Revisiting stimulant use for emotional dysregulation in attention-deficit/hyperactivity disorder (ADHD).

INTRODUCTION: Emotional dysregulation (ED) symptoms are present in a considerable portion of patients with attention-deficit/hyperactivity disorder (ADHD). In recent years, an increasing number of studies investigated the effects of stimulant medications on ED in patients with ADHD. AREAS COVERED: A narrative review of the literature on stimulant treatment for ED is provided, including controlled and observational clinical studies conducted on pediatric and adult samples and neurobiological investigations. Positive effects of stimulants on irritability have been demonstrated in children. Comorbidity with disruptive behavior disorders (DBD) and disruptive mood dysregulation disorder does not prevent stimulant effectiveness. Methylphenidate has also been found to reduce temper problems, affective instability, and emotional over-reactivity in adults with ADHD, although with variable effect sizes. A variety of adverse emotional effects have been reported, especially at high doses and in special populations. However, several possible confounders of treatment-emergent ED have been highlighted. Finally, according to neuroimaging studies, stimulants may mitigate emotional processing anomalies associated with ADHD. EXPERT OPINION: The findings are consistent with models including ED within the core features of ADHD. Stimulant treatment should be prioritized over antipsychotics in ADHD-DBD. It remains to be elucidated whether other medications may be more effective in specific populations with ADHD and/or ED.

Systematic Review and Meta-analysis: Pharmacological and Nonpharmacological Interventions for Persistent Nonepisodic Irritability.

OBJECTIVE: This meta-analysis examined the efficacy of available pharmacological and nonpharmacological interventions for irritability among youth with autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), disruptive behavior disorders (DBD), disruptive mood dysregulation disorder (DMDD), and/or severe mood dysregulation (SMD). METHOD: Literature searches were conducted in October 2020, resulting in 564 abstracts being reviewed to identify relevant papers, with 387 articles being reviewed in full. A random effects model was used for the meta-analysis, with subgroup meta-regressions run to assess effects of study design, intervention type, medication class, and clinical population. RESULTS: A total of 101 studies were included (80 pharmacological, 13 nonpharmacological, 8 combined). Despite high heterogeneity in effects (I2 = 94.3%), pooled posttreatment effect size for decreasing irritability was large (Hedges' g = 1.62). Large effects were found for pharmacological (g = 1.85) and nonpharmacological (g = 1.11) interventions; moderate effects were found for combined interventions relative to monotherapy interventions (g = 0.69). Antipsychotic medications provided the largest effect for reducing irritability relative to all other medication classes and nonpharmacological interventions. A large effect was found for youth with ASD (g = 1.89), whereas a medium effect was found for youth with ADHD/DMDD/DBD/SMD (g = 0.64). CONCLUSION: This meta-analysis provides a comprehensive review of interventions targeting persistent nonepisodic irritability among youth with various psychiatric disorders. Strong evidence was found for medium-to-large effects across study design, intervention type, and clinical populations, with the largest effects for pharmacological interventions, particularly antipsychotic medications and combined pharmacological interventions, and interventions for youth with ASD.

Pharmacotherapy of Disruptive Behaviors in Children with Intellectual Disabilities.

Disruptive behaviors are a class of predominantly externalizing behaviors that include physical aggression, property destruction, temper outbursts, verbal aggression, and some forms of self-injurious behaviors. Externalizing behaviors are also major components of disruptive, impulse-control and conduct disorders, disruptive mood dysregulation disorder, trauma-related and stressor-related disorders, intermittent explosive disorder, personality disorders, and other neuropsychiatric and neurodevelopmental disorders. Disruptive behaviors and associated disorders are among the most frequent reasons for child behavioral health referrals and are the most common reason for referrals among children with intellectual disabilities. The focus of this paper is on the adjunctive role of integrated psychopharmacological treatment in the management of children with disruptive behaviors and co-occurring intellectual disabilities. The decision-making process for adding pharmacotherapy to a comprehensive treatment plan incorporates not only a working knowledge of basic behavioral neurobiology of disruptive behaviors but also an understanding of the strengths and weaknesses of various pharmacotherapies. Importantly, there is little evidence to support the use of psychopharmacologic agents in managing difficult behaviors in children with intellectual disabilities, but with that said, risperidone has the strongest evidence base for its use.

Trends in antipsychotic use for youth with attention-deficit/hyperactivity disorder and disruptive behavior disorders.

PURPOSE: To examine trends in off-label antipsychotic use for youth with attention-deficit/hyperactivity disorder with and without a comorbid disruptive behavior disorder. METHOD: This cross-sectional study of annual trends from 2007 through 2015 used the IQVIA PharMetrics® Plus for Academics data. We identified 165 794 commercially-insured youth 3-18-year-old who had a diagnosis of attention-deficit/hyperactivity disorder and classified them into subgroups with and without disruptive behavior disorders comorbidities. Antipsychotic use, with or without a stimulant, was the primary dependent outcome. Logistic regression estimated the odds of antipsychotic use associated with comorbid attention-deficit/hyperactivity disorder and disruptive behavior disorders, adjusting for age, sex, study year, and other psychotropic use. RESULTS: Over 70% of the 165 794 youth with attention-deficit/hyperactivity disorder were 5-14-year-old and male, and 12% had disruptive behavior disorders. Antipsychotic prevalence, with or without a stimulant, was 4.4% in 2007 and 3.4% in 2015. Stimulants with antipsychotics increased significantly from 2007 to 2015 for females (19.5%-28.7%) and youth 15-18-year-old (25.9%-32.7%). Adjusting for age, sex, study year, and other psychotropic use, youth with a comorbid disruptive behavior had a 2.5 (95% CI: 2.3, 2.7) higher likelihood of receiving an antipsychotic than youth with attention-deficit/hyperactivity disorder and no comorbidities. CONCLUSIONS: Antipsychotic use was associated with comorbid disruptive behaviors in youth with attention-deficit/hyperactivity disorder. Off-label antipsychotic use has increased for females and older adolescents.

Antipsychotic medications and admission to psychiatric residential treatment facilities among youth in foster care diagnosed with disruptive behavior disorders.

Many youth in foster care are diagnosed with disruptive behavior disorder (DBD), a diagnosis indicative of aggression and behavior problems. These youth, who are at high risk for being placed in psychiatric residential treatment facilities (PRTF), are commonly prescribed antipsychotic (AP) medications off-label. However, treating children in the community is an important goal, and although AP medications can have severe side effects, these prescriptions may help to achieve this goal. In this study, we used Medicaid data to determine whether AP medications reduce the risk of admission to PRTF among two groups of children with DBD: those with DBD only and those who were diagnosed with DBD in addition to at least one of two conditions indicated for AP prescribing (psychosis and bipolar disorder.) Event history models show that AP medications are associated with a high rate of admission, which are likely due to the higher mental and behavioral health needs of youth who are prescribed. However, youth diagnosed with both DBD and indications who are prescribed an AP medication have one-tenth the rate of admission of similar youth who are not prescribed. For youth with DBD only, the findings are inconclusive. Given these mixed results, practitioners should follow clinical guidelines; ensuring youth are treated with psychosocial interventions and other psychotropic medications prior to AP prescribing. Agencies should attempt to address systemic factors such as shortages of foster homes, increased availability of therapeutic foster care, and implementation of in-home prevention services. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Diagnostic Trends and Prescription Patterns in Disruptive Mood Dysregulation Disorder and Bipolar Disorder.

OBJECTIVE: Disruptive mood dysregulation disorder (DMDD) was introduced in DSM-5 to distinguish a subset of chronically irritable youth who may be incorrectly diagnosed and/or treated for pediatric bipolar disorder (BPD). This study characterized the rate of new treatment episodes and treated prevalence of BPD and DMDD from a longitudinal electronic health record database and examined the impact of DMDD on prescription trends. METHOD: A retrospective cohort study using 2008-2018 Optum electronic health record data was conducted. Youth aged 10 to < 18 years with ≥ 183 days of database enrollment before the study cohort entry were included. Annual new treatment episode rates per 1,000 patient-years and treated prevalence (%) were estimated. Prescriptions for medications, concomitant diagnoses, and acute mental health service use for 2016-2018 were evaluated. RESULTS: There were 7,677 youths with DMDD and 6,480 youths with BPD identified. Mean age (13-15 years) and ethnicity were similar for both groups. A rise in new treatment episode rates (0.87-1.75 per 1,000 patient-years, p < .0001) and treated prevalence (0.08%-0.35%, p < .0001) of DMDD diagnoses (2016-2018) following diagnosis inception was paralleled by decreasing new treatment episode rates (1.22-1.14 per 1,000 patient-years, p < .01) and treated prevalence (0.42%-0.36%, p < .0001) of BPD diagnoses (2015-2018). More youth in the DMDD group were prescribed medications compared with the BPD group (81.9% vs 69.4%), including antipsychotics (58.9% vs 51.0%). Higher proportions of youth with DMDD vs youth with BPD had disruptive behavior disorders (eg, 35.9% vs 20.5% had oppositional defiant disorder), and required inpatient hospitalization related to their mental health disorder (45.0% vs 33.0%). CONCLUSION: Diagnosis of DMDD has had rapid uptake in clinical practice but is associated with increased antipsychotic and polypharmacy prescriptions and higher rates of comorbidity and inpatient hospitalization in youth with a DMDD diagnosis compared with a BPD diagnosis.

Editorial: Safer Use of Antipsychotics in Youth (SUAY): Should Treatment Be Guided by Symptoms?

Child and adolescent psychiatrists have company as they wrestle with clinical decision making regarding when it is appropriate to prescribe an antipsychotic. Pediatricians face a similar challenge in trying to determine under what circumstances to prescribe an antibiotic. Both classes of medications are powerful and can be lifesaving, but they are not without the risk of associated adverse events and cumulative exposure. Concerns regarding the widespread use of antipsychotics in children and adolescents have been supported by national trends indicating predominance of prescriptions for conditions (attention-deficit/hyperactivity disorder, conduct disorder, oppositional defiant disorder, and impulsive aggression)1,2 other than those approved by the U.S. Food and Drug Administration (psychotic disorders, bipolar disorder with mania, irritability associated with autism spectrum disorder, and tic disorders); the risks of weight gain, diabetes mellitus, and other adverse effects to which youths appear to be more vulnerable than adults3; and potential disparities related to the absence of race and ethnicity in large administrative datasets.4 Previous studies of antipsychotic prescribing patterns predate the widespread use of the diagnosis of disruptive mood dysregulation disorder. A recent study found that 58.9% of youths given a diagnosis of disruptive mood dysregulation disorder were prescribed antipsychotics compared with 51% of youths with a diagnosis of bipolar disorder.5 In this issue of the Journal, Penfold et al.6 report on a novel approach to antipsychotic prescribing focused on symptoms rather than diagnoses developed as the initial phase of a pragmatic clinical trial, Targeted and Safer Use of Antipsychotics in Youth (SUAY), funded by the National Institute of Mental Health and designed to test the effectiveness of targeted interventions on the use of antipsychotics for youth 4 to 17 years old in large health care systems. We offer some perspectives on differences that distinguish this approach; the process used in its development; and its promise, potential pitfalls, and policy and clinical implications.

Neural Responses to Fluoxetine in Youths with Disruptive Behavior and Trauma Exposure: A Pilot Study.

Objective: A preliminary investigation of the impact of a serotonergic agent (fluoxetine) on symptom profile and neural response in youths with disruptive behavior disorders (DBDs) and a history of trauma exposure. Methods: There were three participant groups: (i) Youths with DBDs and trauma exposure who received fluoxetine treatment for 8 weeks (n = 11); (ii) A matched group of youths with DBDs and trauma exposure who received routine regular follow-up in an outpatient clinic (n = 10); and (iii) Typically developing youths (n = 18). All participants conducted an expression processing functional magnetic resonance imaging task twice, 8 weeks apart: (pretreatment and post-treatment for youths with DBDs). Results: Youths with DBDs and trauma exposure who received fluoxetine treatment compared to the other two groups showed: (i) significant improvement in externalizing, oppositional defiant disorder, irritability, anxiety-depression, and trauma-related symptoms; (ii) as a function of fearful expression intensity, significantly decreased amygdala response and increased recruitment of regions implicated in top-down attention control (insula cortex, inferior parietal lobule, and postcentral gyrus) and emotional regulation (ventromedial prefrontal cortex [vmPFC]); and (iii) correlation between DBD/irritability symptom improvement and increased activation of top-down attention control areas (inferior parietal lobule, insula cortex, and postcentral gyrus) and an emotion regulation area (vmPFC). Conclusions: This study provides preliminary evidence that a serotonergic agent (fluoxetine) can reduce disruptive behavior and mood symptoms in youths with DBDs and trauma exposure and that this may be mediated by enhanced activation of top-down attention control and emotion regulation areas (inferior parietal lobule, insula cortex, and vmPFC).

National clinical guideline for assessment and treatment of ADHD in children and young people: quick guide

Professional observers are independent persons who have in-depth knowledge of both children's normal behaviour and development and of ADHD, and who take a multidisciplinary approach to ADHD in their daily work. The observation must be geared to the specific problem with the child in question

Moderators of Treatment for Pediatric Bipolar Spectrum Disorders.

Objective: We review the current limited research on pediatric bipolar spectrum disorder (BPSD) treatment moderators..Method: Four pharmacotherapy and nine psychotherapy moderator studies in youth with pediatric BPSD is summarized.Results: Two pharmacotherapy studies suggest that younger children and those with more aggression fare worse. Regarding preferential outcomes, one study found that older youth respond better to lithium than younger youth; all youth, regardless of age, respond similarly to valproate. One study found non-obese youth and those with comorbid attention deficit hyper-activity disorder respond better to risperidone than lithium. Results are mixed for psychosis and disruptive behavior disorders on risperidone compared to divalproex. Tentatively, youth with generalized anxiety are more likely to respond to valproate while youth with panic preferentially respond to lithium. Psychotherapy findings from two studies suggest that sex, age, race, baseline mania, and past-month suicidal ideation/non-suicidal self-injury do not moderate outcomes. Although not replicated, higher baseline inflammatory markers are associated with greater decreases in depressive symptoms; baseline higher self-esteem and comorbid attention deficit hyperactivity disorder are associated with steeper decreases in (hypo)manic symptoms.Conclusions: Findings are mixed on the role of baseline mood severity, other comorbid disorders, parental depression, family income, and expressed emotion in moderating treatment outcomes. Replication of these possible moderators is needed for both pharmacotherapy and psychotherapy interventions before conclusive results can be determined. Examination of larger samples of youth with BPSD and longer duration follow-up are needed to clarify meaningful treatment moderators.

Effect of relative age on childhood mental health: A cohort of 9,548,393 children and adolescents.

BACKGROUND: The effect of relative age on the diagnoses of attention deficit hyperactivity disorder (ADHD), disruptive behavior disorder (DD), anxiety disorder, and depressive disorder and the prescription for ADHD and antidepressant medications remains unclear. AIM: To clarify the impact of relative age in a school year with the diagnoses of ADHD, DD, anxiety disorder, and depressive disorder and the prescription for ADHD and antidepressant medications. METHODS: The annual cutoff birthdate for entry to school in Taiwan is August 31. The Taiwan National Health Insurance Research Database was used to enroll 9,548,393 children and adolescents aged 3-17 years during the study period (September 1, 2001, to August 31, 2011). The Poisson regression model was performed to examine the likelihood of receiving diagnoses of ADHD, DD, anxiety disorder, and depressive disorder, as well as the prescription of ADHD and antidepressant medications among children born in August (the youngest) and September (the oldest). RESULTS: Both boys and girls born in August had a higher risk of being diagnosed as having ADHD (odds ratio [OR] = boys: 1.65, girls: 1.80), DD (1.29, 1.45), anxiety disorder (1.49, 1.33), and depressive disorder (1.10, 1.10). Furthermore, children born in August were more likely to be prescribed ADHD medication (1.71, 1.72) and antidepressants (1.18, 1.09) compared with those born in September. DISCUSSION: Relative age, as an indicator of neurocognitive maturity, is a critical factor for the likelihood of being diagnosed as having ADHD, DD, anxiety disorder, and depressive disorder among children and adolescents.

Use of Antipsychotics: The Experiences, Views, and Monitoring Practices of Child and Adolescent Psychiatrists in Turkey.

Objectives: The aim of this study is to evaluate the antipsychotics prescribed by child psychiatrists and their applications on the follow-up of these drugs. Methods: The universe of this research included consultant physicians and child psychiatry residents working in the field. A questionnaire has been created that assesses the use of antipsychotics and follow-up processes of physicians. The survey involved 19 questions. Contents of the survey were sociodemographic data, short-term and long-term follow-up of antipsychotic drugs, side-effect intervention strategies, and diagnoses of the most commonly preferred antipsychotic medications. The survey was delivered via e-mail and sent as a message to the child and adolescent psychiatrists in Turkey. Results: One hundred sixty-one physicians working in the field of child and adolescent psychiatry participated in the study. Aripiprazole (32.2%), risperidone (30.4%), and quetiapine (14.9%) were three most commonly prescribed antipsychotics. Disruptive behavior-related disorders (28.9%), behavior problems related to autism spectrum disorder (20.7%), behavior problems related to intellectual disability (14.5%), and attention-deficit/hyperactivity disorder (12.4%) were the most common diagnoses requiring antipsychotics medications. Before starting antipsychotic treatment, the most commonly evaluated parameters were body mass index (BMI) (47.2%), waist circumference (10.5%), blood pressure (28.5%), lipid profile (37%), and blood glucose level (41.6%). When the evaluations made at least in a year after starting antipsychotic drug therapy were examined, 80.2% of physicians reported blood glucose, 79.6% lipid profile, 65.7% BMI, 59.1% blood pressure, and 26.6% waist circumference measurement almost always done. Conclusions: The results showed that the adherence to recommendations in guidelines for the screening of antipsychotic-related side effects was low. This study suggests that interventions should be made about antipsychotic monitoring training to physicians.

In Ataxia-Telangiectasia, Oral Betamethasone Administration Ameliorates Lymphocytes Functionality through Modulation of the IL-7/IL-7Rα Axis Paralleling the Neurological Behavior: A Comparative Report of Two Cases.

Ataxia-Telangiectasia (A-T) is characterized by cerebellar neurodegeneration and immunodeficiency. Recent studies suggest that very low glucocorticoids (GCs) doses may help improve A-T neurological phenotype in some patients. Interestingly, in GCs studies an unexpected improvement of lymphocytes proliferation in some A-T patients has been observed. GCs are able to upregulate IL-7 Rα expression and rescue it from the recycling. In this study, we compared several immunological functions, including PBMC proliferative responses, cell activation events and IL-7/IL-7 Rα axis functionality, with the neurological behavior during an in-vivo GCs treatment between the most Responder patient to GC and the Non-Responder at all. During in-vivo GC treatment, we observed an increase of lymphocyte proliferation upon stimulation with PHA or IL-7 only in the Responder. This finding paralleled the increase in the surface expression of IL-7 R and up-regulation of the CD69 T-cell activation marker. Internalization and recycling of IL-7 R occurred properly only in the Responder. Microarray analysis revealed a remarkable difference in the DE-genes levels among Responder and Non-Responder, mostly concerning miRNAs and Multiple Complex families. Our findings suggest that the improvement of lymphocyte functionality, which correlates to the neurological behavior, is mediated through an effect of GCs on the IL-7/IL-7 Rα axis.

Editorial: Why JAACAP Published an "Inconclusive" Trial: Optimize, Optimize, Optimize Psychostimulant Treatment.

In this issue of the Journal, Blader et al.1 report the results of a double-blind randomized controlled trial (RCT) aimed at assessing the comparative efficacy and tolerability of adjunctive risperidone (RISP), valproex sodium (DVPX), or placebo for aggressive behaviors in children (aged 6-12 years) with attention-deficit/hyperactivity disorder (ADHD) and comorbid oppositional defiant disorder (ODD) or conduct disorder (CD), as well as a prior history of psychostimulant treatment. Participants with aggressive symptoms persisting after an open-label optimization of psychostimulant medication entered the 8-week randomized phase. Weekly sessions of family-based behavioral treatment were offered during both the optimization and the randomized phases. Among the 151 participants who completed the optimization phase (175 were initially enrolled), an unexpected 63.6% met the study criteria for remission, that is, 3 consecutive weeks with subthreshold scores on the Retrospective-Modified Overt Aggression Scale (R-MOAS). Therefore, only 45 participants were eligible for randomization, and 40 (RISP: n = 17; DVPX: n = 14; placebo: n = 9) were included in the primary analysis. Why did JAACAP publish an inconclusive trial? Because, in our view, the lessons that can be learned from this RCT (in particular, from its optimization phase) are highly relevant for both clinicians and trialists in the field. We are confident that the Blader et al. study will contribute to make clinicians in the field more "optimizers" and trialists more "transparent."

Little Agreement on Treating Residual Bipolar Disorder Symptoms in a Child.

BACKGROUND: There is a paucity of studies on treatment of childhood-onset bipolar disorder and its associated comorbidities, which leads to a wide diversity of opinion on choice and sequencing of treatment options. METHODS: From December 2018 to January 2019, a graphic depiction of medications and weekly ratings of symptoms of mania, depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), and oppositional behavior that parents had rated on their 9-year-old child over a period of several years was sent to experts in child and adult bipolar disorder. These responding medical doctors (MDs, 8 child and 18 adult psychiatrists) rated a comprehensive list of medications that they would choose (and with what priority) to treat the child's now improved mood (mania and depression) but continued mild to moderate symptoms of anxiety, ADHD, and oppositional behavior. RESULTS: In the whole group, the drugs most highly endorsed were lamotrigine: 69%, lithium: 62%, lurasidone: 62%, quetiapine: 54%, aripiprazole: 46%, and valproate: 42%. Among the antidepressants, 38% endorsed a selective serotonin reuptake inhibitor, 12% a serotonin-norepinephrine reuptake inhibitor, and 27% bupropion. Of the child MDs, 75% suggested increasing the 1-mg dose of risperidone, while few adult MDs suggested this. Conversely, 56% of the adult MDs suggested using valproate, while only 1 child MD did so. There was little consensus on how to manage ADHD symptoms unresponsive to methylphenidate 36 mg/d. How these treatment options were sequenced also varied widely. CONCLUSIONS: There was wide variation in suggestions on to how to treat persistent symptoms of anxiety, ADHD, and oppositional behavior in a child whose mania and depression had been brought under good control. We surmise that this great diversity in recommendations among experts in child and adult bipolar disorder stems at least partially from inadequate literature on treatment and that a new emphasis on funding and conducting studies on efficacy and effectiveness is needed.

Efficacy of Guanfacine Extended Release in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder and Comorbid Oppositional Defiant Disorder.

OBJECTIVE: To assess the efficacy of the non-stimulant guanfacine extended release (GXR) on attention-deficit/hyperactivity disorder (ADHD) symptoms in children and adolescents, with and without comorbid oppositional defiant disorder (ODD). METHODS: Data were derived from 4 phase 3, randomized, placebo-controlled trials of dose-optimized GXR monotherapy, in which at least 10% of participants had a diagnosis of comorbid ODD. SPD503-312 and SPD503-316 were 10- to 13-week studies of GXR (1-7 mg/d). SPD503-314 and SPD503-307 were 8-week studies of GXR (1-4 mg/d). Efficacy was assessed using the ADHD Rating Scale IV (ADHD-RS-IV) total scores. RESULTS: In total, 1,084 participants were included (SPD503-312 and SPD503-316, n = 537; SPD503-314, n = 333; and SPD503-307, n = 214). GXR was associated with significant improvements in ADHD core symptoms at endpoint in participants with and without ODD (p < 0.01 in all studies). Placebo-adjusted least-squares mean (95% confidence interval) changes from baseline to endpoint in the ADHD-RS-IV total scores in participants with and without ODD were -8.6 (-14.4, -2.8) and -7.3 (-9.5, -5.0) in the pooled data from SPD503-312 and SPD503-316, -12.6 (-19.6, -5.7) and -8.7 (-11.8, -5.5) in SPD503-314, and -12.7 (-17.3, -8.1) and -11.8 (-19.3, -4.4) in SPD503-307, respectively. The corresponding effect sizes were 0.688 and 0.598 in SPD503-312 and SPD503-316, 0.876 and 0.729 in SPD503-314, and 0.962 and 0.842 in SPD503-307. CONCLUSION: The findings demonstrate the efficacy of GXR for treating ADHD in children and adolescents with comorbid ODD.

Editorial: Antidepressants to the Rescue in Severe Mood Dysregulation and Disruptive Mood Dysregulation Disorder?

Children with irritability and outbursts pose a serous therapeutic problem. Many of them have attention-deficit/hyperactivity disorder (ADHD) with emotion dysregulation, which is sometimes captured in the diagnosis of disruptive mood dysregulation disorder (DMDD). Some follow-up data find a connection between DMDD and depression and anxiety in adults. This prompted Towbin and colleagues1 to launch a trial where children (ages 7-17) with DMDD were treated first with methylphenidate (MPH) and then randomized to citalopram (CTP) or placebo over 8 weeks. The response to CTP was complicated by lack of specific measures of both irritable mood and severity of outbursts. Future studies should include standardized and normed parent and teacher measures of both externalizing and internalizing behavior as well as irritability specific measures rating how the child feels. Studies also need better measures of the actual outbursts-not just their frequency but how agitated or aggressive the child gets during an outburst (ie, what the child does) and how long the outbursts last. Measuring DMDD on inpatient units is especially complicated because of the therapeutic nature of the setting. Further work is needed with much larger samples to identify who improves with the treatment, exactly which domains of psychopathology improve and by how much. Finally, It is also critical to conduct longer-term trials to determine the stability of the response beyond 8 weeks.

A Double-Blind Randomized Placebo-Controlled Trial of Citalopram Adjunctive to Stimulant Medication in Youth With Chronic Severe Irritability.

OBJECTIVE: Despite the clinical importance of chronic and severe irritability, there is a paucity of controlled trials for its pharmacological treatment. Here, we examine the effects of adding citalopram (CTP) to methylphenidate (MPH) in the treatment of chronic severe irritability in youth using a double-blind randomized placebo-controlled design. METHOD: After a lead-in phase of open treatment with stimulant, 53 youth meeting criteria for severe mood dysregulation (SMD) were randomly assigned to receive CTP or placebo (PBO) for 8 weeks. A total of 49 participants, 48 of them (98%) meeting disruptive mood dysregulation disorder (DMDD) criteria, were included in the intent-to-treat analysis. The primary outcome measure was the proportion of response based on improvements of irritability at the week 8 of the trial. RESULTS: At the end of the trial, a significantly higher proportion of response was seen in those participants randomly assigned to CTP+MPH compared to PBO+MPH (35% CTP+MPH versus 6% PBO+MPH; odds ratio = 11.70, 95% CI = 2.00-68.16, p = 0.006). However, there were no differences in functional impairment between groups at the end of the trial. No differences were found in any adverse effect between treatment groups, and no trial participant exhibited hypomanic or manic symptoms. CONCLUSION: Adjunctive CTP might be efficacious in the treatment of chronic severe irritability in youth resistant to stimulant treatment alone. CLINICAL TRIAL REGISTRATION INFORMATION: A Controlled Trial of Serotonin Reuptake Inhibitors Added to Stimulant Medication in Youth With Severe Mood Dysregulation; https://clinicaltrials.gov; NCT00794040.

Young Children with Attention-Deficit/Hyperactivity Disorder and/or Disruptive Behavior Disorders Are More Frequently Prescribed Alpha Agonists Than Stimulants.

Objective: To examine medication prescribing patterns for preschool-aged children with diagnoses of attention-deficit/hyperactivity disorder (ADHD) and/or disruptive behavior disorder (DBD). Secondary objectives included determining if prescription patterns varied by gender, insurance type, or comorbid diagnosis of autism spectrum disorder (ASD). Methods: A retrospective, cross-sectional chart review was completed for children ages 2-5 years who were treated at an academic medical center between 2013 and 2016 with a diagnosis of ADHD and/or DBD. Data were analyzed by Fisher's exact and chi-square tests and Cochran-Armitage trend analysis. Results: Of the 966 children who met inclusion criteria, 343 (35.5%) were prescribed ADHD medications. For 2-, 3-, and 4-year olds, the most commonly prescribed medication was an alpha agonist (AA), while for 5-year olds, methylphenidate (MPH) was most commonly prescribed. With advancing age, an increasing number of children were prescribed a stimulant medication and a decreasing number of children were prescribed an AA (p < 0.001). Children were more often prescribed an MPH formulation (48.2%) compared with amphetamine-based stimulants (26.8%). Children without ASD were more likely to be prescribed a stimulant medication (72.1%) when compared with children with ASD (37.0%, p < 0.0001). Children with private insurance were more likely to be prescribed an extended-release stimulant medication when compared with Medicaid patients (34.3% vs. 17.2%, p = 0.004). Conclusion: Both stimulants and nonstimulants are being prescribed regularly in very young children, even before the age of four at an academic medical center. AAs were the most commonly prescribed medication for children 2, 3, and 4 years of age with diagnoses of ADHD, DBD, and ASD. Insurance type, comorbid diagnosis of ASD, and age of child were found to be significantly associated with prescribing a nonpreferred medication.