesis and release, which also might explain the stronger effect of methylphenidate on dopamine release in SHR but not in WKY rats. This hypothesis might enlighten the common therapeutic effect of these drugs, although their action takes place at different levels in catecholaminergic transmission.
In two studies, we studied the comparative sensitivity of different subjective and objective measures to methylphenidate (10 and 20 mg) and secobarbital (100 mg) versus placebo, and diphenhydramine (50 mg) and diazepam (10 and 20 mg) versus placebo in abstinent alcoholics. Subjective measures used were the Visual Analog Mood Scale and the Profile of Mood States. Objective measures were the Stroop and two microcomputer-controlled tasks developed in our lab - a dual pursuit tracking/reaction time task (P-Trak) and a reaction time task with regular and irregular preparatory intervals (PI) of varying length (Reactest). In addition, several baseline measures (Eysenck Personality Inventory, Spielberger State-Trait Anxiety Inventory and NIMH Mood Scale Elderly) were evaluated for their correlation to drug response. All three central nervous system depressants impaired performance on Reactest at the longer PIs and showed a main effect with irregular PIs, but only the 20-mg dose of diazepam impaired reaction time at the shortest PI and showed a main effect with regular PIs. On P-Trak, secobarbital and diazepam 20 mg impaired both tracking and reaction time, while methylphenidate 20 mg improved only the reaction time component. Only diazepam 20 mg affected mood. No effects were noted on the Stroop. The implications of these findings are discussed. Both P-Trak and Reactest with long PIs were more sensitive than VAMS, POMS or Stroop to drug effects. As lower doses of central nervous system depressants impaired reaction time only with longer PIs and showed a main effect only with irregular PIs, cognitive effects of these drugs may be missed if only subjective or short, regular PI tasks are examined.(ABSTRACT TRUNCATED AT 250 WORDS)
In 5 latency-age boys, methylphenidate plasma concentrations following multiple doses of methylphenidate were consistently higher than those obtained after a single dose. Pharmacological and clinical implications are discussed.
The authors report on a one-year follow-up of 76 hyperactive boys who had participated in a comparative study of methylphenidate, imipramine, and placebo. They found that there was a higher rate of discontinuance of imipramine than of methylphenidate in this sample and that both medications decreased the boys' rate of weight gain but had no significant effect on growth in height. This findings is of concern because larger doses than were used in this study are in use elsewhere. Teachers reported that the group of boys who had discontinued either medications showed continued hyperactivity and behavior problems in the classroom at one year. The two treatment groups showed continued improvement at one year in classroom and home behavior and did not suffer significantly from each other.
In this double-blind, crossover study of 8 boys with minimal brain dysfunction, 20 mg of methylphenidate daily was significantly better than 160 mg of caffeine in controlling behavior, especially impulsivity and hyperactivity, and methylphenidate alone was superior to decaffeinated coffee and placebo. The tentative results of this study confirm the primary position of sympathomimetics in the pharmacotherapy of minimal brain dysfunction and, in addition, suggest the involvement of dopamine pathways in this disorder. The authors urge further study of this hypothesis.
Data on 84 nonretarded boys aged 6--12 with the hyperkinetic/MBD syndrome were drawn from a comprehensive, longitudinal investigation in the interest of identifying factors that contribute significantly to variation in clinically rated improvement during treatment with methylphenidate. The size of the multiple correlation (R = .50) indicates that 25% of the variation in the children's response to methylphenidate is jointly predictable from age at referral, degree of perinatal complications, and score on the hyperactivity factor. The authors discuss stepwise multiple regression analysis as the method of choice in drug response prediction studies and the possible effects on the results of such studies of differing definitions of improvements.
Three depressed geriatric patients had a marked therapeutic response to the psychostimulant drug methylphenidate. These patients either had been unable to tolerate tricyclic antidepressants or had a medical illness that contraindicated tricyclic therapy. The lack of adverse effects in our elderly patients and methylphenidate's effectiveness as an antidepressant were consistent with the findings of other investigators. These results suggest that psychostimulants deserve further evaluation as antidepressant agents in the geriatric population.
The authors studied 19 inpatients with major depressive episode or schizoaffective disorder, depressed type, and compared their response to the dexamethasone suppression test (DST) with their response to the methylphenidate stimulation test. They found a significant negative correlation between responses to DST and to methylphenidate.
The authors successfully treated a chronically depressed man with a combination of desipramine and methylphenidate. Methylphenidate did not change his serum desipramine level, and the authors speculate that its ability to potentiate tricyclic responsiveness may be due to its dopaminergic activity.
Effects of methylphenidate on measures related to reading were studied in a group of nine boys who had attention deficit disorder with hyperactivity; a double-blind crossover design using active drug and placebo was used. Administration of methylphenidate improved subjects' performance on language processing tests but not their performance on oral reading measures. The findings provide evidence in support of a two-factor theory of attention deficit disorder.
Although neuroleptics are the major treatment for schizophrenia, there are no effective measures to determine the appropriate or necessary length of neuroleptic maintenance. To test the ability of a psychostimulant challenge to predict relapse following neuroleptic withdrawal, the authors administered methylphenidate and placebo infusions to 11 stable schizophrenic outpatients who had been on a neuroleptic maintenance regimen for at least 6 months. Patients withdrawn from neuroleptics were followed until relapse. All three patients with a positive response to methylphenidate challenge relapsed in 1 to 7 weeks; one of seven negative responders relapsed at week 21. Differences in relapse rates (p = .033) and survival time (p = .005) between negative and positive responders were significant.
State-dependent learning refers to a failure of learning mastered under one drug condition to be remembered when tested under another drug condition. Previous studies of state-dependent learning in hyperactive children receiving stimulants have yielded conflicting results. The authors systematically evaluated learning and transfer of learning in children who were or were not receiving methylphenidate and included several design features intended to optimize the likelihood of demonstrating state-dependent learning. They found no evidence of state-dependent learning. These results diminish concern regarding state-dependent effects in hyperactive children who are positive drug responders and who are clinically administered methylphenidate to control their hyperactivity.
Thirty-seven adult patients meeting the Utah criteria for attention deficit disorder, residual type, were entered into a double-blind crossover trial of methylphenidate and placebo. A moderate-to-marked therapeutic response occurred in 21 (57%) of the patients while receiving methylphenidate and in four (11%) while receiving placebo, a highly significant difference statistically and clinically. The responding patients showed significant improvement in the following areas: attentional difficulty, motor overactivity, affective lability, and impulsivity. The diagnosis of attention deficit disorder, residual type, should be considered in patients with prominent complaints of impulsivity, restlessness, emotional lability, and hot temper who do not suffer from schizophrenia or major mood disorder and do not have symptoms of schizotypal or borderline personality disorders.
Two patients with borderline personality disorder experienced dramatic dysphoric episodes after acute administration of intravenous methylphenidate in a double-blind manner. These dysphoric episodes were similar to those which occurred spontaneously under conditions of psychological stress. Case histories and the behavioral and cardiovascular effects of the infusions are described. The pharmacology of methylphenidate is discussed in order to elucidate possible mechanisms mediating the observed responses to this drug.