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PubMed1997

Effects of the tranquillizer diazepam and the stimulant methylphenidate on alertness and memory.

Effects of alertness and memory of a single dose of diazepam (10 mg) and the central stimulant methylphenidate (20 mg) were studied in healthy volunteers. It was questioned whether opposite effects of diazepam and methylphenidate are not only observed with respect to alertness but also with respect to memory. It was also questioned whether the two drugs equally affect the first (primacy) and last (recency) items in both the immediate and delayed recall of newly learned words. The experiment was performed in a double-blind, placebo-controlled way. 12 subjects were exposed to a subjective alertness scale and a verbal memory test: a 15-word test. Subjective alertness was found to be decreased after diazepam and increased after methylphenidate. Anterograde amnesia was found after diazepam in the memory test. More specifically, the primacy but not the recency effect was reduced during the immediate recall and both were reduced in the delayed recall. methylphenidate had no effect on memory, however a ceiling effect might have obscured a putative drug effect. The results of a second experiment excluded this possibility. In all, the data demonstrate opposite effects of the two drugs on subjective alertness, suggesting opposite effects on vigilance. Opposite effects on memory were not established. This demonstrates that changes in alertness do not run in parallel with changes in memory. A scatter diagram, however, suggests a small effect of alertness on immediate recall. The effects of diazepam were also discussed in terms of the Atkinson and Shiffrin memory theory and it seems that diminished rehearsal processes are one of the key factors in explaining diazepam-induced amnesia.

Adult↗
PubMed1995

Differential effects of methylphenidate and self-reinforcement on attention-deficit hyperactivity disorder.

Six boys aged 9 to 12 years attended a tutoring class focusing on reading for 30 minutes each morning. The investigators employed a modified Latin-square design in which each child began with a 5-day baseline phase followed by six 10-day treatment phases that used drug placebo, noncontingent reinforcers, 0.3 mg/kg methylphenidate, 0.7 mg/kg methylphenidate, and self-reinforcement in various combinations. Amount of academic performance was the major measure of outcome and the target behavior of self-reinforcement. Drug placebo and noncontingent reinforcers had no systematic impact. Methylphenidate had differential effects across the recorded behaviors. Self-reinforcement improved the target behavior; the mean effect size for self-reinforcement was 2.66. The combined effects of methylphenidate and self-reinforcement on academic performance were greater than either of the treatments given alone (mean effect size = 2.89).

Attention Deficit Disorder with Hyperactivity↗
PubMed2000

Amelioration of specific working memory deficits by methylphenidate in a case of adult attention deficit/hyperactivity disorder.

Cognitive neuroscience has provided an extensive literature on the neuroanatomy and psychopharmacology of working memory. However, while it has been shown that children with attention deficit/hyperactivity disorder (AD/HD) have deficits in working memory, relatively little is known about working memory functions in adults diagnosed with AD/HD. Furthermore, it remains to be seen whether methylphenidate (Ritalin), which is used in the treatment of childhood AD/HD can improve performance deficits in adult AD/HD patients. We have used three paradigms of spatial working memory validated in cortical lesion patients, and psychopharmacological and neuroimaging studies, in order to examine the effects of methylphenidate administration in a case of an adult diagnosed with AD/HD. In the AD/HD patient at baseline testing, performance on a test of spatial recognition memory and on a task of self-ordered spatial working memory was shown to be impaired. Importantly, the impairments on the self-ordered spatial working memory task were ameliorated by an acute oral dose of methylphenidate (0.5 mg/kg). These findings provide insights into the possible neurochemical and neuroanatomical substrates of the action of methylphenidate in AD/HD and suggest a useful methodology for further research into this potentially debilitating disorder.

Adult↗
PubMed2000

Cerebral arteritis following methylphenidate use.

Stroke is a well-documented complication of amphetamine abuse. Methylphenidate, chemically and pharmacologically similar to amphetamines, is widely used in the treatment of attention deficit disorder in children. The possibility of vasculitis connected to methylphenidate should not be surprising. A case is reported of stroke associated with ingestion of methylphenidate in an 8-year-old boy. Family history was negative and other causes of vasculitis were excluded. We draw your attention to the risk of using methylphenidate for a long period of time.

Arteritis↗
PubMedDate not supplied

A phase II study of methylphenidate for depression in advanced cancer.

UNLABELLED: This study evaluated the use of methylphenidate for depression in advanced cancer DESIGN: Phase II open-label prospective study. ELIGIBILITY CRITERIA: No previous use of methylphenidate or current use of other antidepressants. EVALUATION: Depression and response to treatment were determined by asking the patient: "are you depressed?" Patients were assessed at baseline and at days 3, 5, and 7. TREATMENT: Starting dose was 5 mg at 8:00 a.m. and 12:00 noon. The dose was titrated for lack of response on any of the assessment days. RESPONSE CRITERIA: A negative response to the question: "are you depressed?" RESULTS: Some 41 patients were enrolled and 30 (15 men, 15 women) completed the study. Median age was 68 years (range: 30-90). Methylphenidate was stopped for six patients because of side effects and five were not evaluable; 21 responded to 10 mg/day on day 3; the other nine responded to 20 mg/day on day 5, 29 maintained their positive response through day 7. Anorexia, fatigue, concentration, and sedation also improved in some. All who completed the study had tolerable side effects, none of which caused treatment to stop. CONCLUSIONS: Methylphenidate is effective for depression in advanced cancer A starting dose of 10 mg in divided doses is effective in most patients. Dose escalation may be needed. Improvement occurs within three days. Close monitoring of side effects is recommended.

Adult↗
PubMedDate not supplied

Use of methylphenidate in patients with cancer.

Cancer and its treatment are often associated with symptoms such as depression, somnolence, cognitive abnormalities, and fatigue. Methylphenidate, a stimulant medication, is commonly used to treat these symptoms. Several small pilot and a few adequately powered studies have assessed the safety and efficacy of methylphenidate in patients with cancer Overall, the studies so far suggest that methylphenidate is well-tolerated in patients with cancer Further, the studies have provided initial evidence of efficacy of this agent in patients with cancer The present article reviews the evidence base behind the use of methylphenidate in these patients.

Central Nervous System Stimulants↗
PubMed1992

Fixed drug eruption of the scrotum due to methylphenidate.

OBJECTIVE: To report two cases of fixed drug eruption induced by methylphenidate. CASE SUMMARY: Two children with attention deficit disorder treated with methylphenidate as a simple drug developed fixed drug eruption of the scrotum. Drug discontinuation was followed by a complete resolution of the skin eruption. Rechallenge resulted in the same drug rash. Macrophage migration-inhibiting factor (MIF) assay with methylphenidate was positive. DISCUSSION: The pathogenesis of fixed drug eruption and the role of MIF assay in the diagnosis of adverse drug reaction is discussed. CONCLUSIONS: Fixed drug rash induced by methylphenidate is a possible but rare phenomenon.

Attention Deficit Disorder with Hyperactivity↗
PubMed2002

An experimental comparison of Pycnogenol and methylphenidate in adults with Attention-Deficit/Hyperactivity Disorder (ADHD).

Twenty-four adults (24 to 53 years old) with Attention-Deficit/Hyperactivity Disorder (ADHD), Combined Type, were studied in a double-blind, placebo-controlled, crossover study of Pycnogenol and methylphenidate. Pycnogenol is an antioxidant derived from the bark of the French maritime pine tree. Methylphenidate is a standard pharmaceutical intervention for ADHD. Anecdotal reports suggest that Pycnogenol improves concentration in adults with ADHD without adverse side effects. Participants received Pycnogenol, methylphenidate, and placebo, each for three weeks, in a randomized and counterbalanced order. Although ADHD symptoms improved during treatment, neither methylphenidate nor Pycnogenol outperformed the placebo control, as measured by self-report rating scales, rating scales completed by the individual's significant other, and a computerized continuous performance test. The conservative dosage levels and relatively brief length of treatment may have contributed to the absence of significant differences among treatment conditions. Implications for future research are noted.

Adjuvants, Immunologic↗
PubMed1998

Methylphenidate therapy improves cognition, mood, and function of brain tumor patients.

PURPOSE: Patients with malignant glioma develop progressive neurobehavioral deficits over the course of their illness. These are caused both by the effects of the disease and the effects of radiation and chemotherapy. We sought to determine whether methylphenidate treatment would improve these patients' neurobehavioral functioning despite their expected neurologic deterioration. PATIENTS AND METHODS: Thirty patients with primary brain tumors underwent neuropsychologic assessment before and during treatment with methylphenidate. Ability to function in activities of daily living and magnetic resonance imaging (MRI) findings were also documented. Patients were assessed on 10, 20, and 30 mg of methylphenidate twice daily. RESULTS: Significant improvements in cognitive function were observed on the 10-mg twice-daily dose. Functional improvements included improved gait, increased stamina and motivation to perform activities, and in one case, increased bladder control. Adverse effects were minimal and immediately resolved when treatment was discontinued. There was no increase in seizure frequency and the majority of patients on glucocorticoid therapy were able to decrease their dose. Gains in cognitive function and ability to perform activities were observed in the setting of progressive neurologic injury documented by MRI in half of the subjects. CONCLUSION: This study demonstrated improved patient function in the setting of a progressive neurologic illness. Methylphenidate should be more widely considered as adjuvant brain tumor therapy.

Adolescent↗
PubMed2003

Patient-controlled methylphenidate for the management of fatigue in patients with advanced cancer: a preliminary report.

PURPOSE: To assess the effects of patient-controlled methylphenidate for cancer-related fatigue. PATIENTS AND METHODS: In this prospective open study, 31 patients with advanced cancer and fatigue who scored >/= 4 on a scale of 0 to 10 received methylphenidate 5 mg by mouth every 2 hours as needed for 7 days (maximum, 20 mg/d). Multiple symptoms were assessed daily; the primary end point, fatigue, was measured using the 0 to 10 scale, and the Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F) was performed at baseline, day 7, and day 28. RESULTS: The following mean (+/- standard deviation) scores for 30 assessable patients improved significantly between baseline and day 7: fatigue (0 to 10 scale), 7.2 +/- 1.6 v 3.0 +/- 1.9 (P <.001); overall well-being (0 to 10 scale), 4.5 +/- 2.2 v 2.8 +/- 2.1 (P <.001); fatigue (FACIT-F) subscore, 17.5 +/- 11.3 v 34.7 +/- 10.0 (P <.001); functional well-being, 14.4 +/- 5.9 v 18.3 +/- 6.6 (P <.001); and physical well-being, 13.5 +/- 6.4 v 21.4 +/- 5.0 (P <.001). Anxiety, appetite, pain, nausea, depression, and drowsiness all improved significantly (P <.05). All patients took afternoon or evening doses, and 28 patients (93%) took three or more doses daily. All patients chose to continue taking methylphenidate after 7 days of treatment. No serious side effects were reported. CONCLUSION: These preliminary results suggest that patient-controlled methylphenidate administration rapidly improved fatigue and other symptoms. Randomized controlled trials are justified.

Adult↗
PubMed1982

The methylphenidate-induced stereotypy in the awake rat: local cerebral metabolism.

The local cerebral metabolic rate for glucose (1=CMRg) was computed in rats with methylphenidate-induced stereotypy using the quantitative 14C-2-deoxyglucose (2-DG) technique. Four rats received methylphenidate 15 mg per kilogram IP. Compared to five control animals, treated rats showed statistically significant (p less than or equal to 0.05) increases in 1-CMRg in globus pallidus, ventral lateral nucleus of the thalamus, subthalamic nucleus, red nucleus, substantia nigra, entopeduncular nucleus, inferior olivary nucleus, and the lateral cerebellar cortex. Significantly, 1-CMRg decreased in area 4 of the motor cortex. The auditory system showed no change in 1-CMRg, demonstrating the specific action of methylphenidate in the rat brain. This technique allows evaluation of the functional anatomy of the entire central nervous system and may be helpful in understanding the mechanisms of methylphenidate-induced stereotypy.

Animals↗
PubMed2005

Methylphenidate may treat apathy independent of depression.

OBJECTIVE: To report a case of apathy treated with methylphenidate in which improvement in apathy was independent of improvement of depression. CASE SUMMARY: A 47-year-old woman with a 20-year history of recurrent major depression was diagnosed as having significant apathy with lack of initiative and motivation. Over the course of a 4-week treatment regimen with methylphenidate, her apathy, as measured by the Apathy Evaluation Scale, improved, with her score decreasing from 57 to 31. During this period, her depression, as assessed by the 21-item Hamilton Rating Scale for Depression, remained unchanged. DISCUSSION: Our report of improvement of apathy with methylphenidate is consistent with other reports in the literature, although previous studies have not specifically used the rating scales to assess apathy. Even though this patient had experienced apathy for a long time, it had not been detected due to lack of direct questioning. In this case, as noted, the improvement of apathy was independent of improvement in depression. CONCLUSIONS: A high degree of suspicion and specific inquiry is required for identification of apathy. Once detected, methylphenidate may be beneficial in its treatment, a strategy that may work independently of augmentation of antidepressants.

Affective Symptoms↗
PubMed1987

Severe precocious emphysema in intravenous methylphenidate (Ritalin) abusers.

Intravenous (IV) drug abuse is known to cause pulmonary tale granulomatosis. Reports have documented a syndrome of pulmonary vascular sclerosis in long-term IV methylphenidate users. Although this would be expected to produce restrictive lung disease, we hereby report six patients who have severe obstructive lung disease. All had used IV methylphenidate for at least four years. One of these patients died of progressive respiratory insufficiency and the others are clinically disabled. Their symptoms and airflow obstruction are more severe than those of most patients with chronic obstructive pulmonary disease. In these individuals, we cannot say that precocious obstructive lung disease is not due to a combination of smoking and other factors, nor can we be certain that methylphenidate is the offending agent. However, this cluster of cases among methylphenidate abusers suggests that long-term IV exposure to this drug might lead to early severe obstructive lung disease.

Adult↗
PubMed2001

Randomized, controlled trial of oros methylphenidate once a day in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: A new once-a-day methylphenidate (MPH) formulation, Concerta (methylphenidate HCl) extended-release tablets (OROS MPH), has been developed. This study was conducted to determine the safety and efficacy of OROS MPH in a multicenter, randomized, clinical trial. METHODS: Children with attention-deficit/hyperactivity disorder (ADHD; n = 282), all subtypes, ages 6 to 12 years, were randomized to placebo (n = 90), immediate-release methylphenidate (IR MPH) 3 times a day (tid; dosed every 4 hours; n = 97), or OROS MPH once a day (qd; n = 95) in a double-blind, 28-day trial. Outcomes in multiple domains were assessed, and data were analyzed using analysis of variance and Kaplan Meier product limit estimates for time to study cessation. The primary time point for analysis was the last available patient visit using last observation carried forward. RESULTS: Children in the OROS and IR MPH groups showed significantly greater reductions in core ADHD symptoms than did children on placebo. This was true both at the end of week 1 and at the end of treatment on the basis of mean teacher and parent IOWA Conners ratings. IR MPH tid and OROS MPH qd did not differ significantly on any direct comparisons. Forty-eight percent of the placebo group discontinued early compared with 14% and 16% in the IR MPH and OROS MPH groups, respectively. CONCLUSIONS: For the treatment of core ADHD symptoms, OROS MPH dosed qd and IR MPH dosed tid were superior to placebo and were not significantly different from each other.attention-deficit/hyperactivity disorder, methylphenidate, OROS, Concerta.

Appetite↗
PubMed2004

The effect of methylphenidate on oppositional defiant disorder comorbid with attention deficit/hyperactivity disorder.

OBJECTIVE: To assess the effect of methylphenidate on the diagnosis of oppositional-defiant disorder (ODD) comorbid with attention-deficit hyperactivity disorder (ADHD). METHOD: We conducted an open-label study in which 10 children and adolescents with a dual diagnosis of ODD and ADHD were assessed for their ODD symptoms and treated with methylphenidate. At least one month after ADHD symptoms were under control, ODD symptoms were reevaluated with the Parent form of the Children Interview for Psychiatric Syndromes (P-ChIPS). RESULTS: Nine of the 10 patients no longer fulfilled diagnostic criteria for ODD after they were treated with methylphenidate for ADHD. CONCLUSION: Methylphenidate seems to be an effective treatment for ODD, as well as for ADHD itself. The implications for the treatment of patients with ODD not comorbid with ADHD needs further investigation.

Adolescent↗
PubMed1980

Behavioral and stimulant treatment of hyperactive children: a therapy study with methylphenidate probes in a within-subject design.

Eight hyperactive children were treated with a behavioral intervention focusing on teacher and parent training over a period of 5 months. Three times, before therapy and after 3 weeks and 13 weeks of intervention, children received methylphenidate during 3-week probe periods. Each week in a probe they received either a placebo, .25 mg/kg, or .75 mg/kg methylphenidate. Classroom observation of on-task behavior suggested that effectiveness of the behavioral intervention was between that of the two dosages of medication before therapy. Both dosages resulted in higher levels of on-task behavior when administered after 13 weeks of behavioral intervention than when administered before therapy. Teacher rating data showed equivalent effects of therapy and the low dosage of methylphenidate alone but a stronger effect of the high dose alone; only the high dose resulted in improved behavior after 13 weeks of behavioral intervention. As a group, only when they received the high dose of methylphenidate after 13 weeks of behavioral intervention did children reach the level of appropriate behavior shown by nonhyperactive controls. However, this level was also reached by two children with the low dose and by one child without medication, and it was not reached by one child. The results suggest that the combination of psychostimulant medication and behavior therapy may be more effective in the short-term than either treatment alone for hyperactive children in school settings. In addition, parent ratings and clinic observation of parent-child interactions suggested that children had improved in the home setting, high-lighting the importance of behavioral parent training in the treatment of hyperactivity.

Attention↗
PubMed1997

An evaluation of methylphenidate as a potential establishing operation for some common classroom reinforcers.

We conducted reinforcer assessments for 3 boys with a diagnosis of attention deficit hyperactivity disorder who alternately received either placebo or previously prescribed methylphenidate. Our purpose was to evaluate whether methylphenidate altered the relative reinforcing effectiveness of various stimuli that are often used in classroom-based behavioral treatment programs (e.g., activities, tangible items). Results showed clear differences for some stimuli between reinforcer assessments conducted when participants had received methylphenidate compared to placebo. Results suggest that methylphenidate might act as an establishing operation for some common classroom reinforcers. Implications for the development and evaluation of behavioral treatments are discussed.

Attention Deficit Disorder with Hyperactivity↗
PubMed1997

Safety issues in the use of methylphenidate. An American perspective.

Methylphenidate is the most widely use psychotropic medication in children in the US. It is both well tolerated and efficacious in the treatment of attention deficit hyperactivity disorder, and is associated with few serious adverse effects. However, the abuse of methylphenidate for the purpose of experiencing a 'high' is hazardous. The use of methylphenidate in combination with other medications increases the risk of adverse effects and drug interactions. Good communication between the physician, patient and family, together with monitoring, increases the likelihood that methylphenidate therapy will be effective and have no adverse consequences.

Attention Deficit Disorder with Hyperactivity↗