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PubMed2006

Methylphenidate (Ritalin)-associated cataract and glaucoma.

Methylphenidate hydrochloride (Ritalin) is the drug of choice for attention deficit hyperactivity disorder (ADHD). However, an association of Ritalin with glaucoma has been reported. We report a case of Ritalin-associated cataract and glaucoma. A 10-year-old boy was diagnosed with ADHD and had received methylphenidate hydrochloride, 60 mg/day for 2 years. He presented with blurred vision. Best-corrected visual acuity was 6/60 in both eyes. Ocular examinations revealed intraocular pressure (IOP) of 30 mmHg under medication, dense posterior subcapsular opacity of lens, pale disc with advanced cupping, and marked constriction of visual field. Despite maximal anti-glaucomatous medication, IOP still could not be controlled. The patient then received combined cataract and glaucoma surgery. Visual acuity improved and IOP was within normal limits in both eyes postoperatively. Large dose of methylphenidate may cause cataract and glaucoma. The mechanism remains unclear. Doctors should be aware of the possible ocular side effects of methylphenidate.

Attention Deficit Disorder with Hyperactivity↗
PubMed2001

Bupropion SR vs. methylphenidate vs. placebo for attention deficit hyperactivity disorder in adults.

Despite the increasing recognition of attention-deficit hyperactivity disorder (ADHD) in adults, there are few controlled trials demonstrating the effectiveness of pharmacological treatments, particularly with nonstimulants. One controlled trial found bupropion SR more effective than placebo in the treatment of ADHD adults. We conducted a controlled study to contrast the effectiveness of bupropion SR and methylphenidate to placebo in ADHD adults. A randomized, double-blind, parallel design was used in this study. Following a 7-day placebo lead-in, 30 ADHD (DSM-IV) subjects (18-60 years old) were randomized to bupropion, methylphenidate, or placebo for 7 weeks. Methylphenidate was titrated over 1 week to a maximum dose of 0.9 mg/kg/d divided into 3 doses while bupropion was titrated over 2 weeks to a maximum dose of 200 mg A.M. and 100 mg P.M. Response rates based on Clinical Global Impression improvement ratings in patients receiving bupropion, methylphenidate, and placebo were 64, 50, and 27%, respectively. The difference in response rates between active treatment and placebo was not statistically significant (p = 0.14). Neuropsychological testing demonstrated trends favoring drug treatment on measures of immediate recall and verbal fluency. While bupropion SR may be a viable clinical alternative for adults with ADHD, further investigation is needed.

Adrenergic Agents↗
PubMed2003

Motor timing deficits in community and clinical boys with hyperactive behavior: the effect of methylphenidate on motor timing.

In a previous paper we showed that community children with hyperactive behavior were more inconsistent than controls in the temporal organization of their motor output. In this study we investigated: (1) various aspects of motor timing processes in 13 clinically diagnosed boys with attention deficit hyperactivity disorder (ADHD) who were compared to 11 community boys with hyperactive behavior and to a control group and (2) the effect of methylphenidate on the motor timing processes in the clinical group with ADHD in a double blind, cross-over, medication-placebo design, including 4 weeks of medication. The clinical group with ADHD, like the community group with hyperactivity, showed greater variability in sensorimotor synchronization and in sensorimotor anticipation relative to controls. The clinical group was also impaired in time perception, which was spared in the community group with hyperactivity. The persistent, but not the acute dose, of methylphenidate reduced the variability of sensorimotor synchronization and anticipation, but had no effect on time perception. This study shows that motor timing functions are impaired in both clinical and community children with hyperactivity. It is the first study to show the effectiveness of persistent administration of methylphenidate on deficits in motor timing in ADHD children and extends the use of methylphenidate from the domain of attentional and inhibitory functions to the domain of executive motor timing.

Analysis of Variance↗
PubMed2004

[Does a morning dose of Methylphenidate Retard reduce hyperkinetic symptoms in the afternoon?].

OBJECTIVES: In order to treat children with Attention-deficit/Hyperactivity Disorder (ADHD) with a once-a-day stimulant several galenic approaches have been tried. The long acting methylphenidate (MPH, Medikinet-Retard) is a preparation with a two-step dynamic to release MPH (step one: acute; step two: prolonged). The efficacy of Medikinet-Retard, a new long-acting methylphenidate preparation, is analyzed based on the assessment of parents in the afternoon. METHODS: In a multicenter drug treatment study (placebo controlled, randomized, double-blind) 85 children (normal intelligence, age 6 to 16 years, diagnosis of ADHD according to DSM-IV) were investigated over 4 weeks with weekly visits. Forty-three children received Medikinet-Retard and forty-two children placebo. The weekly dose titration depending on body weight and symptomatology allowed a final maximum of 60 mg. The effects on ADHD as perveived by the parents were assessed weekly with a German symptom checklist for ADHD according to DSM-IV and ICD-10 (FBB-HKS). The differences between baseline and last week of treatment were compared statistically between groups. RESULTS: There was a large and statistically significant positive drug effect on ADHD symptomatology. The effect size of these differences was d = 1.2 (total score). Effects were found on inattention, hyperactivity and impulsity on the respective subscales. The efficacy of Medikinet-Retard was evaluated by the parents on an average as good. The rate of responders was four-times higher in the verum-group. The correlations of the changed scores in the parent ratings with the respective change scores in the teacher ratings were in the medium range. CONCLUSION: This is the first study with a German long-acting methylphenidate preparation (Medikinet-Retard). According to data based on parents' assessments, the drug showed very good clinical efficacy and safety in children with ADHD. Its two step galenic release of methylphenidate seems to be appropriate for a once-a-day (morning) stimulant in schoolchildren.

Adolescent↗
PubMed2000

An open study of methylphenidate in bipolar depression.

BACKGROUND: The treatment of bipolar depression is problematic. Mood stabilizing agents are often inadequate, while antidepressants may induce mania or mood destabilization. Methylphenidate has been advocated as an effective antidepressant agent in unipolar depression, and depression secondary to medical illness. Amphetamine administration has been shown to reduce manic behavior. These independent observations suggest that methylphenidate may be a safe and effective agent in bipolar depression. METHODS: Fourteen depressed subjects with DSM-IV bipolar illness and a Hamilton-depression (HAM-D) scale score of at least 15 had methylphenidate added to a stable mood stabilizer regiment. Patients were followed weekly for 4 weeks and then biweekly for an additional 8 weeks. RESULTS: HAM-D scores dropped from 16.9 +/- 1.79 SD at baseline to 9.4 +/- 9.73 on week 12 (p = 0.12, t = 1.84, df= 6) and 9.8 +/- 7.56 on last observation carried forward (LOCF) (p = 0.019, t = 2.8, df = 10). Psychiatric symptom assessment scale (PSAS) scores dropped from 17.9 +/- 5.63 at baseline to 4.8 +/- 7.47 at week 12 (p = 0.016, t = 4.02, df= 4) and 6.3 +/- 6.75 on LOCF (p = 0.007, t = 3.74, df = 7). Three individuals stopped secondary to anxiety, agitation, and hypomania, respectively. CONCLUSION: In this brief, open study, methylphenidate was effective and relatively safe in depressed bipolar subjects.

Adult↗
PubMed1998

Discriminative-stimulus and participant-rated effects of methylphenidate, bupropion, and triazolam in d-amphetamine-trained humans.

The discriminative-stimulus and participate-rated effects of a range of doses of d-amphetamine (2.5-20 mg), methylphenidate (5-40 mg), bupropion (50-400 mg), and triazolam (0.0625-0.5 mg) were tested in 5 humans trained to discriminate between oral d-amphetamine (20 mg) and placebo. d-Amphetamine and methylphenidate generally dose dependently increased drug-appropriate responding. Bupropion and triazolam on average occasioned less than or equal to 40% drug-appropriate responding. d-Amphetamine, methylphenidate, and bupropion produced stimulant-like participant-rated effects, while triazolam produced sedative-like effects. These results further demonstrate that the acute behavioral effects of d-amphetamine and methylphenidate overlap extensively in humans, which is concordant with preclinical studies. Bupropion produced some d-amphetamine-like, participant-rated drug effects but did not occasion significant levels of d-amphetamine-appropriate responding. These findings are concordant with previous findings of a dissociation between the discriminative-stimulus and participant-rated effects of drugs.

Adult↗
PubMed1998

Comparison of acute behavioral effects of sustained-release and immediate-release methylphenidate.

The rate of onset of a drug's effect is an important determinant of its abuse potential. This experiment examined the acute behavioral effects of orally administered sustained-release methylphenidate (SR; 20-40 mg), immediate-release methylphenidate (IR; 20-40 mg), and placebo in 10 healthy volunteers. Drug effects were assessed before drug administration and periodically afterwards for 6 hr using drug-effect questionnaires and performance measures that are sensitive to the acute effects of stimulants. The IR formulation produced stimulant-like drug effects (e.g., increased ratings of "good effects") that generally varied as a function of dose and time. The SR formulation produced only transient effects on these measures. These findings are consistent with previous research on the influence of rate of onset using other drugs and suggest that the abuse potential of IR methylphenidate may be greater than that of SR methylphenidate.

Adult↗
PubMed1998

Discriminative and participant-rated effects of methylphenidate in children diagnosed with attention deficit hyperactivity disorder (ADHD).

Despite the demonstrated beneficial effects of methylphenidate and d-amphetamine for the treatment of attention-deficit hyperactivity disorder (ADHD), the discriminative and subjective effects of these compounds in children are not well understood. This study was designed to characterize such effects in children diagnosed with ADHD. In a series of 3 experiments, 17 children were examined to determine whether methylphenidate (n = 12) and d-amphetamine (n = 5) could be reliably discriminated at doses typically used in clinical practice. Under some conditions (e.g., when they were instructed to attend to the drug effects or when a wide range of doses was used), children discriminated methylphenidate (5.0-30.0 mg) from placebo. Children tested under a range of doses of d-amphetamine (2.5-20.0 mg) were unable to discriminate this drug from placebo reliably. Neither methylphenidate nor d-amphetamine produced reliable participant-rated effects.

Adolescent↗
PubMed1997

Unexpected interaction of methylphenidate (Ritalin) with anaesthetic agents.

We report difficulty with conscious sedation of a child taking methylphenidate for attention deficit disorder and possible delayed adverse interaction of ketamine and methylphenidate resulting in severe nausea, vomiting and dehydration. The effects of methylphenidate and its potential interactions with anaesthetic agents is discussed. We suggest that anaesthesiologists who provide sedation or anaesthesia to patients receiving methylphenidate be aware of the potential need for high sedative doses and the possibility of undesirable interactions.

Anesthetics, Dissociative↗
PubMed1999

Effects of methylphenidate analogues on phenethylamine substrates for the striatal dopamine transporter: potential as amphetamine antagonists?

Methylphenidate (MPD) was found to inhibit competitively the striatal dopamine transporter (DAT) and bind at sites on the DAT in common with both cocaine (a non-substrate site ligand) and amphetamine (a substrate site ligand). Some methylphenidate analogues modified on the aromatic ring and/or at the nitrogen were tested to determine whether the profile of inhibition could be altered. None was found to stimulate the release of dopamine in the time frame (< or = 60 s) of the experiments conducted, and each of the analogues tested was found to noncompetitively inhibit the transport of dopamine. It was found that halogenating the aromatic ring with chlorine (threo-3,4-dichloromethylphenidate hydrochloride; compound 1) increased the affinity of MPD to inhibit the transport of dopamine. A derivative of MPD with simultaneous, single methyl group substitutions on the phenyl ring and at the nitrogen (threo-N-methyl-4-methylphenidate hydrochloride; compound 2) bound at a site in common with MPD. A benzyl group positioned at the nitrogen (threo-N-benzylmethylphenidate hydrochloride; compound 3) imparted properties to the inhibitor in which binding at substrate and non-substrate sites could be distinguished. This analogue bound at a mutually interacting site with that of methylphenidate and had a K(int) value of 4.29 microM. Furthermore, the N-substituted analogues (compounds 2 and 3), although clearly inhibitors of dopamine transport, were found to attenuate dramatically the inhibition of dopamine transport by amphetamine, suggesting that the development of an antagonist for substrate analogue drugs of abuse may be possible.

Algorithms↗
PubMedDate not supplied

The influence of methylphenidate on the sympathoadrenal reactivity in children diagnosed as hyperactive.

In order to investigate whether catecholamines play a role in the hyperkinetic child syndrome, we determined noradrenaline and adrenaline plasma levels before and after treatment with methylphenidate. The children were separated into drug responders and non-responders according to the efficacy of methylphenidate on behavioral symptoms. 21 children, 6-13 years of age, participated in this double-blind placebo controlled cross-over study. Conners' questionnaire was used to estimate the extent of the hyperactivity and to assess the drug response. Blood samples were drawn under resting and exercise conditions and plasma catecholamine concentrations determined as an indication of the amine release rate and the reactivity of the sympathoadrenal system. The results may be summarized: The postexercise noradrenaline levels of untreated hyperkinetic children were slightly, but not significantly higher than those of an age-matched control group. After 3-4 weeks of stimulant medication the noradrenaline release induced by physical exercise was significantly lower than after placebo. 12 out of 21 children showed an alleviation of their symptoms during methyl- phenidate therapy and thus could be assumed as drug-responders. When children were separated into drug-responders and non-responders according to the degree of the clinical improvement, both groups showed the same catecholamine release in response to exercise. Methylphenidate reduced the noradrenaline release in 9 out of 11 children in the responder group and in 7 out of 9 children in the non-responder group. In conclusion, catecholamines may be involved in the hyperkinetic child syndrome, but because of the heterogenity of this syndrome the depression of the plasma catecholamines as observed under methylphenidate could not differentiate between drug-responders and non-responders.

Adolescent↗
PubMed2002

Does extended medication with amphetamine or methylphenidate reduce growth in hyperactive children?

The purpose of the present study was to examine growth in children on extended stimulant treatment. Ninety-one hyperactive boys were studied, of whom 68 were treated with amphetamine and 23 with methylphenidate. The age range was 3-10 years. All children were treated with one of these stimulants for a minimum of 1 year. The yearly mean values for height and weight were all between the 25th and 90th percentile of the population norms. During the 1st year of treatment children who used amphetamine showed significantly smaller weight gains than those who used methylphenidate (F = 6.9, df = 64, P < 0.05). Four patients (17%) in the methylphenidate group and 21 (31%) in the amphetamine group had a weight loss during the 1st year, ranging from 0 to 9.5 kg. Within this group of 25 patients there was a significantly higher number of children with a pretreatment weight greater than that of the 50th percentile group (chi-square = 5.59, P < 0.05). All 25 patients showed sufficient weight gain at later examinations. Multiple regression analyses showed that neither cumulative doses nor age had a significant effect on growth when initial weight and height were controlled for. These findings indicate that, for most children, extended treatments with amphetamine or methylphenidate do not have negative effects on growth. However, some children show weight loss during the 1st year of treatment, more often when amphetamine is used. Among those children who may show reduced weight gain, most are above mean weight before treatment begins.

Adolescent↗
PubMed2001

Early methylphenidate administration to young rats causes a persistent reduction in the density of striatal dopamine transporters.

Methylphenidate is widely and effectively used for the treatment of attention deficit hyperactivity disorder during early childhood and adolescence, but until now possible effects of this treatment on brain development and the maturation of monoaminergic systems have not been investigated systematically. This experimental animal study describes the effects of methylphenidate administration (2 mg/kg/day) for 2 weeks to very young (prepubertal) and somewhat older (postpubertal) rats on the densities of dopamine, serotonin, and norepinephrine transporters in the striatum and in the midbrain. As shown by ligand-binding-assays, the K(D) values of all three transporters were unaffected by this treatment. No alterations were found for the Bmax values of [3H]-paroxetine and [3H]-nisoxetine binding, but the density of dopamine transporters (Bmax values of [3H]-GBR binding) in the striatum (but not in the midbrain) was significantly reduced after early methylphenidate administration (by 25% at day 45), and this decline reached almost 50% at adulthood (day 70), that is, long after termination of the treatment. This is the first empirical demonstration of long-lasting changes in the development of the central dopaminergic system caused by the administration of methylphenidate during early juvenile life.

Animals↗
PubMed2003

Response to methylphenidate in children with attention deficit hyperactivity disorder and manic symptoms in the multimodal treatment study of children with attention deficit hyperactivity disorder titration trial.

OBJECTIVE: Recent reports raise concern that children with attention deficit hyperactivity disorder (ADHD) and some manic symptoms may worsen with stimulant treatment. This study examines the response to methylphenidate in such children. METHODS: Data from children participating in the 1-month methylphenidate titration trial of the Multimodal Treatment Study of Children with ADHD were reanalyzed by dividing the sample into children with and without some manic symptoms. Two "mania proxies" were constructed using items from the Diagnostic Interview Schedule for Children (DISC) or the Child Behavior Checklist (CBCL). Treatment response and side effects are compared between participants with and without proxies. RESULTS: Thirty-two (11%) and 29 (10%) participants fulfilled criteria for the CBCL mania proxy and DISC mania proxy, respectively. Presence or absence of either proxy did not predict a greater or lesser response or side effects. CONCLUSION: Findings suggest that children with ADHD and manic symptoms respond robustly to methylphenidate during the first month of treatment and that these children are not more likely to have an adverse response to methylphenidate. Further research is needed to explore how such children will respond during long-term treatment. Clinicians should not a priori avoid stimulants in children with ADHD and some manic symptoms.

Attention Deficit Disorder with Hyperactivity↗
PubMed1998

Effectiveness of methylphenidate in Native American children with fetal alcohol syndrome and attention deficit/hyperactivity disorder: a controlled pilot study.

This pilot study was designed to assess the short-term effectiveness and side effects of methylphenidate in treating symptoms of attention deficit hyperactivity disorder (ADHD) in Native American children (5 to 12 years old) with documented fetal alcohol syndrome (FAS) or partial fetal alcohol syndrome. Using strict criteria for the diagnosis of FAS and ADHD, a randomized double-blind cross-over study of two placebos and a fixed dose of methylphenidate was completed in 4 Native American children in a residential school. Each treatment condition lasted 5 days, and daily observational outcome measures, the Conners Parent Rating Scale (CPRS-48), and the Conners Teacher Rating Scale (CTRS-39), were employed. Methylphenidate significantly improved scores of the Hyperactivity Index Scale on the CPRS-48 and the CTRS-39 but not the Daydreaming-Attention score on the CTRS-39. Side effects were similar to those traditionally found in other populations. The promising preliminary results suggest that a more definitive study of methylphenidate in Native and non-Native children with FAS and ADHD is warranted.

Adolescent↗
PubMed1980

Postoperative effects of methylphenidate.

A double-blind study is described in which the analgesic and analeptic properties of methylphenidate were investigated in 63 patients following surgery. No effect of methylphenidate on postoperative pain was observed. However, methylphenidate reduced sedation up to 30 min after operation, and improved respiratory function up to 180 min in patients receiving halothane. No conclusive evidence of improvement in mood was obtained, and occasional undesirable behavioural effects of methylphenidate were seen.

Adolescent↗
PubMed1986

Treatment of narcolepsy: objective studies on methylphenidate, pemoline, and protriptyline.

Methylphenidate, pemoline, and protriptyline were studied for their treatment efficacy in narcolepsy. A low, intermediate, and high dose level of each drug was studied for 1 week. For methylphenidate the doses were 10, 30, or 60 mg/day; for pemoline, 18.75, 56.25, or 112.5 mg/day; and for protriptyline 10, 30, or 60 mg/day. The order of dose levels was random from subject to subject and the daily dose was divided into thirds and taken in identically appearing capsules morning, noon, and afternoon. Subjects were 6 narcoleptic patients studied on methylphenidate (5 women and 1 man; mean age 54.5 + 11.7 years), 7 narcoleptic patients studied on pemoline (5 women and 2 men; mean age 43.0 + 7.1 years), and 4 narcoleptic patients studied on protriptyline (2 women and 2 men; mean age 42.5 + 16.9 years). Testing consisted of day-long sessions occurring at the end of each dose level and involving a clinical status questionnaire as well as maintenance of wakefulness, Wilkinson addition, and Digit-Symbol Substitution tests. Results were compared with 9 control subjects with no sleep disorder (5 women and 4 men; mean age 39.2 + 8.4 years) who were given placebo that was purported to be a "stimulant drug" and tested in a similar manner. Results demonstrated profound differences in ability to stay awake and perform between narcoleptic patients and controls. Data also suggested that methylphenidate significantly improves ability to stay awake. Pemoline seems to improve ability to perform. Protriptyline does not significantly alter ability to stay awake or to perform.

Adult↗
PubMedDate not supplied

Successful treatment of post-traumatic narcolepsy with methylphenidate: a case report.

Narcolepsy is a rare sequela of brain injury. We report the case of a 27-yr-old male with post-traumatic narcolepsy who was successfully treated with methylphenidate. This patient sustained moderate brain injury from a motorcycle accident. Subsequently, he manifested the classic tetrad of narcolepsy: cataplexy, excessive daytime sleepiness, sleep paralysis, and hypnogogic hallucinations. There was no premorbid seizure or sleep disorder. There was no family history of sleep disorders. Polysomnography and Multiple Sleep Latency Test confirmed the diagnosis of narcolepsy. Sleep latency (time to sleep onset), rapid eye movement sleep latency (time from sleep onset to rapid eye movement sleep onset), and mean multiple sleep latency were all pathologically shortened (2.5, 66, and 1.2 min, respectively). Twenty-four hour electroencephalographic monitoring and magnetic resonance imaging of the brain were normal, as were serum chemistries. Treatment with caffeine was unsuccessful. He was then started on methylphenidate, 10 mg twice daily, which was increased to 30 mg twice daily over a 4-mo period. Cataplexy and excessive daytime sleepiness started to improve 1 mo after adjustments in methylphenidate dosing. Six months after the initiation of methylphenidate therapy, the patient is completely asymptomatic.

Adult↗