Journal of child and adolescent psychopharmacology最新文献

Study Design: Prospective open-label trial. Objectives: The objective of this study was to determine whether buspirone showed preliminary evidence of effectiveness, safety, and tolerability in individuals with Williams syndrome (WS). Methods: This is a 16-week, prospective, flexibly dosed, open-label trial of buspirone in 20 individuals with WS aged 5-65 years. The primary outcome measure was the Pediatric Anxiety Rating Scale (PARS). Results: Buspirone use (mean dose, 22.6 mg per day) was associated with a reduction in anxiety severity, with Cohen's d estimate of -4.02 for the PARS. All 18 participants who completed the study received the Clinical Global Impression-Improvement subscale score for anxiety of "much improved" or "very much improved." No serious or severe adverse events occurred during the trial, and no participants discontinued the study due to adverse events. Conclusion: Buspirone was safe and well tolerated. It was also associated with a reduction in anxiety severity. Given these findings, a double-blind, placebo-controlled study of buspirone in WS is warranted.

Background: Although randomized clinical trials (RCTs) have investigated several treatments for social communication difficulties and repetitive behavior in autism, none has yet shown consistent superiority over placebo. Placebo response in autism RCTs may impede the ability to detect meaningful treatment effects. Objective: We sought to identify individual-level predictors of placebo response in Study of Oxytocin in Autism to improve Reciprocal Social Behaviors (SOARS-B), a 24-week RCT of intranasal oxytocin for social impairment in autistic youth. In our primary analysis, we examined predictors of change in the Aberrant Behavior Checklist-modified Social Withdrawal (ABC-mSW) score at 24 weeks in SOARS-B participants taking placebo. Secondary analyses examined predictors of ABC-mSW change at 12 weeks and of Clinical Global Impressions-Improvement at 24 and 12 weeks. We also examined predictors of response among SOARS-B participants taking oxytocin. Methods: For each analysis, we first used lasso (least absolute shrinkage and selection operator) regression to identify potentially influential predictors from a large group that included demographic factors, rating scale data, and prescribed medications. We then estimated an unpenalized linear regression model for the outcome of interest that included only variables retained by the optimal lasso. We considered variables with statistically significant coefficients to be influential predictors. Results: Higher baseline ABC-mSW score was the only significant predictor of greater ABC-mSW change in the placebo group at 24 and 12 weeks. Conclusions: In SOARS-B, higher baseline severity on a measure of reciprocal social communication predicted greater placebo response. This is consistent with the finding that lower social communication adaptive functioning was associated with greater placebo response in recent RCTs of balovaptan for social impairment in autism. However, it contrasts with findings from a trial of citalopram for repetitive behavior in autism, in which lower baseline severity of a composite of autistic and mood symptoms predicted greater placebo response. This may indicate that different factors contribute to placebo response in different symptom domains.

Purpose: Catatonia is a severe psychomotor and mood-related disorder, which can significantly impact the quality of life for autistic individuals. Often, electroconvulsive therapy (ECT) is required for treatment of catatonia in autism. However, hyperactive, impulsive, and aggressive symptoms are common in this subpopulation. Thus, pharmacologic agents are needed to assist in obtaining intravenous (IV) access and placement of necessary monitoring leads when ECT is pursued. Here we report six patients with autism and hyperactive catatonia who successfully and safely received intramuscular (IM) ketamine to obtain IV access for ECT while prescribed high-dose benzodiazepines for catatonia. Methods: Using SlicerDicer software found within Epic Systems electronic medical record, we conducted a single-site retrospective analysis. All patients had a diagnosis of autism, were treated for hyperactive catatonia with ECT, and required the use of ketamine for safe IV placement. Diagnoses of autism and catatonia were confirmed per the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. Results: Six patients were identified. All patients met criteria for autism, intellectual disability, and catatonia. The patient's ages ranged from 10 to 30 years, and all were prescribed high doses of benzodiazepines for treatment of catatonia, with a mean dose of 24 mg per day in lorazepam equivalents. The patients' symptoms of hyperactive catatonia impaired the ability to obtain IV access. Thus, IM ketamine was received by all patients to facilitate this process. All patients were able to receive ECT. Conclusion: In all cases, IM ketamine was successfully used to obtain IV access and allow patients to receive ECT uneventfully. No serious adverse events were reported despite the coadministration of ketamine with high-dose benzodiazepines in this patient subpopulation.

Introduction: Treatment studies in FMR1 knockout rodent models have found that minocycline and lovastatin each improve synaptic, neurological, and behavioral functioning, and open-label chronic dosing studies in human patients with fragile X syndrome (FXS) have demonstrated modest clinical improvements. Findings from blinded studies are mixed, and there is a limited understanding of electrophysiological target engagement that would facilitate cross-species translational studies. Smaller-scale, acute (e.g., single-dose) drug studies may speed treatment identification by detecting subtle electrophysiological and behavioral changes. Materials and Methods: Twenty-nine participants with FXS (31% female) ages 15-45 years completed a randomized, double-blind, crossover study in which they received a single oral dose of 40 mg of lovastatin, 270 mg of minocycline, or placebo, with a 2-week washout period between dosing visits. Participants completed a comprehensive neuropsychological battery and three EEG paradigms (resting state; auditory chirp; auditory habituation) before and 4 hours after dosing. Results: No serious adverse events were reported, and both drugs were well-tolerated. Compared with placebo, there were no overall treatment effects for any outcomes, including EEG, but several modest drug responses varied as a function of sex and age. Lovastatin treatment was associated with improved spatial awareness in older participants and females compared with minocycline and placebo. Discussion: We show that single-dose drug studies are highly feasible in FXS and that patients with FXS can complete a range of EEG and behavioral tasks, many of which have been shown to be reliable and may therefore be sensitive to subtle drug target engagement. Conclusions: Acute single doses of lovastatin or minocycline did not lead to changes in electrophysiological or performance-based measures. This may be due to the limited effects of these drugs in human patients or limited acute effects relative to chronic dosing. However, the study design was further validated for use in neurodevelopmental populations.

Interest in psychedelic therapies for adults is rapidly growing, with substances like 3,4-methylenedioxymethamphetamine for posttraumatic stress disorder, psilocybin for treatment-resistant depression, and lysergic acid diethylamide for generalized anxiety disorder showing promise. However, research on these therapies in children and adolescents is limited, with no recent trials. Despite this lack of scientific exploration, adolescents may still experiment with these substances for both recreational and therapeutic purposes as accessibility continues to increase. This raises significant concerns, as adolescents are a vulnerable population requiring heightened caution and safety measures. Therefore, we advocate for structured, safe, and well-controlled exploration of psychedelic therapies in adolescents.

Background: Antidepressant medication adherence patterns are inconsistent in adolescents with anxiety and related disorders, and the clinical and demographic features predicting adherence are poorly understood. Methods: In an ongoing single-site prospective trial involving adolescents (aged 12-17) with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition anxiety disorders treated with escitalopram, adherence was measured for 12 weeks using electronic monitoring caps. Adherence patterns were examined using qualitative and unsupervised clustering approaches, and predictors of adherence were evaluated using logistic regression, with demographic (age, sex, and race) and clinical variables (e.g., anxiety severity [Pediatric Anxiety Rating Scale], irritability [Affective Reactivity Index], depressive symptoms [Children's Depression Rating Scale]). Results: Among adolescents (N = 33) aged 14.5 ± 1.8 years (64% female), four adherence patterns were identified: persistent adherence, intermittent adherence, early adherence-late nonadherence, and nonadherence. In a logistic model of a 5-day moving average measure of adherence, social anxiety disorder (β = -0.68 ± 0.19, p = 0.002) and separation anxiety disorder (β = -0.61 ± 0.18, p < 0.001) were associated with lower adherence. In contrast, panic disorder, attention-deficit/hyperactivity disorder, generalized anxiety disorder, and depressive symptoms were not associated with adherence. Baseline anxiety severity was linked to lower adherence (β = -0.199 ± 0.05, p < 0.001). Older age also reduced adherence (β = -0.342 ± 0.05, p < 0.001), with each additional year of age increasing time spent nonadherent by 5% (p < 0.001). Being female (β = 0.451 ± 0.17, p = 0.011) and expecting treatment to be efficacious (β = 0.092 ± 0.04, p = 0.011) increased adherence, while greater irritability was associated with nonadherence (β = -0.075 ± 0.03, p = 0.006). Conclusions: Antidepressant adherence is variable, with distinct patterns, and those with social and separation anxiety disorders were less likely to be adherent. Factors such as older age, severe anxiety, and greater irritability predicted lower adherence, while being female and expecting treatment efficacy were associated with better adherence. Interventions that address specific symptoms or enhance treatment expectations may improve adherence.