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The Medical Letter on Drugs and... Mar 2009
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Clinical Trials as Topic; Delayed-Action Preparations; Dexmethylphenidate Hydrochloride; Humans; Methylphenidate; Treatment Outcome
PubMed: 19305368
DOI: No ID Found -
Journal of Attention Disorders Mar 2009This study evaluates dexmethylphenidate extended release (d-MPH-ER) in adults with ADHD. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study evaluates dexmethylphenidate extended release (d-MPH-ER) in adults with ADHD.
METHOD
Following a 5-week, randomized, controlled, fixed-dose study of d-MPH-ER 20 to 40 mg/d, 170 adults entered a 6-month open-label extension (OLE) to assess long-term safety, with flexible dosing of 20 to 40 mg/d. Exploratory effectiveness outcomes included change from Week 5 on ADHD Rating Scale (ADHD-RS) and proportion of responders on Clinical Global Impressions-Improvement (CGI-I) scale.
RESULTS
103 patients completed OLE, and effectiveness was evaluable in 102 patients. d-MPH-ER was well tolerated; the most common adverse events (>15%) were headache, insomnia, and decreased appetite. Mean improvements in ADHD-RS score were -10.2 for patients switched from placebo to d-MPH-ER (n = 20) and -8.4 for those maintained on d-MPH-ER (n = 82). Respective CGI-I responder rates were 95.0% and 95.1%.
CONCLUSION
Once-daily d-MPH-ER 20 to 40 mg is safe and effective for long-term treatment of adult ADHD.
Topics: Adult; Adverse Drug Reaction Reporting Systems; Attention Deficit Disorder with Hyperactivity; Capsules; Central Nervous System Stimulants; Delayed-Action Preparations; Dexmethylphenidate Hydrochloride; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Methylphenidate; Middle Aged; Personality Assessment; Treatment Outcome; Young Adult
PubMed: 19218542
DOI: 10.1177/1087054708320397 -
Methods and Findings in Experimental... Sep 2008Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from...
Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com.This issue focuses on the following selection of drugs: ABT-263, AC-2307, Aclidinium bromide, Adefovir dipivoxil, ADH-1, Agatolimod sodium, Alefacept, Aliskiren fumarate, Aminolevulinic acid methyl ester, Anakinra, Apaziquone, Aprepitant, Aripiprazole, ASM-8, Atiprimod hydrochloride, AVE-0277, AVE-1642, AVE-8062, Axitinib, Azacitidine, AZD-0530; Bazedoxifene acetate, Bevacizumab, Bexarotene, BI-2536, Biphasic insulin aspart, BMS-387032, BMS-663513, Bortezomib, BQ-123, Brivanib alaninate, BSI-201; Caspofungin acetate, CDX-110, Cetuximab, Ciclesonide, CR-011, Cypher; Daptomycin, Darbepoetin alfa, Dasatinib, Decitabine, Deferasirox, Denosumab, Dexlansoprazole, Dexmethylphenidate hydrochloride, DNA-Hsp65 vaccine, Dovitinib, Drotrecogin alfa (activated), DTaP-HBV-IPV/Hibvaccine, DTaP-IPV-HB-PRP-T, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Elacytarabine, Emtricitabine, Endothelin, Entecavir, Eplivanserin fumarate, Escitalopram oxalate, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Farletuzumab, Fesoterodine fumarate, Fibrin sealant (human), Fulvestrant; Gefitinib, Gemtuzumab ozogamicin, Glufosfamide, GSK-1562902A; Hib-TT; Imatinib mesylate, IMC-11F8, Imidazoacridinone, IMP-321, INCB-18424, Indiplon, Indisulam, INNO-406, Irinotecan hydrochloride/Floxuridine, ITF-2357, Ixabepilone; KRN-951; Lasofoxifene tartrate; Lenalidomide, LGD-4665, Lonafarnib, Lubiprostone, Lumiliximab; MDX-1100, Melan-A/MART-1/gp100/IFN-alfa, Methyl-CDDO, Metreleptin, MLN-2704, Mycophenolic acid sodium salt; Na-ASP-2, Naproxcinod, Nilotinib hydrochloride monohydrate, NPI-2358; Oblimersen sodium, Odanacatib; Paclitaxel nanoparticles, PAN-811, Panobinostat, PBI-1402, PC-515, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Perillyl alcohol, Perphenazine 4-aminobutyrate, PeviPRO/breast cancer, PF-03814735, PHA-739358, Pimecrolimus, Plitidepsin, Posaconazole, Prasterone, Prasugrel, Pregabalin, Prucalopride, PRX-08066; rAAV2-TNFR:Fc, Ranelic acid distrontium salt, Ranibizumab, rCD154-CLL, Retapamulin, RTS,S/SBAS2, rV-PSA-TRICOM/rF-PSA-TRICOM; SG-2000, Sinecatechins, Sirolimus-eluting stent, Sorafenib, SP-1640, Strontium malonate, Succinobucol, Sunitinib malate; Taxus, Teduglutide, Telavancin hydrochloride, Telbivudine, Telmisartan/hydrochlorothiazide, Tenofovir disoproxil fumarate, Tenofovir disoproxil fumarate/emtricitabine, Tocilizumab; Ustekinumab; V-5 Immunitor, Voriconazole, Vorinostat; Xience V, XL-184, XL-647, XL-765; Y-39983, Zibotentan.
Topics: Clinical Trials as Topic; Humans
PubMed: 18985183
DOI: No ID Found -
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 -
CNS Drugs 2008Long-acting methylphenidate formulations provide control of attention-deficit hyperactivity disorder (ADHD) symptoms for up to 12 hours; however, not all formulations... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Long-acting methylphenidate formulations provide control of attention-deficit hyperactivity disorder (ADHD) symptoms for up to 12 hours; however, not all formulations have rapid onset of therapeutic effect, which is essential for providing symptom control during morning hours. The primary objective of this randomized, double-blind, crossover study was to assess the efficacy of dexmethylphenidate extended release (ER) versus placebo by measuring the change from pre-dose to 0.5 hours post-dose on the Swanson, Kotkin, Agler, M-Flynn and Pelham (SKAMP) rating scale.
METHODS
Eighty-six children (6-12 years) with ADHD diagnosed using the DSM-IV criteria were randomized to receive dexmethylphenidate ER 20 mg/day or placebo, sequentially, for 7 days, with the final dose administered in a laboratory classroom setting on day 7 of each treatment period. The primary efficacy comparison was change in the SKAMP-Combined score from pre-dose to 0.5 hours post-dose, with additional secondary assessments at 1, 2, 4, 6 and 8 hours post-dose. Secondary efficacy measures included change from pre-dose at all timepoints in the SKAMP-Attention and SKAMP-Deportment, Math Test-Attempted and Math Test-Correct scores, and change from baseline on the Conners' ADHD/DSM-IV Scale for Parents (CADS-P). In an exploratory analysis, a daily diary card was completed by parents on the children's in-home behaviour before school. Safety was assessed by occurrence of adverse events, monitoring of vital signs and interpretation of ECGs.
RESULTS
Significant improvements were noted at 0.5 hours and at all timepoints post-dose throughout the 8-hour laboratory classroom day for dexmethylphenidate ER vs placebo in the primary outcome measure of the SKAMP-Combined scores (p < 0.001), as well as SKAMP-Attention, SKAMP-Deportment, Math Test-Attempted and Math Test-Correct scores (p < 0.05). The changes from baseline in CADS-P scores were significantly greater with dexmethylphenidate ER than placebo (-16.382 vs -4.622; p < 0.001). Responses to all diary questions indicated significant improvement with dexmethylphenidate ER treatment versus placebo (all p < 0.001). The most common adverse events were abdominal pain (dexmethylphenidate ER 3.5%; placebo 4.7%), headache (dexmethylphenidate ER 3.5%; placebo 2.3%) and increased appetite (dexmethylphenidate ER 0%; placebo 3.5%).
CONCLUSION
Compared with placebo, once-daily dexmethylphenidate ER 20 mg provided rapid and significant improvement at 0.5 hours post-dose in attention, deportment and academic performance, which was sustained for 8 hours post-dose. Overall, once-daily dexmethylphenidate ER 20 mg was well tolerated. In an analysis of parental assessment of diary responses, children appeared more organized, and morning preparation for school was smoother and less frustrating with once-daily dexmethylphenidate ER compared with placebo.
Topics: Analysis of Variance; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Cross-Over Studies; Dexmethylphenidate Hydrochloride; Double-Blind Method; Drug Administration Schedule; Drug Delivery Systems; Drug Evaluation; Female; Humans; Male; Methylphenidate; Personality Assessment; Psychiatric Status Rating Scales; Retrospective Studies; Time Factors; Treatment Outcome
PubMed: 18601306
DOI: 10.2165/00023210-200822080-00006 -
Journal of Child and Adolescent... Jun 2008This study compared the efficacy and safety of extended-release dexmethylphenidate (d-MPH-ER) 20 mg/day and 30 mg/day with extended-release racemic methylphenidate... (Comparative Study)
Comparative Study Randomized Controlled Trial
Efficacy and safety of extended-release dexmethylphenidate compared with d,l-methylphenidate and placebo in the treatment of children with attention-deficit/hyperactivity disorder: a 12-hour laboratory classroom study.
OBJECTIVE
This study compared the efficacy and safety of extended-release dexmethylphenidate (d-MPH-ER) 20 mg/day and 30 mg/day with extended-release racemic methylphenidate hydrochloride (d,l-MPH-ER) 36 mg/day and 54 mg/day, and placebo in children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting.
METHODS
This multicenter, double-blind, crossover study included children (N = 84) 6-12 years of age, stabilized on total daily doses of 40 mg to 60 mg d,l-MPH or 20 mg/day or 30 mg/day d-MPH who were randomized to different treatment sequences. Primary efficacy was measured by the change from pre-dose in Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale-Combined scores at 2 hours post-dose (d-MPH-ER 20 mg/day versus d,l-MPH- ER 36 mg/day). Adverse events were monitored throughout the study period.
RESULTS
Mean change in SKAMP-Combined score at 2 hours post-dose was significantly larger for d-MPH-ER 20 mg/day versus d,l-MPH-ER 36 mg/day (p < 0.001). Both doses of d-MPH-ER had a more rapid onset and greater morning effect relative to d,l-MPH-ER while d,l-MPH-ER had a greater effect at the end of the 12-hour day. All active treatments provided a significant benefit over placebo at most time points to 12 hours post-dosing. Both treatments were well tolerated.
CONCLUSIONS
d-MPH-ER and d,l-MPH-ER improved ADHD symptoms and were well tolerated. While d-MPH-ER had a faster onset of action, d,l-MPH-ER retained greater effect at the end of the 12- hour classroom day.
Topics: Attention Deficit Disorder with Hyperactivity; Chemistry, Pharmaceutical; Child; Cross-Over Studies; Delayed-Action Preparations; Dexmethylphenidate Hydrochloride; Double-Blind Method; Drug Administration Schedule; Female; Headache; Humans; Male; Methylphenidate; Placebos; Schools; Social Environment; Time Factors; Treatment Outcome
PubMed: 18582179
DOI: 10.1089/cap.2007.0015 -
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 -
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 -
Psychopharmacology Bulletin 2008The purpose of this study was to compare the efficacy and safety of extended-release dexmethylphenidate (d-MPH-ER) to that of d,l-MPH-ER and placebo in children with... (Comparative Study)
Comparative Study Randomized Controlled Trial
Treatment of children with attention-deficit/hyperactivity disorder: results of a randomized, multicenter, double-blind, crossover study of extended-release dexmethylphenidate and D,L-methylphenidate and placebo in a laboratory classroom setting.
The purpose of this study was to compare the efficacy and safety of extended-release dexmethylphenidate (d-MPH-ER) to that of d,l-MPH-ER and placebo in children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting. This multicenter, double-blind, crossover study randomized 82 children, 6 to 12 years of age, stabilized on a total daily dose to the nearest equivalent of 40 to 60 mg of d,l-MPH or 20 or 30 mg/day of d-MPH. Patients participated in a screening day and practice day, and were randomized to 1 of 10 sequences of all five treatments in five separate periods. Treatments included d-MPH-ER (20 mg/day), d-MPH-ER (30 mg/day), d,l-MPH-ER (36 mg/day), d,l-MPH-ER (54 mg/day), and placebo. Primary efficacy was measured by the change from predose on the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale-Combined scores at 2-h postdose during the 12-h laboratory assessment (d-MPH-ER 20 mg/day vs. d,l-MPH-ER 36 mg/day). Adverse events were monitored throughout the study period. d-MPH-ER (20 mg/day) was significantly more effective than d,l-MPH-ER (36 mg/day) in the primary efficacy variable, change from predose to 2-h postdose in SKAMP-combined score. In general, d-MPH-ER had an earlier onset of action than d,l-MPH-ER, while d,l-MPH-ER had a stronger effect at 12-h postdose. No serious adverse events were reported. Treatment with either agent was associated with significant improvements in ADHD symptoms. d-MPH-ER and d,l-MPH-ER can be differentiated on what part of the day each is more effective.
Topics: Area Under Curve; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Cross-Over Studies; Delayed-Action Preparations; Dexmethylphenidate Hydrochloride; Double-Blind Method; Female; Humans; Male; Methylphenidate; Placebos
PubMed: 18362868
DOI: No ID Found -
Chest May 2008Fatigue is a common complaint in patients with sarcoidosis. We studied the effectiveness of dexmethylphenidate hydrochloride (d-MPH) in treating sarcoidosis-associated... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Fatigue is a common complaint in patients with sarcoidosis. We studied the effectiveness of dexmethylphenidate hydrochloride (d-MPH) in treating sarcoidosis-associated fatigue.
METHODS
This was a double-blind, randomized, placebo-controlled, crossover trial of d-MPH. Patients were seen weekly and completed Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and Fatigue Assessment Score (FAS) instruments. After a 1-week wash-in period, patients received either d-MPH or placebo. After 8 weeks, the medications were stopped. Following a 2-week wash-out period, patients were crossed over to 8 weeks of the other treatment. FVC and 6-min walk distance (6MWD) were determined initially and after each treatment arm.
RESULTS
Ten patients with sarcoidosis were enrolled: 8 women and 5 African Americans. All were receiving systemic sarcoidosis therapy. Significant improvement in fatigue was reported by patients when receiving d-MPH (FACIT-F, p < 0.001; FAS, p < 0.02). FVC was higher at the end of 8 weeks of d-MPH compared to the baseline values (baseline median, 2.38 L; range, 1.17 to 4.53 L; placebo median, 2.41 L; range, 1.50 to 4.65 L; d-MPH median, 2.56 L; range, 1.50 to 4.96 L; p < 0.01). There was no significant difference in the 6MWD (baseline median, 330 m; range, 60 to 460 m; placebo median, 350 m; range, 180 to 460 m; d-MPH median, 390 m; range, 200 to 460 m). d-MPH was well tolerated.
CONCLUSIONS
Treatment with d-MPH was associated with a significant improvement in sarcoidosis-associated fatigue.
TRIAL REGISTRATION
Clinicaltrials.gov Identifier: NCT00361387.
Topics: Adult; Aged; Central Nervous System Stimulants; Cross-Over Studies; Dexmethylphenidate Hydrochloride; Double-Blind Method; Drug Therapy, Combination; Exercise Test; Fatigue; Female; Follow-Up Studies; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Methylphenidate; Middle Aged; Respiratory Function Tests; Retrospective Studies; Sarcoidosis, Pulmonary; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome; Walking
PubMed: 18263672
DOI: 10.1378/chest.07-2952