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Expert Opinion on Pharmacotherapy Dec 2006Dexmethylphenidate is a chirally pure d-isomer of the racemic mixture of methylphenidate. The extended-release form of this compound was developed using proprietary... (Review)
Review
Dexmethylphenidate is a chirally pure d-isomer of the racemic mixture of methylphenidate. The extended-release form of this compound was developed using proprietary Spheroidal Oral Drug Absorption System technology. The product is approved for the treatment of attention deficit hyperactivity disorder in individuals as young as 6 years old. It represents the first methylphenidate product approved for use in adults. The agent's delivery system is designed to provide an initial release of medication immediately after dosing, with a second release approximately 4 h later. Blood levels first peak at approximately 1.5 h, and the second peak is noted at an average of 6.5 h post-dose. Laboratory classroom studies have demonstrated clinically and statistically meaningful efficacy throughout a 12-h day. Pharmacokinetics, safety and efficacy data are reviewed.
Topics: Attention Deficit Disorder with Hyperactivity; Capsules; Delayed-Action Preparations; Dexmethylphenidate Hydrochloride; Humans; Methylphenidate; Stereoisomerism
PubMed: 17150008
DOI: 10.1517/14656566.7.18.2547 -
Frontiers in Pharmacology 2022Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders having a high influence on social interactions. The number of... (Review)
Review
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders having a high influence on social interactions. The number of approved treatments and clinical trials for ADHD have increased markedly during the recent decade. This analytical review provides a quantitative overview of the existing pharmacological and non-pharmacological methods of ADHD treatments investigated in clinical trials during 1999-2021. A total of 695 interventional trials were manually assessed from clinicaltrial.gov with the search term « ADHD», and trial data has been used for analysis. A clear majority of the studies investigated non-pharmacological therapies (∼80%), including many behavioral options, such as social skills training, sleep and physical activity interventions, meditation and hypnotherapy. Devices, complementary and other alternative methods of ADHD treatment are also gaining attention. The pharmacological group accounts for ∼20% of all the studies. The most common drug classes include central nervous system stimulants (e.g., methylphenidate hydrochloride, lisdexamfetamine dimesylate, amphetamine sulfate, mixed amphetamine salts, a combination of dexmethylphenidate hydrochloride and serdexmethylphenidate chloride), selective noradrenaline reuptake inhibitors (atomoxetine, viloxazine), and alpha2 adrenergic receptor agonists (guanfacine hydrochloride, clonidine hydrochloride). Several studies investigated antidepressants (e.g., bupropion hydrochloride, vortioxetine), and atypical antipsychotics (e.g., quetiapine, aripiprazole) but these are yet not approved by the FDA for ADHD treatment. We discuss the quantitative trends in clinical trials and provide an overview of the new drug agents and non-pharmacological therapies, drug targets, and novel treatment options.
PubMed: 36467081
DOI: 10.3389/fphar.2022.1066988 -
Pharmacotherapy Jun 2019In 2000, the first biphasic modified-release (MR) formulation of methylphenidate (MPH) was approved for the treatment of attention-deficit/hyperactivity disorder (ADHD).... (Review)
Review
In 2000, the first biphasic modified-release (MR) formulation of methylphenidate (MPH) was approved for the treatment of attention-deficit/hyperactivity disorder (ADHD). An immediate-release (IR) MPH pulse (22% of the dose) facilitates rapid onset of stimulant action, while the remaining MR portion of the dose provides for day-long duration of efficacy. A wide array of oral MR-MPH products has subsequently been approved that also allows for once-daily dosing, though each product is characterized by distinctive exposure time courses. This review compares each member of the current MPH armamentarium to assist in the rational selection of a specific MPH regimen for the individualized treatment of patients with ADHD. The IR portion of biphasic MPH formulations now ranges from 15%, 20%, 22%, 25%, 30%, and 37% IR-MPH, as well as a 50% IR-MPH product whose distinctly pulsatile time course closely resembles that of the pre-century "gold standard" twice-daily IR-MPH regimen. Further, transdermal, suspension, and orally disintegrating tablet products are now available to overcome any solid dosage form swallowing difficulties. Most of these formulations are racemic, though in 2001, a chiral switch drug IR-dexmethylphenidate (dexMPH) was approved, followed by biphasic MR-dexMPH (50% IR) in 2005. New U.S. Food and Drug Administration (FDA) partial area under the curve (pAUC) bioavailability metrics have improved discrimination between specific generic MR-MPH products. This has resulted in two Orange Book MR-MPH products being recoded from "AB" (i.e., meets necessary bioequivalence requirements) to "BX" (i.e., insufficient data to confirm bioequivalence). The metabolic drug interaction between MPH and alcohol, which increases MPH bioavailability, potentiates euphoric effects, and heightens abuse liability, is discussed. This review concludes with brief considerations of pharmacogenomic predictors of ADHD first-line drug selection, carboxylesterase allelic variants influencing interindividual MPH metabolism, and novel MPH formulations in the regulatory pipeline.
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Delayed-Action Preparations; Dexmethylphenidate Hydrochloride; Dosage Forms; Drug Administration Schedule; Humans; Methylphenidate; Precision Medicine
PubMed: 30351459
DOI: 10.1002/phar.2190 -
JAMA Oncology Jul 2017Cancer-related fatigue (CRF) remains one of the most prevalent and troublesome adverse events experienced by patients with cancer during and after therapy. (Comparative Study)
Comparative Study Meta-Analysis Review
IMPORTANCE
Cancer-related fatigue (CRF) remains one of the most prevalent and troublesome adverse events experienced by patients with cancer during and after therapy.
OBJECTIVE
To perform a meta-analysis to establish and compare the mean weighted effect sizes (WESs) of the 4 most commonly recommended treatments for CRF-exercise, psychological, combined exercise and psychological, and pharmaceutical-and to identify independent variables associated with treatment effectiveness.
DATA SOURCES
PubMed, PsycINFO, CINAHL, EMBASE, and the Cochrane Library were searched from the inception of each database to May 31, 2016.
STUDY SELECTION
Randomized clinical trials in adults with cancer were selected. Inclusion criteria consisted of CRF severity as an outcome and testing of exercise, psychological, exercise plus psychological, or pharmaceutical interventions.
DATA EXTRACTION AND SYNTHESIS
Studies were independently reviewed by 12 raters in 3 groups using a systematic and blinded process for reconciling disagreement. Effect sizes (Cohen d) were calculated and inversely weighted by SE.
MAIN OUTCOMES AND MEASURES
Severity of CRF was the primary outcome. Study quality was assessed using a modified 12-item version of the Physiotherapy Evidence-Based Database scale (range, 0-12, with 12 indicating best quality).
RESULTS
From 17 033 references, 113 unique studies articles (11 525 unique participants; 78% female; mean age, 54 [range, 35-72] years) published from January 1, 1999, through May 31, 2016, had sufficient data. Studies were of good quality (mean Physiotherapy Evidence-Based Database scale score, 8.2; range, 5-12) with no evidence of publication bias. Exercise (WES, 0.30; 95% CI, 0.25-0.36; P < .001), psychological (WES, 0.27; 95% CI, 0.21-0.33; P < .001), and exercise plus psychological interventions (WES, 0.26; 95% CI, 0.13-0.38; P < .001) improved CRF during and after primary treatment, whereas pharmaceutical interventions did not (WES, 0.09; 95% CI, 0.00-0.19; P = .05). Results also suggest that CRF treatment effectiveness was associated with cancer stage, baseline treatment status, experimental treatment format, experimental treatment delivery mode, psychological mode, type of control condition, use of intention-to-treat analysis, and fatigue measures (WES range, -0.91 to 0.99). Results suggest that the effectiveness of behavioral interventions, specifically exercise and psychological interventions, is not attributable to time, attention, and education, and specific intervention modes may be more effective for treating CRF at different points in the cancer treatment trajectory (WES range, 0.09-0.22).
CONCLUSIONS AND RELEVANCE
Exercise and psychological interventions are effective for reducing CRF during and after cancer treatment, and they are significantly better than the available pharmaceutical options. Clinicians should prescribe exercise or psychological interventions as first-line treatments for CRF.
Topics: Benzhydryl Compounds; Central Nervous System Stimulants; Cognitive Behavioral Therapy; Dexmethylphenidate Hydrochloride; Dextroamphetamine; Exercise Therapy; Fatigue; Glucocorticoids; Humans; Methylphenidate; Methylprednisolone; Modafinil; Neoplasms; Paroxetine; Psychotherapy; Selective Serotonin Reuptake Inhibitors; Wakefulness-Promoting Agents
PubMed: 28253393
DOI: 10.1001/jamaoncol.2016.6914 -
Journal of Child and Adolescent... Mar 2023Serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) is approved for the treatment of patients aged ≥6 years with attention-deficit/hyperactivity disorder (ADHD). A... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety and Tolerability of Serdexmethylphenidate/Dexmethylphenidate Capsules in Children with Attention-Deficit/Hyperactivity Disorder: A 12-Month, Open-Label Safety Study.
Serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) is approved for the treatment of patients aged ≥6 years with attention-deficit/hyperactivity disorder (ADHD). A pivotal double-blind (DB) study of children aged 6-12 years with ADHD demonstrated efficacy for ADHD with good tolerability. In this study, we assessed the safety and tolerability of daily oral SDX/d-MPH for up to 1 year in children with ADHD. This was a dose-optimized, open-label safety study with SDX/d-MPH in children aged 6-12 years with ADHD that included subjects who successfully completed the DB study (rollover) and new subjects. The study consisted of a 30-day screening phase, a dose optimization phase for new subjects only, a 360-day treatment phase, and follow-up. Adverse events (AEs) were assessed from the first day of SDX/d-MPH administration to the end of the study. During the treatment phase, ADHD Rating Scale-5 (ADHD-RS-5) and Clinical Global Impressions-Severity (CGI-S) scale assessments were used to evaluate ADHD severity. Of the 282 subjects enrolled (70 rollover; 212 new), 28 discontinued treatment in the dose optimization phase and 254 entered the treatment phase. By study completion, 127 had discontinued and 155 had completed the study. The treatment-phase safety population included all enrolled subjects who received ≥1 dose of study drug and had ≥1 postdose safety assessment. Of 238 subjects assessed in the treatment-phase safety population, 143 (60.1%) had ≥1 treatment-emergent adverse events (TEAEs), and 36 (15.1%), 95 (39.9%), and 12 (5.0%) had mild, moderate, or severe TEAEs, respectively. The most common TEAEs were decreased appetite (18.5%), upper respiratory tract infection (9.7%), nasopharyngitis (8.0%), decreased weight (7.6%), and irritability (6.7%). There were no clinically meaningful trends in electrocardiograms, cardiac events, or blood pressure events, and none led to discontinuation. Two subjects had eight serious AEs that were unrelated to treatment. There were overall reductions in ADHD symptoms and severity as assessed by ADHD-RS-5 and CGI-S during the treatment phase. In this 1-year study, SDX/d-MPH was found to be safe and well tolerated and comparable with other methylphenidate products, with no unexpected safety findings. SDX/d-MPH also showed sustained efficacy during the 1-year treatment period. ClinicalTrials.gov identifier: NCT03460652.
Topics: Humans; Child; Attention Deficit Disorder with Hyperactivity; Dexmethylphenidate Hydrochloride; Central Nervous System Stimulants; Treatment Outcome; Delayed-Action Preparations; Methylphenidate; Double-Blind Method; Dose-Response Relationship, Drug
PubMed: 36809150
DOI: 10.1089/cap.2022.0076 -
The Medical Letter on Drugs and... May 2002
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dexmethylphenidate Hydrochloride; Dosage Forms; Dose-Response Relationship, Drug; Humans; Methylphenidate; Randomized Controlled Trials as Topic; Stereoisomerism
PubMed: 12011757
DOI: No ID Found -
Drugs 2006Dexmethylphenidate extended release (XR) is an orally administered, bimodal release, capsule formulation of the active d-enantiomer of methylphenidate (MPH), which...
Dexmethylphenidate extended release (XR) is an orally administered, bimodal release, capsule formulation of the active d-enantiomer of methylphenidate (MPH), which inhibits dopamine and norepinephrine (noradrenaline) reuptake to increase their concentration in the extraneuronal space. A single dose of dexmethylphenidate XR mimics the pharmacokinetic profile of two doses of dexmethylphenidate immediate-release formulation administered 4 hours apart, albeit with less fluctuation in plasma concentration. Once-daily dexmethylphenidate XR was more effective than placebo in reducing attention-deficit hyperactivity disorder (ADHD) symptom scores in children, adolescents and adults with ADHD in four randomised, double-blind, placebo-controlled trials of up to 7 weeks' duration. In crossover trials in children (aged 6-12 years), dexmethylphenidate XR 20 mg/day reduced mean ADHD symptom scores 1 hour after administration (by 43% in one trial) and was significantly better than placebo for up to 12 hours. Dexmethylphenidate XR 5-30 mg/day reduced mean ADHD symptom scores by 49%, while scores declined by 16% with placebo in a 7-week trial in children and adolescents (aged 6-17 years). Dexmethylphenidate XR 20, 30 or 40 mg/day reduced ADHD symptom scores by 36-46% versus a 21% reduction with placebo in a 5-week trial in adults (aged 18-60 years). Dexmethylphenidate XR was generally well tolerated in children, adolescents and adults with ADHD, with an adverse-event profile typical of MPH.
Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Delayed-Action Preparations; Dexmethylphenidate Hydrochloride; Dopamine Uptake Inhibitors; Humans; Methylphenidate; Middle Aged; Randomized Controlled Trials as Topic
PubMed: 16620143
DOI: 10.2165/00003495-200666050-00006 -
Expert Opinion on Pharmacotherapy Nov 2009Dexmethylphenidate is a single-isomer stimulant medication approved for the treatment of attention deficit hyperactivity disorder (ADHD). Single-isomer drugs have the...
BACKGROUND
Dexmethylphenidate is a single-isomer stimulant medication approved for the treatment of attention deficit hyperactivity disorder (ADHD). Single-isomer drugs have the potential for decreased undesired effects and improved therapeutic efficacy. Stimulant medications have been the mainstay treatments for ADHD for fifty years, and ability to reduce their adverse effects would be useful in promoting patient compliance with treatment.
OBJECTIVE
To review the literature on the safety and efficacy of dexmethylphenidate.
METHODS
MedLine, PubMed search of dexmethylphenidate research.
RESULTS/CONCLUSIONS
Dexmethylphenidate is a safe and effective treatment for ADHD. Its overall safety and tolerability profile is similar to other members of the psychostimulant class.
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dexmethylphenidate Hydrochloride; Humans; Methylphenidate
PubMed: 19874250
DOI: 10.1517/14656560903386284 -
Journal of Child and Adolescent... May 2023Serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) is approved for the treatment of patients aged ≥6 years with attention-deficit/hyperactivity disorder (ADHD). A...
Serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) is approved for the treatment of patients aged ≥6 years with attention-deficit/hyperactivity disorder (ADHD). A 12-month, open-label safety study with SDX/d-MPH in children with ADHD showed that SDX/d-MPH was well tolerated and comparable with other methylphenidate products. In this analysis of the 12-month study, the objective was to characterize the effect of SDX/d-MPH on growth in children with ADHD over 12 months. This was a analysis of a dose-optimized, open-label, phase 3 safety study of SDX/d-MPH in children aged 6-12 years with ADHD (NCT03460652). Weight and height -score analyses were conducted. -score change from baseline was calculated based on the baseline values for the subjects remaining in the study at the observation time point. Subjects ( = 238) from the treatment-phase safety population included all enrolled subjects who received ≥1 dose of study drug and had ≥1 postdose safety assessment. During treatment, the mean weight and height -scores decreased over time from their respective baselines. At the 12-month time point, mean (standard deviation [SD]) -score changes from baseline for weight and height for the subjects remaining in the study were -0.20 (0.50) and -0.21 (0.39), respectively; however, these mean changes in Z-scores were not clinically significant (change <0.5 SD). Long-term treatment with SDX/d-MPH was associated with modest reductions in expected weight and lower-than-expected increases in height: effects that plateaued or diminished later in treatment. The overall effects of SDX/d-MPH on growth velocity (the change in weight and height from one time point to the next) were minimal, and the range of changes was not considered clinically significant. ClinicalTrials.gov identifier: NCT03460652.
Topics: Child; Humans; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Delayed-Action Preparations; Dexmethylphenidate Hydrochloride; Double-Blind Method; Methylphenidate; Treatment Outcome
PubMed: 37204277
DOI: 10.1089/cap.2023.0012 -
American Journal of Health-system... May 2021Current literature on the safety and efficacy of intermediate- and long-acting formulations of methylphenidate and dexmethylphenidate for attention-deficit/hyperactivity...
PURPOSE
Current literature on the safety and efficacy of intermediate- and long-acting formulations of methylphenidate and dexmethylphenidate for attention-deficit/hyperactivity disorder (ADHD) is evaluated.
SUMMARY
Methylphenidate has been an established treatment for ADHD, but due to its relatively short half-life, numerous intermediate- and long-acting products have been developed. While these extended-release products provide efficacy similar to that of immediate-acting products, the pharmacokinetics and adverse effects can vary. Intermediate-acting methylphenidate products have effects that can last as long as 8 hours, but clinically patients have still required twice-daily dosing. Long-acting products have helped to address these challenges, with recently developed products including controlled-release and bimodal-delivery systems and a patch formulation. Many of these products can be opened and sprinkled on applesauce for ease of administration.
CONCLUSION
Knowledge of the various formulations of methylphenidate and dexmethylphenidate is crucial for appropriate medication selection for control of ADHD symptoms. Knowledge of differences between release mechanisms and the pharmacokinetic properties are essential for appropriate use of these products.
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Delayed-Action Preparations; Dexmethylphenidate Hydrochloride; Half-Life; Humans; Methylphenidate
PubMed: 33954419
DOI: 10.1093/ajhp/zxab069