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Journal of Child and Adolescent... Dec 2011To compare the dose effects of long-acting extended-release dexmethylphenidate (ER d-MPH) and ER mixed amphetamine salts (ER MAS) on attention-deficit/hyperactivity... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To compare the dose effects of long-acting extended-release dexmethylphenidate (ER d-MPH) and ER mixed amphetamine salts (ER MAS) on attention-deficit/hyperactivity disorder (ADHD) symptom dimensions, global and specific impairments, and common adverse events associated with stimulants.
METHODS
Fifty-six children and adolescents with ADHD participated in an 8-week, double-blind, crossover study comparing ER d-MPH (10, 20, 25-30 mg) and ER MAS (10, 20, 25-30) with a week of randomized placebo within each drug period. Efficacy was assessed with the ADHD Rating Scale-IV (ADHD-RS-IV), whereas global and specific domains of impairment were assessed with the Clinical Global Impressions Severity and Improvement Scales and the parent-completed Weiss Functional Impairment Scale, respectively. Insomnia and decreased appetite, common stimulant-related adverse events, were measured with the parent-completed Stimulant Side Effects Rating Scale.
RESULTS
Both ER d-MPH and ER MAS were associated with significant reductions in ADHD symptoms. Improvement in Total ADHD and Hyperactivity/Impulsivity symptoms were strongly associated with increasing dose, whereas improvements in Inattentive symptoms were only moderately associated with dose. About 80% demonstrated reliable change on ADHD-RS-IV at the highest dose level of ER MAS compared with 79% when receiving ER d-MPH. Decreased appetite and insomnia were more common at higher dose levels for both stimulants. Approximately 43% of the responders were preferential responders to only one of the stimulant formulations.
CONCLUSIONS
Dose level, rather than stimulant class, was strongly related to medication response.
Topics: Adolescent; Amphetamines; Appetite; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Cross-Over Studies; Delayed-Action Preparations; Dexmethylphenidate Hydrochloride; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Methylphenidate; Psychiatric Status Rating Scales; Sleep Initiation and Maintenance Disorders
PubMed: 22136094
DOI: 10.1089/cap.2011.0018 -
JCO Oncology Practice Feb 2022The financial toxicity of anticancer drugs is well-documented, but little is known about the costs of drugs used to manage cancer-associated symptoms. (Review)
Review
PURPOSE
The financial toxicity of anticancer drugs is well-documented, but little is known about the costs of drugs used to manage cancer-associated symptoms.
METHODS
We reviewed relevant guidelines and compiled drugs used to manage seven cancer-associated symptoms (anorexia and cachexia, chemotherapy-induced peripheral neuropathy, constipation, diarrhea, exocrine pancreatic insufficiency, cancer-associated fatigue, and chemotherapy-induced nausea and vomiting). Using GoodRx website, we identified the retail price (cash price at retail pharmacies) and lowest price (discounted, best-case scenario of out-of-pocket costs) for patients without insurance for each drug or formulation for a typical fill. We describe lowest prices here.
RESULTS
For anorexia and cachexia, costs ranged from $5 US dollars (USD; generic olanzapine or mirtazapine tablets) to $1,156 USD (brand-name dronabinol solution) and varied widely by formulation of the same drug or dosage: for olanzapine 5 mg, $5 USD (generic tablet) to $239 USD (brand-name orally disintegrating tablet). For chemotherapy-induced peripheral neuropathy, costs of duloxetine varied from $12 USD (generic) to $529 USD (brand-name). For constipation, the cost of sennosides or polyethylene glycol was <$15 USD, whereas newer agents such as methylnaltrexone were expensive ($1,001 USD). For diarrhea, the cost of generic loperamide or diphenoxylate-atropine tablets was <$15 USD. For exocrine pancreatic insufficiency, only brand-name formulations were available, range of cost, $1,072 USD-$1,514 USD. For cancer-associated fatigue, the cost of generic dexamethasone or dexmethylphenidate was <$15 USD, whereas brand-name modafinil was more costly ($1,284 USD). For a 4-drug nausea and vomiting prophylaxis regimen, costs ranged from $181 USD to $1,430 USD.
CONCLUSION
We highlight the high costs of many symptom control drugs and the wide variation in the costs of these drugs. These findings can guide patient-clinician discussions about cost-effectively managing symptoms, while promoting the use of less expensive formulations when possible.
Topics: Antineoplastic Agents; Drug Costs; Drugs, Generic; Financial Stress; Humans; Neoplasms; Pharmacies
PubMed: 34558297
DOI: 10.1200/OP.21.00466 -
Journal of Clinical PsychopharmacologyThis is the first controlled pharmacologic study in either adults or children with uncomplicated, treatment-resistant attention-deficit/hyperactivity disorder (ADHD).... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
This is the first controlled pharmacologic study in either adults or children with uncomplicated, treatment-resistant attention-deficit/hyperactivity disorder (ADHD). This study augmented stimulant therapy with the atypical antipsychotic brexpiprazole. The Food and Drug Administration preapproved primary outcome measure (Conners' Adult ADHD Rating Scale [CAARS]) showed no drug-placebo differences. Often studies showing no efficacy on the prestudy, defined primary outcome variable go unpublished. While this is decried, publishing studies with equivocal results remains rare. This reanalysis highlights trends in secondary measures having implications for treatment and research regarding treatment resistant ADHD.
METHODS
Initially, 559 stimulant-naive and 174 prior stimulant nonresponders received methylphenidate osmotic-release oral system, dexmethylphenidate hydrochloride, lisdexamfetamine, or mixed amphetamine salts. After 5 weeks, 168 stimulant-naive patients and 68 prior stimulant nonresponders who failed treatment were randomized to brexpiprazole or placebo in a 2:1 ratio while the remaining were on the stimulant. Outcome was measured with the CAARS, Montgomery-Asberg Depression Rating Scale, Beck Depression Inventory, Clinical Global Impression, and the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS). The WRAADDS contains 2 factors: attention and emotional dysregulation.
RESULTS
Stimulant-naive patients showed no improvement with adjunctive brexpiprazole. Prior stimulant nonresponders displayed no brexpiprazole effect on the CAARS, Montgomery-Asberg Depression Rating Scale, or Beck Depression Inventory. In contrast, the WRAADDS detected a trend in treatment benefit, primarily through emotional dysregulation symptoms. Adverse effects on brexpiprazole and placebo were equivalent.
CONCLUSIONS
Brexpiprazole might be effective in ADHD adults who are nonresponders to 2 or more stimulants. Future trials in treatment-resistant ADHD should use a 1:1 randomization and use a measure of ADHD symptoms that includes emotional dysregulation.
Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Double-Blind Method; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Psychiatric Status Rating Scales; Treatment Outcome
PubMed: 35977005
DOI: 10.1097/JCP.0000000000001592 -
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 -
Journal of Child and Adolescent... Aug 2009This 5-week, multicenter, double-blind, placebo-controlled, parallel-group investigation is the first fixed-dose study to evaluate efficacy and tolerability of three... (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVE
This 5-week, multicenter, double-blind, placebo-controlled, parallel-group investigation is the first fixed-dose study to evaluate efficacy and tolerability of three doses of (10, 20, or 30 mg, once daily [o.d.]) dexmethylphenidate hydrochloride (HCl) extended-release (d-MPH XR; Focalin XR) across multiple settings to treat pediatric attention-deficit/hyperactivity disorder (ADHD).
RESULTS
ADHD pediatric outpatients (n = 253) diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition, criteria were randomized (1:1:1:1) to receive d-MPH XR (10, 20, or 30 mg o.d.) or placebo. Treatment with d-MPH XR significantly (p < 0.001) reduced the mean score (change from baseline) on Conners'-ADHD/DSM-IV Scales (CADS) as assessed by the teacher CADS-T (dose [mean];10 mg [18], 20 mg [16.9], 30 mg [20.7]) and parents, CADS-P (dose [mean];10 mg [15.8]; 20 mg [17.8]; 30 mg [20.5]) compared to placebo (mean CADS-T [5.7]; CADS-P [4.6]). A significant (p < 0.001) proportion of patients in the three d-MPH XR treatment groups showed improvement on the clinician-rated, Clinical Global Impressions-Improvement (CGI-I) scales (10 mg [73.8%]; 20 mg [71.2%]; 30 mg [77.2 %]) and severity ratings (CGI-S) compared to the placebo group (CGI-I, 22.2%). Adverse events were mild to moderate in severity and similar to previous observations for this class of neurostimulants.
CONCLUSION
All three doses of d-MPH XR (10, 20, or 30 mg o.d), were significantly more effective than placebo in improving ADHD symptoms as confirmed by the teacher, parent and clinician. Additionally, d-MPH XR was well tolerated and demonstrated a consistent safety profile.
Topics: Attention Deficit Disorder with Hyperactivity; Capsules; Child; Delayed-Action Preparations; Dexmethylphenidate Hydrochloride; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Methylphenidate; Nervous System Diseases; Skin Diseases
PubMed: 19702487
DOI: 10.1089/cap.2009.0007 -
CNS Drugs Sep 2014We sought to determine the dose-response effects of extended-release (ER) dexmethylphenidate (d-MPH) and ER mixed amphetamine salts (MAS) on objective measures of sleep. (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of extended-release dexmethylphenidate and mixed amphetamine salts on sleep: a double-blind, randomized, crossover study in youth with attention-deficit hyperactivity disorder.
OBJECTIVE
We sought to determine the dose-response effects of extended-release (ER) dexmethylphenidate (d-MPH) and ER mixed amphetamine salts (MAS) on objective measures of sleep.
METHODS
This was an 8-week, double-blind, placebo-controlled, randomized, two period, crossover study of youth with attention-deficit hyperactivity disorder (ADHD) as confirmed by the Kiddie Schedule for Affective Disorders for School-Age Children-Present and Lifetime version (K-SADS-PL). Children aged 10-17 years were recruited from clinical practice, colleague referrals, and flyers. Participants were randomized to initially receive either d-MPH or MAS. During each 4-week drug period, children received three dose levels (10, 20, and 25/30 mg) in ascending order, with placebo substituted for active medication in a randomized fashion during 1 week of the study. After 4 weeks, participants were switched to the alternative medication for another 4 weeks of treatment. The main outcome measure was sleep duration as measured by actigraphy. Children, parents, and researchers were blinded to drug, dose, and placebo status.
RESULTS
Sixty-five participants met the inclusion criteria and were enrolled in the study. Of these, 37 participants with sufficient sleep data for analysis were included. Sleep schedule measures showed a significant effect for dose on sleep start time (F(1,36) = 6.284; p < 0.05), with a significantly later sleep start time when children were receiving 20- or 30-mg doses, compared with placebo (p < 0.05). A significant dose effect was found on actual sleep duration (F(1,36) = 8.112; p < 0.05), with significantly shorter actual sleep duration for subjects receiving 30 mg compared with those receiving placebo (p < 0.05). There were no significant differences on sleep duration or sleep schedule between the two stimulant medications. The trial is complete and closed to follow-up.
CONCLUSIONS
Higher stimulant doses were associated with reduced sleep duration and later sleep start times, regardless of medication class.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT00393042.
Topics: Actigraphy; Adolescent; Amphetamines; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Cross-Over Studies; Delayed-Action Preparations; Dexmethylphenidate Hydrochloride; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Salts; Sleep; Surveys and Questionnaires; Time Factors; Treatment Outcome
PubMed: 25056567
DOI: 10.1007/s40263-014-0181-3 -
The Annals of Pharmacotherapy Oct 2010To review the efficacy and safety of psychostimulants for negative behavioral symptoms (ie, apathy, excessive daytime sedation) and cognition in patients with dementia. (Review)
Review
OBJECTIVE
To review the efficacy and safety of psychostimulants for negative behavioral symptoms (ie, apathy, excessive daytime sedation) and cognition in patients with dementia.
DATA SOURCES
Literature was accessed through PubMed and MEDLINE (1966-June 2010), using the terms stimulant, psychostimulant, methylphenidate, dexmethylphenidate, amphetamine, dextroamphetamine, lisdexamfetamine, atomoxetine, modafinil, armodafinil, dementia, Alzheimer disease, vascular dementia, Lewy body dementia, mixed dementia, frontotemporal dementia, therapy, treatment, and therapeutic. Additional references identified from the initial search were reviewed.
STUDY SELECTION AND DATA EXTRACTION
All relevant clinical trials published in English and involving primarily older adults with dementia were included. Case reports, review articles, and other preclinical literature were included as appropriate.
DATA SYNTHESIS
Psychostimulants have been employed as a treatment for cognitive and behavioral symptoms in dementia for decades, but the literature has lagged behind this practice. Eight reports on use of psychostimulants as a treatment of apathy in dementia were reviewed. Methylphenidate was the most frequently studied medication and improvements in apathy were consistently noted; however, the magnitude and duration of effect remain unclear. Six studies examining the cognitive effects of a variety of psychostimulants in patients with dementia were reviewed; psychostimulants had little to no effect on cognition. A lack of studies exists to draw conclusions about the use of psychostimulants for the treatment of excessive daytime sedation in dementia. The possibility of psychostimulants to increase blood pressure; elevate heart rate; and lead to irritability, agitation, and psychosis makes careful patient selection critical, especially in older adults with severe cardiovascular disease or other underlying cardiac abnormalities.
CONCLUSIONS
Based on limited studies, methylphenidate is a possible treatment for apathy in patients with dementia. Psychostimulants, as a group, do not appear to be broadly effective treatments for behavioral or cognitive symptoms of dementia. The potential utility of psychostimulants must be balanced with careful patient selection.
Topics: Aged; Apathy; Behavioral Symptoms; Central Nervous System Stimulants; Dementia; Disorders of Excessive Somnolence; Humans; Psychomotor Agitation
PubMed: 20736422
DOI: 10.1345/aph.1P341 -
Current Topics in Behavioral... 2022Since the landmark MTA (Multimodal Treatment of ADHD) trial unequivocally demonstrated the efficacy of methylphenidate, catecholaminergic drugs, especially stimulants,... (Review)
Review
Since the landmark MTA (Multimodal Treatment of ADHD) trial unequivocally demonstrated the efficacy of methylphenidate, catecholaminergic drugs, especially stimulants, have been the therapeutic mainstay in treatment of Attention-Deficit Hyperactivity Disorder (ADHD). We review the new drugs which have entered the ADHD formulary. The lessons learned from drug-candidates that have succeeded in clinical trials together with those that have not have also been considered. What emerges confirms and consolidates the hypothesis that clinically effective ADHD drugs indirectly or directly increase catecholaminergic neurotransmission in the prefrontal cortex (PFC). Attempts to enhance catecholaminergic signalling through modulatory neurotransmitter systems or cognitive-enhancing drugs have all failed. New drugs approved for ADHD are catecholaminergic reuptake inhibitors and releasing agents, or selective noradrenaline reuptake inhibitors. Triple reuptake inhibitors with preferential effects on dopamine have not been successful. The substantial number of failures probably accounts for a continued focus on developing novel catecholaminergic and noradrenergic drugs, and a dearth of drug-candidates with novel mechanisms entering clinical development. However, substantial improvements in ADHD pharmacotherapy have been achieved by the almost exclusive use of once-daily medications and prodrugs, e.g. lisdexamfetamine and Azstarys, which improve compliance, deliver greater efficacy and reduce risks for diversion and abuse.
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Humans; Methylphenidate; Research
PubMed: 35507283
DOI: 10.1007/7854_2022_332 -
Neuropsychiatric Disease and Treatment 2015The efficacy of dexmethylphenidate (d-MPH) has been proven in the treatment of children and adolescents with attention-deficit hyperactivity disorder (ADHD).
BACKGROUND
The efficacy of dexmethylphenidate (d-MPH) has been proven in the treatment of children and adolescents with attention-deficit hyperactivity disorder (ADHD).
OBJECTIVE
The aim of this systematic review is to determine the efficacy, acceptability, and tolerability of d-MPH in child and adolescent ADHD.
METHODS
The searches of SCOPUS, MEDLINE, CINAHL, and Cochrane Controlled Trials Register were performed in February 2015. All randomized controlled trials of d-MPH versus placebo that were performed in children and adolescents with ADHD up to 18 years of age were included in the study. The efficacy was measured by using the pooled mean-endpoint or mean-changed scores of ADHD rating scales and the response rate. Acceptability and tolerability were measured by using the pooled rates of overall discontinuation and discontinuation due to adverse events, respectively.
RESULTS
A total of 1,124 children and adolescents diagnosed as having ADHD were included in this review. In a laboratory school setting, the pooled mean-change and mean-endpoint scores in the d-MPH-treated group were significantly greater than those of the placebo-treated group with standardized mean difference (95% confidence interval [CI]) of -1.20 (-1.73, -0.67), I (2)=95%. Additionally, the pooled mean-changed scores of the ADHD rating scales for teachers and parents in the d-MPH-treated group were significantly greater than that of the placebo-treated group with weighted mean difference (95% CI) of -13.01 (-15.97, -10.05), I (2)=0% and (95% CI) of -12.99 (-15.57, -10.42), I (2)=0%, respectively. The pooled response rate in the d-MPH-treated groups had a significance higher than that of the placebo-treated group. The rates of pooled overall discontinuation and discontinuation due to adverse events between the two groups were not significantly different.
CONCLUSION
Based on the findings in this review, it can be concluded that d-MPH medication is efficacious and tolerable in child and adolescent ADHD. However, the acceptability of d-MPH is no greater than that of the placebo. Further systematic studies may confirm these findings.
PubMed: 26648726
DOI: 10.2147/NDT.S91765 -
Journal of the American Academy of... Nov 2004To evaluate the efficacy and safety of dexmethylphenidate hydrochloride (d-MPH, Focalin) for the treatment of attention-deficit/hyperactivity disorder (ADHD) and to test... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
A double-blind, placebo-controlled trial of dexmethylphenidate hydrochloride and d,l-threo-methylphenidate hydrochloride in children with attention-deficit/hyperactivity disorder.
OBJECTIVE
To evaluate the efficacy and safety of dexmethylphenidate hydrochloride (d-MPH, Focalin) for the treatment of attention-deficit/hyperactivity disorder (ADHD) and to test an a priori hypothesis that d-MPH would have a longer duration of action than d,l-threo-methylphenidate (d,l-MPH).
METHOD
This was a randomized, double-blind study conducted at 12 U.S. centers. One hundred thirty-two subjects received d-MPH (n=44), d,l-MPH (n=46), or placebo (n=42) twice daily for 4 weeks, with titration of the dose based on weekly clinic visits. The primary efficacy variable was change from baseline to last study visit on teacher-completed Swanson, Nolan, and Pelham Rating Scale (Teacher SNAP). Secondary efficacy measures included the change on parent-completed SNAP (Parent SNAP), Clinical Global Impressions Scale-Improvement (CGI-I) score, and Math Test performance. Assessments at home in late afternoon were included to test the hypothesis that d-MPH would have a longer duration of efficacy than d,l-MPH. Safety was assessed through monitoring occurrence and severity of adverse events and discontinuations related to them.
RESULTS
Treatment with either d-MPH (p=.0004) or d,l-MPH (p=.0042) significantly improved Teacher SNAP ratings compared with placebo. The d-MPH group showed significant improvements compared with placebo on the afternoon Parent SNAP ratings (p=.0003) and scores on the Math Test (p=.0236) obtained late in the afternoon at 6:00 p.m. Sixty-seven percent of patients showed improvement on d-MPH and 49% on d,l-MPH based on CGI-I scores. Both d-MPH and d,l-MPH were well tolerated, no patient in the d-MPH group and only two patients each in the d,l-MPH and placebo groups discontinued the study.
CONCLUSIONS
For the treatment of ADHD, an average titrated dose of 18.25 mg/day of d-MPH is as efficacious and safe as an average titrated dose of 32.14 mg/day of d,l-MPH. Both active treatments have large effect sizes. Thus, d-MPH and d,l-MPH appear to provide similar efficacy, and d-MPH may have longer duration of action after twice-daily dosing, but additional studies are needed to determine the statistical and clinical significance of this possibility.
Topics: Administration, Oral; Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dexmethylphenidate Hydrochloride; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Methylphenidate; Placebos; Severity of Illness Index; Stereoisomerism; Treatment Outcome
PubMed: 15502600
DOI: 10.1097/01.chi.0000138351.98604.92