BACKGROUND:Medication-related attitudes are considered an important determinant of adherence to psychopharmacological treatment in adolescents. The Questionnaire on Attitudes Toward Treatment (QATT) was originally developed for adolescents with attention-deficit/hyperactivity disorder, but its applicability in transdiagnostic adolescent psychiatric populations has not been investigated. This study examined medication attitudes and factors associated with noncomplete medication adherence in a transdiagnostic sample of adolescents receiving psychopharmacological treatment. METHODS:This secondary analysis included 75 adolescents (12-17 years) participating in the multicenter SEMA study (Subjective Experience and Medication Adherence in Adolescents with Psychiatric Disorders). Medication adherence was assessed using the Medication Adherence Report Scale (MARS) and the QATT, together with demographic and clinical variables. Adherence was classified as complete or noncomplete. Group comparisons of QATT scores and an exploratory multivariable logistic regression were performed to identify factors associated with noncomplete medication adherence. RESULTS:Forty percent of participants were classified as not completely adherent. Higher QATT scores, indicating less favorable attitudes toward medication, were observed among older adolescents, inpatients, adolescents with internalizing disorders, and participants classified as not completely adherent. In the multivariable logistic regression, higher QATT total scores (odds ratio [OR] = 1.05, 95% confidence interval [CI]: 1.00-1.10; p = 0.048) and polypharmacy (OR = 3.64, 95% CI: 1.03-12.88; p = 0.046) were independently associated with noncomplete medication adherence. CONCLUSION:In this transdiagnostic adolescent psychiatric sample, less favorable medication attitudes, as assessed by the QATT, were associated with noncomplete medication adherence. Assessing medication attitudes may complement routine adherence assessment. Prospective studies are needed to further validate the QATT and determine its utility for identifying adolescents at risk of noncomplete medication adherence.
BACKGROUND:We examined whether the Affective Neuroscience Personality Scales (ANPS), personality traits grounded in neurobiologically defined primary emotions, are associated with selective serotonin reuptake inhibitor treatment response in youths with major depressive episodes. METHODS:This retrospective cohort study analyzed medical records from 142 youths (aged 12-20) at a university hospital. The primary outcome was the Clinical Global Impression (CGI) scale; secondary outcomes were the Children's Depression Inventory (CDI) and the Screen for Child Anxiety Related Emotional Disorders (SCARED). Outcomes were assessed at baseline, 3, and 6 months; demographic, developmental, clinical, and trauma covariates were recorded. Treatment response was defined as a CGI-I score ≤2 at 6 months. RESULTS:Multivariable logistic regression revealed that higher baseline ANPS SADNESS (odds ratio [OR] = 0.92, p = 0.033) and CARE (OR = 0.93, p = 0.043) scores were significantly associated with a lower likelihood of achieving treatment response (CGI-I ≤2). Linear mixed models revealed that higher SADNESS (β = 0.007, p = 0.031) and CARE (β = 0.009, p = 0.005) were associated with a slower rate of improvement in the CGI-S. Additionally, SADNESS and CARE scores were associated with overall CDI and SCARED severity, respectively. CONCLUSIONS:These findings suggest that ANPS SADNESS and CARE may inform personalized treatment approaches in youths with major depressive episodes; however, the retrospective single-center design limits causal inference and the Korean ANPS remains in early stages of psychometric validation in adolescents, underscoring the need for prospective multicenter validation.
BACKGROUND:Catatonia is a severe neuropsychiatric syndrome increasingly recognized in autism spectrum disorder (ASD), where symptom overlap can delay diagnosis. In pediatric populations, it is associated with significant morbidity and requires prompt intervention. Benzodiazepines and electroconvulsive therapy (ECT) are first-line treatments; however, access to ECT may be limited due to legal or institutional constraints. Alternative pharmacological strategies, including N-methyl-D-aspartate (NMDA) receptor antagonists such as amantadine, have been proposed, although evidence remains limited. CASE PRESENTATION:We report a 15-year-old male with ASD who developed progressive catatonia over 1 year, with psychomotor slowing, speech latency, staring, and functional decline requiring hospitalization. Symptoms emerged after using over-the-counter supplements and partially improved after discontinuation. Medical and neurological workup was unremarkable. A lorazepam challenge produced partial improvement, but high-dose benzodiazepines were insufficient. Due to lack of access to ECT, amantadine was initiated and titrated to 200 mg twice daily. Within days, the patient showed marked improvement, including increased speech output, improved psychomotor activity, and enhanced social engagement. Improvement was supported by clinical observations and caregiver reports. DISCUSSION:Catatonia involves dysfunction in dopaminergic (DA), GABAergic, and glutamatergic systems within cortico-striato-thalamo-cortical circuits. In ASD, similar abnormalities in excitatory-inhibitory balance and connectivity have been reported, which may partly explain the overlap in presentation and the potential vulnerability to catatonia. Amantadine may help restore this imbalance through NMDA receptor antagonism and DA modulation. CONCLUSION:Amantadine may be a viable adjunctive treatment for benzodiazepine-insufficient catatonia in adolescents with ASD when lorazepam is insufficient or poorly tolerated and ECT is unavailable. Further research is needed.
BACKGROUND:Post-traumatic stress disorder and trauma-related presentations in children and adolescents frequently co-occur with attention deficit hyperactivity disorder (ADHD), compounding functional impairment. Because evidence-based pediatric treatment options for trauma-related presentations remain limited and symptoms can overlap with ADHD, optimizing the choice of ADHD medications is of clinical importance. OBJECTIVE:This review aimed to map and synthesize the available evidence for the utility of different ADHD medications in children and adolescents with trauma-related presentations. METHODS:A systematic scoping review was undertaken following the Joanna Briggs Institute methodology and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. Medline, Embase, PsycINFO, and gray literature sources were searched for studies published between January 1985 and November 2025. Findings were synthesized narratively and organized by medication class. RESULTS:From 3,626 identified records, 19 were included in the final analysis (15 primary studies and 4 systematic reviews). These consisted of case reports (N = 8), open-label trials (N = 4), retrospective chart reviews (N = 2), and one large-scale electronic health record study. Alpha-2 agonists (guanfacine and clonidine) were associated with the most consistently reported improvements for trauma-related symptoms. Although stimulants and atomoxetine did not show consistent improvement in trauma-related symptoms across available studies, real-world data revealed that stimulant use was associated with reduced hospitalization, emergency department visits, and secondary antipsychotic or mood stabilizer prescribing in comorbid youth. No studies evaluating viloxazine were identified. CONCLUSIONS:Stimulants have been shown to benefit wider long-term psychiatric outcomes, although smaller studies demonstrated a more consistent improvement in specific trauma-related symptoms with alpha-2 agonists. Rather than following a rigid medication sequence, clinicians should adopt a trauma-informed approach that prioritizes or combines treatments based on whether ADHD or trauma is the primary driver of functional impairment. However, because the current evidence is predominantly low quality and lacks controlled trials, these findings must be interpreted with caution.
OBJECTIVE:Severe disruptive behaviors in youth with autism spectrum disorder (ASD) frequently persist despite conventional treatments, contributing to functional impairment. Although clozapine has antiaggressive properties, evidence guiding its use in treatment-resistant cases in autistic youth remains predominantly observational and retrospective. This study aimed to evaluate systematically and prospectively the effectiveness and safety of clozapine for treatment-resistant disruptive behaviors (TR-DB) in youth with ASD under routine conditions. METHODS:This single-arm, open-label trial enrolled participants aged 10-17 with ASD. Inclusion required TR-DB after ≥2 antipsychotic trials and a Clinical Global Impression-Severity score ≥5. Following flexible titration, clozapine was maintained for 12 weeks. The primary outcome was change on the caregiver-rated Aberrant Behavior Checklist-Irritability (ABC-I). Secondary measures included global improvement, autism symptom severity, adaptive behavior, and caregiver quality of life. Response was defined as ≥30% ABC-I reduction plus a CGI-Improvement (CGI-I) of 1 to 2; remission required ≥80% ABC-I reduction and a CGI-I of 1. RESULTS:Thirty-one participants initiated clozapine treatment (mean age 13.4 years; 90.3% male), and 28 completed the trial. ABC-I scores decreased from 32.0 ± 7.7 to 7.4 ± 5.1 (Cohen's dz -2.5; p < 0.001). Overall, 83.9% responded, and 38.7% remitted. Global severity improved from 6.1 ± 0.6 to 3.8 ± 1.6 (p < 0.001). Significant improvements were observed in daily living skills, caregiver quality of life, and reduced polypharmacy. Adverse drug reactions were mostly mild-to-moderate; however, metabolic changes comprised significant weight gain and triglyceride elevation (both p < 0.05). Serious events included seizures (n = 4) and pneumonia (n = 1). CONCLUSIONS:Clozapine was associated with robust, rapid TR-DB reductions and high retention in autistic youth. However, safety risks mandate rigorous monitoring. Controlled trials are needed to confirm efficacy and refine the benefit-risk profile.
Background: CTx-1301 is the first trimodal dexmethylphenidate formulation developed for the treatment of attention-deficit/hyperactivity disorder (ADHD). Methods: In this 5-week, phase 3, fixed-dose study, patients with ADHD aged 6–17 years were randomized to once-daily treatment with CTx-1301 (18.75, 25.0, or 37.5 mg) or placebo. CTx-1301 was initiated at 12.5 mg and uptitrated weekly to reach the assigned fixed dose. The primary endpoint was the change from baseline to week 5 in the ADHD Rating Scale, Version 5 (ADHD-RS-5). Secondary efficacy endpoints included Clinical Global Impression–Severity (CGI-S) and –Improvement (CGI-I). Statistical comparisons were evaluated at a Bonferroni-adjusted significance level of 0.017. Results: The mean age (±standard deviation) of the study population ( N = 103) was 11.3 ± 3.3 years, and the majority of subjects (60.2%) were male. Treatment with CTx-1301 25.0 or 37.5 mg significantly improved ADHD-RS-5 score from baseline compared with placebo ( p ≤ 0.011). Exploratory post hoc analyses revealed effect sizes for the comparison of CTx-1301 and placebo ranging from 0.732 (18.75-mg dose) to 1.185 (37.5-mg dose). Improvement in CGI-S was statistically significant for CTx-1301 37.5 mg versus placebo ( p < 0.001). More than 60% of subjects who received CTx-1301 were much to very much improved on CGI-I compared with 18% for placebo. All adverse events were mild or moderate in severity, no new safety signals were identified, and the safety profile was consistent with the known effects of dexmethylphenidate. Conclusions: CTx-1301 demonstrated dose-related improvements in signs and symptoms of ADHD, although statistical significance is not consistent across all dose groups. The treatment was well tolerated over 5 weeks in children and adolescents with ADHD. Given the limited sample size and reduced statistical power, these findings should be considered preliminary and require confirmation in larger, adequately powered studies.
OBJECTIVES:To identify early markers of acute treatment response among youth with anxiety disorders receiving cognitive behavioral therapy (CBT), selective serotonin reuptake inhibitor (SSRI) monotherapy, or their combination. BACKGROUND:Although many youth with anxiety disorders benefit from CBT or SSRIs, response trajectories vary. Identifying early indicators of nonresponse may guide sequencing strategies and improve timely treatment delivery. METHODS:Using data from the Child/Adolescent Anxiety Multimodal Study, improvement trajectories were modeled for youth (age 7-17) randomized to sertraline monotherapy (N = 133), CBT monotherapy (N = 139), their combination (N = 140), and placebo (N = 76). Patients were stratified by percent change in Pediatric Anxiety Rating Scale (PARS) scores at multiple time points, and logarithmic and logistic time-trend regression models were used to estimate the probability of response. Receiver operating characteristic (ROC) analyses were used to identify thresholds of improvement for predicting response. RESULTS:In the sertraline group, ≥25% improvement in PARS score at week 4 had a higher probability of response by week 12 (60.8%) than <25% improvement (31.7%, p = 0.001). In CBT-treated youth, week 4 PARS improvement was less predictive of response, with ≥25% improvement predicting a 47.9% chance of response compared with 28.6% for <25% improvement (p = 0.025). In the combined treatment, ≥25% improvement predicted a73.3% probability of response, whereas <25% improvement yielded a 51.3% likelihood of response (p < 0.001). ROC analyses similarly suggested that week 4 improvement in PARS scores in the CBT group had near equivocal predictive value, though this improved by week 6 to levels comparable to those of the other treatment groups. At week 6, roughly 25% improvement in PARS score in the combined treatment had the best sensitivity and specificity for predicting response. CONCLUSIONS:Early improvement can predict treatment response in youth with anxiety disorders receiving sertraline monotherapy or combination treatment (sertraline and CBT). Conversely, the absence of early improvement in CBT-treated youth does not reliably predict treatment nonresponse. Treatment-specific thresholds may inform clinical decision making, and support earlier SSRI optimization while allowing more time to observe CBT-related gains.
INTRODUCTION:Neurodevelopmental disorders (NDDs), including Autism Spectrum Disorder (ASD), Fragile X syndrome (FXS), and Rett Syndrome (RTT), share impairments in cognitive and behavioral functioning and may involve an altered excitatory/inhibitory balance modulated by the endocannabinoid system. This systematic review evaluated the safety and efficacy of cannabinoid-based products (CBPs) in these pediatric NDDs. METHODS:We conducted a systematic review according to Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) 2020, including randomized and nonrandomized studies of patients under 18 years treated with cannabidiol (CBD), cannabidivarin (CBDV), tetrahydrocannabinol (THC), or their combinations. Outcomes were adverse events (AEs) and treatment discontinuation, seizure reduction, and behavioral and cognitive changes. Study quality and certainty of evidence were assessed using design-specific risk-of-bias tools and the GRADE approach. RESULTS:Seventeen studies (two randomized controlled trials, observational studies, and case series) met the inclusion criteria. Across diagnoses, CBPs were generally associated with mild-to-moderate AEs and low discontinuation rates. Descriptive pooled proportions suggested behavioral improvements in ASD and FXS and seizure reduction in RTT, with exploratory analyses indicating differential effects of CBD versus CBD + THC on behavioral and cognitive outcomes in ASD. CONCLUSION:CBPs may offer potential benefits for selected behavioral symptoms and comorbid epilepsy in pediatric NDDs, but current evidence is insufficient to support routine clinical use. High-quality randomized controlled trials with standardized outcome measures and long-term follow-up are needed to clarify efficacy, safety, and syndrome-specific effects.
OBJECTIVE:To examine how emotional awareness (the ability to understand and identify one's own emotions) and neural reward circuitry, processes that are associated with depression and undergo significant maturation during adolescence, prospectively predict depressive symptoms in a community sample of youth at varying risk for affective disorders. METHOD:Youth aged 13-19 years (N = 84), risk-enriched for depression (66% with familial history of affective disorders), completed self-report assessments of emotional awareness and depressive symptoms at baseline. Depressive symptoms were also assessed at 1-year follow-up. Neural reward function, as indexed by functional connectivity of the dorsomedial prefrontal cortex (dmPFC) and nucleus accumbens (NAcc), was assessed via a functional magnetic resonance imaging task of winning versus losing monetary rewards at baseline. Controlling for age, biological sex, familial risk status, and baseline depression, linear regressions examined the interaction of emotional awareness and dmPFC-NAcc functional connectivity to predict changes in depressive symptoms over 1 year. RESULTS:Low emotional awareness at baseline predicted more severe depressive symptoms at 1-year follow-up, particularly among youth demonstrating heightened positive dmPFC-NAcc functional connectivity, a pattern potentially indicating over-regulation of reward responding. DISCUSSION:Low emotional awareness and stronger frontostriatal functional connectivity during processing of reward relative to loss are relevant early-emerging risk factors that could jointly lead to future depression. Interventions targeting emotional regulation skills and reward processing may mitigate the onset and course of adolescent depressive symptoms.
Objective: Early behavioral dysregulation places children at elevated risk for later psychopathology. Maternal emotion dysregulation during pregnancy is a transdiagnostic vulnerability that may shape child regulatory development through both prenatal biological influences and postnatal caregiving. However, less is known about the specific postnatal mechanisms through which prenatal emotion dysregulation confers risk for toddler behavioral dysregulation. This study examined whether prenatal maternal emotion dysregulation was associated with toddler behavioral dysregulation indirectly through infant parasympathetic regulation (baseline respiratory sinus arrhythmia; RSA) and postnatal parenting stress.Methods: Participants were 385 mothers and their infants recruited during the third trimester. At the third trimester, maternal emotion dysregulation was assessed using the Difficulties in Emotion Regulation Scale. At 7 months postpartum, parenting stress was measured using the Parenting Stress Index, and infant parasympathetic regulation was assessed using baseline RSA during a neutral resting period. At 18 months, toddler behavioral dysregulation was evaluated using the Infant-Toddler Social Emotional Assessment. We tested direct and indirect pathways among prenatal maternal emotion dysregulation, postnatal parenting stress, infant baseline RSA, and toddler behavioral dysregulation with structural equation models.Results: Higher prenatal maternal emotion dysregulation was associated with greater postnatal parenting stress and lower infant baseline RSA. Postnatal parenting stress was concurrently associated with higher infant baseline RSA and higher toddler behavioral dysregulation. Infant RSA was not directly associated with toddler behavioral dysregulation. Parenting stress partially accounted for associations between prenatal maternal emotion dysregulation and toddler behavioral outcomes.Conclusion: This study provides evidence for prospective indirect pathways in which maternal emotion dysregulation during pregnancy contributes to elevated parenting stress in infancy, which is linked to both infant parasympathetic regulation and toddler behavioral dysregulation. Although prenatal maternal emotion dysregulation was associated with infant baseline RSA, infant RSA was not associated with toddler dysregulation, suggesting partly distinct pathways of physiological and behavioral regulation development. These findings highlight pregnancy and infancy as important periods in early child development.
OBJECTIVE:Irritability and temper outbursts are common presenting concerns in pediatric mental health settings, but systematic monitoring can be difficult to sustain with broad, repeated assessment batteries. This study evaluated the temper outbursts/irritability-2 (TOI-2), an ultra-brief, two-item screener assessing temper outbursts and frequently irritable mood in youth. METHODS:Participants were 1515 youth aged 5-17 years (M = 11.80, SD = 3.60) referred to an outpatient child psychiatry clinic. Female caregivers (90.4% biological mothers) completed the TOI-2 and criterion measures at intake. Convergent and discriminant validity were assessed via correlations with the Affective Reactivity Index (ARI), administered with a current-state timeframe, oppositional defiant disorder (ODD) symptom dimensions, attention-deficit/hyperactivity disorder, conduct disorder (CD), depression, and anxiety. Screening accuracy was evaluated using receiver operating characteristic analysis, with elevated irritability defined as ARI ≥ 4. Clinical utility was examined using screen-positive and screen-negative comparisons and known-group analyses. RESULTS:The TOI-2 showed strong convergence with the ARI and ODD-Irritability symptoms (rs = 0.82). Its association with ODD-Irritability was significantly stronger than with ODD-Behavioral symptoms (r = 0.70; p < 0.001), supporting relative specificity to irritability within the broader disruptive behavior spectrum. ROC analysis indicated excellent classification accuracy, area under the curve = 0.91. Cut scores of ≥2.5 and ≥3.0 both optimized overall performance, Youden's J = 0.66. A threshold of ≥3.0 is recommended for specialty-clinic triage, whereas ≥2.5 may be preferable when maximizing case detection is the priority. Youth who screened positive showed greater symptom severity and poorer adjustment across clinical domains. Known-groups analyses showed the largest TOI-2 elevations among youth meeting symptom-count thresholds for ODD and CD. CONCLUSIONS:The TOI-2 is a psychometrically sound, ultra-brief screener for clinically significant irritability in youth. Positive screens should prompt more comprehensive clinical assessment of irritability, impairment, disruptive behavior, mood symptoms, and treatment needs.
BACKGROUND:Sleep disturbance is common in youth with mood disorders and correlates with mood symptom burden. Insomnia polygenic risk scores (PRS), computed from adult genome-wide association study (GWAS) data, are associated with sleep disturbance among youth within the general population. However, no studies have examined insomnia-PRS in a clinical sample of youth with mood disorders. METHODS:Participants included 374 youth aged 13-20 years, 247 with mood disorders (135 bipolar disorder [BD] and 112 major depressive disorder) and 127 controls. Insomnia-PRS was constructed using an adult insomnia GWAS (N = 360,738). Sleep disturbance was computed using the most severe lifetime insomnia and hypersomnia (i.e., excessive sleep) items from the Kiddie Schedule for Affective Disorders and Schizophrenia Depression Rating Scale. General linear models or logistic regressions examined main effects of insomnia-PRS on sleep disturbance and psychiatric characteristics (mood symptom severity, anxiety comorbidity, suicide risk, global functioning), controlling for age, sex, and genetic principal components. RESULTS:Insomnia-PRS was higher in youth with mood disorders versus controls (p = 0.03, d = 0.24). Insomnia-PRS was associated with insomnia severity in youth with mood disorders (p = 0.03, ηp2 = 0.02), and with mania severity in youth with BD (p = 0.03, ηp2 = 0.03), although the insomnia severity finding did not survive Bonferroni correction. In sex-stratified analyses, insomnia-PRS was significantly associated with insomnia (p = 0.02, ηp2 = 0.03), depression (p = 0.02, ηp2 = 0.03), and mania (p = 0.02, ηp2 = 0.05) severity in females but not males. There were no significant findings for excessive sleep. CONCLUSIONS:This study extends prior findings linking adult-derived insomnia-PRS with insomnia in youth with mood disorders, with evidence of differences related to sex and BD. These preliminary findings suggest that sleep and mood in youth may be sensitive to adult-derived insomnia-PRS.
Background: Management of acute agitation in youth frequently involves intramuscular (IM) antipsychotics; however, little is known about how treatment strategies vary across care settings. Differences between emergency and inpatient psychiatric environments may influence medication selection and dosing. Methods: This retrospective secondary analysis included youth (<18 years) who received IM antipsychotics for agitation across multiple emergency departments and inpatient psychiatric units within a large urban health system (2019-2023). Comparisons between settings examined antipsychotic selection, coadministration of adjunctive medications, and dosing. To account for differences in medication selection, dosing comparisons were conducted within each antipsychotic agent. Secondary outcomes included repeat IM administration and restraint or seclusion within 24 hours. Results: The sample included 158 youth (86 emergency, 72 inpatient). Antipsychotic selection differed significantly by setting, with greater use of haloperidol in emergency settings and chlorpromazine in inpatient settings (p < 0.001). Midazolam coadministration was more common in emergency settings (10.5% vs. 1.4%, p = 0.020). When examined within agents, chlorpromazine doses were higher in inpatient settings (36.7 mg vs. 30.4 mg, p = 0.035), while haloperidol and olanzapine dosing did not differ. Rates of additional IM administration were similar across settings (p = 0.295), although restraint or seclusion was more common in inpatient settings (p < 0.001). Conclusions: Pharmacologic management of pediatric agitation varies by care setting, particularly in antipsychotic selection and adjunctive medication use. Differences in dosing were limited to chlorpromazine, suggesting that variation reflects agent-specific prescribing patterns rather than overall treatment intensity. These findings highlight the influence of clinical context and provider practice patterns in shaping management strategies for pediatric agitation.
BACKGROUND:Down syndrome (DS) is a major genetic cause of intellectual disability. In an animal model of DS, fluoxetine was shown to restore brain architecture and cognitive performance, acting primarily on the hippocampus, with effects persisting after treatment discontinuation. In this translational study, we assessed the safety and tolerability of fluoxetine at the standard labeled dose and explored selected efficacy endpoints to inform future clinical trials. METHODS:The study was approved as a phase I, open-label study. Participants with full trisomy 21 received fluoxetine (10 mg/day) for 6 months, followed by a 6-month observation period. The primary endpoint, safety and tolerability, was evaluated through clinical examinations, biochemistry, plasma fluoxetine and norfluoxetine levels, electroencephalography, and electrocardiography at multiple time-points. As a secondary efficacy endpoint, we selected a set of cognitive tests to explore hippocampus-dependent functions and adaptive behavior. RESULTS:Fourteen children with DS (8.1 ± 1.24 years; range 6-10) were enrolled, and 12 completed the 12-month study. No serious or severe adverse events (AEs) occurred. All AEs resolved without sequelae. Short-term terminal insomnia was observed in two patients. Neuropsychological assessments revealed improvements in visuospatial processing tasks during the study. Analysis of adaptive behavior suggested enhanced expression skills. CONCLUSIONS:These findings indicate that fluoxetine is safe in children with DS. The association with terminal insomnia warrants specific investigation in future trials and strategies to optimize tolerability are discussed. Efficacy analyses highlight the visuospatial processing domain as potentially responsive to treatment, supporting further research.
OBJECTIVE:To evaluate cannabidiol (CBD) in pediatric patients with autism spectrum disorder (ASD), fluent verbal language and an estimated full-scale IQ of 80 or above. BACKGROUND:Preliminary evidence suggests CBD may ameliorate challenges associated with ASD. Whether CBD benefits pediatric ASD without accompanying intellectual or language impairment remains unknown. METHODS:We enrolled 23 participants, ages 7.8-17.8 (Mean [M] = 11.3 ± 2.8) with ASD and IQ ≥ 80 in a 6-week Phase-2 open-label trial of ≥98% CBD (Epidiolex®, 100 mg/mL) at 3, 6, or 9 mg/kg/day using a Bayesian optimal interval dosing design. The primary endpoint was the CBD dose associated with the highest response rate (i.e., Clinical Global Impression Scale-Improvement [CGI-I] score = 1 or 2) on a target symptom domain designated individually based on informant report, standardized scales, and clinical observation. Secondary endpoints were effect sizes of changes from baseline in measures assessing ASD core and associated symptoms, and global functioning. Adverse events (AEs) were assessed weekly. Plasma CBD levels and clinical labs were obtained at the final visit. RESULTS:All 23 enrolled participants completed the trial. The highest response (62%) was observed at 9 mg/kg/day (N = 8). Overall, 10 of 23 patients (44%) were responders. Response varied across domains: Irritability/Tantrums (N = 5, 60%), Social (N = 8, 50%), Anxiety (N = 5, 40%), Restricted, Repetitive Behaviors (N = 4, 25%), and Sleep Problems (N = 1, 0%). Dose correlated with individualized CGI-I (r = -0.42, N = 23, p = 0.04).Individualized domain CGI-Severity scores improved from pre-(M = 4.6 ± 0.5) to post-(M = 3.9 ± 0.8) treatment, t(22) = -4.36, p ≤ 0.001; d = 0.91; 95%CI [0.37,1.03]. Social Responsiveness Scale-2 Total-Score (SRS2-T) had the largest effect size (p ≤ 0.001; d = 1.36, 95% CI [0.78-1.93]).Of 222 reported AEs, 27 unique AEs were considered treatment-related. Most AEs (93%) were mild and expected (82%); none was severe. The most frequent related AEs were increased salivation (30%), increased sleep duration (39%), sleepiness/sedation (26%), increased dream activity (35%), and polyuria (22%). Vital signs, physical exams, weight, liver function tests, and complete blood counts were unaffected. CBD plasma levels did not correlate with response. CONCLUSIONS:In this preliminary study, CBD was well tolerated; AEs were mild-moderate. Mean SRS2-T and subscores decreased significantly with large effect sizes, shifting from the severe to the moderate range. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov Identifier NCT03900923.
OBJECTIVE:Use measurement-based care to assess symptom change across diagnostic categories for adolescents receiving acute-care psychiatric inpatient treatment including both psychopharmacology and dialectical behavior therapy. METHODS:Adolescents were aged 12-17 and hospitalized on a coeducational, acute-care inpatient unit within a psychiatric hospital in New York City. We conducted a retrospective chart review to analyze symptoms across two or more timepoints from the first 15 days of admission using mixed effects regression models to estimate linear change on five outcome measures including Generalized Anxiety Disorder-7 (GAD-7), General Behavior Inventory-Mania subscale (GBI-10M), Patient Health Questionnaire-9 (PHQ-9), Prodromal Questionnaire Brief-21 (PQB-21), and Schwartz Outcome Scale-10 (SOS-10). RESULTS:There were improvements on all five measures. For the GAD-7, GBI-10M, PHQ-9, and PQB-21, the change is negative, indicating a decrease in symptoms. For the SOS-10, the change is positive, suggesting an increase in well-being. The covariance parameters indicate that there is generally significant individual variation around the adolescent's initial assessment as well as significant individual variation around the slope, suggesting that patients change at different rates. The Days × Intercept covariance parameter is generally negative, indicating that adolescents who started with higher symptom severity showed greater symptom reduction. For well-being, the negative change indicates that adolescents with higher well-being on the first assessment showed smaller increases in well-being over time. CONCLUSION:Adolescents experienced improvements in their symptoms of anxiety, mania, depression, psychosis, and well-being during acute psychiatric inpatient treatment. These are notable findings, particularly for demonstrating the impact of psychiatric inpatient treatment on improving symptoms/diagnoses.
