Nonstimulant Medications Research Articles

An Open-Label Extension Study Assessing the Long-Term Safety and Efficacy of Viloxazine Extended-Release Capsules in Adults with Attention-Deficit/Hyperactivity Disorder.

Viloxazine ER (extended-release capsules; Qelbree®) is a nonstimulant medication that has been approved by the United States Food and Drug Administration (FDA) for treatment of attention-deficit/hyperactivity disorder (ADHD) in children (> 6 years old) and adults. This phase 3 open-label extension to a pivotal phase 3, double-blind trial evaluated the long-term safety and continued efficacy of viloxazine ER in adults with ADHD. This was a multicenter, flexible-dose, open-label extension to a phase III, double-blind, placebo-controlled trial (NCT04016779). Viloxazine ER was initiated at 200 mg/day and adjusted (between 200 and 600 mg/day) to achieve optimal efficacy and tolerability. Trial enrollment was halted temporarily (24 March 2020 to 23 July 2020) due to the coronavirus disease 2019 (COVID-19) pandemic. Participants completing double-blind treatment during that time were offered delayed enrollment upon trial requalification. Safety outcomes were the primary objectives. Secondary objectives were efficacy outcomes, including the ADHD Investigator Symptom Rating Scale (AISRS), and were assessed relative to double-blind baseline (or trial re-entry baseline for those whose enrollment was delayed by the COVID-19 pandemic). Overall, 159 participants (133 immediate and 26 delayed rollover) received viloxazine ER, with a mean exposure of 265 ± 254.9 days. Adverse events (AEs) included (> 10% incidence) insomnia (13.8%), nausea (13.8%), headache (10.7%), and fatigue (10.1%). AEs led to discontinuation for 17.6% of participants [most commonly insomnia (2.5%), nausea (2.5%), and fatigue (1.9%)]. AISRS total score [baseline mean ± standard deviation (SD): 37.9 ± 6.3] improved by the first follow-up visit (-11.4 ± 9.5; week 2) with continued improvement at subsequent visits (last on-study visit: -18.2 ± 11.54). Similar patterns of improvement were seen for other measures of efficacy, including quality of life and executive function. Following initial dose optimization, most participants (73%) used viloxazine ER doses ≥ 400 mg/day, with 36% using doses of 600 mg/day. Long-term viloxazine ER use was well tolerated, with no new long-term safety findings. Improvements in ADHD symptoms and associated measures were sustained throughout trial participation. In total, 73% percent of adult participants in this long-term study used viloxazine ER doses of 400 mg or more during maintenance treatment. Clinicaltrials.gov Identifier: NCT04143217.

Economic Evaluation of a Novel Treatment of Attention-Deficit/Hyperactivity Disorder in US Motor Vehicle Drivers

Background: Attention-deficit/hyperactivity disorder (ADHD) affects approximately 4.4% of US adults. ADHD is associated with high-risk driving behavior and costly motor vehicle accidents. DYANAVEL XR (DXR) (Tris Pharma, Inc.) is a once-daily fast-acting amphetamine developed for ADHD treatment. A randomized controlled trial showed that DXR patients were 43% less likely to crash during a driving simulation than individuals taking placebo. Study outcomes suggest a DXR crash rate similar to that of a driver without ADHD, while patients treated with the current standard of care (SOC) have a 52% higher crash risk than non-ADHD drivers. Objective: The aim was to evaluate the economic benefits attributable to improved driving abilities and avoided crashes in DXR patients compared with patients treated with the SOC or those who are untreated. Methods: A cost-impact model estimated 1-year crash-related cost outcomes for DXR-treated patients compared with SOC-treated and untreated ADHD patients. SOC was assumed to consist of a combination of short-, intermediate-, and long-acting ADHD stimulant and non-stimulant medications. DXR crash risk was assumed equivalent to the non-ADHD population risk, as supported by trial data. Crash risk for untreated and SOC-treated ADHD patients were assumed to be 99% and 52% higher than the general US population, respectively. Model outcomes included the cost impact (medication- and crash-related costs) and the number of crashes, injuries, and fatalities avoided with DXR. Results: Treatment with DXR would avoid 0.82 crashes, 0.016 injuries, and 0.036 fatalities per year compared with untreated patients, and 0.036 crashes, 0.007 injuries, and 0.0001 fatalities per year compared with SOC-treated patients. Compared with a population of 25% SOC-treated patients and 75% untreated patients, DXR use would save an average of $4581 per person per year across all age groups when priced at $80 per month, assuming all SOC-treated and untreated patients utilized DXR. When the value of quality-of-life improvement is considered, savings increase over 7-fold. Discussion: Outcomes suggest that DXR may be an economically beneficial treatment compared with SOC for ADHD patients. Conclusions: The economic model showed that DXR is cost-saving compared with no treatment and SOC by reducing the number of motor vehicle crashes in the ADHD population.

Economic Evaluation of a Novel Treatment of Attention-Deficit/Hyperactivity Disorder in US Motor Vehicle Drivers.

Background: Attention-deficit/hyperactivity disorder (ADHD) affects approximately 4.4% of US adults. ADHD is associated with high-risk driving behavior and costly motor vehicle accidents. DYANAVEL XR (DXR) (Tris Pharma, Inc.) is a once-daily fast-acting amphetamine developed for ADHD treatment. A randomized controlled trial showed that DXR patients were 43% less likely to crash during a driving simulation than individuals taking placebo. Study outcomes suggest a DXR crash rate similar to that of a driver without ADHD, while patients treated with the current standard of care (SOC) have a 52% higher crash risk than non-ADHD drivers. Objective: The aim was to evaluate the economic benefits attributable to improved driving abilities and avoided crashes in DXR patients compared with patients treated with the SOC or those who are untreated. Methods: A cost-impact model estimated 1-year crash-related cost outcomes for DXR-treated patients compared with SOC-treated and untreated ADHD patients. SOC was assumed to consist of a combination of short-, intermediate-, and long-acting ADHD stimulant and non-stimulant medications. DXR crash risk was assumed equivalent to the non-ADHD population risk, as supported by trial data. Crash risk for untreated and SOC-treated ADHD patients were assumed to be 99% and 52% higher than the general US population, respectively. Model outcomes included the cost impact (medication- and crash-related costs) and the number of crashes, injuries, and fatalities avoided with DXR. Results: Treatment with DXR would avoid 0.82 crashes, 0.016 injuries, and 0.036 fatalities per year compared with untreated patients, and 0.036 crashes, 0.007 injuries, and 0.0001 fatalities per year compared with SOC-treated patients. Compared with a population of 25% SOC-treated patients and 75% untreated patients, DXR use would save an average of 80 per month, assuming all SOC-treated and untreated patients utilized DXR. When the value of quality-of-life improvement is considered, savings increase over 7-fold. Discussion: Outcomes suggest that DXR may be an economically beneficial treatment compared with SOC for ADHD patients. Conclusions: The economic model showed that DXR is cost-saving compared with no treatment and SOC by reducing the number of motor vehicle crashes in the ADHD population.

First promising non-stimulant (guanfacine) transdermal patch for long-acting treatment of ADHD by solid dispersion technique

Guanfacine (GFC) extended-release tablet (Intuniv®) is an effective non-stimulant medication prescribed for attention deficit hyperactivity disorder (ADHD), presenting limitations regarding patient compliance and safety risks. The study aimed to design a novel long-acting transdermal delivery system of GFC to address these issues. Polyvinylpyrrolidone (PVP)-GFC solid dispersions were constructed by the co-evaporation method to improve drug-loading capacity to approximately 10 % (w/w). A PVP-GFC ratio of 3:1 was determined to prevent drug crystallization and promote rapid dissolution. The mechanisms underlying solid dispersion formation were revealed by XRD, DSC, molecular docking, FTIR, and Raman imaging. Hydrogen-bond interactions between PVP and GFC played a crucial role. The prescription and preparation process were optimized using single-factor and Box-Behnken design experiments. The optimized patch exhibited excellent crystallization resistance and adhesion for at least six months. Additionally, superior rheology, mechanical strength, in vitro drug release, and percutaneous permeation characteristics were observed. In human pharmacokinetic studies, the therapeutic efficacy, skin safety, and adhesion of transdermal patches were initially demonstrated for the three-day treatment of ADHD. Therefore, the innovative work expands the comprehension of solid dispersion techniques and facilitates the industrialization and commercialization of the first non-stimulant transdermal patches, providing a promising alternative for ADHD therapy.

Development of fluorescence probe for spectrofluorimetric determination of viloxazine hydrochloride in pharmaceutical form and rat plasma; additional pharmacokinetic study.

Attention deficit hyperactivity disorder (ADHD) is a neurological condition frequently identified in early childhood and frequently co-occurs with other neuropsychological disorders, particularly autism. Viloxazine hydrochloride, a non-stimulant medication, has recently gained approval for treating attention-deficit hyperactivity disorder. This paper describes the first spectrofluorimetric method for precisely measuring the content of viloxazine in pharmaceutical capsules and rat plasma. This method employed NBD-Cl (4-chloro-7-nitrobenzo-2-oxa-1,3-diazole) as a fluorescent probe, which transformed viloxazine in an alkaline environment into a remarkably sensitive fluorescent adduct. Upon excitation at 476 nm, this adduct becomes detectable at a wavelength of 536 nm. The method was validated using ICH criteria, revealing acceptable linearity across a concentration range of 200-2000 ng/ml and high sensitivity with LOD and LOQ values of 46.774 ng/ml and 141.741 ng/ml, respectively. This method was adeptly applied in a pharmacokinetic study of viloxazine in rat plasma following a single oral dose (10mg/kg), yielding a mean peak plasma concentration (Cmax) of 1721 ng/ml, achieved within 1.5h. Furthermore, the environmental impact of the technique was assessed using two greenness assessment tools, revealing a notable level of eco-friendliness and sustainability.

Attention-deficit/hyperactivity disorder: clinical phenotypes, polymorphism of life-course manifestations, and therapeutic strategies

Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder that manifests in childhood and persists into adulthood. The prevalence of ADHD (USA/worldwide) in children and adolescents is 9.5/5.29 %, in adults — 4.4/2.5 %. The disorder has strong genetic correlations with numerous mental disorders and neurological diseases, in particular with post-traumatic stress disorder, addiction to cannabis, cocaine, recurrent and bipolar affective disorders, behavioral disorders, which is the biological basis of its clinical polymorbidity. Symptoms of ADHD overlap with other clinical manifestations of neurodevelopmental disorders (symptoms of autistic spectrum disorders, speech disorders, movement disorders, dyslexia, cognitive impairment), forming a polymorphic spectrum of pervasive developmental variants. Psychostimulants have been the standard of ADHD treatment for over 50 years. In 2002, atomoxetine became the first nonstimulant medication approved by the Food and Drug Administration for the treatment of ADHD, first in children and later in adult patients. Stimulant and nonstimulant medications have been shown to be effective in different phenotypes of ADHD (comorbidity with other mental and neurological disorders). In case of comorbidity of ADHD with anxiety, tics, atomoxetine has an advantage over stimulants and, together with alpha-2-adrenergic receptor agonists, can be recommended as the first drug. The presence of comorbid anxiety disorder or recurrent depression does not impact the efficacy and side effects of atomoxetine. Thus, atomoxetine is an effective drug and not only improves the symptoms of ADHD, but also plays a certain role in the treatment of patients with comorbid depression and anxiety.

ADHD medication adherence reduces risk of committing minor offenses in adolescents.

This study aimed to investigate the association between adolescents' adherence to attention-deficit/hyperactivity disorder (ADHD) medication and their risk of committing minor offenses. Using two Dutch databases, Statistics Netherlands (CBS) and the Foundation for Pharmaceutical Statistics (SFK), we aimed to investigate the association between adherence to ADHD medication and registered minor offenses between 2005 and 2019 of 18,234 adolescents (12-18 years). We used Cox regression analyses to compare the rate of committing minor offenses of adolescents during periods of high ADHD medication adherence compared to periods of low adherence (i.e., periods with or without sufficient amounts of dispensed medication). We additionally tested associations with adherence to selective serotonin reuptake inhibitors (SSRIs) as control medication and analyzed potential reverse causation. High ADHD medication adherence was associated with a reduced risk of committing a minor offense of between 33% and 38% compared to low adherence periods of ≥3 months (hazard ratio [HR] 0.67, confidence interval [CI] 0.64-0.71) or ≥6 months (HR 0.62, CI 0.59-0.65). The reduction in risk can likely be attributed to ADHD medication, given the absence of effects of SSRIs and no reverse causation. The reduction rate remained between 16% and 55% per sex, stimulant versus non-stimulant medication, different offense categories and further sensitivity analyses. Among adolescents using ADHD medication, rates of criminality were lower during periods of high medication adherence, suggesting that adherence to ADHD medication may contribute to prevention of minor offenses in adolescents.

Can Adverse Event Patterns Inform Shared Decision-Making in ADHD Treatment? A Systematic Review of Evidence From Registration Trials for FDA-Approved Treatments in Adults.

Adult patients and clinicians are faced with several pharmacological options to manage attention-deficit/hyperactivity disorder (ADHD). If types or rates of adverse experiences vary among these options, these differences could inform the shared decision-making process. To discern differentiating evidence-based patterns of risk, we analyzed data from FDA package labels for drugs approved to treat adult ADHD and reports from the registration trials used to create these labels. Three analyses of adverse effects were conducted: placebo-corrected occurrence at rates of 1 in 5, 10, and 20 participants, association with discontinuation, and uniqueness of occurrence within the treatment options. Among the 7 agents approved to treat adult ADHD, the number of types of side effects experienced during a mix of fixed and flexible-dose studies was greatest among the nonstimulant medications, but the stimulant medications had higher rates of occurrence of side effects. The minimum frequency at which all medications had adverse events was 1 in 10 participants. Overall discontinuation rates did not differ among the stimulant medications nor between stimulants and nonstimulants. To our knowledge, this is the first study to compile and compare data from all FDA registration trials for medications approved to treat adult ADHD. This article describes a process by which readily available adverse event reporting data can be used as a tool to inform shared clinical decision-making. While differences in the methodology and outcome reporting of the trials included may limit generalizability, the number of individual patients included and the completeness of the discontinuation data can be used to inform discussions with patients about the relative likelihood of adverse experiences and other patient concerns.

Systematic Review and Meta-Analysis: Effects of Pharmacological Treatment for Attention-Deficit/Hyperactivity Disorder on Quality of Life

We conducted a systematic review and meta-analysis to quantify the effect of attention-deficit/hyperactivity disorder (ADHD) medication on quality of life (QoL), and to understand whether this effect differs between stimulants and non-stimulants. From the dataset of a published network meta-analysis (Cortese etal., 20181), updated on 27th February 2023 (https://med-adhd.org/), we identified randomized controlled trials (RCTs) of ADHD medications for individuals aged 6 years or more with a diagnosis of ADHD based on the DSM (from third to fifth editions) or the International Classification of Diseases (ICD; ninth or tenth revision), reporting data on QoL (measured with a validated scale). The risk of bias for each RCTs was assessed using the Cochrane Risk of Bias tool 2. Multi-level meta-analytic models were conducted with R 4.3.1. We included 17 RCTs (5,388 participants in total; 56% randomized to active medication) in the meta-analyses. We found that amphetamines (Hedge's g= 0.51, 95% CI= 0.08, 0.94), methylphenidate (0.38; 0.23, 0.54), and atomoxetine (0.30; 0.19, 0.40) were significantly more efficacious than placebo in improving QoL in people with ADHD, with moderate effect size. For atomoxetine, these effects were not moderated by the length of intervention, and did not differ between children/adolescents and adults. In addition to being efficacious in reducing ADHD core symptom severity, both stimulant and non-stimulant medications are efficacious in improving QoL in people with ADHD, albeit with lower effect sizes. Future research should explore whether, and to what degree, combining pharmacological and non-pharmacological interventions is likely to further improve QoL in people with ADHD. Effects of pharmacological treatment for ADHD on quality of life: a systematic review and meta-analysis; https://osf.io/;qvgps.

The efficacy of real versus sham external Trigeminal Nerve Stimulation (eTNS) in youth with Attention-Deficit/Hyperactivity Disorder (ADHD) over 4 weeks: a protocol for a multi-centre, double-blind, randomized, parallel-group, phase IIb study (ATTENS)

BackgroundAttention Deficit/Hyperactivity Disorder (ADHD), if severe, is usually treated with stimulant or non-stimulant medication. However, users prefer non-drug treatments due to side effects. Alternative non-medication treatments have so far only shown modest effects. External trigeminal nerve stimulation (eTNS) is a minimal risk, non-invasive neuromodulation device, targeting the trigeminal system. It was approved for ADHD in 2019 by the USA Food and Drug administration (FDA) based on a small proof of concept randomised controlled trial (RCT) in 62 children with ADHD showing improvement of ADHD symptoms after 4 weeks of nightly real versus sham eTNS with minimal side effects. We present here the protocol of a larger confirmatory phase IIb study testing efficacy, longer-term persistency of effects and underlying mechanisms of action.MethodsA confirmatory, sham-controlled, double-blind, parallel-arm, multi-centre phase IIb RCT of 4 weeks of eTNS in 150 youth with ADHD, recruited in London, Portsmouth, and Southampton, UK. Youth with ADHD will be randomized to either real or sham eTNS, applied nightly for 4 weeks. Primary outcome is the change in the investigator-administered parent rated ADHD rating scale. Secondary outcomes are other clinical and cognitive measures, objective hyperactivity and pupillometry measures, side effects, and maintenance of effects over 6 months. The mechanisms of action will be tested in a subgroup of 56 participants using magnetic resonance imaging (MRI) before and after the 4-week treatment.DiscussionThis multi-centre phase IIb RCT will confirm whether eTNS is effective in a larger age range of children and adolescents with ADHD, whether it improves cognition and other clinical measures, whether efficacy persists at 6 months and it will test underlying brain mechanisms. The results will establish whether eTNS is effective and safe as a novel non-pharmacological treatment for ADHD.Trial registration: ISRCTN82129325 on 02/08/2021, https://doi.org/10.1186/ISRCTN82129325.

From Consensus Statement to Pills to Pixels: New Innovations in Attention-Deficit/Hyperactivity Disorder Care.

Objectives: This review aims to present recent innovations and advancements in attention-deficit/hyperactivity disorder (ADHD) care, encompassing international consensus statement, new medication formulations, digital therapeutics, and neurostimulation devices. Methods: A comprehensive literature search of relevant articles published in the past five years was conducted, emphasizing the evidence base, efficacy, safety, and practical implications of these advancements. Results: The World Federation of ADHD Consensus Statement offers an updated diagnostic and treatment framework rooted in global scientific evidence. There are several newer ADHD medication formulations, including a nonstimulant (Viloxazine extended release) and the first transdermal amphetamine patch approved to treat ADHD. These options offer some unique benefits to personalize treatment based on symptom profile, lifestyle, preferences, and response. Digital tools offer additional means to restructure environments for individuals with ADHD, reducing impairment and reliance on others. In addition, digital therapeutics enhance access, affordability, personalization, and feasibility of ADHD care, complementing or augmenting existing interventions. Trigeminal nerve stimulation emerges as a well-tolerated nonpharmacological, device-based treatment for pediatric ADHD, with initial trials indicating effect sizes comparable to nonstimulant medications. Conclusions: These innovations in ADHD care represent clinically significant new treatment options and opportunities for personalized care. Health care professionals should integrate these developments into clinical practice, mindful of individual patient and family needs and preferences. Future research should assess long-term outcomes, cost-effectiveness, and acceptability of these innovations.

Prescribed psychostimulants and other pro-cognitive medications in bipolar disorder: A systematic review and meta-analysis of recurrence of manic symptoms.

Clinicians are often hesitant to prescribe psychostimulants in bipolar disorder (BD) due to concerns of inducing (hypo)mania, despite limited published evidence on associations between prescribed psychostimulant use and recurrence of mood episodes in BD. The current systematic review and meta-analysis evaluated the emergence of (hypo)manic symptoms in patients with BD receiving prescribed psychostimulants or other pro-cognitive medications in euthymic or depressive states. A systematic search was performed of MEDLINE, Embase, and PsychINFO from inception to April 5, 2023 and search of Clinicaltrials.gov and Clinicaltrialsregister.eu for unpublished data. References of included studies were hand-searched. Randomized trials and prospective longitudinal studies that evaluated psychostimulants and non-stimulant medications recommended for the treatment of ADHD by the Canadian ADHD practice guidelines were included. The review was reported in line with PRISMA guidelines and was preregistered on PROSPERO (CRD42022358588). After screening 414 unique records, we included 27 studies, of which five reported data that was quantitatively synthesized (n = 1653). The use of psychostimulants in BD was not associated with increased scores on the Young Mania Rating Scale in patients who were in a euthymic or depressed state (SMD IV -0.17; 95% CI, -0.40 to 0.06) compared to placebo. There was a high degree of study-level heterogeneity (I2 = 80%). A qualitative synthesis of studies revealed a limited risk of medication-induced manic symptoms. Our review provides preliminary evidence to suggest psychostimulants and non-stimulant ADHD medications have a limited risk of precipitating (hypo)mania symptoms. More extensive studies evaluating the safety and efficacy of these medications are warranted.

Minimally Verbal Individuals with Autism Spectrum Disorders/Intellectual Disability and Challenging Behaviors: Can Strategic Psychiatric Treatment Help?

(1) Background: Psychiatrists are increasingly required to treat minimally verbal (MV) individuals with autism spectrum disorder (ASD), intellectual disability (ID) and behavior problems without much published guidance. (2) Methods: We reviewed 80 charts of MV patients managed strategically for challenging behaviors, following IRB approval. Data extracted included demographics, ASD/ID level, diagnoses, epilepsy and medications. In this descriptive study, we examined the course of assessment and treatment and made recommendations for a strategic, person-centered approach. (3) Results: Of 53 males and 27 females, mean age 34 years (range 7–76), all had ID; 75 had ASD (94%). Diagnoses included seizures in 40/80 (50%), frequent aggression (89%), self-injury (80%), attention-deficit hyperactivity disorder (ADHD) (64%) and obsessive compulsive disorder (OCD) (34%). The commonest medication classes adjusted were antiseizure medications, antipsychotics, and non-stimulant ADHD medications. (4) Conclusions: Clinical impressions suggested that this strategic psychiatric approach was beneficial, notably a review of antiseizure and all other medications for polypharmacy, behavioral and other side effects, followed by a review of possible childhood/current ADHD and a trial of low-dose non-stimulant ADHD medications if warranted. Low-dose risperidone was often effective and tolerable for irritability and self-injury.

Diagnosis and Treatment of ADHD in the Pediatric Population.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in childhood with approximately 6 million children (age 3 to 17 years) ever diagnosed based on data from 2016-2019. ADHD is characterized by a constant pattern of inattention and/or hyperactivity-impulsivity symptoms that interferes with development or functioning. Specific criteria from the Diagnostic and Statistical Manual of Mental Disorders, 5th edition Text Revision assist with the diagnosis with multiple guidelines available providing non-pharmacologic and pharmacologic recommendations for the treatment of ADHD in the pediatric population. While all guidelines similarly recommend behavioral and/or stimulant therapy as first-line therapy based on age, not all stimulant products are equal. Their differing pharmacokinetic profiles and formulations are essential to understand in order to optimize efficacy and safety for patients. Additionally, new stimulant products and non-stimulant medications continue to be approved for use of ADHD in the pediatric population and it is important to know their differences in formulation, efficacy, and safety to other products currently available. Lastly, due to drug shortages, it is important to understand product similarities and differences to select alternative therapy for patients.

Adolescents’ Use of Medications for Attention-Deficit/Hyperactivity Disorder and Subsequent Risk of Nonmedical Stimulant Use

PurposeThis national prospective multicohort study examined the relationship between US adolescents’ use of stimulant therapy for attention-deficit/hyperactivity disorder (ADHD) and subsequent risk of nonmedical stimulant use (i.e., nonmedical use of prescription stimulants and cocaine use) during young adulthood, relative to nonstimulant therapy and population controls. MethodsNationally representative multicohort panels of 11,905 US 12th-grade students were surveyed via self-administered questionnaires at baseline (age 18) and followed prospectively over six years into young adulthood (ages 19‒24). ResultsThere were no statistically significant differences between adolescents who used stimulant therapy for ADHD compared to those who used only nonstimulant medications and population controls in their adjusted odds of nonmedical stimulant use incidence or prevalence during young adulthood, after adjusting for baseline covariates. DiscussionThe findings offer preliminary support that adolescents who use prescription stimulant or nonstimulant medications for ADHD when clinically indicated are not at greater risk for nonmedical stimulant use during young adulthood.

Viloxazine: A New Non-Stimulant Treatment for Attention-Deficit/Hyperactivity Disorder (ADHD)


 IntroductionViloxazine is an antidepressant medication classified as an SNRI (serotonin and norepinephrine reuptake inhibitor). In April 2021, it received FDA approval in the United States for the treatment of ADHD in children aged 6 to 17. Subsequently, in May 2022, it was also approved for the treatment of adults with ADHD [1]. Viloxazine, available in extended-release capsules, represents novel non-stimulant medication option for patients with ADHD.Aim of the studyOur aim was to review the viloxazine in the fields of ADHD treatment, summarize current knowledge and analyze the first treatment results.
 
 
 Methods and materialsA review of the literature available in the PubMed database was performed, using the key words: „Viloxazine" ; „ADHD treatment" ; „ADHD”, „attention deficit hyperactivity disorder”, „attention deficit hyperactivity disorder treatment”; „ADHD non-stimulant treatment”; „ADHD non-stimulant”; „ADHD non-stimulant drugs”, „SPN-812”
 
 
 ConclusionViloxazine presents a promising non-stimulant alternative for ADHD treatment with more favorable pharmacokinetics, new way of possible administration and fewer adverse effects, particularly within the cardiovascular system, than other available ADHD medication options. While these findings are encouraging, continual research is imperative to establish the long-term safety profile.

Prescribed psychotropic medication patterns among treated Foster Care enrollees: a single institution study.

While several state-based studies have shown that children in foster care are more likely to be prescribed psychotropic medications and experience concomitant medication use both within and among medication class, these patterns have not been explored in the state of Nevada, which lacks state mandated oversight of psychotropic prescribing for foster care enrolled youth. Data from an electronic medical record system from a single institution were analyzed to examine the prevalence of psychotropic prescribing and concomitant medication use in children ages 2 to 19 who were enrolled and received psychotropic prescriptions between July 2019 to June 2022. Out of 569 distinct psychotropic medication treatment episodes within this cohort, the most frequent psychotropic classes prescribed were non-stimulant ADHD medications (alpha-agonists and atomoxetine, 31.5%), atypical antipsychotics (22.1%), antidepressants (20.6%), and stimulants (16.0%). The use of stimulants and non-stimulant ADHD medications decreased in older age groups while the use of antidepressants and antipsychotics increased in older age groups. During the three-year period studied, 24.0% of psychotropic medications prescriptions increased in dosage. Treatments were prescribed for only one month in 43.8% of youth. In children prescribed psychotropic medications, concomitant medication use for at least 60 days occurred in 28.0% of children who had any psychotropic medication prescribed. Within the cohort of 273 foster care enrolled subjects aged 2 to 19 years old who received psychotropic medication prescriptions, non-stimulant ADHD medications (both alpha-agonists and atomoxetine) and atypical antipsychotics were more commonly co-prescribed additional psychotropic medication compared to other co-prescribed medication categories. This study illustrates prescribing patterns in a community mental health clinic focused on judicious prescribing of psychotropic medications in foster care enrolled youth. Despite this, 41% of the youth treated in this clinic received at least one prescription for psychotropic medication, and of those, 27.8% were prescribed more than one psychotropic medication at the same time. More studies are necessary to understand the underlying causes of high prevalence of concomitant medication use and prescribing practices of psychotropic medications use in foster care involved pediatric populations.

Trends in Incident Prescriptions for Behavioral Health Medications in the US, 2018-2022

The COVID-19 pandemic reportedly increased behavioral health needs and impacted treatment access. To assess changes in incident prescriptions dispensed for medications commonly used to treat depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), and opioid use disorder (OUD), before and during the COVID-19 pandemic. This was a cross-sectional study using comprehensive, population-level, nationally projected data from IQVIA National Prescription Audit on incident prescriptions (prescriptions dispensed to patients with no prior dispensing from the same drug class in the previous 12 months) dispensed for antidepressants, benzodiazepines, Schedule II (C-II) stimulants, nonstimulant medications for ADHD, and buprenorphine-containing medication for OUD (MOUD), from US outpatient pharmacies. Data were analyzed from April 2018 to March 2022. Incident prescriptions by drug class (by prescriber specialty, patient age, and sex) and drug. Interrupted time-series analysis to compare changes in trends in the monthly incident prescriptions dispensed by drug class and percentage changes in aggregate incident prescriptions dispensed between April 2018 and March 2022. Incident prescriptions dispensed for the 5 drug classes changed from 51 500 321 before the COVID-19 pandemic to 54 000 169 during the pandemic. The largest unadjusted percentage increase in incident prescriptions by prescriber specialty was among nurse practitioners across all drug classes ranging from 7% (from 1 811 376 to 1 944 852; benzodiazepines) to 78% (from 157 578 to 280 925; buprenorphine MOUD), whereas for patient age and sex, the largest increases were within C-II stimulants and nonstimulant ADHD drugs among patients aged 20 to 39 years (30% [from 1 887 017 to 2 455 706] and 81% [from 255 053 to 461 017], respectively) and female patients (25% [from 2 352 095 to 2 942 604] and 59% [from 395 678 to 630 678], respectively). Trends for C-II stimulants and nonstimulant ADHD drugs (slope change: 4007 prescriptions per month; 95% CI, 1592-6422 and 1120 prescriptions per month; 95% CI, 706-1533, respectively) significantly changed during the pandemic, exceeding prepandemic trends after an initial drop at the onset of the pandemic (level changes: -50 044 prescriptions; 95% CI, -80 202 to -19 886 and -12 876 prescriptions; 95% CI, -17 756 to -7996, respectively). Although buprenorphine MOUD dropped significantly (level change: -2915 prescriptions; 95% CI, -5513 to -318), trends did not significantly change for buprenorphine MOUD, antidepressants, or benzodiazepines. Incident use of many behavioral health medications remained relatively stable during the COVID-19 pandemic in the US, whereas ADHD medications, notably C-II stimulants, sharply increased. Additional research is needed to differentiate increases due to unmet need vs overprescribing, highlighting the need for further ADHD guideline development to define treatment appropriateness.

Long-Term Safety and Efficacy of Stimulant vs. Non-Stimulant Medications in ADHD Treatment: A Comparative Meta-Analysis Over Two Years

Long-Term Safety and Efficacy of Stimulant vs. Non-Stimulant Medications in ADHD Treatment: A Comparative Meta-Analysis Over Two Years

Practical clinical guidelines and pharmacological treatment for attention-deficit hyperactivity disorder in Asia.

Attention-deficit hyperactivity disorder (ADHD) is characterized by persistent symptoms of inattention, hyperactivity, and impulsivity. Both, stimulant and nonstimulant medications have been approved for the treatment of this disorder. Several Western guidelines recommend the use of prescribed Food and Drug Administration (FDA)-approved medications for ADHD along with parental training in behavior management and behavioral classroom intervention. In 2022, new Japanese guidelines for ADHD were issued, which recommended school environment management and psychosocial treatment as the first-line treatment, with pharmacological treatment added as the second-line treatment. Although Japanese guidelines, including pharmacological treatments, have been established, the guidelines and utilization of ADHD medications across Asian regions are unclear. Therefore, to appropriately evaluate the strategy of pharmacological treatments for ADHD, we investigated Asian regional guidelines for ADHD medication in children. We also reviewed the guidelines in Malaysia, Singapore, India, and the Republic of Korea and found that these guidelines differ from Western guidelines.