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PubMed2006

Association of 4-repeat allele of the dopamine D4 receptor gene exon III polymorphism and response to methylphenidate treatment in Korean ADHD children.

In the present study, we investigated the association between the 4-repeat allele at the dopamine receptor D4 (DRD4) gene and the response to treatment with methylphenidate (MPH) in Korean children with attention deficit hyperactivity disorder (ADHD). The study subjects were 83 children with ADHD (8.40+/-1.73 years) who were recruited from two child psychiatric clinics in South Korea. All of the drug-naive ADHD children were treated with MPH for about 8 weeks. An improvement of more than or equal to [corrected] 50% in the ADHD Rating Scale-IV (ARS) scores after 8 weeks of treatment compared with the baseline ARS scores before the treatment was considered as a 'good response', whereas an improvement of less than [corrected] 50% was considered as a 'poor response'. After the genotyping for DRD4 was performed, we investigated the association between the genotype at DRD4 and the response to MPH treatment. We performed a comparison of the response to MPH treatment between the two largest groups, viz. the subjects with and without the 4/4 genotype at DRD4. According to the ARS scores of the subjects as assessed by their parents and by their teachers, we found that while 71.1 and 80.0% (32/45 and 24/30), respectively, of those with a good response to MPH treatment showed the 4/4 genotype at DRD4, only 31.6 and 37.7% (12/38 and 20/53), respectively, of those with a poor response to MPH treatment showed the 4/4 genotype at DRD4 (Pearson chi2-values=12.926 and 13.737, respectively, both df=1, and both p<0.01). Our findings support the existence of an association between the 4-repeat allele at DRD4 and good response to MPH in Korean ADHD children.

Alleles↗
PubMed2000

Effects of methylphenidate (Ritalin) on auditory performance in children with attention and auditory processing disorders.

A double-blind, placebo-controlled study was used to investigate the effects of methylphenidate (Ritalin) on tests of auditory processing in children diagnosed with both Attention Deficit Hyperactivity Disorder (ADHD) and Central Auditory Processing Disorder (CAPD). Thirty-two subjects received three Central Auditory Processing (CAP) tests and the Auditory Continuous Performance Test (ACPT), a measure of attention/impulsivity, at two separate test sessions: once when medicated with Ritalin and once when nonmedicated (placebo). Sixteen subjects were assigned randomly to receive their medication first and 16 to receive the placebo first. A counterbalanced 2 x 2 mixed factorial analysis of variance was conducted for each of the four dependent variables: Staggered Spondaic Word (SSW), Phonemic Synthesis (PS), Speech-in-Noise (SN), and ACPT measures. Analyses revealed that Ritalin did not have a significant effect on any of the three CAP measures. However, ACPT performance was significantly better (p < .000) for the Ritalin versus placebo condition.

Attention Deficit Disorder with Hyperactivity↗
PubMed2002

Methylphenidate hydrochloride for excessive daytime sleepiness in a patient with myotonic dystrophy.

A 28-year-old man with a history of myotonic dystrophy (MyD) is described. His progressively worsening excessive daytime sleepiness (EDS) was treated with methylphenidate hydrochloride. Polysomonography (PSG), the multiple sleep latency test (MSLT), middle latency-evoked response, and auditory event-related potentials were used to assess the cause of EDS. The PSG detected small numbers of central sleep apneic episodes. Mean sleep latency, which was determined by MSLT, increased from 5 min before treatment to 14 min after treatment. The Pa, P1, and N1 amplitudes at the Cz site increased after treatment, but P3 latency remained unchanged. These observations suggest that EDS and impairment of cognitive and information processing seen in a patient with MyD may be caused by a central nervous system disorder.

Adult↗
PubMed2003

Effect of methylphenidate on dopamine/DARPP signalling in adult, but not young, mice.

Methylphenidate (MPH), a dopamine uptake inhibitor, is the most commonly prescribed drug for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children. We examined the effect of MPH on dopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP-32) phosphorylation at Thr34 (PKA-site) and Thr75 (Cdk5-site) using neostriatal slices from young (14-15- and 21-22-day-old) and adult (6-8-week-old) mice. MPH increased DARPP-32 Thr34 phosphorylation and decreased Thr75 phosphorylation in slices from adult mice. The effect of MPH was blocked by a dopamine D1 antagonist, SCH23390. In slices from young mice, MPH did not affect DARPP-32 phosphorylation. As with MPH, cocaine stimulated DARPP-32 Thr34 phosphorylation in slices from adult, but not from young mice. In contrast, a dopamine D1 agonist, SKF81297, regulated DARPP-32 phosphorylation comparably in slices from young and adult mice, as did methamphetamine, a dopamine releaser. The results suggest that dopamine synthesis and the dopamine transporter are functional at dopaminergic terminals in young mice. In contrast, the lack of effect of MPH in young mice is likely attributable to immature development of the machinery that regulates vesicular dopamine release.

Aging↗
PubMed2001

Treatment for hyperactive children: homeopathy and methylphenidate compared in a family setting.

The sharp increase of the prescription of methylphenidate (MPD) in hyperactive children in recent years is a matter of increasing uneasiness among professionals, parents and politicians. There is little awareness of treatment alternatives. The purpose of this prospective trial was to assess the efficacy of homeopathy in hyperactive patients and to compare it MPD. The study was performed in a paediatric practice with conventional and homeopathic backgrounds. Children aged 3-17 y, conforming to the DSM-IV criteria for attention deficit hyperactivity disorder (ADHD) with a Conners Global Index (CGI) of 14 or higher were eligible for the study. All of them received an individual homeopathic treatment. When clinical improvement reached 50%, the parents were asked to reevaluate the symptoms. Those who did not improve sufficiently on homeopathy were changed to MPD, and again evaluated after 3 months. One hundred and fifteen children (92 boys, 23 girls) with a mean age of 8.3 y at diagnosis were included in the study. Prior to treatment the mean CGI was 20.63 (14-30), the mean index of the homeopathy group 20.52 and of the MPD-group 20.94. After an average treatment time of 3.5 months 86 children (75%) had responded to homeopathy, reaching a clinical improvement rating of 73% and an amelioration of the CGI of 55%. Twenty-five children (22%) needed MPD; the average duration of homeopathic (pre-) treatment in this group was 22 months. Clinical improvement under MPD reached 65%, the lowering of the CGI 48%. Three children did not respond to homeopathy nor to MPD, and one left the study. In cases where treatment of a hyperactive child is not urgent, homeopathy is a valuable alternative to MPD. The reported results of homeopathic treatment appear to be similar to the effects of MPD. Only children who did not reach the high level of sensory integration for school had to be changed to MPD. In preschoolers, homeopathy appears a particularly useful treatment for ADHD.

Adolescent↗
PubMedDate not supplied

Methylphenidate enhances both intracortical inhibition and facilitation in healthy adults.

Transcranial magnetic stimulation was used to investigate the effect of the psychostimulant drug methylphenidate (MPH) on motor cortex excitability in healthy adults (n = 12) in a placebo-controlled, crossover design study. MPH caused an enhancement of intracortical inhibition as well as intracortical facilitation. Enhancement of both of these TMS parameters was unexpected and suggests that MPH exerts its action on the motor cortex not only through the dopaminergic neurotransmitter system.

Adult↗
PubMed2003

Methylphenidate down-regulates the dopamine receptor and transporter system in children with attention deficit hyperkinetic disorder (ADHD).

Adults suffering from Attention Deficit Hyperactivity Disorder (ADHD) are known to have disturbed central dopaminergic transmission. With Single Photon Emission Computed Tomography (SPECT) we studied brain dopamine transporter and receptor activity in six boys with ADHD. Three months after initiation of treatment with methylphenidate we found a down-regulation of the post-synaptic dopamine receptor with a maximum of 20 % and a down-regulation of the dopamine transporter with a maximum of 74.7 % in the striatal system. This corresponded to a positive clinical response evaluated by neuropsychological questionnaires and tests. We suggest that dopamine transporter imaging by SPECT might be used to monitor psychostimulant treatment in children suffering from ADHD.

Attention Deficit Disorder with Hyperactivity↗
PubMed1984

Computer analyzed EEG in methylphenidate-responsive hyperactive children.

Computer-based analyses of the EEG-records were performed in 18 hyperkinetic children. Thirteen of these patients displayed a positive response to clinical treatment with methylphenidate. Discriminant analyses of native EEG-records and differences between the spectrums from the EEG with and without medication made it possible to properly classify 73.3 or 80%, respectively, of all patients. Even based on a relatively small sample it is possible to make predictions as to the effectivity of stimulant treatment solely on the basis of EEG-findings.

Attention Deficit Disorder with Hyperactivity↗
PubMed2004

Differential locomotor responses in male rats from three strains to acute methylphenidate.

Genetic variability is an important consideration in the study of the effect of drugs on humans and animals. Specifically, the effect of drugs on behavior varies from one rat strain to another. Methylphenidate (MPI), commonly known as Ritalin, is a psychostimulant with a pharmacological profile similar to amphetamine and cocaine, and is widely used in the treatment of attention deficit/hyperactivity disorder (ADHD). The purpose of this study was to examine the acute dose-response characteristics of MPD on three different male rat strains: spontaneously hypertensive/hyperactive rats (SHR), Wistar-Kyoto (WKY) rats, and Sprague-Dawley (SD) rats. Results showed clear differences in the pattern of behavioral response to the various MPD doses among the three rat strains. The 0.6 mg/kg MPD dose had no effect on any of the strains. At the dose of 2.5 mg/kg MPD, WKY rats reached peak locomotor activity within the initial 10 min, whereas SHR and SD rats reached peak activity in approximately 30 min. Furthermore, the effects on locomotor activity of SHR were longer in duration and higher in locomotor activity, whereas the effects on SD rats were shorter in duration and amplitude. Following the 10.0 mg/kg MPD, WKY, and SD mats reached their peak locomotor activity within 80 min post-injection, whereas SHR reached their peak locomotor activity within the initial 10 min post-injection. In addition, the SHR strain exhibited increased behavioral sensitivity to MPD as expressed by the latency, duration, and amplitude of their response. In conclusion, the dose-response experiment on the acute effects of MPD demonstrated that there are genetic differences in the responses to MPD.

Animals↗
PubMed1976

Chronic methylphenidate effects on learning in an F2 generation.

This study investigated chronic methylphenidate effects on the learning of undrugged second generation offspring. Seventy-two albino rats were tested on avoidance conditioning. The results indicated that (a) the learning of the undrugged offspring was affected, (b) differential sex effects were obtained, and (c) some difficulty was encountered in reproduction.

Animals↗
PubMed1994

Methylphenidate and information processing. Part 1: Differentiation between responders and nonresponders; Part 2: Efficacy in responders.

Part 1 of this study attempted to discriminate clinical responders and nonresponders to methylphenidate (MPH) on the basis of neuropsychological deficit profiles. Part 2 addressed the question to what extent MPH might ameliorate these deficits. Hyperactive clinical responders (n = 30) and nonresponders (n = 28) to MPH, were compared to normal controls (n = 27) on selective and sustained attention tasks and on conventional psychological and neurological measures. The responders took part in a randomized double-blind placebo-controlled crossover study. They ingested a placebo (PL) or MPH (0.3-0.6 mg/kg/day) during 4 weeks, and were then tested. After crossover, another period of 4 weeks was concluded by a second test series. Compared to controls, both responders and nonresponders showed attention deficits in encoding, memory search, and decision operations, as well as in focused and sustained attention, vigilance, and use of feedback. These deficits were the most severe in the responders. Anamnestic data, IQ scores, and neurological variables did not discriminate between groups. MPH selectively alleviates attention deficits. MPH did not affect divided attention, except for an increased accuracy of response organization. The drug, however, greatly improved focused and sustained attention, vigilance, impulsivity, and the behavioral adaptivity to feedback.

Attention↗
PubMed2002

Megadose intranasal methylphenidate (ritalin) abuse in adult attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is commonly co-occurring with other psychiatric disorders including substance use disorders. Stimulants have proven to be the pharmacological treatment of choice of ADHD along the life span. Contrary to media hype which compared the addictive potential of methylphenidate (MPD) to cocaine, only a handful of case studies on the abuse of prescription MPD by ADHD patients have been published. This case study centers on the treatment management and aftercare implications of an adult ADHD patient who abused 700 mg of prescribed MPD intranasally during a 3-day binge.

Administration, Intranasal↗
PubMed2005

Does methylphenidate improve inhibition and other cognitive abilities in adults with childhood-onset ADHD?

We examined the effect of methylphenidate (Mph) on inhibition and several other cognitive abilities in 43 adults with Attention Deficit Hyperactivity Disorder (ADHD) by use of Conners' Continuous Performance Test (CPT) and the Change Task (ChT), an extension of the Stop Signal Test (SST). In a double blind, cross-over, placebo controlled study with Mph, tests were administered during the third week of individually titrated treatment with Mph (maximum dose 1 mg / kg / day) and during the third week of treatment with placebo. We established large medication effects for commission errors, standard error of mean reaction time, and attentiveness on the CPT, as well as moderate medication effects for mean reaction time on the CPT and response re-engagement speed on the ChT. For Stop Signal Reaction Time (SSRT) on the ChT, we also established large effects of Mph, but only in a group of participants who showed slow SSRTs on placebo. Mph indeed ameliorates inhibition, which is the core problem of ADHD, and certain other cognitive abilities in adults with ADHD.

Adult↗
PubMed2004

Cost-effectiveness of dexamphetamine and methylphenidate for the treatment of childhood attention deficit hyperactivity disorder.

OBJECTIVE: To analyze from a health sector perspective the cost-effectiveness of dexamphetamine (DEX) and methylphenidate (MPH) interventions to treat childhood attention deficit hyperactivity disorder (ADHD), compared to current practice. METHOD: Children eligible for the interventions are those aged between 4 and 17 years in 2000, who had ADHD and were seeking care for emotional or behavioural problems, but were not receiving stimulant medication. To determine health benefit, a meta-analysis of randomized controlled trials was performed for DEX and MPH, and the effect sizes were translated into utility values. An assessment on second stage filter criteria ("equity", "strength of evidence", "feasibility" and "acceptability to stakeholders") is also undertaken to incorporate additional factors that impact on resource allocation decisions. Simulation modelling techniques are used to present a 95% uncertainty interval (UI) around the incremental cost-effectiveness ratio (ICER), which is calculated in cost (in A$) per DALY averted. RESULTS: The ICER for DEX is A$4100/DALY saved (95% UI: negative to A$14 000) and for MPH is A$15 000/DALY saved (95% UI: A$9100-22 000). DEX is more costly than MPH for the government, but much less costly for the patient. CONCLUSIONS: MPH and DEX are cost-effective interventions for childhood ADHD. DEX is more cost-effective than MPH, although if MPH were listed at a lower price on the Pharmaceutical Benefits Scheme it would become more cost-effective. Increased uptake of stimulants for ADHD would require policy change. However, the medication of children and wider availability of stimulants may concern parents and the community.

Adolescent↗
PubMed2001

Gabapentin and methylphenidate treatment of a preadolescent with attention deficit hyperactivity disorder and bipolar disorder.

Gabapentin is an anticonvulsant drug released in the United States in 1993 for use as adjunctive therapy in refractory partial epilepsy. The mechanism of action of gabapentin is unknown, but the drug has very favorable pharmacokinetics and a good safety profile, which allows its use in high-risk patients. Several reports have described the successful use of gabapentin for bipolar disorders in adults, but there are no controlled studies in the use of gabapentin in children and adolescents. We describe a 12-year-old boy with a history of attention deficient hyperactivity disorder (ADHD), reading disorder, mixed receptive and expressive language disorder, encopresis, and bipolar disorder II who was treated with gabapentin 200 mg/day added to methylphenidate 30 mg/day. Within 3 weeks the improvement and stabilization of mood symptoms was remarkable, as noted by mother, teacher, and clinician, and remained so for 6 months of follow-up. Comorbid bipolar disorder and ADHD is a hotly debated topic in the child and adolescent psychiatric literature, with rates of comorbid ADHD and bipolar disorder ranging from 22% to 90%. Controlled studies are needed to evaluate the possible antimanic mood stabilizing and/or antidepressant properties or gabapentin in youths.

Acetates↗
PubMed2001

Efficacy of Adderall and methylphenidate in attention deficit hyperactivity disorder: a reanalysis using drug-placebo and drug-drug response curve methodology.

Because methylphenidate (MPH) is currently the most widely prescribed medication for attention deficit hyperactivity disorder (ADHD), several studies have used this as the touch-stone for evaluating the efficacy of a newer stimulant, Adderall. In a parallel-groups study of MPH (n = 20), Adderall (n = 20), and placebo (n = 18), Pliszka et al. (2000) reported that both medications were superior to placebo in improving parent, teacher, and clinician ratings of ADHD and associated behaviors. Compared with MPH, Adderall led to significantly more improvements in teacher and clinician ratings. The present study extends these results by addressing the issue of clinical significance using drug-placebo and drug-drug response curve analyses of the same data. The goal of this method is to answer the following questions about drug-placebo or drug-drug differences: Is the effect clinically meaningful? What does the effect tell us about individual responses? Is the effect due to symptom improvement, the prevention of worsening, or both? Our results show that the efficacy of Adderall to improve functioning is seen throughout the full range of improvement scores. In contrast, MPH showed a substantial effect for "mildly" and "much improved" but not for "very much improved." Our analyses also show that both Adderall and MPH prevent worsening of symptoms. They further suggest that, compared with the Conners Teacher Rating Scale, the Clinical Global Impressions scale may be more sensitive to improvements at the "well end" of the spectrum of functioning.

Algorithms↗
PubMed2002

Methylphenidate-related growth impairment.

Growth deficit associated with stimulants in children who have attention deficit hyperactivity disorder (ADHD) has long been the subject of scientific discussion. More recent studies describe the effects on the final height of children with ADHD who are treated with methylphenidate (MPH) as only slight. There are only a handful of reports of severe growth deficits attributed to MPH that are associated with gastrointestinal side effects. We describe a 10-year-old boy with ADHD and chronic asthma who underwent corticosteroid therapy and developed an almost complete growth arrest during MPH treatment. Growth hormone (GH) stimulation tests and measurement of GH-dependent growth factors point to the influence of MPH on GH secretion with subsequent impaired growth. One may conclude that some children are at risk of serious growth decrement when treated with MPH. The growth of children should thus be monitored carefully, even if there are no alarming gastrointestinal side effects from MPH. We found that the determination of growth velocity was a sensitive marker for the evaluation of growth impairment in our patient.

Attention Deficit Disorder with Hyperactivity↗
PubMed2002

Methylphenidate improves Stroop naming speed, but not response interference, in children with attention deficit hyperactivity disorder.

OBJECTIVE: The goal of this study was to investigate the effect of methylphenidate (MPH) on response interference, as measured by the Stoop Color and Word Test, in children with attention deficit hyperactivity disorder (ADHD). Response interference is a core component of response inhibition that has been shown to be impaired in children with ADHD. METHODS: A clinic-referred sample of school-aged children with a confirmed Diagnostic and Statistical Manual of Mental Disorders (4th ed.) diagnosis of ADHD and good reading skills (n = 31) completed the Stroop Color and Word Test in an acute, randomized, placebo-controlled, crossover trial with three single fixed doses of MPH. RESULTS: MPH did not improve response interference on the Stroop Color and Word Test but did significantly improve color naming and word naming abilities. CONCLUSION: Response interference, as measured by the Stroop Color and Word Test, is not improved by MPH in children with ADHD. In addition, findings demonstrate strongly positive MPH effects on the highly effortful process of color naming, which has previously been demonstrated as impaired in children with ADHD. MPH was also shown to have a positive but smaller effect on word naming speed.

Attention Deficit Disorder with Hyperactivity↗