There has been recent concern for the rising rates of catatonia diagnosis in pediatric populations. We set out to determine if the rates of catatonia diagnosis have risen at an academic pediatric medical center. The clinical records of 131 patients were obtained from encounters during 2018-2023 in which a diagnosis of catatonia was made in the pediatric emergency department or inpatient medical hospital. Ordinary least squares regression and linear regression analyses were used to determine if the prevalence of catatonia diagnoses, underlying diagnostic category, and Bush-Francis Catatonia Rating Scale scores changed over time. A 10-fold increase was observed in catatonia diagnoses between 2018 and 2023. A statistically significant relationship between the year of pediatric catatonia diagnoses was discovered ( = 0.01), with an value of 0.83 suggesting that approximately 83% of the variance can be attributed to the passage of time. Both medical and psychiatric causes of catatonia showed an upward trend over the course of the study period. The average Bush-Francis Catatonia Rating Scale scores showed a slight upward trend but were not statistically significant. In this sample of pediatric patients hospitalized at a large academic medical center, the rate of catatonia diagnoses related to both medical and psychiatric causes rose between 2018 and 2023. These data are consistent with previous evidence highlighting an increase in catatonia diagnoses during this period. The COVID-19 pandemic and increasing awareness of catatonia in children may have contributed to this trend. These data support the importance of investigation into this trend and improving education on catatonia for clinicians and the public.

Neuroleptic malignant syndrome (NMS), catatonia, and serotonin syndrome (SS) are unique neuropsychiatric conditions that share overlapping clinical features. A 14-year-old boy presented to the hospital for surgical resection of a pineal gland teratoma. Following surgery, he developed cerebellar cognitive and affective syndrome, which led to dramatic behavioral changes, including suicidal behavior and agitation. Throughout his postsurgical course, he exhibited signs and symptoms concerning for overlapping NMS, catatonia, and SS. Through this case we highlight the complex neurophysiology of three neuropsychiatric syndromes, review the treatment course for this patient, and raise awareness that these neuropsychiatric syndromes can occur concurrently.

Despite the increased risk for psychopathology in individuals with neurogenetic syndromes, very few psychopharmacology trials have been conducted in these populations. The objective of this perspectives article is to describe recruitment challenges and potential solutions for psychopharmacology trials in neurogenetic syndromes. We describe recruitment challenges and lessons learned from an open-label trial of fluoxetine for the treatment of depression in adults with Down syndrome (DS). These challenges are contrasted with a successful open-label trial of buspirone for the treatment of anxiety in Williams syndrome. Factors that contributed to recruitment challenges include limited research on the clinical presentation of depression in DS and the relatively small target population. This experience highlights the importance of foundational research studies on the phenomenology of target symptoms and burden of disease, as well as disseminating that information to the patient/family community. Partnership with a local family organization with close ties to the patient population can assist in overcoming recruitment barriers. The successes and challenges of early psychopharmacology clinical trials in neurogenetic syndromes should be considered for future trials.

Improving early recognition and accurate diagnosis of major depressive disorder (MDD) in childhood is a pressing concern. Quantitative electroencephalogram (qEEG) may be an effective, noninvasive diagnostic biomarker for MDD. Prior work by our team demonstrated decreased resting connectivity, as measured by qEEG coherence, in a heterogeneous group of adolescents with MDD compared with age and gender-matched healthy controls (HCs). This study explored qEEG coherence as a predictor of MDD diagnosis in a prospective, longitudinal sample of medication-free, adolescents with MDD versus HCs. Twenty-eight adolescents with MDD (Children's Depression Rating Scale score ≥40) and 27 age and gender-matched HCs (age 14-17, 78% female) received a baseline resting 32-channel EEG. Brain-wide coherence between channel pairs was calculated for the frequency bands (alpha, beta, theta, and delta) and compared between MDD youth and HC. Random forest classifiers were used to predict individual MDD status using baseline qEEG coherence. Models were trained and tested using 10-repeated, 10-fold cross-validation, and performance was evaluated with the area under the receiver operating characteristic curve (AUC-ROC). The contribution of individual predictors was assessed using permutation importance. Model significance was assessed using permutation testing (B = 1000 resamples). Random forest models predicted depression status with a trend-level of significance (mean AUC-ROC = 0.65, = 0.08). Among the most predictive channel pairs, adolescent MDD was characterized by lower coherence in T7-P7 ( < 0.05), Fz-Cz, and Fp2-F8 as well as higher coherence in P4-O2 and Cz-Pz. This study provides preliminary evidence that multivariate patterns of qEEG may inform the diagnosis of adolescent MDD. Specific aberrant patterns of coherence within the default mode network and cognitive control network were characteristic of adolescent MDD. Ongoing work will seek to replicate these findings in a larger cohort.

This article presents the protocol for an open-label clinical trial examining the effectiveness of atomoxetine augmentation in adolescents with nonsuicidal self-injury (NSSI) and attention problems and reports preliminary findings from the initial group of participants. Adolescents ( = 27) aged 13-18 years who met the criteria for NSSI according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and had either full or subclinical attention-deficit/hyperactivity disorder (ADHD) were recruited. All participants had not received ADHD medication for at least 4 weeks prior to enrollment. Psychiatric diagnoses were confirmed using the Kiddie Schedule for Affective Disorders and Schizophrenia. After 12 weeks of adjunctive atomoxetine treatment, NSSI severity (primary outcome) was measured using the Inventory of Statements About Self-Injury. Secondary outcomes included the Children's Depression Rating Scale (CDRS), the Children's Depression Inventory (CDI), the Screen for Child Anxiety Related Emotional Disorders (SCARED), and DuPaul's ADHD Rating Scale (ARS). Additional assessments targeting factors related to NSSI included demographic characteristics, childhood adversity, personality functioning, continuous performance task, and functional near-infrared spectroscopy. Twenty-three participants (22 female, 1 male) completed the trial (mean final dose: 58.3 ± 13.7 mg), while four discontinued (two voluntarily, two due to adverse events). Significant improvements were observed in CDRS ( < 0.001), CDI ( = 0.031), and NSSI severity ( = 0.007). In the ADHD group, significant improvements were observed in CDRS ( = 0.017) and NSSI severity ( = 0.034), with a trend toward improvement in CDI ( = 0.058). The subclinical ADHD group showed significant improvement in CDRS ( = 0.006), with a trend toward improvement in NSSI severity ( = 0.083). Atomoxetine augmentation may reduce NSSI severity in adolescents with attention problems, particularly in those with comorbid ADHD, warranting further investigation in larger controlled trials.

Depression is a prevalent co-occurring condition in youth living with HIV. This report is a secondary analysis of a multisite cluster randomized trial evaluating the efficacy of a health and wellness cognitive behavioral therapy (CBT) combined with a medication management algorithm utilizing measure-based care (COMB-R) compared with enhanced standard of care (ESC). We describe and compare antidepressant prescribing strategies (i.e., antidepressant treatment, type of antidepressant) for youth living with HIV at COMB-R sites to those at ESC sites over the 24-week intervention. We also describe self-reported adherence to antidepressants. Participants (12-24 years) were youth living with HIV diagnosed with moderate to severe depression (Quick Inventory of Depressive Symptomatology [QIDS], Clinician-Rated score ≥11). Thirteen sites were randomly assigned to either the COMB-R arm or the ESC arm. Site-level means were compared using -tests. While there was no difference at baseline in prescribing antidepressants, there was a significantly higher mean percentage of SSRI use at the COMB-R sites at week 24, compared with ESC sites (49.1% vs. 24.2%, = 0.009). Although the COMB-R group had better outcomes on response and remission by week 24, there were no consistent within-group patterns in depression outcomes by group based on antidepressant treatment. The two groups differed in adherence in the last 30 days, with the COMB-R group reporting more missed medication. Our results support the use of the medication management algorithm and measure-based care for the treatment of depression in youth living with HIV. Although treating depression, particularly in youth living with HIV, remains very complex, these findings provide some potential factors to guide future research. Overall, this report supports the importance of medication management in the context of a collaborative treatment model with CBT in improving depression outcomes.

The current study aimed to investigate the efficacy of probiotics in alleviating anxiety in children and adolescents. Randomized placebo-controlled trials (RCTs) recruiting children and adolescents were identified through searching major databases using the main keywords "Probiotics" and "Anxiety." Outcomes included improvement in anxiety and treatment acceptability. Continuous and categorical data were expressed as effect size based on standardized mean difference (SMD) and odds ratios (ORs), respectively, with 95% confidence intervals. Meta-analysis of seven RCTs involving 912 participants (mean age = 8.21) showed no significant improvement in anxiety (SMD = -0.09, = 0.54) between the probiotics and placebo groups. However, subgroup analysis revealed probiotics-associated anxiety improvement (SMD = -0.55, = 0.02) in studies enrolling individuals with neurodevelopmental disorders but not in those without (SMD = 0.12, = 0.48). A significant difference was noted between studies recruiting participants with such diagnoses and those without (SMD = -0.55 vs. 0.12, = 0.05). Moreover, probiotics-related improvement in anxiety was found in individuals diagnosed with autism spectrum disorder (ASD) (SMD = -0.35, = 0.03) but not attention deficit hyperactivity disorder (ADHD) (SMD = -0.21, = 0.38). Overall dropouts exhibited no difference between the probiotics and placebo groups (OR = 0.90, = 0.36). Our results showed efficacy of probiotics against anxiety compared with placebos only in participants diagnosed with neurodevelopmental disorders, especially ASD. Nevertheless, insufficient evidence derived from limited studies (i.e., three trials for ASD and two for ADHD) requires further investigations for verification.

Evidence for medical cannabis use and effectiveness in autism has begun to accumulate but remains limited, even as clinical interest has rapidly increased. In Israel, medical cannabis may be prescribed for autism with severe behavioral disturbances under strict Ministry of Health criteria requiring prior trials of two Food and Drug Administration (FDA)-approved antipsychotics. Using a large real-world dataset, this study aimed to characterize autistic individuals prescribed medical cannabis and evaluate adherence to national guidelines. A retrospective cohort study was conducted using electronic medical records from Clalit Health Services, Israel's largest Health Maintenance Organization. All individuals with a documented autism diagnosis between 1990 and 2025 were identified ( = 36,610) and classified as cannabis-prescribed ( = 462) or not-prescribed ( = 36,148). Demographic and clinical characteristics were compared, including prior use of FDA-approved antipsychotics. Only 1.2% of individuals with autism were prescribed medical cannabis. Of these, 4.3% of prescriptions were issued for children under 5 years of age. The cannabis-prescribed group was diagnosed earlier (median 3 vs. 5 years, < 0.001) and had higher rates of ADHD (42% vs. 30%), intellectual disability (12% vs. 5%), and epilepsy (14% vs. 6%) (all < 0.001). While 69% had used at least one FDA-approved antipsychotic medication prior to cannabis initiation, only 28% had documented trials of both, as required by national guidelines. Marked sociodemographic disparities were also observed: the cannabis-prescribed group had a higher socioeconomic status (median SES 7 vs. 6, < 0.001) and lower representation of Arab individuals (2.7% vs. 11%, < 0.001). Medical cannabis use among autistic individuals was rare and mainly observed among those with more complex clinical profiles and higher socioeconomic backgrounds. Most prescriptions did not fully comply with guidelines requiring prior antipsychotic trials. These findings underscore the need for enhanced regulatory oversight, equitable access, and longitudinal research to evaluate real-world outcomes and guide evidence-based clinical practice.

To characterize the size and course of placebo response in attention-deficit/hyperactivity disorder (ADHD), with informant and moderator effects, and illustrate its importance by comparison to Multimodal Treatment Study of ADHD (MTA) 3-month data. In two randomized clinical trials parents and teachers rated DSM-IV ADHD symptoms (Sx) on pill placebo at baseline (BL), 8, 12, and 16 weeks for 57 children age 5-12 with ADHD (25 inattentive, 32 combined type) and on an intense 12-week nonmedical control condition (NMCC) for 27 children age 6-12. Parent- and teacher-rated placebo effects peaked at 12 and 8 weeks, respectively. Changes from BL are significant ( = 0.001) by parent and teacher on inattentive Sx ( = .60, .56 for pill placebo; = 1.48, .51 for NMCC) and on hyperactive/impulsive Sx by parent ( = 0.48 pill; = 1.26 NMCC). Teacher-rated hyperactive/impulsive show greater placebo effect September-January than February-May ( = 0.017). Teacher-rated inattentive Sx shows a significant ( = 0.033) interaction of season*subtype. Compared to placebo data, MTA treatments show significant benefit ( = 0.000) at 3 months on both inattentive and HYP/IMP symptoms for medication management and combination groups but not for behavioral treatment (Beh) or community comparison groups, except for teacher-rated HYP/IMP for Beh ( = 0.002). Parent/teacher ratings show a medium placebo effect for pill placebo and a large effect ( > 1.2) by parent for intense, complex NMCC, suggesting that parent-rated placebo response depends on the complexity/intensity of the control condition. Raters agree on inattentive but diverge on HYP/IMP Sx. Teachers' perceptions of HYP/IMP severity change by season. Pill placebo data indirectly support the 3-month efficacy of two MTA treatments, combination and medication management.

Evaluating antidepressant side effects in children and adolescents is important, as side effects can significantly impact treatment adherence and outcomes. While there are tools to assess side effects globally encompassing various body systems, their administration time can be substantial, limiting their practical use in clinical settings. This is especially challenging in pediatric practice, where providers need to collect information from both patients and guardians. The Frequency, Intensity, Burden of Side Effects Rating-Child (FIBSER-C) was developed to address this need and assesses side effect frequency, intensity, and burden; however, its psychometric properties have not been examined in pediatric samples. The analytic sample included = 746 youth among the first 1000 participants who completed FIBSER-C and were taking antidepressant medication(s). The construct validity of FIBSER-C was examined by confirmatory factor analysis; internal consistency was evaluated using Cronbach's alpha (α); convergent and divergent validity were assessed by examining its association with depression severity and functioning measures. FIBSER-C showed a single-factor structure, with standardized item loadings of 0.73, 0.83, and 0.89. The scale showed good internal consistency (Cronbach's α = 0.85). The FIBSER-C total score was weakly and positively associated with total PHQ-A, Patient-Reported Outcomes Measurement Information System (PROMIS)-Pain, PROMIS-Pain Severity, and PROMIS-Fatigue and was weakly and inversely associated with PROMIS-Physical Function. The FIBSER-C had has good internal consistency and a single-factor solution. The associations between side effect burden and depression severity, as well as functioning domains, were weak. Further research should explore the consistency and stability of the scale over time.

Aggression and irritability are common challenges in children with autism spectrum disorder (ASD), often requiring pharmacological management. Divalproex, an anticonvulsant and mood stabilizer, is used off-label for these symptoms, but its effectiveness remains unclear. This systematic review evaluates the efficacy and safety of divalproex in managing aggression and irritability in children with ASD. A systematic review was conducted following PRISMA guidelines, registered with PROSPERO (CRD420251029754). Searches were performed in PubMed, Embase, PsycINFO, and Web of Science, identifying studies involving children with ASD treated with divalproex, valproic acid, or valproate sodium. Data were extracted on study design, sample size, intervention details, outcomes, and adverse effects. Ten studies met inclusion criteria, comprising three randomized controlled trials, one open-label trial, and six case reports. Intravenous (IV) divalproex demonstrated rapid reductions in aggression, suggesting potential for acute stabilization. However, oral divalproex produced inconsistent results for chronic aggression and irritability. Adverse effects included weight gain, sedation, and behavioral activation, with toxicity risks in polypharmacy settings. Divalproex may offer value for acute management of aggression in children with ASD when administered intravenously. Its role in chronic management is less clear, with inconsistent outcomes and notable side effects. Clinicians should prioritize regular serum monitoring and consider alternative options for chronic use. Further research is needed to clarify its clinical role, particularly in diverse patient populations.

Children with intellectual disability (ID) are more susceptible to adverse effects from standard psychiatric medications, often necessitating the use of off-label treatments. In the limited studies to date, Clonidine has displayed evidence of benefit in treating attention-deficit/hyperactivity disorder (ADHD), sleep onset difficulties, behaviors that challenge, and tics. This naturalistic study involved a cross-sectional survey completed by 4 consultant psychiatrists, detailing 50 children with ID treated with Clonidine over a 3-year period. Data collected included treatment indications, dosage, and retrospective Developmental Disabilities Modification of Children's Global Assessment Scalescores to evaluate functioning before treatment and again 6-12 months later. Among children who remained stable on Clonidine, ordinal regression analyses revealed that total Clonidine dose, level of ID, concomitant medications, and comorbid diagnoses significantly predicted improved functioning at 2 months, which was sustained after 1 year of treatment with Clonidine. Clonidine is useful to treat ADHD, sleep difficulties, tics, and behaviors that challenge. Clonidine was generally well tolerated and appears to be an effective treatment option for children with ID. This will inform the clinical practice of both pediatricians and psychiatrists who support and treat children with ID.

This randomized controlled pilot trial examined whether adjunctive triple chronotherapy (TCT) in adolescents hospitalized with major depressive disorder (MDD) was (1) feasible, and (2) suggested to be more effective in managing depression and accompanying symptoms at 60 days postdischarge, compared to adolescents with depression who received treatment-as-usual (TAU). TCT participants underwent sleep deprivation for up to 36 hours, sleep phase advancement for four days, and daily exposure to light therapy. Both arms received medication management and group therapy during the inpatient stay. Outpatient visits occurred on Days 7/10, 30, and 60. Outcomes included depression, anxiety, insomnia, self-harm, suicidality, and quality of life. Sixty-four adolescents were enrolled, 32 into TCT, 32 into TAU. The mean age was 15 years, the majority were female, Caucasian, and non-Hispanic/non-Latino. Compared to baseline, both TCT and TAU participants showed a significantly lower Patient Health Questionnaire-Adolescent (PHQ-A) score by Day 4 (TCT: = 31, =20.4 ± 3.54 vs. = 17, =9.12 ± 6.98, < 0.001; TAU: = 32; =20.1 ± 3.99 vs. = 10; =8.6 ± 5.93, < 0.001) and by Day 60 (TCT: = 11, =7.45 ± 5.22, < 0.001; TAU: = 14, =13.36 ± 7.25, < 0.001). For between-group differences, TCT participants reported significantly lower PHQ-A scores at Day 60 compared to TAU participants ( = 11, =7.45 ± 5.22 vs. = 14, =13.36 ± 7.25, = 0.03). Anxiety and insomnia were significantly lower at treatment end in the TCT arm ( = 11, =1.91 ± 1.97 vs. = 14; =4.64 ± 2.79, = 0.009) and ( = 11, =6.55 ± 6.64 vs. = 14; =12.21 ± 6.76, = 0.05), respectively. Retention was a challenge; approximately 2/3 of the sample dropped out by study end. TCT is a potentially effective adjunctive treatment for MDD in adolescents.

The use of psychotropic medication among children and adolescents has increased, but long-term studies on inpatients are scarce. In Finland, nationwide inpatient data among children and adolescents (<18 years) were collected on one day from three different years, 2000, 2011, and 2018. Medication use was analyzed according to medication groups, individual medications, and the number of medications. Additional information included diagnoses and severity measures of suicidality, violence, and functional impairment. Logistic regression was used to analyze the changes between 2000 and 2018 and between 2011 and 2018. The most robust increase was observed in attention-deficit/hyperactivity disorder medications (between 2000 and 2018 odds ratio [OR]: 21.74, 95% confidence interval [CI]: 7.75-58.82 and between 2011 and 2018 OR: 2.20, 95% CI: 1.37-3.52), followed by antipsychotics (OR: 3.15, 95% CI: 2.34-4.24 and OR: 1.35, 95% CI: 1.02-1.81, respectively), and antidepressants (between 2000 and 2018 OR: 1.87, 95% CI: 1.36- 2.57). The use of benzodiazepines decreased notably between 2011 and 2018 (OR: 0.09, 95% CI: 0.03-0.22). When diagnoses and severity measures were included in the multivariate analysis, the increases were associated with respective diagnoses, being adolescent, and the severity of the condition. Medication use increased vastly between 2000 and 2018, but levelled off between 2011 and 2018. Explanations include changes in clinical practices, the surface of new medications, increased awareness of neuropsychiatric disorders, and the replacement of benzodiazepines. More information on the long-term effects of increased use of antipsychotics and multi-medication is warranted.