Journal of child and adolescent psychopharmacology最新文献

Introduction: Autism spectrum disorder (ASD) is characterized by deficits in social behavior and executive function (EF), particularly in cognitive flexibility. Whether transcranial magnetic stimulation (TMS) can improve cognitive outcomes in patients with ASD remains an open question. We examined the acute effects of prefrontal TMS on cortical excitability and fluid cognition in individuals with ASD who underwent TMS for refractory major depression. Methods: We analyzed data from an open-label pilot study involving nine participants with ASD and treatment-resistant depression who received 30 sessions of accelerated theta burst stimulation of the dorsolateral prefrontal cortex, either unilaterally or bilaterally. Electroencephalography data were collected at baseline and 1, 4, and 12-weeks posttreatment and analyzed using a mixed-effects linear model to assess changes in regional cortical excitability using three models of spectral parametrization. Fluid cognition was measured using the National Institutes of Health Toolbox Cognitive Battery. Results: Prefrontal TMS led to a decrease in prefrontal cortical excitability and an increase in right temporoparietal excitability, as measured using spectral exponent analysis. This was associated with a significant improvement in the NIH Toolbox Fluid Cognition Composite score and the Dimensional Change Card Sort subtest from baseline to 12 weeks posttreatment (t = 3.79, p = 0.005, n = 9). Improvement in depressive symptomatology was significant (HDRS-17, F (3, 21) = 28.49, p < 0.001) and there was a significant correlation between cognitive improvement at week 4 and improvement in depression at week 12 (r = 0.71, p = 0.05). Conclusion: These findings link reduced prefrontal excitability in patients with ASD and improvements in cognitive flexibility. The degree to which these mechanisms can be generalized to ASD populations without Major Depressive Disorder remains a compelling question for future research.

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: 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.

Background: Bipolar disorder often begins in adolescence or early adulthood, characterized by recurrent manic episodes that can lead to neurodegenerative brain changes and functional decline. While several oral second-generation antipsychotics are Food and Drug Administration (FDA)-approved for mania, adherence to maintenance treatment is frequently poor due to factors such as anosognosia, cognitive dysfunction, impulsivity, side effects aversion, and substance use. Long-acting injectable (LAI) antipsychotics, approved for adults with bipolar mania or schizoaffective disorder (bipolar type), offer a potential solution for adolescents with similar conditions. This study reports on the efficacy of LAI antipsychotics in managing bipolar mania in adolescents, tracking outcomes over up to a year with baseline and follow-up Young Mania Rating Scale (YMRS) assessments. Methods: The study included 116 adolescents with a mean age of 16.17 years (66% male, 48% white, 23% black). Of these, 73% were diagnosed with bipolar mania and 22% with schizoaffective disorder, bipolar type. The mean illness duration was 1.9 years, with a baseline YMRS score of 33.8 and a body mass index (BMI) of 23.4 kg/m². LAI antipsychotics administered included aripiprazole, paliperidone, and risperidone, given at intervals of 1, 2, or 3 months. Results: YMRS scores showed substantial improvement, declining to 21.7 at 1 month, 12.3 at 2 months, 4.9 at 6 months, and 3.0 at 1 year. Common side effects were increased appetite and weight gain (mean BMI rose to 26.3 kg/m²). There were no dropouts, although 12% of participants switched formulations due to side effects. Notably, 86.2% of adolescents improved sufficiently to return to school or work. While 28.4% experienced depressive episodes, there were no suicide attempts or deaths during the 4- to 14-month follow-up. Discussion: This study demonstrates that LAI antipsychotics can effectively stabilize adolescents with bipolar mania or schizoaffective disorder, bipolar type, showing a marked decline in YMRS scores and high rates of remission and functional recovery. Despite the lack of FDA approval for LAI antipsychotics in those younger than 18, our results from off-label use suggest significant efficacy and tolerability. Further FDA clinical trials are needed to explore LAI antipsychotic formulations in adolescents to address the needs of this high-risk, nonadherent population.

Introduction: Transcranial magnetic stimulation (TMS) is a promising intervention for adolescents with treatment-resistant depression (TRD). However, the durability of TMS-related improvement in adolescents is unclear. This 6-month study followed adolescents with TRD who had responded to TMS and provided TMS retreatment for adolescents with a partial relapse. Methods: The study enrolled adolescents (12-21 years) with TRD who had at least a partial response to sham or active TMS in a randomized controlled trial. Partial response was defined as ≥25% reduction of Hamilton Depression Rating Scale-24 (HAMD24). Participants with a partial relapse (≥1 point increase in Clinical Global Impression-Severity) received retreatment with daily 10 Hz TMS sessions until depressive symptom severity returned to the baseline score or after 30 TMS treatments. Results: There were 84 eligible participants, 66 were enrolled, and 41 completed the 6-month study. Twenty-eight participants (42%) were retreated with TMS. TMS retreatment courses had a mean of 22 sessions. At the 6-month follow-up, the complete sample exhibited reduced depressive symptoms (mean HAMD24 of 5.24) compared with baseline at entry into follow-up (mean HAMD24 of 8.21). Baseline depressive symptom severity was positively correlated with the risk of partial relapse, while the number of previous TMS interventions showed no correlation with the risk of partial relapse. TMS was well tolerated. Conclusions: This is the largest, long-term follow-up study with TMS retreatment for adolescents with TRD. These findings demonstrate the feasibility and clinical effects of a TMS retreatment protocol for adolescents with TRD, following a standard course of acute TMS.

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.

Introduction: While available for decades, the use of bupropion has increased in recent years. To provide an updated review on the use of bupropion, this article aimed to describe bupropion prescription details, potential indication, and treatment duration in children, young adults, and adults starting bupropion treatment. Methods: Individuals aged 6-64 newly initiating bupropion hydrochloride treatment were identified from commercial claims data (MarketScan, 1/1/2016-12/31/2022). New bupropion use was defined as at least 1 year without any prior bupropion dispensed prescription. Potential indications for bupropion treatment were identified from inpatient/outpatient records (ICD-10-CM diagnoses) in the 30 days prior to bupropion initiation. All analyses were stratified by age: children (6-17 years), young adults (18-29 years), and adults (30-64 years) and treatment duration up to 1 year was estimated with Kaplan-Meier estimation. Results: The study sample included 39,833 children, 177,710 young adults, and 548,557 adults newly initiating bupropion treatment. Bupropion extended-release 24-hour 150 mg was the most common (62%) formulation and dose at initiation. Depression was the most prevalent potential indication (children = 57%, young adults = 47%, adults = 36%) and attention-deficit/hyperactivity disorder (ADHD) was the next most common potential indication in children (25%) and young adults (12%); tobacco cessation and weight loss also identified as potential indications. Twenty-two percent of bupropion initiators were on concurrent selective serotonin reuptake inhibitor treatment. In children, suicidal ideation (16.3%), poisoning (5.9%), and anorexia or bulimia nervosa (2.2%) were relatively common diagnoses prior to bupropion initiation. Overall, 39%-45% remained on bupropion treatment for at least 6 months, with variation by potential indication. Conclusion: The antidepressant bupropion is prescribed to children, young adults, and adults for a variety of indications in the United States, with depression and ADHD the most common indications in children. As the prescribing of bupropion becomes more widespread, additional safety and effectiveness data will be necessary to inform prescribing decisions, particularly in populations with unknown efficacy.

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.

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.