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Methylphenidate in a patient with depression and respiratory insufficiency.

OBJECTIVE: We report a case of severe depression in an elderly and critically ill patient with multiple medical complications who was treated with a combination of methylphenidate and sertraline. The objective of this report is to outline the usefulness of methylphenidate as an antidepressant in a patient with respiratory insufficiency. METHOD: Case description. RESULTS: The patient had a positive clinical response with initial mental confusion due to methylphenidate. An initial dose of 2.5 mg/day allowed antidepressant response and improvement of respiratory function permitting the removal of mechanical ventilation. CONCLUSION: Methylphenidate may be useful for patients with severe medical conditions including ventilatory insufficiency.

Aged↗

Effects of imipramine and methylphenidate on perceptual-motor performance of hyperactive children.

Perceptual-motor effects of imipramine and methylphenidate were evaluated in a double-blind study of 47 hyperactive children. No effects were found for imipramine, although methylphenidate improved performance on several tests. Improvement due to methylphenidate was not related to base-line scores. A discriminant function was computed to compare baseline perceptual-motor scores of the hyperactive and 41 normal children. Only half of the hyperactive children were clearly discriminated from normal children by the discriminant function. The digit-span test, which was not sensitive to methylphenidate, effectively discriminated hyperactive from normal children.

Adolescent↗

Effects of methylphenidate on working memory in pigeons.

To assess the effects of methylphenidate on working memory, pigeons were trained in a delayed matching-to-sample task. Delay interval duration (0.2, 1, 3, 6, or 12 sec) was varied within sessions in order to separate delay-dependent from delay-independent effects of the drug on performance. A reduction in the sample response requirement from five responses to one response effectively reduced attention to the stimulus and impaired overall accuracy. Methylphenidate was administered in doses of 0.0 (saline control), 0.25, 2.5, and 10 mg/kg. Relative to performance with saline, accuracy was significantly reduced with 10 mg/kg methylphenidate to the same extent in both fixed ratio (FR) 1 and FR 5 conditions. The smaller doses had no effect, and there was no evidence that accuracy improved with drug administration. Intercepts and slopes of exponential functions fitted to measures of discriminability plotted as a function of delay showed that methylphenidate affected delay-independent aspects of performance (initial discriminability), but not delay-dependent aspects (rate of forgetting).

Animals↗

Methylphenidate: its pharmacology and uses.

Methylphenidate is a commonly used medication in the United States. This central nervous system stimulant has a mechanism of action distinct from that of amphetamine. The Food and Drug Administration has approved methylphenidate for the treatment of attention-deficit/hyperactivity disorder and narcolepsy. Treatment with methylphenidate has been advocated in patients with traumatic brain injury and stroke, cancer patients, and those with human immunodeficiency virus infection. Placebo-controlled trials have documented its efficacy as an adjunctive agent in the treatment of depression and pain. This article reviews the current understanding of the mechanism of action and efficacy of methylphenidate in various clinical conditions.

Attention Deficit Disorder with Hyperactivity↗

Treatment of depression with methylphenidate in patients difficult to wean from mechanical ventilation in the intensive care unit.

BACKGROUND: Mechanical ventilation is often required to support patients in the intensive care unit (ICU) with life-threatening cardiovascular, respiratory, or neuromuscular disorders. Occasionally, difficulties related to weaning patients from this support occur owing to depression. The traditional and newer-generation antidepressant drugs have a relatively long latency of response that interferes with rehabilitation attempts in the ICU. Psychostimulants such as methylphenidate show a rapid onset of antidepressant activity and a benign side effect profile. METHOD: As consulting psychiatrists in the consultation-liaison service of a university hospital, we treated 7 patients with complex ICU courses presenting prolonged mechanical ventilation and psychomotor retardation associated with markedly depressed mood (DSM-IV criteria) by giving them methylphenidate. Methylphenidate was started on the first day at a dose of 2.5 mg p.o. in the morning and was increased by 2.5 mg each day with twice-a-day dosing in the morning and at noon until the patient responded or showed side effects. A maximum dose of 15 mg/day was not exceeded. Outcome evaluation was performed using the Clinical Global Impressions scale. RESULTS: Five (71 %) of 7 patients showed marked or moderate improvement in mood and activity within 3 to 4 days, and discontinuation of ventilator support was achieved within 8 to 14 days. Side effects with these 5 patients were not encountered. Of the remaining 2 patients (29%), 1 developed psychomotor agitation and anxiety within 4 days. Another patient showed only minimal improvement with regard to activity. CONCLUSION: Methylphenidate might be a rapidly effective and safe treatment for depression in difficult-to-wean patients hospitalized for life-threatening medical illness in the ICU. Implications for future research for this population of patients warrant formal randomized, prospective, clinical case-control evaluation.

Adult↗

Perceptual and response interference in children with attention-deficit hyperactivity disorder, and the effects of methylphenidate.

Fourteen children with attention-deficit hyperactivity disorder (ADHD) and 14 normal control children were compared with respect to stimulus- and response-related processes. Subjects with ADHD took part in two additional sessions under methylphenidate or placebo. In both experiments, performance and electrophysiological measures such as the P2, N2, and P3 components of event-related potential and electromyogram (EMG) activity were measured during an Eriksen flanker task. In both groups of children, reaction times (RTs) to arrow stimuli incongruent with the target were longer than those to neutral stimuli (response interference), which were again slower than RTs to target-alone stimuli (perceptual interference). Children with ADHD made more errors to incongruent stimuli and showed more response interference. For correct responses, no differences between the groups in response interference effects on reaction time, P2, N2, and P3 latency, or EMG onset were found. Methylphenidate had a general enhancing effect on accuracy but did not specifically reduce interference from the flanking stimuli. Methylphenidate had no effects on RT, N2 and P2 latency, P3 amplitude or latency, or EMG activity. The conclusion that methylphenidate did not influence response processes contrasts sharply with findings reported by authors using the Sternberg memory search task.

Adolescent↗

Attentional capacity, a probe ERP study: differences between children with attention-deficit hyperactivity disorder and normal control children and effects of methylphenidate.

In the present study it was investigated whether the smaller P3s in attention-deficit hyperactivity disorder (ADHD) children are caused by a shortage of capacity underlying P3 processes or whether they are due to a capacity allocation problem. Also, effects of methylphenidate on these processes were investigated. Performance and event-related potentials (ERPs) of 14 ADHD and 14 control children were measured using an irrelevant-probe technique. Three types of task irrelevant visual probes (standards, deviants, and novels) were presented against the background of two visual tasks that varied in task difficulty. The parietal P3 wave was measured in response to task stimuli and probes. ADHD subjects made significantly fewer correct detections than normal controls in both the easy and the hard tasks. Controls showed an enhanced P3 to task-relevant stimuli in the hard task, whereas ADHD children did not. Probe (novel) P3 amplitudes decreased from the easy to the hard task to the same extent in both groups. Methylphenidate enhanced the percentage of correct responses and task P3 amplitudes in both the easy and the hard task but probe P3 amplitudes were not influenced by methylphenidate. It was concluded that ADHD children do not suffer from a shortage in attentional capacity; rather, the evidence is in favor of a problem with capacity allocation. Furthermore, methylphenidate had enhancing effects on performance and ERPs, but did not improve the capacity-allocation deficit.

Adolescent↗

Methylphenidate and narcolepsy: new indication. When modafinil fails.

(1) Narcolepsy (daytime bouts of drowsiness) is sometimes associated with cataplexy, and can be incapacitating. The best-assessed treatment is modafinil, which has no demonstrated efficacy on cataplexy. (2) After many years of off-license use in the treatment of narcolepsy, methylphenidate is now licensed for this indication in France. (3) According to the results of our literature search, which includes a clinical expert report from Novartis Pharma, the file on methylphenidate in narcolepsy is mainly based on "clinical experience": only three case series, totalling fewer than 200 patients, have been published. (4) These non comparative studies suggest an effect of high dose methylphenidate on daytime drowsiness and cataplexy. (5) The adverse effects of methylphenidate are those of amphetamine psychostimulants, i.e. mainly neuropsychological disorders, cardiovascular effects, loss of appetite and a limited risk of excessive use by some patients.

Benzhydryl Compounds↗

[Utilization of methylphenidate(Ritalin) in France].

Methylphenidate (Ritalin) is the only psychostimulant approved in France and indicated in attention deficit hyperactivity disorder in children over 6 years. It is under restricted prescription and distribution conditions. As such, it requires a hospital initiated prescription from either a neurology, psychiatry or pediatric specialist and it is covered by the "narcotics" schedule. The French Pharmacovigilance database spontaneous adverse drug reactions reporting, since it was approved in 1995, were analyzed. 21 adverse drug reactions were reported. In 16 cases, methylphenidate was suspected. They were generally non-serious, mild side effects and in most cases promptly resolved. These results do not suggest methylphenidate misuse in France or an overuse in between 1300 and 4000 treated children, to date. Until more information is available concerning the long-term effects of methylphenidate, and in order to limit misuse, inappropriate or overuse, the current prescription and dispensing regulation should be maintained in France, and could well be developed in other countries.

Attention Deficit Disorder with Hyperactivity↗

[Memory functions in children with attention deficit/hyperactivity disorder--the effects of methylphenidate on them].

The memory functions or capacities in attention-deficit/hyperactivity disorder (AD/HD) are still not clear, though it has been pointed that the working memory in AD/HD could be impaired due to difficulties of motor inhibition or self-regulation. We examined the Auditory Verbal Learning Test (AVLT) and the Rey-Osterrieth Complex Figure Test (RCFT) in addition to the memory tasks of ordinary intelligence tests (WISC-III and K-ABC) in children with AD/HD. Whether these results could be improved by methylphenidate administration or not was also evaluated. Over the half cases had normal results without medication. Some cases in whom methylphenidate were clinically effective showed improved memory functions, especially in the auditory long-term memory, after methylphenidate administration. In conclusion, memory capacities seem normal in AD/HD. Methylphenidate does not have an effect on the memory capacities, but may improve the strategies in which the short-term memory can be effectively transferred to the long-term memory.

Attention Deficit Disorder with Hyperactivity↗

Efficacy and side effects of methylphenidate for poststroke depression.

BACKGROUND: Depression after stroke impedes the rehabilitation process and causes additional suffering to patient and family. Few studies have systematically examined pharmacologic treatments of poststroke depression. In the present paper, the use of the stimulant methylphenidate is studied in a depressed, elderly stroke population. METHOD: Ten subjects (mean age = 73.2 years) meeting DSM-III-R criteria for major depression were followed-up during a 3-week efficacy and side effect trial involving methylphenidate. Subjects were selected from rehabilitation patients referred for psychiatric consultation. RESULTS: A total of 80% (8 of 10) of the subjects showed either a full or partial response as measured by Hamilton Rating Scale for Depression scores. The incidence of problematic side effects was low, and no subjects had to be discontinued from the study. CONCLUSION: Results of this methylphenidate trial for poststroke depression in elderly patients suggest that it is a safe and effective treatment for poststroke depression. Future studies are called for in which methylphenidate is compared with placebo controls and antidepressant medication.

Age Factors↗

[Increasing trend in prescription of methylphenidate in general practices in the north-east of The Netherlands, 1998-2003].

OBJECTIVE: To obtain information on the frequency of and the indications for prescription of methylphenidate in general practices in the north-east of The Netherlands. DESIGN: Descriptive. METHOD: Data were collected from 1998 to 2003 from 6 general practices in the north-east of The Netherlands (17 general practitioners, approximately 30,000 patients) that were affiliated to the Registration Network in Groningen. The number of new and existing patients who were prescribed methylphenidate was calculated by age group per 1000 person-years per calendar year. The indication on which the drug was prescribed was looked at, as was the number of patients who were referred to a specialist on that indication. RESULTS: The number of new users per 1000 person-years more than doubled from 17 in 1999 to 42 in 2003. In all years studied the highest number of new users fell into the age group 5-9 years. The total number of users per 1000 person-years tripled (boys: 1.8 in 1998 and 6.2 in 2003; girls: 0.5 in 1998 and 0.8 in 2003). The prevalence of use in boys was 3 to 8 times as high as that of girls and increasing more quickly. In people under 59 years of age attention deficit hyperactivity disorder (ADHD) was the most frequent indication (55%). In the group aged > or = 60 years methylphenidate was mainly prescribed in the palliative phase of somatic morbidity. Over half of the 140 new patients (57%) were referred nor to a specialist in the year before neither in the year after the first prescription of methylphenidate.

Adolescent↗

[Sympathomimetic syndrome caused by autointoxication with methylphenidate].

A 31-year-old man claimed that he had ingested more than 100 tablets of methylphenidate (10 mg), 20 tablets ofibuprofen (400 mg) and 2 bottles of wine. At admission, signs of sympathomimetic syndrome were observed, including agitation, hallucinations, mydriasis and sinus tachycardia. The patient was treated with activated charcoal and an oral laxative. Given the possibly lethal dose of methylphenidate, the patient was admitted to the intensive care unit for observation. He made a full recovery and was discharged 36 hours after admission. Toxicological analysis indicated a plasma-ethanol concentration of 0.27% and a maximum serum-methylphenidate concentration of 176 microg/l (therapeutic range: 5-40 microg/l). The active metabolite ethylphenidate was also present at toxic concentrations. Treatment of potentially lethal methylphenidate poisoning includes prevention of absorption, careful observation and support of vital functions as necessary.

Adult↗

Intravenous methylphenidate abuse. Prototype for prescription drug abuse.

Data are presented from a case series of 22 patients who abused methylphenidate hydrochloride (Ritalin-SR). The abuse pattern and symptoms of toxicity were similar to that seen with cocaine hydrochloride and amphetamine sulfate addiction; yet, the morbidity and mortality seen in this case series were greater than usual for a group of patients involved in intravenous drug abuse. We describe the characteristics of the methylphenidate abuse syndrome in terms of the pharmacology of methylphenidate, the constituents of the Ritalin-SR preparation, and the disease of chemical dependence. We propose solutions to the problem of methylphenidate abuse.

Adult↗

Intranasal abuse of prescribed methylphenidate by an alcohol and drug abusing adolescent with ADHD.

A rare case is described where an adolescent with attention deficit hyperactivity disorder diagnosed in childhood subsequently developed alcohol and drug abuse. He later developed intranasal methylphenidate abuse and dependence after realizing that urine drug screens were expected to be positive for prescribed methylphenidate. This report is to alert physicians to the rare possibility of intranasal methylphenidate abuse in chemically dependent teenagers treated for ADHD and also to the possibility of group methylphenidate abuse at special education schools where many teenagers may be treated with stimulant medication.

Administration, Intranasal↗

Methylphenidate in depressed medically ill patients.

BACKGROUND: The purpose of the authors' study was to evaluate the efficacy of methylphenidate in the medically ill depressed patients and to examine the factors that appear to affect therapeutic response and side effects. METHOD: Hospital charts were reviewed for 29 patients who received trials of methylphenidate for treatment of depressive disorders while admitted to a medical/surgical unit. RESULTS: Of the 29 patients, 16 (55%) had moderate or marked improvement, all within 2 days of commencing treatment with the maximal dose. Of the 25 nondelirious patients, 16 (64%) had moderate or marked improvement, and the presence of delirium was significantly associated with decreased response. Therapeutic response was significantly correlated with maximum methylphenidate dose. Side effects were noted in 8 (28%) patients; most side effects were mild (tachycardia or agitation), and all reversed after the medication was discontinued. CONCLUSIONS: Methylphenidate provides a safe and effective alternative to tricyclic antidepressants in medically ill populations but appears to be less effective in the presence of delirium.

Adjustment Disorders↗

Efficacy of methylphenidate among mentally retarded children with attention deficit hyperactivity disorder.

Twelve children with IQ scores of 50 to 74 (educable mental retardation) who met rigorous diagnostic criteria for attention deficit hyperactivity disorder participated in a double-blind crossover study of the efficacy of two doses of methylphenidate compared with placebo. Dependent measures included behavioral ratings, classroom work output, laboratory measures of attention and learning, and direct observations of social behavior. Improvement with medication on the Conners Hyperactivity Index was observed in 75% of subjects. Significant increases in work output, on-task behavior, and attentional skills were associated with methylphenidate. However, gains in measures of attention were not associated with improvement in learning, as measured by a paired associate learning task. Additionally, no significant increases in appropriate social interactions during free play were associated with methylphenidate. The results suggest that mentally retarded children with attention deficit hyperactivity disorder respond to methylphenidate at similar rates and in similar domains to that of the nonretarded population.

Analysis of Variance↗

Behavioral response to methylphenidate and treatment outcome in first episode schizophrenia.

In order to examine the relationship of behavioral response to psychostimulants and acute treatment response, we administered methylphenidate (0.5 mg/kg i.v.), an indirect dopamine (DA) agonist, to 38 patients who met Research Diagnostic Criteria (RDC) for definite or probable schizophrenia or schizoaffective disorder, were experiencing their first acute episode of psychosis, and had received less than 12 weeks or no prior lifetime neuroleptic exposure. Following baseline methylphenidate infusions, patients received a standardized regimen of acute neuroleptic treatment. Methylphenidate produced an increase in psychopathology reflected by a worsening of both positive and negative symptoms. Using a priori criteria, 61 percent of patients exhibited psychotic symptom activation, and 39 percent showed no change. Activation during methylphenidate infusion during the initial acute phase of illness was not correlated with time to achieve antipsychotic treatment response but was associated with side-effect vulnerability.

Adolescent↗