Cumulative incidence of schizophrenia-spectrum disorders in children and adolescents with neurodevelopmental disorders: A retrospective cohort study.

To determine which factors are associated with use of atomoxetine (ATX) relative to stimulant medications (STIMs) for treatment initiation in adults with attention-deficit/hyperactivity disorder (ADHD). A similar exploratory analysis of the use of ATX versus STIMs in children has been published previously. This was an exploratory analysis using a retrospective observational cohort design applied to administrative pharmacy and medical claims from an integrated managed care database. Patients were identified if they had at least 1 administrative claim with a diagnosis for ADHD. Treatment .initiation. was defined as a new prescription for an ADHD medication preceded by 3 months without similar therapy. Two separate analyses were done, one comparing medication starts for ATX with those of any STIM, the other comparing starts of ATX with long-acting stimulants (LA-STIMs). Logistic regression analyses of prior-year administrative claims were used to compare the frequencies of differential predictors of the use of medication. There were 10,359 patients aged >18 years who initiated ATX or a STIM between April and December of 2003 and had at least 1 claim with a diagnosis for ADHD (International Classification of Diseases, Ninth Revision, Clinical Modification codes 314.0x). Approximately one third (28 of 82) of the comparisons related to patient demographics, diagnostic history, and previous treatment history was found to be related to the use of ATX versus STIMs and/or LA-STIMs. Patients were more likely to have received ATX than a STIM if they had prior diagnoses of bipolar disorder (odds ratio [OR] 1.47; 95% confidence interval [CI], 1.16-1.87), alcohol dependence (OR 1.80; 95% CI, 1.26-2.58), anxiety (OR 1.21; 95% CI, 1.05-1.40), previous use of antipsychotic medication (OR 1.55; 95% CI, 1.22-1.96), or previous antidepressant use (OR 1.14; 95% CI, 1.01-1.28). Prior use of behavioral services greater than 12 visits was associated with the use of ATX relative to STIMs (OR 1.46; 95% CI, 1.20-1.77) but not for ATX relative to LA-STIMs. Conversely, ATX was used less often than STIMs for initiation in younger adults aged 18 to 24 years (OR 0.66; 95% CI, 0.58-0.74), female patients (OR 0.89, 95% CI, 0.80-0.99), patients with personality disorders (OR 0.53; 95% CI, 0.34-0.82), and those with prior use of STIMs (OR 0.62; 95% CI, 0.56-0.69). The majority of comparisons (54 of 82) related to demographics, diagnostic history, and previous treatment history did not show statistically significant associations. During the first year of ATX.s market introduction, some differences in the frequency of various clinical factors were found in adults treated with ATX compared with those patients who received STIMs. This association may suggest that STIMs and ATX are used to address different treatment needs in adults with ADHD. Future studies will need to determine the significance of the practice pattern differences inferred here and if they persist after ATX has been on the market longer.

This present study investigated the prevalence and the factors associated with the use, misuse, and diversion of prescribed stimulant medication for attention-deficit hyperactivity disorder (ADHD) in a sample of middle and high school students. As part of a school-based, self-administered web survey in May 2002, students from a Midwestern public school district in the United States in grades six through eleven (n = 1536) reported on three aspects of prescription stimulants; they reported on their use, misuse, and diversion (e.g., trading, selling, offering) of stimulant medication for ADHD. The total student sample was 57% White, 40% African American, and 3% from other racial and ethnic groups. Gender and school level were approximately equally distributed in the student sample, and 81% of students had plans to attend college. The illicit use of stimulant medication was reported by 4.5% of the overall sample. Of the students who reported prescription stimulant use, 23.3% reported being approached to sell, give, or trade their prescription drugs. After adjusting for sociodemographic factors, the odds for illicit use of stimulant medication was lower among African American students and higher among those students with no plans for attending college. When compared with students who did not use stimulants or who did not misuse their own prescriptions, students who reported illicit use of stimulant medications also reported significantly higher rates of alcohol and other drug use. High schools students had the highest odds for being approached to divert their stimulant medications. Our findings suggest that community-based approaches are needed to reduce the illicit use and diversion of stimulant medications within middle and high school student populations.

Cerebral palsy (CP) is a term encompassing a group of nonprogressive, noncontagious conditions causing mild, moderate or severe disorders of neurodevelopment. Objective: Objective of this study was to analyze the possible prenatal etiological factors for the emergence of neurodevelopmental disorders (NDs) and CP from the medical records of 100 children with neuromotor disabilities who were treated in Special Hospital for Children with Neuro-developmental and Movement Disorders, Goljak, Croatia. Results: ND and CP were more often diagnosed in children with birth weight below 2500 g which was statistically proved at the level of significance reaching 0.05, although significant correlation was low for both parameters reaching 0.21. There are both statistically significant differences and the statistically significant correlation between the three gestational age categories within ND and CP. There were more children with the birth weight below 2500 g in the CP than in the ND group and the difference was statistically significant. In the CP group, there were more children with the lower gestational age than in the ND group, which was statistically highly significant. This difference, together with correlation is significant at the level of 0.01. Conclusion: Further studies on the etiology of NDs are needed, with particular focus on the intrauterine risk factors.

Given the increase in attention-deficit/hyperactivity disorder (ADHD) diagnoses and stimulant medication use among female adults, this study describes the prevalence trends of perinatal ADHD stimulant medication use in British Columbia, Canada, along with characteristics and patterns of use. Using linked population-based administrative data, we included all pregnant people with deliveries between January 2000 and December 2021. ADHD stimulant medication use was defined as filled prescriptions for dextro-/amphetamine, methylphenidate, or lisdexamfetamine. Prevalence trends were examined by medication type and age group. Characteristics were compared between those with and without prenatal stimulant medication dispensations. Patterns of use and discontinuation were assessed from 1 year preconception to 1 year postpartum. Our cohort included 899,679 pregnancies. Prenatal ADHD stimulant medication use increased by 3.9 users per 1000 pregnancies (from 0.4 to 4.3/1000), primarily driven by dextro-/amphetamine. Medication use increased among all age groups, but was highest among pregnant people under 20 years old. Pregnant people taking stimulant medications were more likely to be nulliparous and lower in income, have hypertension and higher BMI, smoke during pregnancy, use other psychotropic medications, and deliver by cesarean section. Among those who used stimulant medications within 1 year preconception, 77% discontinued treatment before or during pregnancy. While use increased again within 12 months postpartum, it remained 45% lower than preconception levels. The 11-fold increase in ADHD stimulant medication use during pregnancy and the high rate of discontinuation highlight the need for more research on the risks and benefits of medication for parent and child health.

Youth with attention-deficit hyperactivity disorder (ADHD) are more vulnerable to developing obesity. Stimulant medication use, an evidence-based treatment for ADHD, is associated with lower body mass index (BMI) and higher blood pressure among non-overweight youth. The purpose of this study was to examine the longitudinal influence of ADHD and stimulant medication use on BMI and blood pressure among a sample of 456 youth with overweight and obesity treated in a paediatric weight management clinic. Mixed linear modelling examined the main and interactive effects of time by ADHD status and stimulant medication use on BMI and blood pressure. Youth without ADHD experienced a significantly faster decrease in BMI compared to youth with ADHD (p < 0.001). Youth with ADHD who were taking stimulant medication had a significantly faster decrease in BMI compared to youth with ADHD who were not taking stimulant medication (p = 0.009). There was no significant effect of ADHD status or stimulant medication use on diastolic or systolic blood pressure trajectories over time (ps >0.05). Results from this study suggest that youth with ADHD who are not taking stimulant medication may not benefit from clinical weight management to the same extent as either youth without ADHD or youth with ADHD who are taking a stimulant medication.

IntroductionAttention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition that can persist from childhood into adulthood. Stimulant medications such as methylphenidate and amphetamine derivatives are the mainstay of treatment, yet their potential immunomodulatory effects remain unclear. While most upper respiratory tract infections (URTIs) are benign and self-limiting, some may result in healthcare visits and lost productivity. Proposed mechanisms linking stimulant use to infection risk include sympathetic nervous system activation, hypothalamic-pituitary-adrenal axis modulation, stimulant-induced insomnia, and reduced salivary flow - all of which may impair mucosal immunity. This study aimed to evaluate whether stimulant medication use in ADHD is associated with increased risk of URTIs using a large real-world dataset.MethodsWe performed a retrospective cohort study using the TriNetX research network, which aggregates de-identified electronic health records from 149 healthcare organizations worldwide (>170 million patients). ADHD patients were identified by International Classification of Diseases, 10th Revision (ICD-10) codes F90.0-F90.2. Two cohorts were defined: ADHD patients without stimulant prescriptions (control; n = 1,798,001) and ADHD patients prescribed stimulants (medication cohort; n = 1,099,756; amphetamine, dextroamphetamine, lisdexamfetamine, methylphenidate, modafinil, or dexmethylphenidate). We did not include antidepressants and antipsychotics in the cohorts or in their comparison. The outcome was a diagnosis of URTI (ICD-10 J00-J06). Risk estimates, Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazards modeling were performed within TriNetX, with significance set at p < 0.05.ResultsA total of 2,897,757 ADHD patients were included (mean age 21.2 ± 15 years; 42.1% female). URTI incidence was higher in the medication cohort (31.2%, n = 343,385) than in controls (28.5%, n = 512,849). Stimulant exposure was associated with increased URTI risk: risk difference 0.027 (95% confidence interval (CI): 0.026-0.028; p < 0.001), risk ratio 1.095 (95% CI: 1.091-1.099), and odds ratio 1.138 (95% CI: 1.132-1.144). Kaplan-Meier analysis demonstrated significantly lower URTI-free survival in medicated patients (log-rank χ² = 2285.0; p < 0.001). The hazard ratio for URTI in the medicated cohort was 1.111 (95% CI: 1.106-1.116; p < 0.001). Median survival without URTI was 3757 days in controls versus 3176 days in the medicated group.DiscussionStimulant-treated ADHD patients exhibited an 11% higher relative risk of URTI compared with unmedicated patients. Some possible mechanisms may include immune suppression via catecholamine-mediated shifts in cytokine profiles, sleep disruption leading to impaired host defenses, and medication-induced xerostomia, reducing mucosal protection. Our findings align with prior clinical and epidemiologic studies reporting higher infection rates in ADHD populations, although prior results have been mixed.ConclusionIn this large multi-institutional analysis, stimulant use in ADHD was moderately associated with increased URTI risk. These findings warrant consideration in risk-benefit discussions for ADHD treatment, particularly for patients with frequent infections or compromised immunity. Future prospective studies should explore dose-response effects, adherence, and biologic mediators to clarify causality and guide preventive strategies.

Computational linguistic investigation in schizophrenia and autism spectrum disorders.

Stimulant medication is commonly prescribed as treatment for attention-deficit/hyperactivity disorder (ADHD). While we previously found that short-term stimulant-treatment influences apparent cortical thickness development in an age-dependent manner, it remains unknown whether these effects persist throughout development into adulthood. Investigate the long-term age-dependent effects of stimulant medication use on apparent cortical thickness development in adolescents and adults previously diagnosed with ADHD. This prospective study included the baseline and 4-year follow-up assessment of the "effects of Psychotropic drugs On the Developing brain-MPH" ("ePOD-MPH") project, conducted between June-1-2011 and December-28-2019. The analyses were pre-registered (https://doi.org/10.17605/OSF.IO/32BHF). T1-weighted MR scans were obtained from male adolescents and adults, and cortical thickness was estimated for predefined regions of interest (ROIs) using Freesurfer. We determined medication use and assessed symptoms of ADHD, anxiety, and depression at both time points. Linear mixed models were constructed to assess main effects and interactions of stimulant medication use, time, and age group on regional apparent cortical thickness. A total of 32 male adolescents (aged mean ± SD, 11.2 ± 0.9 years at baseline) and 24 men (aged mean ± SD, 29.9 ± 5.0 years at baseline) were included that previously participated in the ePOD-MPH project. We found no evidence for long-term effects of stimulant medication use on ROI apparent cortical thickness. As expected, we did find age-by-time interaction effects in all ROIs (left prefrontal ROI: P=.002, right medial and posterior ROIs: P<.001), reflecting reductions in apparent cortical thickness in adolescents. Additionally, ADHD symptom severity (adolescents: P<.001, adults: P=.001) and anxiety symptoms (adolescents: P=0.03) were reduced, and more improvement of ADHD symptoms was associated with higher medication use in adults (P=0.001). We found no evidence for long-term effects of stimulant-treatment for ADHD on apparent cortical thickness development in adolescents and adults. The identified age-dependent differences in apparent cortical thickness development are consistent with existing literature on typical cortical development.

Medical outcomes of children with neurodevelopmental disorders after SARS-CoV-2 vaccination: A six-month follow-up study

Introduction: stimulant and anorectic medications promote, respectively, a temporary increase in energy and a decrease in appetite. Prolonged and unsupervised use is inappropriate and may lead to adverse effects such as dependence, cardiovascular disorders, and psychological disturbances. Objective: to analyze the prevalence and socioeconomic factors associated with the use of anorectic and stimulant medications among high school adolescents. Methods: this cross-sectional, school-based study was conducted between March and December 2023, with 4,614 students from public and private schools in the Metropolitan Region of Vitória, Espírito Santo, Brazil. Sampling was stratified and random, considering school type and municipality. Data were collected through a self-administered questionnaire developed on the REDCap platform and analyzed using descriptive statistics and Poisson regression with robust variance in Stata software, version 17.0. Results: the prevalence of lifetime use of anorectic and stimulant medications without medical prescription was 9.0%, and 4.0% reported current use. Among these adolescents, 47.2% initiated consumption at the age of 15 years or older. The most common sources of access were family members (21.5%) or taking pills secretly at home (18.0%). Experimentation was more prevalent among girls (PR = 1.90; 95%CI: 1.48–2.22), non-cisgender individuals (PR = 1.37; 95%CI: 1.12–1.68), and LGBTQIA+ adolescents (PR = 1.55; 95%CI: 1.30–1.85). Students from social class B and those attending private schools also showed higher prevalence rates. Current use was more frequent among females (PR = 2.36; 95%CI: 1.65–3.37), LGBTQIA+ individuals (PR = 1.78; 95%CI: 1.21–2.62), and Black adolescents (PR = 1.81; 95%CI: 1.15–2.84). Higher consumption was also observed among adolescents from upper socioeconomic classes (A/B) and those engaged in paid work. Conclusion: the use of anorectic and stimulant medications among adolescents is often initiated after the age of fifteen and commonly occurs within the household environment. Its occurrence is associated with socioeconomic and identity-related factors. These findings emphasize the need for public health policies and intersectoral educational strategies to promote rational drug use and reduce the psychosocial risks of self-medication during adolescence.

Dr. Gould Replies

Individuals diagnosed with autism spectrum disorder (ASD) often experience a higher occurrence of comorbid attention deficit hyperactivity disorder (ADHD). Stimulant medications are frequently prescribed to manage ADHD. In rare instances, the use of stimulant medications has been linked to the development of psychotic symptoms. This is a case of a 13-year-old male diagnosed with ASD and comorbid ADHD, anxiety, and depression, who presented with an abrupt onset of psychosis, which manifested about a week after the initiation of lisdexamfetamine. The psychotic symptoms subsided upon discontinuation of lisdexamfetamine; however, there was a re-emergence of severe ADHD symptoms that proved resistant to non-stimulant medications. The patient experienced significant improvement without any recurrence of psychosis after being prescribed extended-release methylphenidate. Notably, there are no established clinical guidelines to assist in selecting one stimulant over another in the treatment of ADHD comorbid with ASD. The authors recommend considering the methylphenidate class of stimulants as a first-line treatment for ADHD in individuals with ASD, citing better tolerability compared to amphetamines.

BackgroundAdults with attention-deficit/hyperactivity disorder (ADHD) may experience sleep problems doubly suffering from the disease and side effects of stimulant medications. Physical activity (PA) is known to produce numerous beneficial effects in adults. However, it was not well-characterized whether PA would still be effective in this situation. The main objective of the current study was to examine the relationship between PA and sleep among adult ADHD patients who were using stimulant medications and quantify the form of this association.MethodsAdult ADHD participants with stimulant medications use condition from the National Health and Nutrition Examination Survey (NHANES) database between January 1, 2013, and March 2020 (prepandemic) were included in the cross-sectional analysis. Weighted logistic regression was performed to assess the relationship between PA level and sleep. A restricted cubic spline model was used to relax the linear relationship assumptions and investigate the associations between the risk of trouble sleeping and time spent engaging in moderate-to-vigorous PA per week.ResultsA total of 162 eligible adult ADHD participants who reported using stimulant medicines were included. Participants who adhered to the general recommendation of guidelines in the US of 150 min per week of moderate-to-vigorous PA had a significant lower risk of complaining of trouble sleeping (OR: 0.26, 95% CI: 0.10–0.67, p = 0.006), and this association was seen in men (OR: 0.23, 95% CI: 0.09–0.56, p = 0.002), but was not seen in women (OR: 0.71, 95% CI: 0.27–1.88, p = 0.500). Restricted cubic spline analysis showed that the incidence of trouble sleeping gradually decreased after at least 105 min of moderate-intensity PA per week in participants (OR: 1.02, 95% CI: 0.92–1.14). A significant difference appeared after 341 min (OR: 0.87, 95% CI: 0.76–0.99), and the curve leveled after 1,250 min (OR: 0.60, 95% CI: 0.46–0.79).ConclusionOur findings observed associations between PA and sleep condition in the adult ADHD patients with stimulant medication use population. Moderate-to-vigorous PA may be beneficial to sleep in adults with ADHD who were using stimulants and thus should be recommended as part of a healthy lifestyle. Gender difference should be considered as an important factor for further studies to examine these associations and explore potential mechanisms.

PRACTICE PARAMETER FOR THE USE OF STIMULANT MEDICATIONS

Schizophrenia before the age of 18 years is usually divided into two categories. Early-onset schizophrenia (EOS) presents between the ages of 13 and 17 years, whereas very-early-onset schizophrenia (VEOS) presents at or before the age of 12 years. Previous studies have found that neurodevelopmental difficulties in social, motor, and linguistic domains are commonly observed in VEOS/EOS patients. Recent research has also shown a high prevalence of neurodevelopmental disorders (e.g., intellectual disability, communication disorders, autism spectrum disorder, neurodevelopmental motor disorders) in VEOS/EOS patients, indicating genetic overlap between these conditions. These findings lend support to the neurodevelopmental continuum model, which holds that childhood neurodevelopmental disorders and difficulties and psychiatric disorders (e.g., schizophrenia) fall on an etiological and neurodevelopmental continuum, and should not be considered discrete entities. Based on this literature, in this study we focused on the overlap between neurodevelopmental disorders and schizophrenia investigating, in a large sample (N = 230) of VEOS/EOS children and adolescents, the clinical differences, at the onset of psychosis, between VEOS/EOS with neurodevelopmental disorder or neurodevelopmental difficulties and VEOS/EOS with no diagnosed neurodevelopmental disorder or neurodevelopmental difficulties. The findings showed that, in children and adolescents with a neurodevelopmental disorder or neurodevelopmental difficulties, psychosis onset occurred at an earlier age, was associated with more severe functional impairment (e.g., global, social, role), and was characterized by positive symptoms (e.g., grandiose ideas, perceptual abnormalities, disorganized communication) and disorganized symptoms (e.g., odd behavior or appearance, bizarre thinking). Instead, in children and adolescents without a neurodevelopmental disorder or neurodevelopmental difficulties, psychosis onset was mainly characterized by negative symptomatology (e.g., social anhedonia, avolition, expression of emotion, experience of emotions and self, ideational richness). Given these differences, the presence of a neurodevelopmental disorder or neurodevelopmental difficulties should be carefully investigated and integrated early into the assessment and treatment plan for VEOS/EOS patients.