Journal of child and adolescent psychopharmacology最新文献

Background: Many individuals with autism spectrum disorder (ASD) experience gastrointestinal (GI) symptoms, which can impact social interactions, exacerbate social communication deficits, and decrease the quality of life. GI symptoms have been shown to be correlated with the autonomic nervous system and endocrine response to stress in some people with ASD. Furthermore, propranolol, a central and peripheral beta-adrenergic antagonist that inhibits the stress response, has been shown to provide GI relief for some individuals with ASD, but not others. This pilot study examined whether baseline (i.e., resting) heart rate variability (HRV), a biomarker that is sensitive to the stress response, predicted the response to propranolol in decreasing GI symptoms. Methods: In this pilot study, a sample of 37 individuals with ASD participated in a 12-week open-label trial of propranolol. The Gastrointestinal Severity Index and HRV were collected at baseline (i.e., prior to taking propranolol) and again at the end of the 12-week trial period. Results: Higher HRV was associated with the greatest reduction in GI symptoms, with a strong effect size, but only for adolescents and young adults (15-24 years old). Baseline HRV and GI change scores were not significantly correlated for younger children (7-14 years old). Conclusions: The results from this open-label pilot trial suggest that autistic adolescents and young adults with higher baseline HRV, indicating greater parasympathetic tone, may respond better to propranolol and show the greatest reduction in GI symptoms. The data from this pilot should be interpreted with caution until larger, randomized, double-blinded, placebo-controlled trials of propranolol for GI symptoms in ASD are completed.

Objectives: Randomized controlled trials (RCTs) are the gold standard for evaluating medication efficacy. The absence of a universal definition of treatment response, based on the degree of symptom improvement measured by standardized rating scales in the field of attention-deficit/hyperactivity disorder (ADHD), makes it difficult to compare treatment outcomes across RCTs. Here, we aimed to assess to what extent and how "treatment response" is defined across RCTs of ADHD medications. Methods: We identified eligible RCTs via the MED-ADHD database (https://med-adhd.org/), which compiles RCTs evaluating the efficacy and safety of pharmacological treatments for children, adolescents, and adults with ADHD, based on a comprehensive search in multiple electronic databases, including PubMed, BIOSIS Previews, CINAHL, the Cochrane Central Registry of Controlled Trials, and EMBASE, up to 17 January 2025, alongside additional unpublished information gathered from manufacturers/study authors. Results: Out of 167 RCTs in MED-ADHD, 88 defined treatment response based on reductions in ADHD core symptom severity using rating scale scores. The most frequently used threshold was a ≥30% reduction in attention-deficit/hyperactivity disorder (ADHD-RS) scores, with other RCTs using ≥25%, ≥40%, or ≥50%. In addition, RCTs applied similar cutoff values to alternative scales, including Conner's Adult ADHD Rating Scale, SNAP-IV, Adult ADHD Investigator Rating Scale, and Wender-Reimherr Adult Attention Deficit Disorder Scale. However, 79 studies did not specify any response threshold. Conclusion: Our review underscores and quantitatively defines the inconsistency in the definition of treatment response across ADHD medication trials, highlighting the urgent need for the field to reach a consensus on the use of a standardized definition of "treatment response" for each rating scale, based on the percentage reduction in ADHD core symptom severity.

Objective: Pharmacoepidemiologic research shows increasing use of polypharmacy to manage behavioral treatment of youth. Methods to increase precision, for example, competing risk analysis, to capture psychotropic patterns of concomitant stimulant treatment changes over time have not been explored. Methods: A retrospective cohort study was derived from Medicaid enrollment data, prescription drug, and clinician-reported diagnosis claims data from 2007 to 2014. Youths aged 2-17 years with 1-7.5 years of continuous enrollment who were new users of stimulants were followed. Major outcomes include detailed changes of concomitant use according to the number of psychotropic classes (NPC); competing risk assessment of patient factors according to NPC; and time factors related to changes in NPC. Results: Among 30,294 new stimulant users, 75.5% remained on stimulant monotherapy and 24.5% had stimulant concomitant regimens. Among the latter, great flux was observed, revealing exposure to combinations changed substantially across time. As a proportion of all changes, retention of the maximum NPC was observed for 65.3% of 2 concomitant classes, 56.2% of 3 concomitant classes, and 57.1% and 56.2% of 4 and 5 concomitant classes, respectively. Median duration according to NPC showed a linear decrease in time from 223 days for 2 classes, 172 days for 3 classes, 141 days for 4 classes, and 113 days for 5 classes combinations. By contrast, the path to maximum NPC regimens took median times of 491-833 days as NPC increased from 2 to 4 concomitant classes. Competing risk analysis demonstrated significantly increased hazard ratios according to the number of concomitant classes for 12-17-year-olds, patients with foster care or disability coverage, and those with 3-4 years of continuous enrollment. Conclusions: Detailed NPC changes illustrate great flux in concomitant stimulant patterns among Medicaid-insured youth. Competing risk analysis brings more precise patient characteristics risk information to assess NPC changes compared with a binary model.

Objective: Rates of mental illness among young people remain elevated, and the utilization of youth mental health services is expected to increase. Yet, there is limited knowledge on real-world medication usage and prescribing at these services. Hence, the aim of this study was to explore the medication prescribing patterns at a headspace center, an Australian youth mental health service. Methods: A retrospective cross-sectional study of medical records was conducted. Demographic data, clinical information, prescribed medications, and reasons for use of young people who attended an intake assessment at headspace Camperdown over a 13-month period, February 2021-February 2022, were analyzed. Data collection focused on medication molecule, strength, dose, prescriber designation, and indication. Data were analyzed descriptively. Results: Records for 608 participants were included. The median age at intake was 19.9 years old (interquartile range: 16.1-22.4), and most participants identified as female (n = 372, 61.2%). Anxiety (n = 246, 40.5%) and low mood (n = 95, 15.6%) were the most common presenting concerns. Almost half of participants (n = 291, 47.9%) reported using medication/s at intake, and almost one in five participants (n = 119, 19.6%) were prescribed a medication at the service. The most prescribed medications at headspace were melatonin (24.0%) and quetiapine (12.3%), as well as the antidepressants escitalopram (15.1%), sertraline (11.2%), and fluoxetine (7.3%). Conclusions: This study provides insights into the prescribing practices at a single headspace center. Further investigations are needed to explore the impacts of off-label prescribing for young people, particularly in relation to melatonin and quetiapine, where safety and efficacy in young people have not been well established.

Introduction: Prior studies have demonstrated that, in both adults and youth, bipolar disorder (BD) is a polygenic illness. However, no studies have examined polygenic risk scores (PRSs) in relation to the longitudinal course of mood symptoms in youth with BD. Methods: This study included 246 youth of European ancestry with BD (7-20 years old at intake) from the Course and Outcome of Bipolar Youth study and Centre for Youth Bipolar Disorder. Mood symptom severity was assessed at intake and, for 168 participants, prospectively for a median of 8.7 years. PRSs for BD, schizophrenia (SCZ), major depressive disorder (MDD), and attention-deficit/hyperactivity disorder (ADHD) were constructed using genome-wide summary statistics from independent adult cohorts. Results: Higher BD-PRS was significantly associated with lower most severe lifetime depression score at intake (β = -0.14, p = 0.03). Higher SCZ-PRS and MDD-PRS were associated with significantly less time spent in euthymia (SCZ-PRS: β = -0.21, p = 0.02; MDD-PRS: β = -0.22, p = 0.01) and more time with any subsyndromal mood symptoms (i.e., any mania, mixed, or depression symptoms; SCZ-PRS: β = 0.15, p = 0.04; MDD-PRS: β = 0.17, p = 0.01) during follow-up. PRSs for BD and ADHD were not significantly associated with any longitudinal mood variable. Conclusions: This exploratory analysis was the first to examine psychiatric PRSs in relation to the prospective course of mood symptoms among youth with BD. Results from the current study can serve to guide future youth BD studies with larger sample sizes on this topic.

Introduction: SARS-CoV-2 (COVID-19) infection has been implicated in the onset of neuropsychiatric symptoms in adults and children. While outcomes of COVID-19 infection and vaccination have been tracked in the general pediatric population, little is known of their impact on children with preexisting neuropsychiatric syndromes, including pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). The aim of this study is to understand the prevalence and severity of COVID-19 symptoms and PANS/PANDAS symptoms following COVID-19 infection or vaccination in children with PANS/PANDAS. Methods: We analyzed retrospective COVID-19 survey data from caregivers of youth with PANS/PANDAS at Massachusetts General Hospital (MGH; n = 57) and the International PANS Registry (IPR; n = 478). Surveys were conducted online between late 2021 and early 2022 to collect COVID-19 infection and vaccination histories, side effects, and changes in PANS/PANDAS symptoms. Descriptive results are reported, stratified by case and sibling groups within the IPR sample. Results: Among patients with test-confirmed COVID-19 (MGH: n = 20, IPR: n = 65 cases, n = 16 siblings), mild/minor COVID-19 symptoms were common (62-75%). All patients with preexisting PANS/PANDAS-related symptoms at the time of COVID-19 infection experienced an exacerbation of PANS/PANDAS symptoms, while remitted patients did not report any PANS/PANDAS symptoms. Following the first COVID-19 vaccine dose (MGH: n = 45, IPR: n = 150 cases, n = 44 siblings), fatigue was the predominant side effect (30-56%). Most patients did not report new (59-81%) or worsened (71-82%) PANS symptoms post-vaccination, irrespective of symptomatic status at vaccination. Vaccine hesitancy often stemmed from concerns that the vaccination would cause an exacerbation of PANS/PANDAS symptoms. Conclusions: In two samples of children with PANS/PANDAS, symptoms of COVID-19 following infection and vaccination were common and generally mild to moderate. Children experiencing PANS/PANDAS symptoms at the time of COVID-19 infection experienced an increase in PANS/PANDAS symptom severity.

Background: Approximately 20%-40% of individuals with Tourette syndrome (TS) have rage attacks (RAs), which are recurrent, explosive behavioral outbursts that can cause significant functional impairment. Despite the impact of RA in TS, there has been limited research on treatment, and most studies have focused on pharmacologic interventions. Nonpharmacologic interventions have the potential to improve symptoms with fewer side effects. Mightier, a video game-based biofeedback therapy, may help teach emotional regulation through heart rate control and has the potential to improve RA in youth with TS. Objective: To evaluate the feasibility and acceptability of Mightier as a therapeutic intervention for RA in youth with TS. Methods: Subjects aged 6-12 years old with a diagnosis of TS and RA were enrolled between October 2021 and May 2022 into a 20-week single-arm trial. Feasibility was assessed by the rate of enrollment, screen failures, and retention and device engagement. We also evaluated efficacy by assessing rage severity (Clinical Global Impressions of Rage), Rage Outbursts and Anger Rating Scale (ROARS) and overall aggression severity (Modified Overt Aggression Scale [MOAS]) pre- and postintervention. CGI-Improvement (CGI-I) was completed postintervention. Results: We enrolled 11 participants. The study was feasible based on enrollment rate (one participant every 2.5 months), screen failures (n = 1), and retention rate (91%). Mean weekly play time was 38 (SD 18) minutes/week. No adverse effects were reported. Median rage severity scores improved across all assessment measures. All participants reported overall improvement on the post-intervention CGI-I. Conclusions: This Mightier study was feasible in terms of recruitment and retention. Participants with TS and RA used the device often and engaged with the device throughout the 12-week intervention period. Rage severity overall improved across the various outcome measures, and all participants had at least some improvement by parent report. Mightier may be a helpful tool for reducing rage severity in children with RA and TS.