Switch to Lisdexamfetamine in the Treatment of Attention-Deficit Disorder at a Psychiatric Outpatient Clinic for School-Aged Children: A Danish Cohort Study.

Objectives: This study aimed to examine switch from first-line methylphenidate (MPH) to lisdexamfetamine (LDX) in school-aged children with attention-deficit/hyperactivity disorder (ADHD). Methods: This is a retrospective observational study based on systematic review of patient records of all children (7-13 years) diagnosed with ADHD and referred to a Danish specialized outpatient clinic. The study included 394 children switching from MPH to LDX as either second-line or third-line treatment (atomoxetine [ATX] as second-line treatment) during the study period from April 1, 2013, to November 5, 2019. Results: One in five children switched from MPH to LDX at some point during the study period. The most frequent reasons for switching to LDX were adverse effects (AEs; 70.0% for MPH, 68.3% for ATX) and lack of efficiency (52.0% for MPH, 72.7% for ATX). Top five AEs of LDX were decreased appetite (62.4%), insomnia (28.7%), irritability/aggression (26.1%), weight decrease (21.1%), and mood swings (13.9%). MPH and LDX had similar AE profiles, yet most AEs were less frequent after switching to LDX. At the end of the study period, the majority were prescribed LDX as second-line rather than third-line treatment (86.1% in 2019). However, the likelihood of LDX as second-line treatment decreased with the number of psychiatric comorbidities, ADHD symptom severity as assessed by parents, and if AEs were a reason for MPH discontinuation. Among children observed for at least 1 year after initiation of LDX, 41.3% continued LDX treatment for a year or longer. LDX continuation was less likely if AEs were a reason for MPH discontinuation. Similarly to MPH and ATX, the most frequent reasons for LDX discontinuation were AEs (74.4%) and lack of efficiency (34.7%). Implications: The findings support LDX as an important option in the personalized treatment of children with ADHD and may support prescribers in the clinical decision-making on switching medication.

Psychosis with use of amphetamine drugs, methylphenidate and atomoxetine in adolescent and adults.

BACKGROUND: Use of psychostimulants and relative drugs has increased worldwide in treatment of attention-deficit hyperactivity disorder (ADHD) in adolescents and adults. Recent studies suggest a potential association between use of psychostimulants and psychotic symptoms. The risk may not be the same between different psychostimulants. OBJECTIVE: To assess whether amphetamine or atomoxetine use is associated with a higher risk of reporting symptoms of psychosis than methylphenidate use in adolescents and adults, particularly in patients with ADHD. METHODS: Using VigiBase, the WHO's pharmacovigilance database, disproportionality of psychotic symptoms reporting was assessed among adverse drug reactions related to methylphenidate, atomoxetine and amphetamines, from January 2004 to December 2018, in patients aged 13-25 years. The association between psychotic symptoms and psychostimulants was estimated through the calculation of reporting OR (ROR). FINDINGS: Among 13 863 reports with at least one drug of interest, we found 221 cases of psychosis with methylphenidate use, 115 with atomoxetine use and 169 with a prescription of an amphetamine drug. Compared with methylphenidate use, amphetamine use was associated with an increased risk of reporting psychotic symptoms (ROR 1.61 (95% CI 1.26 to 2.06)]. When we restricted the analysis to ADHD indication, we found a close estimate (ROR 1.94 (95% CI 1.43 to 2.64)). No association was found for atomoxetine. CONCLUSION: Our study suggests that amphetamine use is associated with a higher reporting of psychotic symptoms, compared with methylphenidate use. CLINICAL IMPLICATIONS: The prescription of psychostimulants should consider this potential adverse effect when assessing the benefit-risk balance.

Methylphenidate and Short-Term Cardiovascular Risk.

Importance: There are concerns about the safety of medications for treatment of attention-deficit/hyperactivity disorder (ADHD), with mixed evidence on possible cardiovascular risk. Objective: To assess whether short-term methylphenidate use is associated with risk of cardiovascular events. Design, Setting, and Participants: This retrospective, population-based cohort study was based on national Swedish registry data. Participants were individuals with ADHD aged 12 to 60 years with dispensed prescriptions of methylphenidate between January 1, 2007, and June 30, 2012. Each person receiving methylphenidate (n = 26 710) was matched on birth date, sex, and county to up to 10 nonusers without ADHD (n = 225 672). Statistical analyses were performed from September 13, 2022, to May 16, 2023. Main Outcomes and Measures: Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias, 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a bayesian within-individual design. Analyses were stratified by history of cardiovascular events. Results: The cohort included 252 382 individuals (15 442 [57.8% men]; median age, 20 (IQR, 15-31) years). The overall incidence of cardiovascular events was 1.51 per 10 000 person-weeks (95% highest density interval [HDI], 1.35-1.69) for individuals receiving methylphenidate and 0.77 (95% HDI, 0.73-0.82) for the matched controls. Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41; 95% HDI, 1.09-1.88) compared with matched controls (IRR, 1.18; 95% HDI, 1.02-1.37). The posterior probabilities were 70% for at least a 10% increased risk of cardiovascular events in individuals receiving methylphenidate vs 49% in matched controls. No difference was found in this risk between individuals with and without a history of cardiovascular disease (IRR, 1.11; 95% HDI, 0.58-2.13). Conclusions and Relevance: In this cohort study, individuals receiving methylphenidate had a small increased cardiovascular risk vs matched controls in the 6 months after treatment initiation. However, there was little evidence for an increased risk of 20% or higher and for differences in risk increase between people with and without a history of cardiovascular disease. Therefore, before treatment initiation, careful consideration of the risk-benefit trade-off of methylphenidate would be useful, regardless of cardiovascular history.

Efficacy and safety of established and off-label ADHD drug therapies for cognitive impairment or attention-deficit hyperactivity disorder symptoms in bipolar disorder: A systematic review by the ISBD Targeting Cognition Task Force.

BACKGROUND: Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD). This systematic review by the ISBD Targeting Cognition Task Force therefore aimed to investigate the possible benefits on cognition and/or ADHD symptoms and safety of established and off-label ADHD therapies in BD. METHODS: We included studies of ADHD medications in BD patients, which involved cognitive and/or safety measures. We followed the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed, Embase and PsycINFO from inception until June 2023. Two authors reviewed the studies independently using the Revised Cochrane Collaboration's Risk of Bias tool for Randomized trials. RESULTS: Seventeen studies were identified (N = 2136), investigating armodafinil (k = 4, N = 1581), methylphenidate (k = 4, N = 84), bupropion (k = 4, n = 249), clonidine (k = 1, n = 70), lisdexamphetamine (k = 1, n = 25), mixed amphetamine salts (k = 1, n = 30), or modafinil (k = 2, n = 97). Three studies investigated cognition, four ADHD symptoms, and 10 the safety. Three studies found treatment-related ADHD symptom reduction: two involved methylphenidate and one amphetamine salts. One study found a trend towards pro-cognitive effects of modafinil on some cognitive domains. No increased risk of (hypo)mania was observed. Five studies had low risk of bias, eleven a moderate risk, and one a serious risk of bias. CONCLUSIONS: Methylphenidate or mixed amphetamine salts may improve ADHD symptoms in BD. However, there is limited evidence regarding the effectiveness on cognition. The medications produced no increased mania risk when used alongside mood stabilizers. Further robust studies are needed to assess cognition in BD patients receiving psychostimulant treatment alongside mood stabilizers.

The Impact of Methylphenidate on Pubertal Maturation and Bone Age in ADHD Children and Adolescents: Results from the ADHD Drugs Use Chronic Effects (ADDUCE) Project.

OBJECTIVE: The short-term safety of methylphenidate (MPH) has been widely demonstrated; however the long-term safety is less clear. The aim of this study was to investigate the safety of MPH in relation to pubertal maturation and to explore the monitoring of bone age. METHOD: Participants from ADDUCE, a two-year observational longitudinal study with three parallel cohorts (MPH group, no-MPH group, and a non-ADHD control group), were compared with respect to Tanner staging. An Italian subsample of medicated-ADHD was further assessed by the monitoring of bone age. RESULTS: The medicated and unmedicated ADHD groups did not differ in Tanner stages indicating no higher risk of sexual maturational delay in the MPH-treated patients. The medicated subsample monitored for bone age showed a slight acceleration of the bone maturation after 24 months, however their predicted adult height remained stable. CONCLUSION: Our results do not suggest safety concerns on long-term treatment with MPH in relation to pubertal maturation and growth.

Methylphenidate and Sleep Difficulties in Children and Adolescents With ADHD: Results From the 2-Year Naturalistic Pharmacovigilance ADDUCE Study.

OBJECTIVE: Short-term RCTs have demonstrated that MPH-treatment significantly reduces ADHD-symptoms, but is also associated with adverse events, including sleep problems. However, data on long-term effects of MPH on sleep remain limited. METHODS: We performed a 2-year naturalistic prospective pharmacovigilance multicentre study. Participants were recruited into three groups: ADHD patients intending to start MPH-treatment (MPH-group), those not intending to use ADHD-medication (no-MPH-group), and a non-ADHD control-group. Sleep problems were assessed with the Children's-Sleep-Habits-Questionnaire (CSHQ). RESULTS: 1,410 participants were enrolled. Baseline mean CSHQ-total-sleep-scores could be considered clinically significant for the MPH-group and the no-MPH-group, but not for controls. The only group to show a significant increase in any aspect of sleep from baseline to 24-months was the control-group. Comparing the MPH- to the no-MPH-group no differences in total-sleep-score changes were found. CONCLUSION: Our findings support that sleep-problems are common in ADHD, but don't suggest significant negative long-term effects of MPH on sleep.

Methylphenidate for treating fatigue in palliative cancer care - effect and side effects in real-world data from a palliative care unit.

BACKGROUND: Methylphenidate can be used for the treatment of cancer-related fatigue (CRF), although randomized controlled trials have shown conflicting results. The aim of this study was to use 'real-world' data to evaluate the effect and side effects of using methylphenidate in palliative cancer care with a focus on the late palliative phase and dose-response. METHOD: A retrospective review of medical records from a palliative care unit in Sweden was performed to evaluate the effect and adverse events (AEs) of using methylphenidate to treat CRF. Univariable and multivariable regression was performed and odds ratio (OR) calculated. Adjustments were made for sex, age, cancer type, dose and starting treatment <4 weeks before death. RESULTS: Of the 2,419 screened patients, 112 had been treated with methylphenidate for CRF. The treatment was assessed as being effective in 51 patients (46%). Twenty-six patients (23%) experienced AEs that were generally mild, including anxiety, palpitations, and insomnia. Patients starting the treatment <4 weeks before death (n = 54) were less likely to have an effect from treatment compared to those starting earlier; adjusted OR 0.24 (95% CI 0.10-0.55). Doses of 20 mg and above were well-tolerated and had a higher frequency of effect in the crude data but not after adjustment for confounding factors. CONCLUSION: Methylphenidate is generally effective and well-tolerated for the treatment of CRF in palliative care. However, patients with a short life expectancy (<4 weeks) seem to benefit less from the treatment regardless of age, cancer type and dose.

Prescription Stimulant Use During Pregnancy and Risk of Neurodevelopmental Disorders in Children.

Importance: Use of medications for attention-deficit/hyperactivity disorder (ADHD) during pregnancy is increasing in the US. Whether exposure to these medications in utero impacts the risk of neurodevelopmental disorders in children is uncertain. Objective: To evaluate the association of childhood neurodevelopmental disorders with in utero exposure to stimulant medications for ADHD. Design, Setting, and Participants: This cohort study included health care utilization data from publicly insured (Medicaid data from 2000 to 2018) and commercially insured (MarketScan Commercial Claims Database data from 2003 to 2020) pregnant individuals aged 12 to 55 years in the US with enrollment from 3 months prior to pregnancy through 1 month after delivery, linked to children. Children were monitored from birth until outcome diagnosis, disenrollment, death, or end of the study (December 2018 for Medicaid and December 2020 for MarketScan). Exposures: Dispensing of amphetamine/dextroamphetamine or methylphenidate in the second half of pregnancy. Main Outcomes and Measures: Autism spectrum disorder, ADHD, and a composite of any neurodevelopmental disorder were defined using validated algorithms. Hazard ratios were estimated comparing amphetamine/dextroamphetamine and methylphenidate to no exposure. Results: The publicly insured cohort included 2 496 771 stimulant-unexposed, 4693 amphetamine/dextroamphetamine-exposed, and 786 methylphenidate-exposed pregnancies with a mean (SD) age of 25.2 (6.0) years. The commercially insured cohort included 1 773 501 stimulant-unexposed, 2372 amphetamine/dextroamphetamine-exposed, and 337 methylphenidate-exposed pregnancies with a mean (SD) age of 31.6 (4.6) years. In unadjusted analyses, amphetamine/dextroamphetamine and methylphenidate exposure were associated with a 2- to 3-fold increased risk of the neurodevelopmental outcomes considered. After adjustment for measured confounders, amphetamine/dextroamphetamine exposure was not associated with any outcome (autism spectrum disorder: hazard ratio [HR], 0.80; 95% CI, 0.56-1.14]; ADHD: HR, 1.07; 95% CI, 0.89-1.28; any neurodevelopmental disorder: HR, 0.91; 95% CI, 0.81-1.28). Methylphenidate exposure was associated with an increased risk of ADHD (HR, 1.43; 95% CI, 1.12-1.82]) but not other outcomes after adjustment (autism spectrum disorder: HR, 1.06; 95% CI, 0.62-1.81; any neurodevelopmental disorder: HR, 1.15; 95% CI, 0.97-1.36). The association between methylphenidate and ADHD did not persist in sensitivity analyses with stricter control for confounding by maternal ADHD. Conclusions and Relevance: The findings in this study suggest that amphetamine/dextroamphetamine and methylphenidate exposure in utero are not likely to meaningfully increase the risk of childhood neurodevelopmental disorders.

Protocol of a monocentric, double-blind, randomized, superiority, controlled trial evaluating the effect of in-prison OROS-methylphenidate vs. placebo treatment in detained people with attention-deficit hyperactivity disorder (BATIR).

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is characterized by difficulty paying attention, poor impulse control, and hyperactive behavior. It is associated with several adverse health and social outcomes and leads to an increased risk of criminality and recidivism. Worldwide, ADHD is thus highly prevalent in prisons. However, ADHD treatment has been neglected in such environments. Stimulant medications such as osmotic-release oral system methylphenidate (OROS-MPH) are first-line treatments in the general population, but they are under-prescribed in prisons due to concerns about abuse, even though such claims are not empirically supported. This project aims to compare the efficacy of a 3-month in-prison OROS-MPH vs. placebo treatment on the severity of core ADHD symptoms and relevant in- and post-prison outcomes. METHODS: This study is a phase III, double-blinded, randomized, superiority, controlled trial of OROS-MPH vs. placebo. After randomization, the participants will receive 3 months of treatment with OROS-MPH or placebo (1:1 ratio) while incarcerated. Upon release, all participants will be offered the treatment (OROS-MPH) for 1 year but will remain blinded to their initial study group. The study will be conducted at the Division of Prison Health, Geneva, Switzerland, among incarcerated men (n = 150). Measures will include (1) investigator-rated ADHD symptoms, (2) acute events collected by the medical and prison teams, (3) assessment of the risk of recidivism, (4) medication side effects, (5) medication adherence, (6) study retention, (7) health care/prison costs, and (8) 1-year recidivism. Analyses will include bivariable and multivariable modeling (e.g., regression models, mixed-effects models, survival analyses) and an economic evaluation (cost-benefit analysis). DISCUSSION: We expect that early identification and treatment of ADHD in prison will be an important public health opportunity and a cost-effective approach that is likely to reduce the vulnerability of incarcerated individuals and promote pathways out of criminal involvement. The study will also promote standards of care for people with ADHD in prison and provide recommendations for continuity of care after release. TRIAL REGISTRATION: ClinicalTrials.gov NCT05842330 . Registered on June 5, 2023. Kofam.ch SNCTP000005388. Registered on July 17, 2023.

Methylphenidate dose-response in children with ADHD: evidence from a double-blind, randomized placebo-controlled titration trial.

Methylphenidate (MPH) is highly efficacious in reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) in children. Generally increased doses are found to result in better symptom control; however, it remains unclear whether this pattern can be observed at the individual level, given the large heterogeneity in individual dose-response relationships and observed placebo responses. A double-blind, randomized, placebo-controlled cross-over trial was used to compare weekly treatment with placebo and 5, 10, 15 and 20 mg of MPH twice daily on parent and teacher ratings of child ADHD symptoms and side effects. Participants were 5-13-year-old children with a DSM-5 diagnosis of ADHD (N = 45). MPH response was assessed at group and individual levels and predictors of individual dose-response curves were examined. Mixed model analysis showed positive linear dose-response curves at group level for parent and teacher rated ADHD symptoms and parent rated side effects, but not for teacher rated side effects. Teachers reported all dosages to improve ADHD symptoms compared to placebo, while parents only reported > 5 mg/dose as effective. At the individual level, most (73-88%) children, but not all, showed positive linear dose-response curves. Higher severity of hyperactive-impulsive symptoms and lower internalizing problems, lower weight, younger age and more positive opinions towards diagnosis and medication partly predicted steeper linear individual dose-response curves. Our study confirms that increased doses of MPH yield greater symptom control at a group level. However, large interindividual variation in the dose-response relationship was found and increased doses did not lead to greater symptom improvement for all children. This trial was registered in the Netherlands trial register (# NL8121).

Cardiovascular Safety of Atomoxetine and Methylphenidate in Patients With Attention-Deficit/Hyperactivity Disorder in Japan: A Self-Controlled Case Series Study.

OBJECTIVE: To investigate the association between atomoxetine or methylphenidate use and arrhythmia, heart failure (HF), stroke, and myocardial infarction (MI) in attention-deficit/hyperactivity disorder (ADHD) patients mainly focused on the people of working age. METHODS: In a self-controlled case series study using a Japanese claims database, we identified events of arrhythmia, HF, stroke, and MI among 15,472 atomoxetine new users and 12,059 methylphenidate new users. Adjusted incidence rate ratios (aIRRs) of outcome events were estimated using multivariable conditional Poisson regression. RESULTS: An increased risk of arrhythmia was observed during the first 7 days after the initial atomoxetine exposure (aIRR 6.22, 95% CI [1.90, 20.35]) and in the subsequent exposure (3.23, [1.58, 6.64]). No association was found between methylphenidate exposure and arrhythmia, nor between atomoxetine or methylphenidate exposure and HF. The limited number of stroke and MI cases prevented thorough analysis. CONCLUSIONS: Clinicians should consider monitoring for arrhythmia after patients initiating or re-initiating atomoxetine.

High-Dose Methylphenidate and Carboxylesterase 1 Genetic Variability in Patients With Attention-Deficit/Hyperactivity Disorder: A Case Series.

PURPOSE/BACKGROUND: Methylphenidate (MPH) is widely used to reduce symptoms of attention-deficit/hyperactivity disorder. Methylphenidate is metabolized by the carboxylesterase 1 (CES1) enzyme. Some patients need a very high dose of MPH to reach desired clinical effects, without having adverse effects. This may be due to differences in MPH pharmacokinetics (PK), potentially caused by DNA variants in CES1 , the gene encoding the enzyme that metabolizes MPH. Here we describe 3 patients requiring high-dose MPH and investigated the CES1 gene. METHODS/PROCEDURES: The 3 patients were using short-acting MPH in a dose of 180 to 640 mg instead of the maximum advised dose of around 100 mg MPH in the Netherlands. Plasma concentrations of MPH were determined at scheduled time points (day-curve). Methylphenidate plasma concentrations were used for PK analysis using an earlier published 2-compartment PK population model of MPH. Individual data of the 3 patients were compared with simulated population data, when equivalent doses were used. In addition, CES1 was genotyped (number of gene copies and single nucleotide polymorphisms) using real-time polymerase chain reaction. FINDINGS/RESULTS: Pharmacokinetic analysis in all 3 patients showed lower plasma concentrations of MPH in comparison with the population data. The mean absorption time and volume of distribution of the central compartment were equal, but the elimination clearance was higher. However, CES1 genotyping revealed no variations that could explain a higher metabolism of MPH. IMPLICATIONS/CONCLUSIONS: In these 3 cases, we could not demonstrate a correlation between MPH clearance and known genetic variants of the CES1 gene.

Treatment with psychostimulants and atomoxetine in people with psychotic disorders: reassessing the risk of clinical deterioration in a real-world setting.

BACKGROUND: Although attention-deficit hyperactivity disorder (ADHD) is often comorbid with schizophrenia spectrum and other psychotic disorders (SZSPD), concerns about an increased risk of psychotic events have limited its treatment with either psychostimulants or atomoxetine. AIMS: To examine whether the risk of hospital admission for psychosis in people with SZSPD was increased during the year following the introduction of such medications compared with the year before. METHOD: This was a retrospective cohort study using Quebec (Canada) administrative health registries, including all Quebec residents with a public prescription drug insurance plan and a diagnosis of psychotic disorder, defined by relevant ICD-9 or ICD-10 codes, who initiated either methylphenidate, amphetamines or atomoxetine, between January 2010 and December 2016, in combination with antipsychotic medication. The primary outcome was time to hospital admission for psychosis within 1 year of initiation. State sequence analysis was also used to visualise admission trajectories for psychosis in the year following initiation of these medications, compared with the previous year. RESULTS: Out of 2219 individuals, 1589 (71.6%) initiated methylphenidate, 339 (15.3%) amphetamines and 291 (13.1%) atomoxetine during the study period. After adjustment, the risk of hospital admission for psychosis was decreased during the 12 months following the introduction of these medications when used in combination with antipsychotics (adjusted HR = 0.36, 95% CI 0.24-0.54; P < 0.0001). CONCLUSIONS: These findings suggest that, in a real-world setting, when used concurrently with antipsychotic medication, methylphenidate, amphetamines and atomoxetine may be safer than generally believed in individuals with psychotic disorders.

Association of Psychopharmacological Medication Preference with Autistic Traits and Emotion Regulation in ADHD.

Background: This study intends to evaluate the relationship between medication switching and autistic traits, emotion dysregulation, and methylphenidate side effects in children with attention deficit hyperactivity disorder (ADHD). Methods: Children with ADHD, ages 9-18, treated with methylphenidate (MTP) (n = 23), and switched to atomoxetine (ATX) (n = 20) were included. All participants were interviewed with K-SADS-PL to confirm ADHD diagnosis and exclude comorbid psychiatric disorders. The participants then completed Difficulty in Emotion Regulation Scale (DERS) and Autism-Spectrum Quotient (AQ) and their parents completed Autism Spectrum Screening Questionnaire (ASSQ) and Barkley Stimulant Side Effect Rating Scale(BSSERS). Results: The MTP group scored higher than the ATX group in ASSQ, AQ, and the lack of emotional clarity subscale of DERS, while the ATX group had higher scores in the emotional non-acceptance subscale of DERS. No differences were found between the MTP and ATX groups in methylphenidate side-effect severity. Multiple regression analyses revealed that non-acceptance of emotions predicted the switch to ATX while lack of emotional clarity predicted the maintenance of MTP therapy, rather than autistic traits. Conclusions: This study highlights emotion regulation difficulties and how different emotional profiles may influence medication selection in children with ADHD.

Methylphenidate-associated chest pain in a child.

A young child was diagnosed with autism spectrum disorder with comorbid attention-deficit/hyperactivity disorder. His hyperactivity, impulsivity and absence of awareness towards danger increased his risk of harm and hence methylphenidate was indicated. Unfortunately, he developed chest pain eight months after the treatment initiation. We then stopped the stimulant and changed his treatment to atomoxetine, after which he no longer had chest pain. In the following illustrated case, we will discuss the cardiac side effect of methylphenidate.

An updated safety review of the current drugs for managing ADHD in children.

INTRODUCTION: Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly prevalent condition that causes persistent problems with attention and/or hyperactivity-impulsivity and often results in significant impairment when left untreated. Medications for this disorder continue to evolve and provide new treatment options. Ongoing review of related medication safety and tolerability remains an important task for prescribers. AREAS COVERED: This manuscript provides an updated safety review of medications used to treat ADHD in children and adolescents. PubMed and OneSearch online databases were utilized to search for literature relevant to the topic of ADHD medications and safety. Clinical trials of medications used to treat ADHD, systematic reviews and meta-analyses, and articles covering specific safety issues (adverse or unfavorable events) such as cardiovascular effects, seizures, impact on growth, depression, suicidal ideation, substance use disorders, psychosis, and tics are described. EXPERT OPINION: Available pharmacologic treatments for ADHD have favorable efficacy, safety and tolerability and allow many patients to achieve significant improvement of their symptoms. Despite the availability of multiple stimulant and non-stimulant formulations, some individuals with ADHD may not tolerate available medications or attain satisfactory improvement. To satisfy unmet clinical needs, ADHD pharmaceutical research with stimulant and nonstimulant formulations targeting dopamine, norepinephrine, and novel receptors is ongoing.

Pediatric attention deficit hyperactivity disorder (ADHD): 2022 updates on pharmacological management.

INTRODUCTION: Pediatric attention-deficit disorder (ADHD) impacts a significant percentage of the population world-wide. Pharmacologic treatments have been shown to be safe and effective for managing symptoms. Various medication formulations exist, and new medication agents are continually approved each year. AREAS COVERED: This article offers an overview of ADHD, an overview of both stimulant and non-stimulant medication options as well as an overview of stimulant misuse. It explores the medication mechanisms of action and side effect profiles, as well as offering an in-depth summary of the novel agents recently approved and soon-to-be approved for use in youth. PubMed and Medline were utilized. Search terms included children, adolescents, ADHD, and medication. FDA package inserts were reviewed for all medications. EXPERT OPINION: New formulations of medications include an evening administered, extended, and delayed-release form of methylphenidate (DR/ER MPH), a methylphenidate pro-drug (serdexmethylphenidate) and an amphetamine patch. The availability of a new SNRI (selective norepinephrine reuptake inhibitor), viloxazine extended-release (VER), and the pending approval of a triple reuptake inhibitor (centanafadine) provides welcome additions to the prescriber's toolbox.

This article is a review of pharmacological treatment options for pediatric attention-deficit disorder (ADHD). It provides an overview of ADHD, an overview of the current stimulant and non-stimulant medication options as well as detailed information on the newer psychopharmacological options to assist in the education of the wide array of medication options for treatment. As ADHD is a heterogeneous illness, a wide array of medication options is helpful in the clinician's toolbox. Learning the mechanisms of action along with the side effect profile for newer medication options is the focus of this review. There are new options for patches and new combinations for long-acting and delayed-release formulations as well as new non-stimulant options which target different receptors.