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Pediatric Pulmonology Sep 2022
Topics: Chlorides; Cystic Fibrosis Transmembrane Conductance Regulator; Dexmethylphenidate Hydrochloride; Guanfacine; Humans; Metabolic Syndrome; Mutation; Sweat
PubMed: 35570399
DOI: 10.1002/ppul.25975 -
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 -
Journal of Chromatographic Science Apr 2023A simple, robust stability indicating RP-HPLC method was developed for simultaneous quantification of serdexmethyl phenidate and dexmethyl phenidate in a fixed capsule...
A simple, robust stability indicating RP-HPLC method was developed for simultaneous quantification of serdexmethyl phenidate and dexmethyl phenidate in a fixed capsule dosage form. This is the first method to be reported for simultaneous estimation and quantification of degradation products produced from forced stressing of the dosage form as per ICH guidelines. The chromatographic separation was attained on Waters X-terra C18 column using a mixture of trifluoro acetic acid and acetonitrile (70:30 v/v) as mobile phase with a flow rate of 1 mL, monitored at 265 nm over a run time of 10 min. Serdexmethyl phenidate and dexmethyl phenidate were eluted with retention times of 2.71 min and 7.33 min, respectively. The method displayed linear responses in the range of 4.2-63 μg/mL (0.9994) for serdexmethyl phenidate and 0.9 to 3.5 μg/mL (0.9998) for dexmethyl phenidate, respectively. The percentage recoveries of the two drugs were found within the acceptable limits. Forced degradation was conducted and showed considerable degradation in various stress conditions. It also confirms the specificity of the method as no interference peaks were observed concerning for to stress products. This method can be routinely used in quality control labs for simultaneous determination of respective drugs in marketed dosage form.
Topics: Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Methylphenidate; Capsules
PubMed: 35152281
DOI: 10.1093/chromsci/bmac011 -
Journal of Child and Adolescent... Nov 2021To evaluate the efficacy and safety of once-daily serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) capsules (Azstarys) compared with placebo in children with... (Randomized Controlled Trial)
Randomized Controlled Trial
To evaluate the efficacy and safety of once-daily serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) capsules (Azstarys) compared with placebo in children with attention-deficit/hyperactivity disorder (ADHD) in a randomized, double-blind, dose-optimized laboratory classroom study. Children ages 6-12 with ADHD were enrolled. During a 3-week, open-label, Dose Optimization Phase, subjects initiated treatment with 39.2 mg/7.8 mg/day of SDX/d-MPH and were titrated weekly to an optimal dose (maximum dose of 52.3/10.4 mg). During the double-blind Treatment Phase, subjects were randomized to receive their optimal dose of SDX/d-MPH or placebo for 7 days. On day 7, efficacy was assessed in the laboratory classroom using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP). To evaluate safety, adverse events (AEs), vital signs, and electrocardiograms were assessed, and suicide risk was assessed. A total of 149 subjects completed the study. In the primary efficacy analysis, the mean postdose change from baseline in SKAMP-Combined scores averaged over the laboratory classroom day was significantly improved with SDX/d-MPH versus placebo (least-squares mean treatment difference [95% confidence interval]: -5.41 [-7.10 to -3.71]; < 0.001). A significant treatment effect for SDX/d-MPH compared with placebo was observed from 1 to 10 hours postdose. A analysis more comparable with that conducted in similar studies indicated a 0.5- to 13-hour onset and duration of efficacy. Both average postdose PERMP-Attempted and PERMP-Correct score changes from baseline were significantly improved among those treated with SDX/d-MPH versus placebo ( < 0.001 for both). No serious AEs were reported. During the Dose Optimization Phase, two-thirds of subjects reported AEs; the most common being insomnia and decreased appetite. SDX/d-MPH showed significant improvement in ADHD symptoms compared with placebo in children 6-12 years of age, with a rapid onset and extended duration of treatment effect. SDX/d-MPH was safe, with AEs comparable with those observed with other stimulant treatments.
Topics: Attention Deficit Disorder with Hyperactivity; Capsules; Central Nervous System Stimulants; Child; Delayed-Action Preparations; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Laboratories; Methylphenidate; Treatment Outcome
PubMed: 34714120
DOI: 10.1089/cap.2021.0077 -
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 -
The Medical Letter on Drugs and... Oct 2021
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Double-Blind Method; Drug Approval; Drug Combinations; Drug Interactions; Humans; Methylphenidate; Randomized Controlled Trials as Topic; United States; United States Food and Drug Administration
PubMed: 34550957
DOI: No ID Found -
Ochsner Journal 2021Both psychiatric disorders and diverse medications used to treat them have been associated with alopecia. The objective of our study was to investigate the existence of...
Both psychiatric disorders and diverse medications used to treat them have been associated with alopecia. The objective of our study was to investigate the existence of an association between attention-deficit/hyperactivity disorder (ADHD) stimulant medication (ASM) and various types of alopecia. We conducted a retrospective case-control medical record review of patients between the ages of 6 and 18 years seen in dermatology clinics during a 10-year period. Cases included patients diagnosed with alopecia areata (AA), alopecia totalis (AT), or alopecia universalis (AU). We matched 3 controls on age and sex to each case. We reviewed patients' medical records for the following medications: lisdexamfetamine, amphetamine/dextroamphetamine, dexmethylphenidate, and methylphenidate. We examined the association between medications used to treat ADHD and diagnoses of AA, AT, and/or AU by calculating a series of odds ratios and 95% CIs. We identified 124 cases (110 with AA, 11 with AT, and 3 with AU) and 372 controls. We found a strong association between AU and ASM use (<0.0071). No relationship between ASM use and other types of hair loss was found. Although the sample size of cases with AU was small, we found a significant association between AU and ASM. While further study is needed, practitioners may consider close monitoring of patients with AA who use ASM for the development of worsening disease and discontinue the medication if the patient experiences an increase in hair loss that appears to be progressing to AU.
PubMed: 34239372
DOI: 10.31486/toj.20.0025 -
JAMA Pediatrics Sep 2021Although there is no pharmacological treatment for autism spectrum disorder (ASD) itself, behavioral and pharmacological therapies have been used to address its symptoms...
IMPORTANCE
Although there is no pharmacological treatment for autism spectrum disorder (ASD) itself, behavioral and pharmacological therapies have been used to address its symptoms and common comorbidities. A better understanding of the medications used to manage comorbid conditions in this growing population is critical; however, most previous efforts have been limited in size, duration, and lack of broad representation.
OBJECTIVE
To use a nationally representative database to uncover trends in the prevalence of co-occurring conditions and medication use in the management of symptoms and comorbidities over time among US individuals with ASD.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective, population-based cohort study mined a nationwide, managed health plan claims database containing more than 86 million unique members. Data from January 1, 2014, to December 31, 2019, were used to analyze prescription frequency and diagnoses of comorbidities. A total of 26 722 individuals with ASD who had been prescribed at least 1 of 24 medications most commonly prescribed to treat ASD symptoms or comorbidities during the 6-year study period were included in the analysis.
EXPOSURES
Diagnosis codes for ASD based on International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision.
MAIN OUTCOMES AND MEASURES
Quantitative estimates of prescription frequency for the 24 most commonly prescribed medications among the study cohort and the most common comorbidities associated with each medication in this population.
RESULTS
Among the 26 722 individuals with ASD included in the analysis (77.7% male; mean [SD] age, 14.45 [9.40] years), polypharmacy was common, ranging from 28.6% to 31.5%. Individuals' prescription regimens changed frequently within medication classes, rather than between classes. The prescription frequency of a specific medication varied considerably, depending on the coexisting diagnosis of a given comorbidity. Of the 24 medications assessed, 15 were associated with at least a 15% prevalence of a mood disorder, and 11 were associated with at least a 15% prevalence of attention-deficit/hyperactivity disorder. For patients taking antipsychotics, the 2 most common comorbidities were combined type attention-deficit/hyperactivity disorder (11.6%-17.8%) and anxiety disorder (13.1%-30.1%).
CONCLUSIONS AND RELEVANCE
This study demonstrated considerable variability and transiency in the use of prescription medications by US clinicians to manage symptoms and comorbidities associated with ASD. These findings support the importance of early and ongoing surveillance of patients with ASD and co-occurring conditions and offer clinicians insight on the targeted therapies most commonly used to manage co-occurring conditions. Future research and policy efforts are critical to assess the extent to which pharmacological management of comorbidities affects quality of life and functioning in patients with ASD while continuing to optimize clinical guidelines, to ensure effective care for this growing population.
Topics: Adolescent; Amphetamines; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Bupropion; Child; Child, Preschool; Cohort Studies; Comorbidity; Data Mining; Depressive Disorder, Major; Dexmethylphenidate Hydrochloride; Dextroamphetamine; Female; Health Services Accessibility; Humans; Insurance; Lisdexamfetamine Dimesylate; Male; Managed Care Programs; Prevalence; Retrospective Studies
PubMed: 34097007
DOI: 10.1001/jamapediatrics.2021.1329 -
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 -
PloS One 2021Patient access and adherence to chronic medications is critical. In this work, we evaluate whether disruptions related to Covid-19 have affected new and existing...
Patient access and adherence to chronic medications is critical. In this work, we evaluate whether disruptions related to Covid-19 have affected new and existing patients' access to pharmacological therapies without interruption. We do so by performing a retrospective analysis on a dataset of 9.4 billion US prescription drug claims from 252 million patients from May, 2019 through August, 2020 (about 93% of prescriptions dispensed within those months). Using fixed effect (conditional likelihood) linear models, we evaluate continuity of care, how many days of supply patients received, and the likelihood of discontinuing therapy for drugs from classes with significant population health impacts. Findings indicate that more prescriptions were filled in March 2020 than in any prior month, followed by a significant drop in monthly dispensing. Compared to the pre-Covid era, a patient's likelihood of discontinuing some medications increased after the spread of Covid: norgestrel-ethinyl estradiol (hormonal contraceptive) discontinuation increased 0.62% (95% CI: 0.59% to 0.65%, p<0.001); dexmethylphenidate HCL (ADHD stimulant treatment) discontinuation increased 2.84% (95% CI: 2.79% to 2.89%, p<0.001); escitalopram oxalate (SSRI antidepressant) discontinuation increased 0.57% (95% CI: 0.561% to 0.578%, p<0.001); and haloperidol (antipsychotic) discontinuation increased 1.49% (95% CI: 1.41% to 1.57%, p<0.001). In contrast, the likelihood of discontinuing tacrolimus (immunosuppressant) decreased 0.15% (95% CI: 0.12% to 0.19%, p<0.001). The likelihood of discontinuing buprenorphine/naloxone (opioid addiction therapy) decreased 0.59% (95% CI: 0.55% to 0.62% decrease, p<0.001). We also observe a notable decline in new patients accessing these latter two therapies. Most US patients were able to access chronic medications during the early months of Covid-19, but still were more likely to discontinue their therapies than in previous months. Further, fewer than normal new patients started taking medications that may be vital to their care. Providers would do well to inquire about adherence and provide prompt, nonjudgmental, re-initiation of medications. From a policy perspective, opioid management programs seem to demonstrate a robust ability to manage existing patients in spite of disruption.
Topics: Analgesics, Opioid; Antidepressive Agents; Antipsychotic Agents; COVID-19; Central Nervous System Stimulants; Contraceptive Agents, Hormonal; Datasets as Topic; Drug Prescriptions; Humans; Immunosuppressive Agents; Insurance, Pharmaceutical Services; Medication Adherence; Pandemics; Retrospective Studies; United States
PubMed: 33793663
DOI: 10.1371/journal.pone.0249453