Journal of child and adolescent psychopharmacology最新文献

Objective: The incidence of neuroleptic malignant syndrome (NMS), a rare, potentially fatal adverse effect of antipsychotics, among children and youth is unknown. This cohort study estimated NMS incidence in antipsychotic users age 5-24 years and described its variation according to patient and antipsychotic characteristics. Methods: We used national Medicaid data (2004-2013) to identify patients beginning antipsychotic treatment and calculated the incidence of NMS during antipsychotic current use. Adjusted hazard ratios (HRs) assessed the independent contribution of patient and antipsychotic characteristics to NMS risk. Results: The 1,032,084 patients had 131 NMS cases during 1,472,558 person-years of antipsychotic current use, or 8.9 per 100,000 person-years. The following five factors independently predicted increased incidence: age 18-24 years (HR [95% CI] = 2.45 [1.65-3.63]), schizophrenia spectrum and other psychotic disorders (HR = 5.86 [3.16-10.88]), neurodevelopmental disorders (HR = 7.11 [4.02-12.56]), antipsychotic dose >200mg chlorpromazine-equivalents (HR = 1.71 [1.15-2.54]), and first-generation antipsychotics (HR = 4.32 [2.74-6.82]). NMS incidence per 100,000 person-years increased from 1.8 (1.1-3.0) for those with none of these factors to 198.1 (132.8-295.6) for those with 4 or 5 factors. Findings were essentially unchanged in sensitivity analyses that restricted the study data to second-generation antipsychotics, children age 5-17 years, and the 5 most recent calendar years. Conclusion: In children and youth treated with antipsychotics, five factors independently identified patients with increased NMS incidence: age 18-24 years, schizophrenia spectrum and other psychotic disorders, neurodevelopmental disorders, first-generation drugs, and antipsychotic doses greater than 200 mg chlorpromazine-equivalents. Patients with 4 or 5 of these factors had more than 100 times the incidence of those with none. These findings could improve early identification of children and youth with elevated NMS risk, potentially leading to earlier detection and improved outcomes.

Objective: To evaluate the comparative efficacy of pharmacological interventions for children and adolescents with a dual diagnosis of persistent tic disorders or Tourette disorder and attention-deficit/hyperactivity disorder (TD + ADHD). Methods: We searched CENTRAL, Embase, PubMed, PsycInfo, Web of Sciences, ClinicalTrials.gov, and WHO ICTRP up to September 2023 to identify double-blinded randomized controlled trials (RCTs) assessing pharmacological interventions for children and adolescents with TD + ADHD. Outcomes were change in ADHD symptoms (primary) and tics (secondary) severity. Standardized mean difference (SMD) was calculated and pooled in random-effects network meta-analysis. The Confidence in Network Meta-Analysis framework was adopted to determine certainty of evidence. Results: We included 8 RCTs involving 575 participants. Network meta-analyses demonstrated that α2 agonists (SMD, 95% confidence interval [CI] ADHD: -0.72 [-1.13 to -0.31]; TD: -0.70 [-0.96 to -0.45]) and stimulants + α2 agonists (ADHD: -0.84 [-1.54 to -0.13]; TD: -0.60 [-1.04 to -0.17]) were more efficacious than placebo for ADHD symptoms and tics severity. Stimulants alone were more efficacious than placebo for ADHD symptoms severity only, but they did not worsen tics (ADHD: -0.54 [-1.05 to -0.03]; TD: -0.22 [-0.49 to 0.05]). There were no significant differences between any pairs of medications that were found efficacious against placebo for ADHD symptoms or tics severity. Certainty in the evidence varied from low to very low. Conclusions: Stimulants are efficacious for ADHD symptoms severity and do not increase tics severity in TD + ADHD. α2 agonists are efficacious for both ADHD symptoms and tics severity in TD + ADHD. These findings should inform guidelines and help guide shared decision-making to choose a medication for children with TD + ADHD.

Objective: To compare the proportion of children and adolescents with incident psychotropic medication use from 2019 through 2022. Methods: This cross-sectional study used the IQVIA PharMetrics^® Plus for Academics health plan claims database. Our study sample consisted of children and adolescents ages 6-18 who had at least one psychotropic medication in March 2019-February 2022. We examined psychotropic medication use in three distinct study periods: pre-pandemic (March 2019 to February 2020), pandemic-year-1 (March 2020-February 2021), and pandemic-year-2 (March 2021-February 2022). Incident use was defined as no evidence of psychotropic medication in the 12 months preceding the child and adolescent's first psychotropic dispensing in each study period. We estimated incident psychotropic use in the three study periods. Average marginal effects tested for significant differences in psychotropic initiation, overall and stratified by age and sex. Results: In our sample of 42,346 children and adolescents who were dispensed any psychotropic medication during the study period, incident psychotropic users were 27.8% in pre-pandemic, 26.0% in pandemic-year-1, and 27.8% in pandemic-year-2. Incident use of antidepressants was 51.4% in pandemic-year-1 and 54.6% in pandemic-year-2. The probability of incident psychotropic use was 2.4% lower in pandemic-year-1 than in the pre-pandemic year (p < 0.001). The proportion of 6-11-year-olds and females initiating a psychotropic was higher in pandemic-year-2 than pre-pandemic. Conclusion: Incident psychotropic use was most notable in younger and female children 2 years after the pandemic onset.

Introduction: It is essential not to delay behavior management and control for aggression, violence, and impulsive behavior in young people. Clozapine has been widely used in adolescents and adults to manage violence and aggression in Schizophrenia. However, there are limited data on the use of clozapine in children, and no systematic review has addressed its use in this population. Objective and Methods: To better understand the conditions under which clozapine is used as a therapeutic alternative for nonschizophrenic diagnoses and to assess the current evidence supporting its prescription to children, a systematic review was conducted. The review followed PRISMA guidelines and was registered in PROSPERO under the ID CRD42024537707. Results: The review identified that all the studies used clozapine to address externalizing behavior, particularly aggressive behavior, and found positive outcomes supporting its use for treating children with treatment-resistant aggression. The studies also found that clozapine was well-tolerated in all cases. However, the studies were limited and mainly consisted of open trials without a control group. Conclusion: Further high-quality research is needed to establish precise guidelines for using clozapine in children.

Introduction: Hyperactive catatonia is often unrecognized in pediatric patients due to its clinical heterogeneity, though it is often seen in children with neurodevelopmental disabilities, especially autism spectrum disorder (ASD). Emerging evidence implicates hyperactive catatonia in more cases of self-injury and aggression in ASD than previously thought. Objectives: The study seeks to describe cases of hyperactive catatonia in SYNGAP-1 mutation and examine existing literature for symptomatic overlap between previously-described clinical and behavioral phenotypes of individuals with SYNGAP-1 mutations and catatonia. Methods: The study describes two cases of an adolescent and a young adult with SYNGAP-1 mutation and ASD presenting with hyperactive catatonia, which are the first reports of catatonia in individuals known to have a pathogenic variant in SYNGAP-1. A systematic review was undertaken during which 101 articles were screened. 13 articles were then examined for neurological and behavioral features present in participants with SYNGAP-1 mutations which are seen in catatonia. Results: The systematic review demonstrates that clinical features suggestive of catatonia are frequently seen among individuals with SYNGAP-1 mutations, including verbal impairment, psychomotor symptoms, aggression, oral aversion, and incontinence. These features were also present in the cases of catatonia in SYNGAP-1 mutations presented here. Both patients showed clinical improvement with use of a long-acting benzodiazepine, and one patient showed benefit from electroconvulsive therapy. Conclusions: This symptomatic overlap revealed in the systematic review, including symptoms seen in the reported cases, raises the possibility that diagnoses of catatonia may have been missed in the past in individuals with SYNGAP-1 mutations. Self-injurious behavior and aggression, which are hallmarks of hyperactive catatonia, are commonly part of the behavioral phenotype of SYNGAP-1-related disorders. Clinicians should consider catatonia as a cause of such symptoms in individuals with SYNGAP-1 mutations, as effective treatment can result in significant improvement in safety and quality of life.

Introduction: Exposure to a range of stressful life events (SLE) is implicated in youth psychopathology. Previous studies point to a discrepancy between parents'/children's reports regarding stressful life events. No study systematically assessed the correlation between such discrepancies and psychopathology in depressed youth. This study was designed to assess parent-youth discrepancies regarding stressful life events and its association with severity of psychopathology at baseline and response to selective serotonin reuptake inhibitor (SSRI) treatment in depressed youth. Methods: Reports regarding stressful life events were assessed in children/adolescents suffering from depressive/anxiety disorders using the life events checklist (LEC), a self-report questionnaire measuring the impact of negative life events (NLE) and positive life events (PLE), as reported by the children and their parents. The severity of depression/anxiety disorders and response to antidepressant treatment were evaluated and correlated with both measures of LEC. Results: Participants were 96 parent-child dyads (39 boys, 57 girls) aged 6-18 years (mean = 13.90 years, SD = 2.41). Parents reported more NLE and higher severity of NLE events than their children (number of NLE: 7.51 ± 4.17 vs. 6.04 ± 5.32; Cumulative severity of NLE: 24.95 ± 14.83 vs. 17.24 ± 12.94). Discrepancy in PLE, but not NLE, was associated with more severe psychopathology and reduced response to treatment. Discussion: Discrepancy in informant reports regarding life events in depressed/anxious youth, especially regarding PLE, is associated with more severe psychopathology and reduced response to pharmacotherapy. It is essential to use multiple reporters in assessing stressful life events in children.

Objectives: Stimulants, such as methylphenidate (MPH) and amphetamines, represent the first-line pharmacological option for attention-deficit/hyperactivity disorder (ADHD). Randomized controlled trials (RCTs) have demonstrated beneficial effects at a group level but could not identify characteristics consistently associated with varying individual response. Thus, more individualized approaches are needed. Experimental studies have suggested that the neurobiological response to a single dose is indicative of longer term response. It is unclear whether this also applies to clinical measures. Methods: We carried out a systematic review of RCTs testing the association between the clinical response to a single dose of stimulants and longer term improvement. Potentially suitable single-dose RCTs were identified from the MED-ADHD data set, the European ADHD Guidelines Group RCT Data set (https://med-adhd.org/), as updated on February 1, 2024. Quality assessment was carried out using the Cochrane Risk of Bias (RoB) 2.0 tool. Results: A total of 63 single-dose RCTs (94% testing MPH, 85% in children) were identified. Among these, only a secondary analysis of an RCT tested the association between acute and longer term clinical response. This showed that the clinical improvement after a single dose of MPH was significantly associated with symptom improvement after a 4-week MPH treatment in 46 children (89% males) with ADHD. The risk of bias was rated as moderate. A further RCT used near-infrared spectroscopy, thus did not meet the inclusion criteria, and reported an association between brain changes under a single-dose and longer term clinical response in 22 children (82% males) with ADHD. The remaining RCTs only reported single-dose effects on neuropsychological, neuroimaging, or neurophysiological measures. Conclusion: This systematic review highlighted an important gap in the current knowledge. Investigating how acute and long-term response may be related can foster our understanding of stimulant mechanism of action and help develop stratification approaches for more tailored treatment strategies. Future studies need to investigate potential age- and sex-related differences.

Introduction: Professional guidelines recommend that providers routinely monitor children prescribed second-generation antipsychotics (SGA) to reduce the risk of adverse metabolic events associated with the medication. Despite this guidance, many studies show low rates of monitoring compliance. In this study, we interviewed child psychiatrists for their views of possible barriers to monitoring. Methods: Semi-structured qualitative interviews, developed according to the Regehr model of influences upon patient-provider decision making, were conducted with child and adolescent psychiatrists in current practice and recruited by convenience and snowball sampling. Interviews were conducted through internet video meetings and were recorded. Interview data were analyzed following Framework Analysis qualitative methods. Results: We recruited and completed interviews with 17 psychiatrists. Patient-level barriers included travel difficulties, limited family time for health care appointments, patient fear of blood draws, and more. Provider-level barriers included professional judgment versus guideline guidance, perceived family burden, assumption of low-risk, short-term SGA use, and more. Organizational level barriers included lack of organizational mandates or incentives, limited appointment time per patient, lack of care coordination, lack of co-located labs, personnel turnover, and more. Barriers at the social and cultural level include stigma and low health literacy. Conclusion: These practicing prescribers provided a wide range of possible barriers to metabolic monitoring in children and adolescents prescribed SGAs. The next step is to explore which may be present in certain settings, and to pilot quality improvement interventions. Addressing barriers can reduce risk of metabolic disorders arising from long-term use of SGAs in children and adolescents.