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Journal of Clinical Pharmacology Feb 2004Attention deficit hyperactivity disorder (ADHD) in children is effectively treated by racemic oral methylphenidate (dl-MPH). The d-isomer (d-MPH) has been developed as... (Clinical Trial)
Clinical Trial
Attention deficit hyperactivity disorder (ADHD) in children is effectively treated by racemic oral methylphenidate (dl-MPH). The d-isomer (d-MPH) has been developed as an improved treatment for ADHD since only half the racemic dose is used. This study, performed in healthy subjects, assessed the effect of food on the pharmacokinetics of dexmethylphenidate hydrochloride (d-MPH HCl) in a single dose (2 x 10-mg tablets), two-way crossover with d-MPH administered to subjects in both a fasting state or after a high-fat breakfast. There were no serious or unexpected adverse events during the course of this study, with most events reported in comparable numbers of fed and fasted subjects. The bioequivalence of d-MPH was similar with or without food, with 90% confidence intervals of 88.2% to 104.6% and 105.9% to 118.2% for ln(C(max)) and ln[(AUC(0-infinity))], respectively. There was a marginal but statistically significant 1-hour increase in t(max) in the fed versus fasted state, reflecting an absorption delay. The rate of formation of the major metabolite, d-ritalinic acid (d-RA), was marginally decreased ( approximately 14%) after food. The extent of exposure to d-RA was similar (within 1.2%) between both treatments. There was a marginal but statistically significant difference in mean t(max) for d-RA between fed and fasted conditions, with peak concentration occurring 1.5 hours later after d-MPH administration with food. There was no measurable in vivo chiral inversion of d-MPH to l-MPH in plasma. In addition, the metabolism of d-MPH was stereospecific as d-MPH only produced d-RA. In summary, food had no substantial effect on the bioavailability of d-MPH, with an equivalent rate and extent of exposure obtained. Therefore, d-MPH can be administered without regard to food intake.
Topics: Adult; Area Under Curve; Biological Availability; Central Nervous System Stimulants; Cross-Over Studies; Dexmethylphenidate Hydrochloride; Fasting; Female; Food-Drug Interactions; Half-Life; Humans; Intestinal Absorption; Male; Methylphenidate; Postprandial Period; Stereoisomerism; Therapeutic Equivalency
PubMed: 14747426
DOI: 10.1177/0091270003261899 -
Postgraduate Medicine Sep 2008Attention-deficit/hyperactivity disorder (ADHD) is associated with impairments in educational, occupational, neuropsychological, and social functioning in adults.... (Review)
Review
Attention-deficit/hyperactivity disorder (ADHD) is associated with impairments in educational, occupational, neuropsychological, and social functioning in adults. Successful diagnosis and treatment of the disorder in adults can be a challenge because recent and integrative clinical guidelines are lacking and diagnostic criteria are based on making a retrospective diagnosis of childhood-onset ADHD. To develop evidence-based recommendations for the treatment of ADHD in adults, the scientific literature was reviewed, including primary clinical studies, meta-analyses, and available clinical guidelines. Studies show that stimulant therapy is highly effective and safe in the management of ADHD in adults, with similar response rates to those reported in children at doses that are equivalent on a mg/kg basis. Long-acting stimulants, such as OROS methylphenidate (OROS MPH, Concerta), dexmethylphenidate (d-MPH, Focalin), and mixed amphetamine salts extended release (MAS XR, Adderall XR), have durations of action of up to 10 to 12 hours, which permit once-daily dosing. For adults with ADHD who do not respond to stimulant therapy or who have a comorbid condition in which a stimulant is contraindicated, the nonstimulant atomoxetine (Strattera) may be an appropriate alternative. For many adults, cognitive-behavioral therapy in addition to pharmacotherapy may improve treatment response. Attention-deficit/hyperactivity disorder medications may increase blood pressure and heart rate in adults, so patients should be monitored.
Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Cognitive Behavioral Therapy; Humans; Practice Guidelines as Topic
PubMed: 18824823
DOI: 10.3810/pgm.2008.09.1905 -
Expert Opinion on Pharmacotherapy 2015Attention deficit/hyperactivity disorder (ADHD) persists into adulthood in about 50% of the affected children, with high rates of comorbidity with bipolar disorder (BD).... (Review)
Review
INTRODUCTION
Attention deficit/hyperactivity disorder (ADHD) persists into adulthood in about 50% of the affected children, with high rates of comorbidity with bipolar disorder (BD). Stimulants and atomoxetine (ATX) are effective treatments for ADHD, but their use in adults with comorbid BD (ADHD-BD) has not been extensively studied and may be problematic.
AREAS COVERED
The aim of the paper is to summarize the available literature regarding the use of these medications in ADHD-BD adult patients. Results of randomized-controlled and open-label trials, case reports, and case series are reviewed. We also reviewed data relative to some specific issues of this comorbidity in adults, especially substance use disorder, malingering, and stimulants misuse.
EXPERT OPINION
ADHD-BD may be associated with more severe symptoms, course, and worst outcome of both conditions. The frequent coexistence with alcohol and substance abuse may further complicate treatment management. Stimulants are the most effective medications for ADHD, but their use may be contraindicated in the presence of a comorbid drug abuse or in patients that simulate or exaggerate ADHD symptoms in order to obtain stimulants for diversion or abuse. ATX may be effective in the treatment of ADHD symptoms in BD patients, with a modestly increased risk of (hypo)manic switches and destabilization of the mood disorder when utilized in association with mood stabilizers. In the majority of the cases, a hierarchical approach is desirable, with mood stabilization preceding the treatment of ADHD symptoms. Although systematic trials on the use of stimulants and ATX in ADHD-BD comorbidity in adulthood are necessary, both treatments should be considered possible options to be carefully evaluated once the patient has been stabilized.
Topics: Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Central Nervous System Stimulants; Comorbidity; Humans; Substance-Related Disorders; Treatment Outcome
PubMed: 26364896
DOI: 10.1517/14656566.2015.1079620 -
The Journal of Clinical Psychiatry May 2009The U.S. Food and Drug Administration has approved 3 medications, atomoxetine and the extended-release formulations of amphetamine salts and dexmethylphenidate, for the...
The U.S. Food and Drug Administration has approved 3 medications, atomoxetine and the extended-release formulations of amphetamine salts and dexmethylphenidate, for the treatment of adult attention-deficit hyperactivity disorder (ADHD). Different formulations of the same drugs, as well as other agents and cognitive-behavioral therapy, have been tested to determine efficacy in ADHD alone and in ADHD with comorbid substance use disorders, mood disorders, and anxiety disorders. A deficit in research exists in regard to these comorbidities in adults with ADHD.
Topics: Adrenergic Uptake Inhibitors; Adult; Amphetamines; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Cognitive Behavioral Therapy; Combined Modality Therapy; Comorbidity; Humans; Substance-Related Disorders
PubMed: 19552859
DOI: 10.4088/jcp.7129br5c -
Clinical Therapeutics May 2008Efficacious and well-tolerated medications are available for the treatment of attention-deficit/hyperactivity disorder (ADHD). Stimulants such as methylphenidate (MPH)... (Review)
Review
BACKGROUND
Efficacious and well-tolerated medications are available for the treatment of attention-deficit/hyperactivity disorder (ADHD). Stimulants such as methylphenidate (MPH) and amphetamines are the most widely used medications approved by the US Food and Drug Administration for the treatment of ADHDin children.
OBJECTIVE
This article reviews the literature on the development and use of medications for the treatment of ADHD in children.
METHODS
A search of MEDLINE was conducted toidentify relevant studies and critical reviews on the treatment of ADHD in children. The main criteria for inclusion of a study were that it have a controlled design, enroll >100 subjects if a clinical trial and >20 subjects if a classroom study, assess symptoms with the most widely used scales and tests,and be published from 2000 to 2008.A few older pivotal studies were also included.
RESULTS
Many studies have reported the long-term efficacy and tolerability of immediate-release formulations of MPH. The disadvantages of such formulations include the need for multiple daily dosing and a potential for abuse. Various extended-release formulations of MPH have been found effective in controlled studies enrolling large numbers of children with ADHD. The efficacy and tolerability of dexmethylphenidate, the active D-isomer of MPH, in an extended-release formulation have also been reported. An extended-release formulation of mixed amphetamine salts (MMAS-XR) that is dosed once daily has been found to be efficacious and well tolerated. The non-stimulant atomoxetine has been reported to be well tolerated and efficacious, although it may not be as effective as stimulants; this formulation is, however, less likely than stimulants to be associated with abuse and diversion. A recently approved prodrug stimulant, lisdexamfetamine dimesylate (LDX), was developed to provide a long duration of effect that is consistent throughout the day, with a reduced potential for abuse. In a placebo-controlled study in children with ADHD, less intersubject variability in T(max), C(max), and AUC from time zero to the last quantifiable concentration was seen in the 8 subjects who received LDX (percent coefficient of variation, 15.3, 20.3, and 21.6, respectively) compared with the 9 subjects who received MAS-XR (52.8, 44.0, and 42.8).In 2 clinical trials, significantly greater improvements in teacher and parent ratings of ADHD symptoms were seen with LDX compared with placebo (P<0.001).A study of the abuse potential of LDX evaluated subjective responses to the effects of oral LDX and immediate-release d-amphetamine in adults with a history of stimulant abuse. LDX was associated with a significantly lower abuse-related liking effect than d-aamphetamine (P = 0.039).
CONCLUSIONS
Currently available treatments for ADHD in children are efficacious and well tolerated, but many of them are limited by the requirement for multiple daily dosing and abuse potential. LDX, a long-acting prodrug of d-amphetamine, has been reported to be effective and appears to overcome some of these limitations.
Topics: Amphetamines; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dexmethylphenidate Hydrochloride; Humans; Methylphenidate; Norepinephrine Plasma Membrane Transport Proteins; Prodrugs; Propylamines
PubMed: 18555941
DOI: 10.1016/j.clinthera.2008.05.006 -
Journal of Clinical Psychopharmacology Jun 2008Methylphenidate (MPH) is very effective in the treatment of attention-deficit/hyperactivity disorder (ADHD) in both children and adults. Blockade of the dopamine... (Review)
Review
Methylphenidate (MPH) is very effective in the treatment of attention-deficit/hyperactivity disorder (ADHD) in both children and adults. Blockade of the dopamine transporter is thought to produce the therapeutic effects of MPH by increasing concentrations of dopamine within the central nervous system. Although MPH is a racemic compound composed of a 50:50 mixture of dexmethylphenidate (d-MPH) and l-methylphenidate (l-MPH), animal and human studies have confirmed that the d-MPH isomer is responsible for the pharmacodynamic effect of MPH. Positron emission tomography scan images in rats and baboons treated with radiolabeled MPH have confirmed the specificity of the d-isomer and lack of specific binding of the l-isomer. Clinical studies evaluating d-MPH in both children and adults with ADHD have confirmed the efficacy and safety of the stereoselective isomer in the treatment of ADHD. The immediate-release formulation of d-MPH produces effects similar to d,l-MPH in children as measured by teacher-assessed Swanson, Nolan, and Pelham scores, Math test results, Conners Teacher and Parent Rating Scales, Attention Deficit Disorder Rating Scale, Global Assessment of Functioning scale, and Clinical Global Impression-Improvement scores. An extended-release formulation with a rapid onset of action and sustained benefit over 12 hours provides similar clinical benefit in children and adults with ADHD with excellent tolerability and the advantage of once-daily dosing.
Topics: Animals; Attention Deficit Disorder with Hyperactivity; Brain; Central Nervous System Stimulants; Corpus Striatum; Delayed-Action Preparations; Dexmethylphenidate Hydrochloride; Dopamine; Humans; Methylphenidate; Papio; Positron-Emission Tomography; Stereoisomerism; Structure-Activity Relationship
PubMed: 18480679
DOI: 10.1097/JCP.0b013e3181744aa6 -
The Annals of Pharmacotherapy Jun 2009To review recent literature on the different stimulant preparations regarding efficacy and safety in children and adolescents with attention-deficit/hyperactivity... (Review)
Review
OBJECTIVE
To review recent literature on the different stimulant preparations regarding efficacy and safety in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and describe advantages and disadvantages of the many available dosage formulations.
DATA SOURCES
Literature retrieval was performed through PubMed/MEDLINE (2005-December 2008) using the terms methylphenidate, amphetamines, central nervous system stimulants, and attention-deficit/hyperactivity disorder. In addition, reference citations from publications identified were reviewed and drug manufacturers were contacted for any possible additional references.
STUDY SELECTION AND DATA EXTRACTION
Double-blind clinical trials found using the search criteria listed above were included for review. Open-label studies and studies prior to 2005 were included if no double-blind trials were published for that formulation within the time period reviewed.
DATA SYNTHESIS
The literature reviewed here demonstrates the efficacy and safety of stimulant medications in children and adolescents with ADHD. However, there are 19 different formulations of stimulants, leading to confusion and errors in prescribing and dispensing of these drugs. Knowing and understanding the advantages and disadvantages of the different formulations can lead to individualized treatment. Formulations like Concerta, Focalin-XR, Adderall-XR, and Vyvanse provide the convenience of once-daily dosing. Each of these provides varying amount of stimulants at different times of the day. Vyvanse has a unique delivery system that may lower the risk of patients abusing their medication. Daytrana gives patients more control over their dosing by being able to choose when the patch is removed; it is also a feasible alternative for children who cannot swallow pills. For patients who cannot swallow tablets or capsules, the capsules of Focalin-XR, Adderall-XR, Metadate-CD, and Ritalin-LA can be opened and sprinkled on applesauce.
CONCLUSIONS
Stimulants are effective medications to treat the symptoms of ADHD. The multiple available dosage forms allow for individualization of treatment.
Topics: Adolescent; Amphetamines; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Controlled Clinical Trials as Topic; Dexmethylphenidate Hydrochloride; Dosage Forms; Humans; Methylphenidate; Practice Patterns, Physicians'
PubMed: 19470858
DOI: 10.1345/aph.1L523 -
Movement Disorders Clinical Practice Oct 2022To clarify patterns of comorbid atopic disorders in children with tic disorders compared to controls, and to evaluate whether medications commonly used for treatment of...
OBJECTIVE
To clarify patterns of comorbid atopic disorders in children with tic disorders compared to controls, and to evaluate whether medications commonly used for treatment of tics and attention deficit hyperactivity disorder (ADHD) are associated with differing risks of atopy.
BACKGROUND
Inflammatory mechanisms are increasingly recognized as playing a role in a range of neuropsychiatric disorders. The association between tic disorders, ADHD, obsessive-compulsive disorder (OCD) and atopic disorders is uncertain.
METHODS
We performed a retrospective cohort study using the global electronic health records database TriNetX. Using odds ratios, we compared the risk of atopy in children with tic disorder (n = 4508), ADHD (n = 83,569), and/or OCD (n = 1555) to controls (n = 758 290). To analyze the risk of developing atopy with use of different medications commonly prescribed to treat tics and ADHD, we performed a separate analysis including children with tic disorder, ADHD, and/or OCD who had initiated treatment with one of these medications. Binary logistic regression controlling for age and sex was used to calculate odds ratios.
RESULTS
Children with tic disorder, ADHD, or OCD were more likely than controls to have comorbid atopy. Children who had taken clonidine, guanfacine, methylphenidate, or dexmethylphenidate were more likely to develop an atopic disorder than controls.
CONCLUSIONS
Our study suggests a link between atopic disorders and tic disorders, ADHD, and OCD. Although the underlying mechanism for this association remains unclear, medication use may play a role.
PubMed: 36247912
DOI: 10.1002/mdc3.13506 -
European Journal of Clinical... Mar 2013Attention deficit hyperactivity disorder (ADHD) in adulthood is increasingly diagnosed and treated. Methylphenidate is frequently advocated as a first-line... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) in adulthood is increasingly diagnosed and treated. Methylphenidate is frequently advocated as a first-line pharmacological treatment.
PURPOSE
The aim of our study was to compare all-cause discontinuation rate of methylphenidate and its pharmaceutical presentations with placebo in adults with ADHD.
METHODS
This was a systematic review and meta-analysis of randomized controlled trials comparing methylphenidate with placebo in adults with ADHD. All-cause treatment discontinuation was the primary endpoint. The efficacy in reducing ADHD symptoms and safety were the secondary endpoints.
RESULTS
Twelve studies (2,496 patients) met the inclusion criteria. Four racemic methylphenidate and one dexmethylphenidate presentations were investigated. The rate of all-cause treatment discontinuation was greater with methylphenidate than with placebo, but this difference was not statistically significant [odds ratio (OR) 1.19, 95 % confidence interval (95 % CI) 0.82-1.74, P = 0.37, I(2) = 64 %] This finding reached the conventional threshold of statistical significance after one outlier study was excluded (OR 1.44, 95 % CI 1.14-1.82, P = 0.002, I(2) = 0). Methylphenidate was more efficacious than placebo for reducing ADHD symptoms and it was associated with a higher proportion of patients dropping out due to adverse effects.
CONCLUSIONS
Despite reducing ADHD symptoms, methylphenidate showed no advantage over placebo in terms of treatment discontinuation. More attention should be given in the future to the endpoint "all-cause treatment discontinuation" when making regulatory decisions and developing clinical guidelines involving the treatment of ADHD in adulthood.
Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Chi-Square Distribution; Dexmethylphenidate Hydrochloride; Drug Administration Schedule; Endpoint Determination; Female; Humans; Male; Methylphenidate; Odds Ratio; Patient Dropouts; Randomized Controlled Trials as Topic; Research Design; Treatment Outcome
PubMed: 22983311
DOI: 10.1007/s00228-012-1390-7 -
Harm Reduction Journal Oct 2017As postsecondary students' use of "study drugs" becomes more popular with increasingly reported negative effects on health and academic performance, failing... (Review)
Review
As postsecondary students' use of "study drugs" becomes more popular with increasingly reported negative effects on health and academic performance, failing prohibitionist policies to reduce consumption, and ambiguity in literature towards best practices to address this population, we present a literature review that seeks effective solutions educational institutions can apply to improve outcomes for students who use drugs. Motivations for use, effects of the substances, an analysis of efforts to control use from educational institutions, and suggestions on promoting most effective outcomes based on harm reduction, are described. Theory, quantitative, and qualitative works from systematic reviews, cohort studies, and epidemiological assessments are examined on the "study drugs" methylphenidate, dextroamphetamine, and amphetamine, also known as Adderall, Ritalin, Focalin, and Concerta. There is a focus on postsecondary students ages 18-25 in North America. Results show important risk factors for drug use including low perceived self-efficacy or enjoyment in courses, poor accommodation of special needs, reliance on external validation, having a low GPA, and experiencing a mental health issue. There is much misconception on the health and academic effects of these drugs in literature, among students, and on online knowledge sources. We suggest these drugs do not improve GPA and learning, while they might temporarily increase memory, but with detrimental negative health effects. Campaigns that address underlying factors of use can be most successful in mitigating harms.
Topics: Academic Success; Adolescent; Adult; Amphetamines; Central Nervous System Stimulants; Dexmethylphenidate Hydrochloride; Female; Harm Reduction; Humans; Male; Methylphenidate; Motivation; Prescription Drug Misuse; Risk Factors; Students; Substance-Related Disorders; Young Adult
PubMed: 28985738
DOI: 10.1186/s12954-017-0194-6