Extended-release Methylphenidate Research Articles

A Post-Hoc Analysis of Emotional Lability With Delayed-Release/Extended-Release Methylphenidate in Children Aged 6 to 12 Years of Age Participating in Two Phase 3 Clinical Trials

Objective: DR/ER-MPH (formerly HLD200) is an evening-dosed delayed-release and extended-release methylphenidate approved for the treatment of ADHD in patients ≥6 years. Post hoc analyses of two pivotal Phase 3 trials: HLD200-107 (NCT02493777) and HLD200-108 (NCT02520388) evaluated emotional lability (EL) with DR/ER-MPH treatment. Methods: Differences in Conners Global Index—Parent (CGI-P) EL subscale scores and age- and gender-adjusted T-scores over an open-label titration phase (HLD200-107) and between treatment and placebo groups at endpoint (HLD200-108) were evaluated. Results: In HLD200-107 (N = 117) mean CGI-P EL subscale scores improved from 5.3 to 1.3 (p < .0001) after 6 weeks; in HLD200-108 significant improvements were observed in the treatment group (n = 81) versus placebo (n = 80; 3.11 vs. 4.08; p = .0053). T-scores showed an improvement with DR/ER-MPH treatment in both trials. Few emotional adverse events (AEs) were reported. Conclusion: DR/ER-MPH treatment resulted in statistically significant improvements in EL to the level of non-ADHD peers as contextualized by T-scores.

Recent updates on treatment patterns in patients with treated attention-deficit/hyperactivity disorders from a nationwide real-world database in South Korea.

The prevalence of attention-deficit/hyperactivity disorder (ADHD) is steadily increasing across Korea. We analyzed ADHD patients with ADHD medications (Rx) characteristics and treatment patterns compared to patients without Rx and identified the differences between pediatric-/adult- and active-/transient-patients with Rx. Using a nationwide claims dataset from 2020 to 2021, we conducted a prevalence-based cross-sectional study and analyzed the recent patients' characteristics and patterns among ADHD patients. Among 132 017 ADHD patients with Rx, differences from 20 312 without Rx across all characteristics except sex. We found significant differences in characteristics and treatment patterns between pediatric-/adult- and active-/transient-patients with Rx. Age-specific sex ratios notably diverged in pediatric patients (61.2%), but remained similar in adults, revealing significant psychiatric comorbidities differences. Active-patients peaked at 6-11 years (41.4%), while transient-patients at 18-30 years (36.1%). Predominantly, methylphenidate (89.7%), atomoxetine (27.8%), and clonidine (2.8%) were prescribed, with 85% experiencing treatment changes within methylphenidate formulations. In pediatric patients, extended-release methylphenidate was preferred (56.1%), adults favored oral delivery system methylphenidate (71.5%), and active-patients had higher treatment rates than transient-patients across all patterns, with low monotherapy rates. This study provides epidemiologic insights into recent characteristics and treatment patterns of ADHD patients with Rx in Korea, providing valuable evidence for identifying those actively receiving ADHD treatment in future healthcare policy decisions.

Tardive and Acute Dystonic Reactions Probably Related to Extended Release Methylphenidate in an Early Adolescent with ADHD

Tardive and Acute Dystonic Reactions Probably Related to Extended Release Methylphenidate in an Early Adolescent with ADHD

Onverwacht uterien bloedverlies bij methylfenidaat

Unexpected methylphenidate-induced uterine bleeding In most countries, methylphenidate appears to be the main pharmacological treatment for attention deficit hyperactivity disorder (ADHD). The global prevalence of ADHD is estimated to be approximately 2.5% in adults and 5-7% in children. This case report examines the link between the initiation of extended-release methylphenidate and the occurrence of unexpected uterine bleeding in a patient, aiming to determine if there is any scientific basis for considering this symptom as a side effect of methylphenidate. Although there are some suspicions in the literature, the evidence is still too limited to explain a causal relationship between methylphenidate and unexpected uterine bleeding. In recent years, scientific studies have shown a growing awareness of ADHD in the female population, while women and girls were previously diagnosed with ADHD much less frequently and much later. However, this phenomenon of underrepresentation of women still occurs in the available scientific literature, especially in somewhat older studies. In future research, an important challenge lies in further monitoring any potential effects of methylphenidate on the female reproductive system, adequately reporting contraceptive use in study populations, as well as detailing all adverse events and reasons for study dropouts.

A convolution-based in vitro-in vivo correlation model for methylphenidate hydrochloride delayed-release and extended-release capsule.

Delayed-release and extended-release methylphenidate hydrochloride (JORNAY PM®) is a novel capsule formulation of methylphenidate hydrochloride, used to treat attention deficit hyperactivity disorder in patients 6 years and older. In this paper, we develop a Level A invitro-in vivo correlation (IVIVC) model for extended-release methylphenidate hydrochloride to support post-approval manufacturing changes by evaluating a point-to-point correlation between the fraction of drug dissolved invitro and the fraction of drug absorbed invivo. Dissolution data from an invitro study of three different release formulations: fast, medium, and slow, and pharmacokinetic data from two invivo studies were used to develop an IVIVC model using a convolution-based approach. The time-course of the drug concentration resulting from an arbitrary dose was considered as a function of the invivo drug absorption and the disposition and elimination processes defined by the unit impulse response function using the convolution integral. An IVIVC was incorporated in the model due to the temporal difference seen in the scatterplots of the estimated fraction of drug absorbed invivo and the fraction of drug dissolved invitro and Levy plots. Finally, the IVIVC model was subjected to evaluation of internal predictability. This IVIVC model can be used to predict invivo profiles for different invitro profiles of extended-release methylphenidate hydrochloride.

2.32 Development of an Interactive Pharmacokinetic Dose-Dependent Duration Model for Delayed-Release and Extended-Release Methylphenidate

2.32 Development of an Interactive Pharmacokinetic Dose-Dependent Duration Model for Delayed-Release and Extended-Release Methylphenidate

Low Doses of Melatonin to Improve Sleep in Children with ADHD: An Open-Label Trial.

Only a few studies assessing the sleep effects of low doses of melatonin (aMT) have been performed in the past, most of them in adults, and only one in subjects with attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to provide evidence of the changes induced by aMT doses as low as 1 mg in the sleep pattern of pediatric patients with ADHD under treatment with methylphenidate (MPH). Children and adolescents (7-15 years) with ADHD who were receiving extended-release MPH were recruited. A seven-week sleep diary was collected prior to starting a four-week treatment with 1 mg of aMT (30 min before bedtime). Seven-day actigraphic assessments of sleep were performed before and after treatment. Twenty-seven patients (17 males, 62.96%) participated in the study, who had been receiving MPH for 1.57 (1.11) months. A significant increase in sleep duration (TST) was observed after one month of treatment (463 (49) min to 485 (41) min; p < 0.040), with nonsignificant improvements in sleep-onset latency (SOL), nocturnal awakenings, or sleep efficiency. Only minor adverse effects were reported. Low doses of melatonin (1 mg) are able to increase TST in children and adolescents with ADHD receiving treatment with psychostimulants, with an adequate tolerability profile. Further placebo-controlled trials adjusting the time of aMT administration to the individual circadian profile should explore the effects of low doses of this hormone to shorten SOL in this population of patients.

0601 An Atypical Cause of Hallucinations in Type 1 Narcolepsy

Abstract Introduction Narcolepsy is a disorder of hypersomnolence affecting between 1:5000-1:10,000 individuals. Type 1 Narcolepsy can be differentiated from Type 2 Narcolepsy by the presence of cataplexy. Visual hallucinations are reported in 50-80% of T1 Narcoleptics and ~25% of T2 Narcoleptics. This is thought to be a REM-related phenomenon occurring at transitions of sleep and wakefulness. Auditory hallucinations or paranoid delusions are more rare. We report a case of a 17 year old patient who experienced psychotic symptoms after trialing more than one class of stimulants. Methods This was primarily a retrospective case review. A subsequent literature search was performed reviewing similar reports of psychosis secondary to medications used to treat Narcolepsy. Results The patient is a 17 year old female who was 10 years old at the time of her diagnosis of Narcolepsy T1. At onset, the patient had reported cataplexy and visual hallucinations occurring at the time of sleep onset and wakening. After finding minimal help with stimulants, by age 15 she was maintained on sodium oxybate 6 grams per night for her cataplexy and started modafinil 200mg BID for wakefulness. She then reported new auditory hallucinations and hyperreligiosity and was admitted to inpatient psychiatry where both medications were discontinued. She was subsequently started on extended release methylphenidate and within 2 months had a recurrence of auditory hallucinations and hyperreligiosity resulting in two consecutive inpatient hospitalizations for psychosis. Conclusion Psychosis induced by medications for Narcolepsy has been reported in the literature where sodium oxybate and stimulants are the most common offending agents. Symptoms primarily related to modafinil or armodafinil are less frequently described. Most medications used to treat Narcolepsy may directly or indirectly act on dopamine pathways, which in theory have the propensity to lead to psychotic symptoms. Small studies of patients with Narcolepsy have reported psychosis in less than 1-2% of Modafinil users. Larger meta-analyses of patients with both Narcolepsy and Schizophrenia, have not found an increased likelihood for uncontrolled psychotic symptoms while on modafinil. Further case studies are needed to elucidate the relationship between stimulants and risk of psychosis in Narcolepsy patients. Support (if any)

Real-World Efficacy and Safety of Extended-Release Methylphenidate (PRC-063) in the Treatment of ADHD in Pediatric and Adult Subjects: Results of a Phase IV Multicenter Comparison With Lisdexamfetamine Dimesylate

Objective: To evaluate the real-world efficacy, safety, and functional outcomes of PRC-063 (multilayer-release methylphenidate) versus lisdexamfetamine (LDX) in ADHD subjects in a phase IV, open-label study. Method: The primary endpoint was the change in the ADHD-DSM-5 Rating Scale (ADHD-5-RS) total score from baseline to Month 4. Secondary endpoints included a non-inferiority comparison between PRC-063 and LDX and measures of functioning and evening behavior. Results: One hundred forty-three pediatric and 112 adult subjects were enrolled. Mean ADHD-5-RS scores (standard deviation) were reduced in pediatric (−16.6 [10.4]) and adult (−14.8 [10.6]) subjects treated with PRC-063 (p < .001). PRC-063 was non-inferior to LDX in the pediatric population but not in the adult population. Significant improvements were demonstrated in quality of life and functionality. Both medications were well-tolerated; more adverse events led to study discontinuation in pediatric subjects treated with LDX versus PRC-063. Conclusion: PRC-063 and LDX significantly improved ADHD symptomatology and functioning and were well-tolerated.

Late diagnosis of attention deficit hyperactivity disorder and cocaine abuse

IntroductionAdult ADHD diagnosis sometimes represents a challenge for the clinician, due to the comorbid psychiatric diseases that are often associated and which complicate de recognition of the primary symptoms of ADHD. The prevalence of ADHD in adult populations is 2’5% and it is a relevant cause of functional impairment.ObjectivesPresentation of a clinical case of a male cocaine user diagnosed with adult ADHD.MethodsLiterature review on adult ADHD and comorbid substance abuse.ResultsA 43-year-old male who consulted in the Emergency Department due to auditory hallucinosis in the context of an increase in his daily cocaine use. There were not delusional symptoms associated and judgment of reality was preserved. Treatment with olanzapine was started and the patient was referred for consultation. In psychiatry consultations, he did not refer sensory-perceptual alterations anymore, nor appeared any signals to suspect so, and he was willing to abandon cocaine use after a few appointments. He expressed some work concerns, highlighting that in recent months, in the context of a greater workload, he had been given several traffic tickets for “distractions.” His wife explained that he had always been a inattentive person (he forgets important dates or appointments) and impulsive, sometimes interrupting conversations. In the Barkley Adult ADHD Rating Scale he scored 32 points.He was diagnosed with adult ADHD and treatment with extended-release methylphenidate was started with good tolerance and evolution, with improvement in adaptation to his job and social environment. Since then, the patient has moderately reduced the consumption of drugs, although he continues to use cocaine very sporadically.ConclusionsEarly detection of ADHD and its comorbidities has the potential to change the course of the disorder and the morbidity that will occur later in adults. Comorbidity in adult ADHD is rather the norm than the exception, and it renders diagnosis more difficult. The most frequent comorbidities are usually mood disorders, substance use disorders, and personality disorders. Treatment of adult ADHD consists mainly of pharmacotherapy supported by behavioral interventions. When ADHD coexists with another disorder, the one that most compromises functionality will be treated first and they can be treated simultaneously. The individual characteristics of each patient must be taken into account to choose the optimal treatment.Disclosure of InterestNone Declared

Dikkat Eksikliği ve Hiperaktivite Bozukluğu Olan Çocuklarda Kullanılan Uzun Etkili Metilfenidat Bileşiklerinin ve Atomoksetinin Kardiyak Fonksiyonlar Üzerindeki Etkileri

Objectives: Methylphenidate (MPH) and Atomoxetine (ATX) are most commonly prescribed for the treatment of Attention Deficit And Hyperactivity Disorder (ADHD). Despite their widespread use, there are concerns about their cardiovascular safety. In this study, we aimed to investigate the effects of ADHD medications on cardiac functions.&#x0D; Methods: Forty-six children with ADHD disorder using osmotic-release oral system methylphenidate (OROS-MPH), 46 using extended-release methylphenidate (ER-MPH), and 46 using ATX for at least six months were included in the patient groups. 46 children with normal cardiac findings were included as the control group. All participants were evaluated using a sociodemographic information form, physical examination, 12-channel electrocardiography (ECG), transthoracic 2D echocardiography, Doppler echocardiography, and tissue Doppler imaging (TDI).&#x0D; Results: Statistically significant differences were observed in terms of A wave velocity (p=0,002), E/A (p

Efficacy of stimulants for preschool attention-deficit/hyperactivity disorder: A systematic review and meta-analysis.

Robust synthesis of evidence to support treatment recommendations for preschoolers with attention-deficit/hyperactivity disorder (ADHD) is lacking. The aim of this systematic review and meta-analysis was to review currently available evidence to evaluate the efficacy and acceptability of stimulants for preschool children with ADHD. We searched electronic databases (CENTRAL, Embase, PubMed) from the database inception to March, 2022; and clinical trial registries through WHO ICTRP from the database inception to July, 2022, and selected double-blinded randomized controlled trials (RCTs) that compared stimulants against placebo for the treatment of preschoolers (age≤7years) with ADHD. Change in ADHD symptom severity was the primary outcome (efficacy) and all-cause dropout rates (acceptability) was the secondary outcome. Data were pooled with random-effects models weighted by theinverse of the variance. Risk of bias of individual studies were assessed with the Cochrane Risk of Bias tool version 2. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the quality of evidence. This study is registered with PROSPERO (CRD42022348597). Five RCTs (three methylphenidate immediate-release, one methylphenidate extended-release, and one lisdexamfetamine) were included. The analysis of efficacy was based on 489 participants. Meta-analysis of change in ADHD symptom severity demonstrated a significant effect in favor of stimulants over placebo (standardized mean difference=-0.59; 95% CI -0.77, -0.41; p<0.0001). There was no evidence of heterogeneity but some concerns about publication bias. Regardless, the confidence of evidence was considered moderate. For acceptability, stimulants did not lead to an increased rate of all-cause discontinuation rates in comparison to placebo (OR=0.59; 95% CI 0.15, 2.37; p=0.45) but the confidence of estimate was very low. Our findings demonstrated that stimulants are efficacious in reducing ADHD symptoms among preschool children. Clinicians should consider the use of stimulants when making treatment recommendations for preschoolers with ADHD.

Efficacy and Safety of PRC-063 for Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-analysis From Randomized Controlled Trials

Objective: A new formulation of extended-release methylphenidate (PRC-063) was approved to treat ADHD. This meta-analysis was conducted to study the efficacy and safety of PRC-063 for ADHD. Method: We searched for published trials to October 2022 in several databases. Results: A total of 1,215 patients from 5 RCTs were included. We observed significant improvement for PRC-063 in ADHD Rating Scale (ADHD-RS; MD = −6.73, 95% CI [−10.34, −3.12]) compared with placebo. The effect of PRC-063 on the sleep problems due to ADHD was not statistically different from placebo. Six subscales of Pittsburg Sleep Quality Index (PSQI) showed no statistical significance between PRC-063 and placebo. The result showed no significant difference comparing PRC-063 with placebo in serious treatment-emergent adverse events (TEAEs) (RR = 0.80, 95% CI [0.03, 19.34]). In subgroup analysis according to age, PRC-063 was more efficacious in minors compare to adults. Conclusion: PRC-063 is an efficacious and safe treatment for ADHD, especially in children and adolescents.

Attention-Deficit/Hyperactivity Disorder in a Patient with Lujan-Fryns Syndrome: A Case Report

Introduction: Lujan-Fryns syndrome (LFS), a rare genetic anomaly first described in 1984, is characterized by a unique constellation of clinical features primarily attributed to mutations in the MED12 gene. These features include intellectual disability, behavioral complexities, and distinct somatic attributes. Although formal psychiatric criteria are lacking, numerous case studies have revealed a co-occurrence of LFS with psychological manifestations, including attention-deficit/hyperactivity disorder (ADHD). This case report explores the intricate relationship between LFS and ADHD, shedding light on potential diagnostic and therapeutic strategies. Case Presentation: We present the clinical profile of a 13-year-old male diagnosed with LFS, who exhibited hyperactivity and inattention symptoms, leading to a diagnosis of ADHD. The patient’s history included full-term birth, developmental delays, and speech challenges, necessitating special education. Treatment for ADHD included methylphenidate extended-release, behavioral modification techniques, and clonidine, resulting in significant symptom improvement. Marfanoid features were present, and LFS was confirmed through genetic testing. Comprehensive care with a multi-disciplinary approach addressed the associated medical concerns. Conclusion: Recognizing and addressing the co-occurrence of LFS and ADHD is crucial. This complex interplay presents diagnostic and therapeutic challenges requiring a multidisciplinary approach. The absence of specific medications for LFS-associated ADHD highlights the need for customized treatments. This case report enhances our understanding of their relationship, paving the way for further research to improve clinical care for individuals with both these conditions.

GROWTH TRAJECTORIES OF CHILDREN AND ADOLESCENTS WITH ADHD TREATED WITH DELAYED-RELEASE/EXTENDED-RELEASE METHYLPHENIDATE (JORNAY PM®): A PILOT STUDY OF REAL-WORLD DATA FROM A LARGE US CLAIMS DATABASE

Stimulants are associated with a slowed growth rate in pediatric patients with ADHD. DR/ER-MPH (formerly HLD200; trade name: JORNAY PM®) is an evening-dosed, delayed-release, and extended-release methylphenidate released in the colon; it has no immediate-release component and provides a dose-dependent duration of effect for individuals with ADHD. Herein, we report real-world weight and height changes in patients newly prescribed DR/ER-MPH in its first year of availability vs patients treated with 2 established branded stimulants, osmotic release oral system (OROS) MPH (Concerta®) and lisdexamfetamine dimesylate (LDX; Vyvanse®).

Functional outcomes of extended-release methylphenidate and atomoxetine in children: retrospective chart analysis

BackgroundRecent guidelines emphasize the importance of functional outcomes in children with attention-deficit/hyperactivity disorder (ADHD). Here, we assess the functional outcomes of the oral delivery system of osmotic-release methylphenidate (OROS-MPH) and atomoxetine (ATX) from the retrospective review of the chart for the last 2 years in the clinic.ResultsLinear mixed-effects models were performed with outcome measures of difference in ADHD symptoms and functional impairment. After 9–12 weeks, OROS-MPH and ATX were statistically equivalent for total Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) scores (difference in slope is β = 0.004, p = 1.000). However, OROS-MPH was superior to ATX in terms of school domain (difference in slope is β = 0.139, p < 0.001); ATX was superior in the family domain (slope difference in slope is β = 0.103, p < 0.001). The other domains of functioning both were not responsive to pharmacotherapy and were similar between the two medications.ConclusionsOptimal management should monitor functional progress in ADHD beyond the core symptoms. As expected, ADHD medications provide a distinct pattern of functional improvement. Pharmacotherapy alone offers promising and reliable outcomes to improve school and family functions in ADHD. Some functional improvements did not respond to the medication; therefore, many of the techniques derived from behavioral interventions should be considered.

How does extended-release (ER) methylphenidate compare with placebo in adults with attention deficit hyperactivity disorder (ADHD)?

How does extended-release (ER) methylphenidate compare with placebo in adults with attention deficit hyperactivity disorder (ADHD)?

Analysis of Daily Sleep Diary Measures From Multilayer Extended-Release Methylphenidate (PRC-063) Studies in Children and Adults With ADHD

Objective: To compare the effect of a once-daily extended-release methylphenidate formulation (PRC-063) versus placebo on sleep, measured via daily electronic diary in two clinical trials in pediatric (6–12 years) and adult (≥18 years) patients with attention deficit hyperactivity disorder (ADHD). Method: A diary was completed by adult patients or parents/caregivers of pediatric patients during two randomized, double-blind, placebo-controlled laboratory classroom studies. Following dose optimization of PRC-063, patients were randomized to 1 week of double-blind treatment with PRC-063 or placebo before attending a full-day laboratory classroom session. Results: In the studies, 148 pediatric patients and 239 adult patients were randomized to either PRC-063 or placebo. When compared with the diaries of placebo patients, the sleep diaries in both pediatric and adult patients showed no statistical difference in total sleep time, efficiency, or latency. Conclusion: PRC-063 did not impact subjective measures of sleep versus placebo in pediatric and adult patients with ADHD.

Stimulants.

Stimulants have been available for the treatment of attention-deficit/hyperactivity disorder (ADHD) for more than 70years and are the most effective medications available. During the past 2decades, several new immediate-release (IR) and extended-release methylphenidate (MPH) and amphetamine (AMPH) formulations have become available. These products differ by dose form (capsules, tablets, oral suspensions, oral disintegrating tablets, and patch), by onset and duration of effect, and by bioavailability. The side effect profile is generally similar for all compounds. Although the products are similar, individual patients may have a better response or tolerability to a particular class (MPH or AMPH) or formulation.

Methylphenidate Use for Emotional Dysregulation in Children and Adolescents with ADHD and ADHD and ASD: A Naturalistic Study.

Emotional dysregulation (ED) is common in attention-deficit/hyperactivity disorder (ADHD). Nonetheless, research on ADHD in children with autism spectrum disorder (ASD) and ADHD is still ongoing. Several studies suggest that methylphenidate (MPH) may be effective for ED in ADHD, while there is not enough evidence about its use in ASD with comorbid ADHD. This naturalistic study aims to investigate the effectiveness of immediate- and extended-release MPH in the treatment of ED in 70 children and adolescents (6–18 years), with a diagnosis of ADHD (n = 41) and of ASD with comorbid ADHD (n = 29), using the Child Behavior Checklist—Attention/Aggressive/Anxious (CBCL-AAA). Their parents completed the CBCL twice—first during the summer medication-free period, that is, at least one month after drug interruption; and again after three months of treatment restart. Results demonstrate that MPH is associated with a statistically significant reduction in ED in ADHD and ASD, without substantial adverse events, supporting the use of psychostimulants for the treatment of ED in these neurodevelopmental disorders.