Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Methylphenidate”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 811 records · Page 45Linked to original sources
PubMed1992

Methylphenidate reduces abnormalities of stimulus classification in adolescents with attention deficit disorder.

Forty-eight adolescents with attention deficit disorder (ADD) received placebo and methylphenidate (M = 35.21 mg/day) for 3 consecutive weeks each. ADD patients who received placebo in the first phase of treatment were compared with unmedicated normal adolescents. ADD and normal adolescents did not differ in slope of reaction time as a function of memory load in a Sternberg (1969) memory task. These results may be interpreted as reflecting normal rates of memory search in ADD. However, in comparison with normal subjects, ADD subjects made disproportionately more errors to targets and lacked faster latencies of the P3b component of event-related potentials for targets than nontargets. These findings suggest abnormalities in stimulus classification. Methylphenidate did not affect ADD patients' rates of memory search, but it did reduce misclassifications of targets at high memory loads. The drug also evoked the normal pattern of slower P3b latencies for nontargets by shortening latencies for targets. Thus the stimulant reduced ADD adolescents' abnormalities in stimulus classification.

Adolescent↗
PubMed1989

Effects of methylphenidate on responding under extinction in the presence and absence of conditioned reinforcement.

Pigeons pecked a key during sessions that began with a variable number of reinforcers under a second-order schedule of food presentation. Every 30sec, on the average, a key peck was followed immediately by one of two consequences: (a) food presentation, accompanied by a stimulus complex that consisted of houselight off, key color change, tone presentation, and hopper-light illumination, or (b) the stimulus complex alone. Following the last food presentation, 20min of one of two types of extinction began. The two types of extinction were: (a) standard extinction (key pecks had no consequence) and (b) key pecks produced, on a variable-interval schedule, the stimulus complex previously paired with food. Consequently, it was possible to study performance under extinction during which responses either did or did not result in occasional presentation of a food-paired stimulus complex. Methylphenidate (5, 10 and 20mg/kg) occasionally was administered before sessions containing each type of extinction. At moderate doses methylphenidate produced higher response rates during extinction when the stimulus complex was presented than when it was not. These results support previous findings with rats that stimulant drugs can enhance responding during extinction when responding produces conditioned reinforcers, and illustrate this effect in a novel, within-subject design.

Journal Article↗
PubMed1999

Neuropsychological correlates of methylphenidate treatment in adult ADHD with and without depression.

The purpose of this study was to characterize the neuropsychological profiles of adult patients with attention deficit hyperactivity disorder (ADHD) alone and ADHD with active comorbid depression, and to evaluate changes in the neuropsychological profile in these two groups following a trial of methylphenidate. Forty patients with ADHD were classified into two groups based on their affective status resulting in a group of 21 patients with ADHD alone and 19 patients with ADHD and active comorbid symptoms of depression (ADHD-D). All subjects received a comprehensive neuropsychological evaluation including measures of cognitive, motor and affective functioning before and after treatment. Fifteen normal controls were also assessed at a yoked time interval. At baseline, both patient groups showed impairment in verbal memory, motor and processing speed, visual scanning, and auditory and visual distractibility. Following treatment, both patient groups showed improvement across all neuropsychological measures while controls remained relatively stable over time. Improvement in neuropsychological test performance was not related to gender, affective status or referral source. Patients with active comorbid symptoms of depression show a similar neuropsychological profile and appear equally likely to benefit from methylphenidate intervention as patients with ADHD alone.

Journal Article↗
PubMed1977

Gilles de la Tourette's syndrome. Familial occurrence and precipitation by methylphenidate therapy.

Gilles de la Tourette's syndrome was independently ascertained in two male cousins once removed. Previous studies have shown familial clustering of individuals with tics, but no consistent pattern of inheritance of Tourette's syndrome has been apparent. The onset and later exacerbation of symptoms in our younger patient were associated with the administration of CNS stimulants given for excessive motor activity. The adverse effects of methylphenidate and dextroamphetamine therapy on Tourette's syndrome supports the hypothesis that this condition results from a relative excess of CNS catecholaminergic activity. Physicians prescribing these agents should inquire about the presence of tics in patients and their families.

Adult↗
PubMed1985

Methylphenidate therapy for aggression in a man with ring 22 chromosome. Report and literature review.

A 28-year-old mentally retarded man with ring 22 chromosome [r(22)] had deterioration of mood and behavior, decreased speech, bradykinesia, and decline of fine motor skills over a three-year period, which were further exacerbated by treatment with phenothiazines. A trial of methylphenidate hydrochloride resulted in rapid improvement of mood, behavior, and to a small extent, motor function. This finding suggests that dopamine depletion may play a role in the behavioral deterioration seen in this disorder. The possibility that genes that control dopamine metabolism may be present on chromosome 22 is raised. The phenotype of this patient is compared with the 25 reported cases of r(22).

Adult↗
PubMed2005

Continuity of methylphenidate treatment for attention-deficit/hyperactivity disorder.

OBJECTIVE: To compare the continuity of methylphenidate hydrochloride (MPH) therapy among youth Medicaid beneficiaries treated for attention-deficit/hyperactivity disorder with immediate-release (IR) or extended-release (ER) MPH formulations. Method An analysis was conducted of statewide California Medicaid claims (2000-2003) focusing on children and adolescents, ages 6 to 17 years, who started ER-MPH or IR-MPH treatment for attention-deficit/hyperactivity disorder. The study cohorts were limited to youth who had not filled a prescription for MPHs, amphetamines, pemoline, or atomoxetine for 6 months preceding the index prescription and remained eligible for Medicaid benefits for the following 12 months. The study groups were compared with respect to background demographic traits and clinical characteristics. Mean and median duration of MPH treatment episodes were defined to terminate if a gap of 30 or more days occurred from the end of the last prescription supply to the start of the next prescription. Survival time ratios were used to assess treatment duration controlling for group differences in background characteristics. RESULTS: As compared with patients initiating IR-MPH treatment, patients initiating ER-MPH treatment had a significantly longer mean estimated duration of treatment (ER-MPH, 140.3 days [95% confidence interval (CI), 136.3-144.4 days] vs IR-MPH, 103.4 days [95% CI, 101.3-103.4 days]). Similar results were found in analyses stratified by patient age, race/ethnicity, and sex. Controlling for group differences in age, sex, race/ethnicity, coprescribed psychotropic medications, other treated mental disorders, case management, managed care participation, and seasonal effects, ER-MPH treatment initiation was associated with an average 37% longer duration of treatment than IR-MPH treatment (survival time ratio, 1.37 [95% CI, 1.32-1.42]). Among patients treated with ER-MPH, treatment initiation with an osmotic release oral system MPH (Concerta) was associated with significantly longer mean duration (147.2 days [95% CI, 142.6-151.7 days]) than treatment initiation with Metadate CD (controlled delivery) (113.0 days [95% CI, 100.9-125.1 days]) or Ritalin LA (long acting) (101.1 days [95% CI, 91.2-111.0 days]), respectively. CONCLUSIONS: Extended-release MPH formulations were associated with greater continuity of MPH treatment than IR formulations in the study population. Initial selection of an ER formulation may help to prolong continuity of MPH therapy among youth Medicaid beneficiaries with attention-deficit/hyperactivity disorder.

Adolescent↗
PubMed2000

Analysis of methylphenidate and its metabolite ritalinic acid in monkey plasma by liquid chromatography/electrospray ionization mass spectrometry.

Methylphenidate (MP, Ritalin) is a psychotropic drug widely prescribed to children for treating the symptoms of attention deficit disorder with and without hyperactivity. Because little information exists about the effects of chronic MP administration on cognitive function in children, measures of behavior changes in non-human primates are important surrogates. An essential component of such studies is the determination of MP plasma levels under chronic and acute dosing conditions. An analytical method was developed that provided sufficient sensitivity to measure low levels of the active parent drug (lower limit of quantitation = 0.25 ng/mL) and the inactive metabolite, ritalinic acid (RA), in monkey plasma as well as the ability to conveniently analyze large numbers of samples. The method uses a polymeric reversed-phase sorbent for solid phase extraction, an efficient reverse-phase high performance liquid chromatography (HPLC) separation, deuterated internal standards for isotope dilution quantification of MP and RA, and detection by sensitive electrospray ionization mass spectrometry (ES-MS) with a single quadrupole instrument. The method responses are linear over the range of plasma concentrations of MP and RA observed in monkeys, gives respective analyte recoveries of 75 and 60% with reasonable precision and accuracy, and demonstrates robust MS performance for rapid determination of MP/RA plasma levels. The average peak MP concentration (ca. 16 ng/mL) and half-lives for MP and RA elimination in monkeys (1.79 and 2.31 h, respectively) were not significantly different under acute vs. chronic dosing conditions and were comparable to values previously reported from human studies.

Animals↗
PubMed2000

Liquid-liquid extraction using 96-well plate format in conjunction with liquid chromatography/tandem mass spectrometry for quantitative determination of methylphenidate (Ritalin) in human plasma.

Methylphenidate (MPH; Ritalin: methyl-alpha-phenyl-2-piperidinacetate hydrochloride) is utilized for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. Recently, we described a rapid enantioselective liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the determination of the enantiomers of MPH (Rapid Commun. Mass Spectrom. 1999; 13: 2054). A lower limit of quantification (LLOQ) of 87 pg/mL was attained for the human plasma assay. The present paper describes a high-throughput sample preparation procedure in conjunction with racemic LC/MS/MS analysis for MPH with a LLOQ of 50 pg/mL. A semi-automated robotics method using liquid-liquid extraction (LLE) in a 96-well plate format was developed and validated. The correlation coefficients were > or =0.998 for MPH indicating good fits of the regression models over the range of the calibration curve. The accuracy and precision of the semi-automated approach were comparable to those obtained using the manual sample preparation technique reported previously (vide supra). The current method can easily be adapted to the enantioselective LC/MS/MS assay of MPH. The assay was simple, fast, specific, and exhibited excellent ruggedness.

Attention Deficit Disorder with Hyperactivity↗
PubMed1999

Methylphenidate treatment for bulimia nervosa associated with a cluster B personality disorder.

OBJECTIVES: Psychotherapy and antidepressant medication are helpful to many patients with bulimia nervosa (BN). However, a substantial number of bulimics respond poorly to such treatments. Recent studies suggest that many of the poor responders have cluster B personality disorders. In some ways, the symptomatology of bulimics who have a comorbid cluster B disorder resembles that of patients with attention deficit hyperactivity disorder (ADHD). In particular, individuals in both groups frequently have a high level of impulsivity. Such a resemblance raised the question of whether administration of methylphenidate (MPH), a drug used to treat ADHD, would have therapeutic effects in this subgroup of BN patients. METHODS: In a pilot study, we administered MPH to 2 patients with BN and cluster B traits and found beneficial effects. These patients had not responded to adequate trials of psychotherapy and selective serotonin reuptake inhibitors (SSRIs). RESULTS: MPH treatment was effective. Both Patients had decreased binging and purging. DISCUSSION: MPH may be useful for bulimics with cluster B personality disorder who respond poorly to conventional treatment. Further studies of MPH administration may be worthwhile. Due to the potential risks, however, clinical treatment with this agent is not recommended at this time.

Adult↗
PubMed2000

Synergistic interactions between nicotine and cocaine or methylphenidate depend on the dose of dopamine transporter inhibitor.

There is a greater prevalence of cigarette smoking among cocaine-dependent individuals and hyperactive children treated with stimulants (e.g., methylphenidate, MP). However, little is known about the neurochemical basis of the interaction between nicotine and cocaine or MP. It is thought that the reinforcing effects of cocaine and MP are due partly to increases in synaptic DA in the nucleus accumbens (NAc). These measurable increases are secondary to the blockade of the DA transporter. In contrast, nicotine stimulates acetylcholine receptors located presynaptically on dopaminergic projections from the ventral tegmental area (VTA) to the NAc and increases DA transmission. Here we investigate the effects of nicotine on NAc DA in animals simultaneously injected with cocaine or MP. Coadministration of nicotine (0.4 mg/kg s.c.) and cocaine (10 mg/kg i.p.) or MP (5 mg/kg i.p.) increased the extracellular NAc DA levels in an additive manner, while coadministration of nicotine (0. 4 mg/kg s.c.) and a higher dose of cocaine (20 mg/kg) or MP (10 mg/kg) clearly produced a synergistic elevation in NAc DA. These findings suggest that the degree of DA transporter (DAT) occupancy contributes to the synergistic interaction between nicotine and cocaine or MP.

Animals↗
PubMed2007

No significant association between response to methylphenidate and genes of the dopaminergic and serotonergic systems in a sample of Brazilian children with attention-deficit/hyperactivity disorder.

Few studies on pharmacogenetics of Attention-Deficit/Hyperactivity Disorder (ADHD) have been conducted. Most of them evaluated dopaminergic genes resulting in positive and negative findings. We assessed effects of polymorphisms in candidate dopaminergic (DRD4, DAT1) and serotonergic genes (HTR1B, HTR2A, and 5-HTT) on the response to treatment in 111 patients for whom methylphenidate (MPH) was prescribed. Outcome measures (Swanson, Nolan, and Pelham scale-version IV, Children Global Assessment Scale, Barkley's Stimulants Side Effects Rating Scale) were assessed at baseline and 1 month after the intervention. No significant association was detected between polymorphisms assessed and both response and side effects to MPH. Prospective multi-site controlled studies with larger sample sizes are needed in order to disentangle the role of candidate genes in response to ADHD treatment.

Adolescent↗
PubMedDate not supplied

The absorption of sustained-release methylphenidate formulations compared to an immediate-release formulation.

A crossover study in 18 subjects evaluated the plasma concentration-time profile of two different 20 mg sustained-release (SR) methylphenidate (MPH) tablets administered before breakfast, compared to a 10 mg immediate-release (IR) tablet administered before breakfast and again 5 h later, before lunch. Plasma MPH concentrations were determined using a sensitive and precise gas chromatography-mass spectrometry method, incorporating a deuterated internal standard. The mean peak MPH concentration was 6.4 ng ml-1 for the IR product versus 4.6 ng ml-1 and 4.8 ng ml-1 for the two SR formulations. Peak concentrations occurred at 3.3 h after dosing with the SR products, compared to 1.5 h after the first dose of the IR product. The extent of absorption for the three products, as determined from areas under the plasma concentration-time curves, were within 5 per cent of each other. There was no significant difference in rate or extent of absorption between the two SR formulations.

Biological Availability↗
PubMed2004

In vitro dissolution and in vivo oral absorption of methylphenidate from a bimodal release formulation in healthy volunteers.

PURPOSE: The objective of this study was to evaluate the in vitro dissolution and in vivo absorption of D,L-threo-methylphenidate (MPH) from a novel bimodal release formulation (Ritalin LA capsule) compared with an immediate-release formulation (Ritalin IR tablet) in healthy volunteers. METHODS: The bimodal release formulation contains 50% of the dose in the immediate-release (IR) beads and 50% in polymethacrylate-coated, delayed-release (DR) beads. To better understand the impact of dissolution from the DR beads on oral absorption of MPH, three Ritalin LA formulations with different dissolution profiles for the DR beads (referred to as slow-, medium and fast-release formulations) were prepared, and tested together with the immediate-release formulation in 18 healthy male and female volunteers after a single oral dose under fasted conditions. The rate and extent of oral absorption of MPH were evaluated based on the overall Cmax, tmax and AUC values, as well as the Cmax, tmax and AUC values for each individual peak of the bimodal plasma concentration-time profile. The in vivo absorption-time profile was also examined by deconvolution. RESULTS: All three Ritalin LA formulations demonstrated similar bimodal plasma concentration-time profiles with two peak concentrations observed at approximately 2 and approximately 6 h post dose, mimicking that of Ritalin IR tablets given 4 h apart. Deconvolution results showed that the absorption of MPH was biphasic, with a rapid absorption phase between 0 to approximately 2 h, and a somewhat slower second absorption between approximately 3-6 h, consistent with the in vitro bimodal release characteristics of Ritalin LA formulation. The three Ritalin LA formulations were bioequivalent to one another based on the overall Cmax and AUC values and the corresponding values describing the first and second peaks, although their in vitro dissolution profiles for the DR beads were different. Compared with Ritalin IR, the Ritalin LA formulation demonstrated a similar rate of absorption for the first peak, a lower second Cmax and a higher trough concentration between peaks, as well as similar overall plasma AUC. CONCLUSIONS: Following a single oral drug administration, Ritalin LA demonstrated a two-peak plasma concentration-time profile, similar to that of the IR formulation given 4 h apart, but with less fluctuation in the plasma concentration-time profile. The in vivo biphasic absorption of MPH appeared to be well correlated with the bimodal dissolution characteristics of this new Ritalin LA formulation, and some changes in the dissolution profiles for the DR beads appeared not to affect the overall bioavailability of MPH in humans.

Administration, Oral↗
PubMed2004

Toxicokinetic assessment of methylphenidate (Ritalin) in a 13-week oral toxicity study in dogs.

Ritalin or methylphenidate (MPH) is often prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. The therapeutic activity of MPH is principally due to D-threo-[2R,2'R]-MPH. Hence, in order to establish a kinetic relationship between doses and exposure levels in a non-rodent species, a 13-week oral (capsule) toxicity study of D-threo-[2R,2'R]-MPH was performed in beagle dogs. A previously reported chiral liquid chromatography tandem mass spectrometry (LC-MS/MS) with a limit of quantification (LLOQ) of 1.09 ng/ml was utilized. The results of this study indicated that MPH appeared to be rapidly absorbed in dogs following oral administration. The peak concentration was reached within 1-2 h. Based on the area under the curve (AUC) values, the plasma exposure of D-MPH was over-proportional to the dose. With the exception of two groups of animals (male/female, 7.5 mg/kg/day on day 1 and male/female, 3.0 mg/kg/day on week 7), the data showed no difference in MPH concentrations between the male and female dogs. Taking the statistical variations into account, concentrations of D-MPH that were observed after 7.5 mg/kg/day doses of D-MPH and 15 mg/kg/day doses of the racemate were similar. Following the racemate doses, the concentrations of L-MPH were consistently higher than those of the D-isomer. No accumulation of MPH was observed after 13 weeks of repeated daily administration.

Administration, Oral↗
PubMed2004

Toxicokinetic assessment of methylphenidate (Ritalin) enantiomers in pregnant rats and rabbits.

Ritalin or methylphenidate (MPH) is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. The present report describes the determination of plasma concentrations of D-threo- and L-threo-enantiomers of MPH in toxicokinetic (TK) studies in pregnant Wistar Hannover rats and New Zealand white rabbits following repeated daily oral dosing of D,L-MPH (racemate). A previously reported chiral liquid chromatography tandem mass spectrometric (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1.09 ng/mL was utilized. Oral (gavage) doses of 7, 25 and 75 mg/kg/day of racemic MPH were selected for the rat study. An over-proportional increase in exposure was observed with increasing doses of MPH racemate, the effect being more profound with the D- than the L-enantiomer. In contrast, Cmax values of both enantiomers were approximately proportional to the dose. Oral (gavage) doses of 20, 60 and 200 mg/kg were selected for the rabbit study. In general, for the D-isomer, an over-proportional increase in exposure was observed with increasing doses of MPH racemate. Conversely, for the L-isomer, a slight under-proportionality was detected in exposure with increasing doses of D,L-MPH. For mean Cmax, while L-isomer exhibited dose proportionality with increasing doses of MPH racemate, the D-isomer appeared to be over-proportional. Herein, the experimental design and observed TK parameters in each study are presented.

Animals↗
PubMed1991

In vitro hydrolysis of RR,SS-threo-methylphenidate by blood esterases--differential and enantioselective interspecies variability.

Enantioselective in vitro hydrolysis of methylphenidate (MPH) by the blood esterases of seven mammalian species is reported. The species included rats, rabbits, dogs, cattle, horses, monkeys, and humans. In vitro incubations up to 8 h were carried out in plasma, red blood cells, and whole blood of the various species. Enantioselective differences were evident among the different species on comparison of the data obtained from the three biological fluids. The esterases present in plasma appeared to show greater activity in the hydrolysis of MPH in all species where comparison with the other two biofluids was possible. Only in the case of humans did esterases present in plasma and red blood cells demonstrate opposite enantioselectivity in the hydrolysis of MPH. Thus after 8 h incubation, the RR-MPH/SS-MPH ratios in plasma and red blood cells were 0.31 and 1.16, respectively.

Animals↗
PubMed2002

Subchronic methylphenidate administration has no effect on locomotion, emotional behavior, or water maze learning in prepubertal mice.

Methylphenidate hydrochloride (Ritalin, MPH) is frequently prescribed as a treatment for children with attention deficit hyperactivity disorder (ADHD), yet little research has been conducted to determine its potential long-term neurobehavioral effects. We assessed the effects of subchronic MPH administration (2.5, 5, 10, 20, 40, or 80 mg/kg) on male CD-1 mice treated from 26 to 32 days of age. When tested at 33 days of age in the open field and elevated plus maze, there were no significant differences in spontaneous locomotion, exploration, or fear- and anxiety-related behaviors. Testing from 34 to 37 days of age in a water maze task revealed no significant effects of any dose of MPH on learning in this simple paradigm. While it is difficult to extrapolate directly from these results to clinical effects in humans, our results indicate that preexposure of mice to MPH late in the postnatal developmental period does not appear to alter later behavior. We are currently conducting additional studies to further probe the potential effects of MPH administration during development and to examine various contributing factors including stage of development, duration of MPH administration, complexity of the task used to assess behavioral changes, and type of cognitive process being analyzed (attention, nonspatial working memory, etc.).

Affect↗