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 thes...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...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.
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...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.
J Child Adolesc Psychopharmacol
· 2025 Oct · PMID 40658025
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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 encompassi...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.
Investigators and government agencies have expressed concern about the high percentage of foster youth who receive psychotropic medication, the number of psychotropic medications prescribed, and the extended duration for...Investigators and government agencies have expressed concern about the high percentage of foster youth who receive psychotropic medication, the number of psychotropic medications prescribed, and the extended duration for which many foster youth receive psychotropic medication. One contributor to the duration of medication use is the absence of clear guidelines for de-prescribing in pediatric psychiatry. The present study evaluated whether medication review letters crafted by medical professionals and sent to caregivers prompted a reduction in psychotropic medication in foster youth. The caretaker or caseworker of 52 foster children, 38 males, under 16 years of age, who received medication through Medicaid, was sent a letter assessing the use of psychotropic medication and identifying areas of concern. Recipients were encouraged to discuss the letter with the child's prescriber. These children had been referred to a university-affiliated organization that provided behavioral interventions to other children, but the children in the present study did not receive behavioral interventions from the organization. The use of psychotropic medication was assessed for 18 months before and 24 months after the letter was sent. The control group had comparable demographics and medication-use parameters. The trajectories of medication count before and after a letter (for cases) or a "phantom" letter (for controls) was sent were compared. The medication review letter precipitated a decrease in medication count over the year after the letter was sent for 9- to 12-year-olds. For 13- to 16-year-olds, an increasing trend in medication use was halted. No effect was seen for 5- to 8-year-olds. No such changes occurred in the control groups. A single personalized letter, tailored to a child's medication list, was provided to caregivers to share with prescribers. This decreased or halted an increase in the use of psychotropic medications for children in foster care who were 9 years old or older.
Current standards for treatment of anorexia nervosa (AN) in children and adolescents include Family-Based Treatment and nutrition restoration. The use of aripiprazole for AN has been detailed through case series and one...Current standards for treatment of anorexia nervosa (AN) in children and adolescents include Family-Based Treatment and nutrition restoration. The use of aripiprazole for AN has been detailed through case series and one retrospective review analyzing the change in outcomes on body mass index and weight restoration. The goal of this descriptive study was to evaluate the impact of aripiprazole on food avoidant behaviors (FABs) and to describe prescribing patterns, including dosing and tolerability. This was a retrospective, descriptive, matched, cohort study of pediatric patients with AN admitted to an eating disorders program (EDP) between January 1, 2018, and December 31, 2023. Patients were included in this study if they had a diagnosis of AN and were started on aripiprazole for eating disorder cognitions. Patients were matched 1:2 to a control group based on age, sex, and length of stay. A total of 42 patients on aripiprazole were analyzed and matched to 84 controls. Aripiprazole was associated with a reduction in FABs with a mean change over the evaluated time period of 3.5 versus 0.9 ( = 0.026). The mean starting dose of aripiprazole was 1.9 mg/day, with a mean discharge dose of 2.8 mg/day. Aripiprazole was overall well-tolerated. Aripiprazole was associated with an improvement in FABs among children and adolescents admitted to an EDP. Additionally, low-dose aripiprazole improved weight, likelihood of achieving target weight, and was well-tolerated.
Obsessive compulsive disorder (OCD) is a chronic psychiatric condition that significantly impairs various domains, including social, academic, and overall functioning. While antidepressants and psychotherapy-specifically...Obsessive compulsive disorder (OCD) is a chronic psychiatric condition that significantly impairs various domains, including social, academic, and overall functioning. While antidepressants and psychotherapy-specifically cognitive behavioral therapy-are the standard first-line treatments, there is considerable variability in the use of augmenting agents, particularly antipsychotics. This study examines treatment patterns in children and adolescents with OCD. This population-based retrospective cohort study utilized the TriNetX research network to identify patients aged 6-18 with an OCD diagnosis (F42, = 37,355). Treatment patterns were analyzed based on sociodemographic factors (age, gender, and race/ethnicity) and clinical settings (inpatient vs. outpatient). Odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated, with Cox proportional hazards models used to adjust for potential confounders. The average age of OCD diagnosis in youth was 10.9 years, with a balanced gender distribution. Psychiatric comorbidities were common, particularly anxiety disorders (53%), attention-deficit hyperactivity disorder (47%), and mood disorders (37%). Antidepressants were prescribed to 55% of patients, with sertraline and fluoxetine being the most common, while 22% were prescribed antipsychotics, primarily aripiprazole and risperidone. In addition, 31% had billable therapy codes. Racial and ethnic minority groups received less treatment overall, with lower odds of receiving antidepressants (OR 0.51-0.74) and therapy (OR 0.75) among Black youth. In contrast, Black youth were more likely to be prescribed antipsychotics (OR 1.18). Among those prescribed antipsychotics, 47% had prior antidepressant use, 22% had billed psychotherapy, and only one-sixth had both before starting antipsychotics. Inpatient hospitalization, as an indicator of symptom severity, was strongly associated with antipsychotic prescriptions (adjusted HR: 3.03, 95% CI: 2.85, 3.21). There is considerable variability in the pharmacological management of pediatric OCD, with frequent use of antipsychotics even before first-line treatments. The low utilization of psychotherapy suggests gaps in adherence to evidence-based care. These findings highlight the need for improved adherence to OCD treatment guidelines, with a focus on increasing access to psychotherapy.
J Child Adolesc Psychopharmacol
· 2025 Dec · PMID 40485273
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To describe the rates and predictors of youth and parent satisfaction following engagement in one of three evidence-based treatments or a placebo control for youth anxiety. In a multisite randomized controlled trial (RC...To describe the rates and predictors of youth and parent satisfaction following engagement in one of three evidence-based treatments or a placebo control for youth anxiety. In a multisite randomized controlled trial (RCT) of youth ages 7-17 ( = 426) and parents ( = 429) comparing cognitive behavioral therapy (CBT), sertraline (SRT), the combination of the two (COMB), and placebo (PBO), we examined satisfaction at the end of acute treatment and assessed predictors including clinical change, pretreatment expectations, reactions to treatment assignment, and therapeutic relationship using multiple hierarchical linear regressions. Satisfaction was high across all treatments. Both parents and youth reported the highest satisfaction with COMB, followed by CBT and SRT, and the least satisfaction with PBO. Parents were more satisfied than youth, and remitters were more satisfied than nonremitters. In CBT-containing arms, a stronger child-therapist relationship at week 6 predicted greater parent and youth satisfaction. Higher expectations of improvement at pretreatment predicted greater youth, but not parent, satisfaction in CBT and SRT. Posttreatment, youth and parents report greater satisfaction with combination therapy over the monotherapies and PBO. Satisfaction patterns largely mirror clinical outcomes. An early strong youth-reported therapeutic alliance is key to satisfaction in CBT, highlighting the importance of child-therapist alignment when selecting anxiety treatments.
The objective of this review is to review existing evidence on the management and prevention of agitation and aggression in the pediatric psychiatric inpatient setting with emphasis on general unit structure, organizatio...The objective of this review is to review existing evidence on the management and prevention of agitation and aggression in the pediatric psychiatric inpatient setting with emphasis on general unit structure, organization, and milieu programming when discussing prevention. For management of agitation and aggression, the review focuses on de-escalation, as-needed medication, and restraint and seclusion. The existing literature search was conducted, yielding 1836 English language citations. An additional 109 studies were identified by citation search. Among them, 287 full-text studies were assessed for eligibility, and 107 studies were included for review. Studies were included if the contents of studies were shown to prevent agitation or aggression in pediatric psychiatric inpatient units, with focuses on staffing, staff training, milieu programming, and environmental changes. Studies were also included if the contents of studies discussed management of agitation and aggression with focuses on de-escalation, restraint and seclusion, and as-needed medication use. We recognized multiple challenges while summarizing existing evidence in our field, including lack of definition, knowledge, and standardized measurement of agitation and aggression. Challenges further extend to heterogeneity and a constellation of small studies that are not controlled. However, existing evidence supports that management and prevention of agitation and aggression start with attention to staffing, staff training, and milieu programming. Evidence for the use of as-needed (pro re nata) medication for the management of agitation and aggression in pediatric populations is limited.
Cuellar A, Henry ME, Smith JR
… +3 more, Turner K, Horvath R, Luccarelli J
J Child Adolesc Psychopharmacol
· 2025 Sep · PMID 40387601
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Electroconvulsive therapy (ECT) is an effective treatment for severe and treatment-resistant psychiatric disorders, particularly depression and catatonia. ECT requires intravenous (IV) access, which can pose a barrier fo...Electroconvulsive therapy (ECT) is an effective treatment for severe and treatment-resistant psychiatric disorders, particularly depression and catatonia. ECT requires intravenous (IV) access, which can pose a barrier for pediatric patients and those with neurodevelopmental disorders who may have difficulty tolerating IV placement. This case series highlights individualized pharmacologic and nonpharmacologic strategies that facilitate IV placement in pediatric and neurodivergent patients receiving ECT. We reviewed the medical records of five patients aged 14-27 who required ECT but experienced barriers to tolerating IV placement and described strategies used to overcome these limitations. We describe five strategies: (1) oral anxiolytic premedication, (2) planned physical restraint, (3) intramuscular (IM) ketamine induction, (4) inhalational sevoflurane anesthesia, and (5) placement of an implanted venous access device. Using these strategies, all patients were able to tolerate IV placement and ECT treatment. Consistent treatment protocols, multidisciplinary planning, and engagement of outpatient care teams facilitated the success of these interventions. Pediatric and neurodivergent patients face unique barriers to ECT, particularly related to IV placement. Our case series demonstrates that individualized, multidisciplinary approaches can enable successful ECT treatment. These findings underscore the importance of adaptive strategies to promote health equity and ensure access to effective psychiatric interventions in special needs populations.
Multiple factors influence symptom severity in Attention Deficit/Hyperactivity Disorder (ADHD). We examined four of these: diet, sleep hygiene, exercise, and lighting, in the International Collaborative ADHD Neurofeedbac...Multiple factors influence symptom severity in Attention Deficit/Hyperactivity Disorder (ADHD). We examined four of these: diet, sleep hygiene, exercise, and lighting, in the International Collaborative ADHD Neurofeedback (ICAN) randomized clinical trial, which found large significant improvement with both active neurofeedback and control condition without treatment difference. A total of 142 participants aged 7-10 had breakfast and lunch intake and exercise recorded at each neurofeedback session. Parents completed the Children's Sleep Habits Questionnaire (CSHQ). Parents and teachers rated inattention on Conners3. Lifestyle changes were correlated with inattention changes. At baseline, CSHQ correlated with parent-rated inattention ( = 0.17, = 0.04), and length of sleep correlated with teacher-rated inattention ( = 0.20, = 0.03). From baseline to treatment end food group variety ( = 0.029, = 0.22) and sleep problems ( < 0.0001, d = -0.49) improved significantly, exercise time and protein intake marginally ( = 0.06 - 0.08). Parent-rated inattention improvement correlated with CSHQ improvement (Rho = 0.26, = 0.002) and marginally with protein intake increase (Rho = 0.18, = 0.06). The three components of the light-emitting-diode (LED)-induced circadian pathway hypothesis were significant. Most measures improved, but few significantly. How much they impact classroom attention remains unclear. Although parent ratings of inattention improvement correlated with sleep problems improvement, composited parent/teacher ratings (primary outcome) did not. The circadian pathway hypothesis associated with LED lighting was supported. These findings warrant further studies examining the role sleep hygiene can play in improving ADHD symptoms. Meanwhile, attention to sleep hygiene seems appropriate in any treatment plan for ADHD.
Randomized controlled trials (RCTs) are the gold standard for evaluating medication efficacy. The absence of a universal definition of treatment response, based on the degree of symptom improvement measured by standardiz...Randomized controlled trials (RCTs) are the gold standard for evaluating medication efficacy. The absence of a universal definition of treatment response, based on the degree of symptom improvement measured by standardized rating scales in the field of attention-deficit/hyperactivity disorder (ADHD), makes it difficult to compare treatment outcomes across RCTs. Here, we aimed to assess to what extent and how "treatment response" is defined across RCTs of ADHD medications. We identified eligible RCTs via the MED-ADHD database (https://med-adhd.org/), which compiles RCTs evaluating the efficacy and safety of pharmacological treatments for children, adolescents, and adults with ADHD, based on a comprehensive search in multiple electronic databases, including PubMed, BIOSIS Previews, CINAHL, the Cochrane Central Registry of Controlled Trials, and EMBASE, up to 17 January 2025, alongside additional unpublished information gathered from manufacturers/study authors. Out of 167 RCTs in MED-ADHD, 88 defined treatment response based on reductions in ADHD core symptom severity using rating scale scores. The most frequently used threshold was a ≥30% reduction in attention-deficit/hyperactivity disorder (ADHD-RS) scores, with other RCTs using ≥25%, ≥40%, or ≥50%. In addition, RCTs applied similar cutoff values to alternative scales, including Conner's Adult ADHD Rating Scale, SNAP-IV, Adult ADHD Investigator Rating Scale, and Wender-Reimherr Adult Attention Deficit Disorder Scale. However, 79 studies did not specify any response threshold. Our review underscores and quantitatively defines the inconsistency in the definition of treatment response across ADHD medication trials, highlighting the urgent need for the field to reach a consensus on the use of a standardized definition of "treatment response" for each rating scale, based on the percentage reduction in ADHD core symptom severity.
Smith JR, Sengstack DG, McCoy AB
… +5 more, Lim S, Marler S, Williams ZJ, Hossain N, Luccarelli J
J Child Adolesc Psychopharmacol
· 2025 Sep · PMID 40302606
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Catatonia is a highly morbid psychomotor disorder that impacts autistic adults and children. There is very little literature that describes outpatient catatonia management practices, none of which discusses the use of th...Catatonia is a highly morbid psychomotor disorder that impacts autistic adults and children. There is very little literature that describes outpatient catatonia management practices, none of which discusses the use of the electronic health record (EHR). Thus, we conducted this study to analyze patient messages in a specialized catatonia clinic. We conducted a retrospective analysis of messaging practices in the EHR for patients in a specialized clinic with autism and catatonia from July 1, 2021, to May 31, 2024. Catatonic symptom severity was recorded via the Bush Francis Catatonia Rating Scale (BFCRS), Kanner Catatonia Severity Scale (KCS), and Kanner Catatonia Examination (KCE). We conducted Spearman and Pearson correlation coefficients to determine whether a relationship exists between the frequency of patient messages, catatonic symptoms, and length of follow-up. A total of 12,972 messages were sent to the health system or received by the patient or their family. Of those, 6375 (49.1%) messages were sent from the family to the health system. Relationships between message frequency to the health system and all baseline catatonia severity scores (BFCRS, KCS, KCE) were not statistically significant, although message frequency was strongly associated with length of follow-up ( = 0.65, < 0.001). A total of 5555 (42.8%) messages were sent directly to or received from providers in the catatonia specialty clinic. The rate of messages to providers in the catatonia clinic was 2.9 messages/day. The frequency of patient messaging was high in this catatonia specialty clinic. Health systems should consider this possibility when planning for similar service lines.