Closing the gap: unmet needs of individuals with impulsive aggressive behavior observed in children and adolescents.

Impulsive aggressive (IA, or impulsive aggression) behavior describes an aggregate set of maladaptive, aggressive behaviors occurring across multiple neuropsychiatric disorders. IA is reactive, eruptive, sudden, and unplanned; it provides information about the severity, but not the nature, of its associated primary disorder. IA in children and adolescents is of serious clinical concern for patients, families, and physicians, given the detrimental impact pediatric IA can have on development. Currently, the ability to properly identify, monitor, and treat IA behavior across clinical populations is hindered by two major roadblocks: (1) the lack of an assessment tool designed for and sensitive to the set of behaviors comprising IA, and (2) the absence of a treatment indicated for IA symptomatology. In this review, we discuss the clinical gaps in the approach to monitoring and treating IA behavior, and highlight emerging solutions that may improve clinical outcomes in patients with IA.

Practitioner Review: Emotional dysregulation in attention-deficit/hyperactivity disorder - implications for clinical recognition and intervention.

BACKGROUND: Because emotional symptoms are common in attention-deficit/hyperactivity disorder (ADHD) patients and associate with much morbidity, some consider it to be a core feature rather than an associated trait. Others argue that emotional symptoms are too nonspecific for use as diagnostic criteria. This debate has been difficult to resolve due, in part, to the many terms used to describe emotional symptoms in ADHD and to concerns about overlap with mood disorders. METHODS: We sought to clarify the nature of emotional symptoms in ADHD by reviewing conceptual and measurement issues and by examining the evidence base regarding specificity of such symptoms for ADHD. We reviewed the various terms used to define emotional symptoms in ADHD, clarify how these symptoms are demarcated from mood disorders, and assess the possibility that symptoms of emotional impulsivity and deficient emotional self-regulation should be considered as core symptoms. We addressed psychiatric comorbidities, the effects of ADHD treatments on associated emotional dysregulation, and the utility of current rating scales to assess emotional symptoms associated with ADHD. RESULTS: Emotional symptoms are common and persistent in youth and adults with ADHD. Although emotional symptoms are common in other psychiatric disorders, emotional impulsivity (EI), and deficient emotional self-regulation (DESR) may be sufficiently specific for ADHD to function as diagnostic criteria. CONCLUSIONS: Emotional symptoms in ADHD cause clinically significant impairments. Although there is a solid theoretical rationale for considering EI and DESR to be core symptoms of ADHD, there is no consensus about how to define these constructs sin a manner that would be specific to the disorder. An instrument to measure EI and DESR which demarcates them from irritability and other emotional symptoms could improve the accuracy of diagnostic criteria for ADHD.

Late-life onset bipolar disorder presenting as a case of pseudo-dementia: a case discussion and review of literature.

Depression and comorbid cognitive impairment in the elderly can be difficult to distinguish from dementia. Adding to the complex differential is that depression may be part of a bipolar illness rather than a unipolar mood disorder. A diligent workup and close monitoring of patients can inform appropriate treatment and can make the difference between recovery and persistence of symptoms. The present case will illustrate how a comprehensive workup utilizing extensive data gathering, laboratory workup, use of neuropsychological testing, neuroimaging, and timely treatment can lead to successful clinical outcomes that can be sustained for many years.

Characteristics of children with juvenile bipolar disorder or disruptive behavior disorders and negative mood: can they be distinguished in the clinical setting?

BACKGROUND: Because of continuing controversy over distinguishing juvenile bipolar disorder (JBD) from disruptive behavior disorders (DBDs) in the clinical setting, we investigated whether referred children with a DBD and a negative mood component could be differentiated from those diagnosed with JBD. The distinction is important because treatments differ. METHODS: In this single-site sample, 96 children with non-attention-deficit/hyperactivity DBD and depression were compared with 27 JBD children and 187 psychiatric comparison children on measures assessing behavior, functional impairment, symptom severity, psychopathology, and comorbid psychiatric diagnosis. RESULTS: Few differences were found between children with DBD and depression and those with JBD on measures of conduct problems, oppositionality, aggression, hostility, and psychopathology. More functional impairment was found in the JBD group who also had higher rates of comorbid posttraumatic stress disorder (PTSD), substance use disorders, and suicidality than the other groups. CONCLUSIONS: These results do not support the specificity of aggression as a defining criterion for JBD and clinicians assessing such patients also should consider complex DBDs with an associated depressive component in the differential diagnosis. Children with JBD must be specifically assessed for comorbid developmental trauma, substance abuse, and suicidality. The association between JBD and PTSD needs further investigation in clinical research.

The Many Faces (and Names) of Mood Dysregulation.

Explosive outbursts in children and adolescents have been long identified by clinicians and have been described using many different conceptualizations and terms. The topography of explosive outbursts is complex, heterogeneous, and includes the interactions of different emotional and behavioral constructs. Included here are pre-existing central nervous system vulnerabilities including psychiatric and neurologic diagnoses, various contributing emotions that generally carry a negative valence, and aggressive behaviors that are usually overt and reactive. Emotional impulsivity and deficient emotional self-regulatory mechanisms may contribute to episode severity and duration.

Child abuse and aggression among seriously emotionally disturbed children.

Abused children may be at risk for problems with aggression. In a sample of 397 seriously emotionally disturbed children, reactive aggression was associated with documented history of physical abuse but not sexual abuse. Girls were equally likely to be classified as reactively aggressive regardless of physical abuse history, but boys with physical abuse histories were 50% more likely to be classified as reactively aggressive than boys with no physical abuse history. Proactive aggression was unrelated to physical or sexual abuse history. The association of physical abuse and reactive aggression warrants further scientific study and attention in clinical assessment and treatment with seriously emotionally disturbed children.

Psychotropic medications and substances of abuse interactions in youth.

The majority of youth with substance use disorders (SUDs) manifest one or more co-occurring psychiatric disorders. Consequently, many of these youths are being prescribed with psychotropic medications. As prescribing rates continue to increase for early-onset psychiatric disorders, potential risk for substance of abuse-psychiatric medication interactions may be enhanced. Because this type of drug-drug interaction has received little attention in the scientific literature, the authors conducted a systematic literature search examining the potential interactive adverse effects between psychotropic medications and substances of abuse in youth. Regardless of the scarcity of psychotropic medications-substance of abuse interactions found, it is important to stay vigilant due to the continued introduction of new classes of medications as well as the ever-changing map of street drugs.

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.

A linguistic analysis of in-office dialogue among psychiatrists, parents, and child and adolescent patients with ADHD.

OBJECTIVE: The aim was to evaluate in-office discussions of ADHD and psychiatric comorbidities. METHOD: Naturally occurring interactions among 11 psychiatrists, 32 patients and their parents were recorded, with a focus on "complicated" patients (i.e., having or suspected to have >or= 1 psychiatric comorbidities and/or learning disabilities in addition to ADHD). Participants were interviewed separately post visit. Transcripts were analyzed using validated sociolinguistic methodologies. RESULTS: Some 62% of patients were male, with an average age of 12.5 years, and 79% had a family history of ADHD. Visits were psychiatrist-driven, focusing on medication management and school performance, leaving management of comorbidities largely unaddressed. Post visit, 78% of parents and psychiatrists disagreed on patients' "most concerning behavior." Parents most often reported concern about aggression and oppositionality. Psychiatrists and parents emphasized different aspects of patients' personality, using deficit- and strength-based models, respectively. CONCLUSION: Psychiatrists and parents interpreted the relationship between ADHD and comorbidities differently. The significant incidence of misalignment regarding worrisome behaviors warrants further exploration.

Does Anxiety Modify the Risk for, or Severity of, Conduct Problems Among Children With Co-Occurring ADHD: Categorical and Dimensional and Analyses.

OBJECTIVE: The goal was to examine whether anxiety modifies the risk for, or severity of, conduct problems in children with ADHD. METHOD: Assessment included both categorical and dimensional measures of ADHD, anxiety, and conduct problems. Analyses compared conduct problems between children with ADHD features alone versus children with co-occurring ADHD and anxiety features. RESULTS: When assessed by dimensional rating scales, results showed that compared with children with ADHD alone, those children with ADHD co-occurring with anxiety are at risk for more intense conduct problems. When assessment included a Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) diagnosis via the Schedule for Affective Disorders and Schizophrenia for School Age Children-Epidemiologic Version (K-SADS), results showed that compared with children with ADHD alone, those children with ADHD co-occurring with anxiety neither had more intense conduct problems nor were they more likely to be diagnosed with oppositional defiant disorder or conduct disorder. CONCLUSION: Different methodological measures of ADHD, anxiety, and conduct problem features influenced the outcome of the analyses.

New Formulations of Stimulants: An Update for Clinicians.

In the last 15 years, there has been a marked increase in the number of available stimulant formulations with the emphasis on long-acting formulations, and the introduction of several novel delivery systems such as orally dissolving tablets, chewable tablets, extended-release liquid formulations, transdermal patches, and novel "beaded" technology. All of these formulations involve changes to the pharmaceutical delivery systems of the two existing compounds most commonly employed to treat attention-deficit/hyperactivity disorder (ADHD), amphetamine (AMP) and methylphenidate (MPH). In addition to these new formulations, our knowledge about the individual differences in response has advanced and contributes to a more nuanced approach to treatment. The clinician can now make increasingly informed choices about these formulations and more effectively individualize treatment in a way that had not been possible before. In the absence of reliable biomarkers that can predict individualized response to ADHD treatment, clinical knowledge about differences in MPH and AMP pharmacodynamics, pharmacokinetics, and metabolism can be utilized to personalize treatment and optimize response. Different properties of these new formulations (delivery modality, onset of action, duration of response, safety, and tolerability) will most likely weigh heavily into the clinician's choice of formulation. To manage the broad range of options that are now available, clinicians should familiarize themselves in each of these categories for both stimulant compounds. This review is meant to serve as an update and a guide to newer stimulant formulations and includes a brief review of ADHD and stimulant properties.

Maladaptive Aggression: With a Focus on Impulsive Aggression in Children and Adolescents.

Objective: Aggressive behavior is among the most common reasons for referral to psychiatric clinics and confers significant burden on individuals. Aggression remains poorly defined; there is currently no consensus on the best ways to recognize, diagnose, and treat aggression in clinical settings. In this review, we synthesize the available literature on aggression in children and adolescents and propose the concept of impulsive aggression (IA) as an important construct associated with diverse and enduring psychopathology. Methods: Articles were identified and screened from online repositories, including PubMed, PsychInfo, the Cochrane Database, EMBase, and relevant book chapters, using combinations of search terms such as "aggression," "aggressive behavio(u)r," "maladaptive aggression," "juvenile," and "developmental trajectory." These were evaluated for quality of research before being incorporated into the article. The final report references 142 sources, published from 1987 to 2019. Results: Aggression can be either adaptive or maladaptive in nature, and the latter may require psychosocial and biomedical interventions when it occurs in the context of central nervous system psychopathology. Aggression can be categorized into various subtypes, including reactive/proactive, overt/covert, relational, and IA. IA in psychiatric or neurological disorders is reviewed along with current treatments, and an algorithm for systematic evaluation of aggression in the clinical setting is proposed. Conclusions: IA is a treatable form of maladaptive aggression that is distinct from other aggression subtypes. It occurs across diverse psychiatric and neurological diagnoses and affects a substantial subpopulation. IA can serve as an important construct in clinical practice and has considerable potential to advance research.

A Novel Assessment Tool for Impulsive Aggression in Children with Attention-Deficit/Hyperactivity Disorder.

Objective: To establish the validity and reliability of a provisional 30-item impulsive aggression (IA) diary in children (ages 6-12 years, inclusive) with attention-deficit/hyperactivity disorder (ADHD). Methods: The provisional 30-item IA diary was administered for 14 days to parents of children with ADHD and IA symptoms (n = 103). Key inclusion criteria: confirmed ADHD diagnosis; signs of IA as measured by a Retrospective-Modified Overt Aggression Scale (R-MOAS) score ≥20 and an Aggression Questionnaire score of -2 to -5. Analyses included inter-item correlations, exploratory factor analysis (EFA), item response theory (IRT) modeling, internal consistency, test-retest reliability (TRT), concurrent validity (estimated by correlation between the IA diary and the R-MOAS/Nisonger Child Behavior Rating Form), and known-groups methods. Results: The prevalence rates of 15 (50.0%) items were found to be too low (<1%) for analysis; three items with prevalence rates ≤1% were retained, as content validity was deemed high by clinical experts. The remaining 12 behavior items had prevalence rates of 2.7%-73.6%. EFA and IRT models confirmed two subdomains in the IA diary included within a general domain of IA behavior frequency, yielding a single total behavioral frequency score (TBFS). Internal consistency was high for this TBFS (marginal reliability = 0.86 and α = 0.73). TRT for the TBFS, based on the intraclass correlation coefficient, was 0.8. Concurrent validity of TBFS with R-MOAS ranged from r = 0.49 to r = 0.62. Conclusion: The final 15-item IA diary is a reliable, psychometrically validated IA measurement tool that will allow clinicians and researchers to assess the frequency of IA behavior.

Application of the Impulsive Aggression Diary in Adolescents with Attention-Deficit/Hyperactivity Disorder.

Objective: Impulsive aggression (IA) is a maladaptive form of aggressive behavior that is an associated feature of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). As one of the most common forms of aggressive behavior, IA is a serious clinical concern. Recognition, monitoring, and management of IA symptoms are complicated by the lack of IA-specific psychometric instruments and evidence-based treatments. A recently developed electronic observer-reported outcome instrument has been validated in children for monitoring the frequency of 15 IA-related behaviors in the context of ADHD. This study seeks to first determine if the behaviors included in the pediatric IA diary are applicable to adolescents with ADHD, and second, compare the reliability of adolescent versus parent reporters. Methods: We evaluated the utility of the pediatric IA diary through concept elicitation and cognitive interviews with 17 pairs of parents and adolescents (aged 13-17 years) with IA and ADHD, supplemented with 15 new behaviors potentially applicable to adolescents. Results: The behaviors most frequently reported by adolescents included arguing (93.8%), raising their voice/shouting/yelling (93.8%), hitting others (87.5%), slamming (87.5%), pushing/shoving (81.3%), breaking (75.0%), fighting (75.0%), throwing (75.0%), and cursing (68.8%). The behaviors most commonly reported by parents included raising their voice/shouting/yelling (94.1%), arguing (88.2%), being disrespectful/mean/rude (88.2%), slamming (88.2%), throwing (88.2%), cursing (82.4%), hitting others (82.4%), pushing/shoving (82.4%), breaking (76.5%), name-calling (76.5%), and threatening (70.6%). Of all commonly reported behaviors, only being "disrespectful/mean/rude" and "breaking" are not part of the pediatric IA diary, likely due to the imprecision of these terms. No significant usability issues were found for the IA diary device. Conclusions: These findings suggest that the 15-item pediatric IA diary should be applicable to adolescent populations to appropriately characterize IA behaviors in individuals with ADHD. Furthermore, this study indicated that parents may be more reliable reporters of IA behavior than adolescents.

Repeated risperidone administration during puberty prevents the generation of the aggressive phenotype in a developmentally immature animal model of escalated aggression.

Risperidone has been shown to be clinically effective for the treatment of aggressive behavior in children, yet until recently no information was available regarding whether risperidone exhibits aggression-specific suppression in preclinical studies employing validated developmentally immature animal models of escalated aggression. Recently, using a pharmacologic animal model of escalated offensive aggression, we reported that acute risperidone treatment selectively and dose-dependently reduces the expression of the adult aggressive phenotype, with a significant reduction in aggressive responses observed at 0.1 mg/kg, i.e., a dose within the range administered to children and adolescents in the clinical setting. This study examined whether repeated exposure to risperidone during puberty would prevent the generation of the highly escalated aggressive phenotype in this animal model. To test this hypothesis, the aggression-eliciting stimulus (i.e., cocaine hydrochloride, 0.5 mg/kg/dayx28 days) was co-administered with an aggression-suppressing dose of risperidone (i.e., 0.1 mg/kg/day) during different time frames of puberty and for varied lengths of time (i.e., 1-4 weeks), and then animals were scored for targeted measures of offensive aggression during late puberty. Risperidone administration prevented the generation of the adult aggressive phenotype, with a complete blockade of matured offensive responses (i.e., lateral attacks and flank/rump bites) seen only after prolonged periods of exposure to risperidone (i.e., 3-4 weeks). The selective prevention of these aggressive responses, while leaving other measures of aggression intact (e.g., upright offensive postures), suggest that risperidone is acting in a highly discriminatory anti-aggressive fashion, targeting neurobehavioral elements important for the mature aggressive response pattern.

Randomized controlled pilot study of quetiapine in the treatment of adolescent conduct disorder.

OBJECTIVE: The aim of this study was to examine whether quetiapine is superior to placebo in the treatment of adolescents with conduct disorder. METHODS: This was a 7-week, randomized, double-blind, placebo-controlled pilot study with two parallel arms. Nine youths were randomly assigned to receive quetiapine, and 10 youths were randomly assigned to receive placebo. Patients were assessed weekly throughout the trial. Quetiapine was dosed twice daily, and medications could be titrated flexibly through the end of study week 5. The dose was fixed for the final 2 weeks of the study. The primary outcome measures were the clinician-assessed Clinical Global Impressions-Severity (CGI-S) and-Improvement (CGI-I) scales. Secondary outcome measures included parent-assessed quality of life, the overt aggression scale (OAS), and the conduct problems subscale of the Conners' Parent Rating Scale (CPRS-CP). RESULTS: The final mean dose of quetiapine was 294 +/- 78 mg/day (range 200-600 mg/day). Quetiapine was superior to placebo on all clinician-assessed measures and on the parent-assessed quality of life rating scale. No differences were found on the parent-completed OAS and CPRS-CP. Quetiapine was well tolerated. One patient randomized to quetiapine developed akathisia, requiring medication discontinuation. No other extrapyramidal side effects occurred in patients receiving active drug. CONCLUSIONS: This methodologically controlled pilot study provides data that quetiapine may have efficacy in the treatment of adolescents with conduct disorder. Because of the preliminary nature of the study, further research with larger samples is needed to confirm these findings.

Separation anxiety and panic disorder in clinically referred youth.

This study examined whether youngsters with separation anxiety disorder (SAD) and panic disorder (PD) had experienced more separation-related events than youngsters with SAD (without comorbid PD). We also examined whether age of onset of SAD and comorbidity with other psychological disorders was related to the occurrence of PD. We compared youngsters who were diagnosed with SAD and PD (N=31) with youngsters who were diagnosed with SAD without comorbid PD (N=63) for the number of separation-related events, severity of psychopathology, and parent and child CBCL ratings, age of onset of SAD, and the number of comorbid diagnoses. The findings indicate that youngsters with SAD and PD had a later age of onset of SAD and more extensive psychopathology and functional impairment than youngsters with SAD (without comorbid PD). Contrary to hypothesis, there were no differences between the groups in the occurrence or number of separation-related events.

ADHD with comorbid oppositional defiant disorder or conduct disorder: discrete or nondistinct disruptive behavior disorders?

OBJECTIVE: In children with ADHD who have comorbid disruptive behavior diagnoses distinctions between oppositional defiant disorder (ODD) and conduct disorder (CD) remain unclear. The authors investigate differences between ODD and CD in a large clinical sample of children with ADHD. METHOD: Consecutively referred and systematically assessed male children and adolescents with either ADHD (n = 65), ADHD with ODD (n = 85), or ADHD with CD (n = 50) were compared using structured diagnostic interviews and parent, teacher, and clinician rating scales. RESULTS: In children with ADHD, significant differences emerged between ODD and CD in the domains of delinquency, overt aggression, and ADHD symptom severity; ADHD with CD was most severe, followed by ADHD with ODD, and ADHD had the least severe symptoms. Distinctions between ADHD with CD and the other two groups were found for parenting, treatment history, and school variables. CONCLUSION: Within the limits of a cross-sectional methodology, results support clinically meaningful distinctions between ODD and CD in children with ADHD.

Risperidone exerts potent anti-aggressive effects in a developmentally immature animal model of escalated aggression.

BACKGROUND: Risperidone has been shown to be clinically effective for the treatment of aggressive behavior in children, yet no information is available regarding whether risperidone exhibits aggression-specific suppression in preclinical studies that use validated developmentally immature animal models of escalated aggression. Previously, we have shown that exposure to low doses of the psychostimulant cocaine-hydrochloride (.5 mg/kg intraperitoneally) during the majority of pubertal development (postnatal days [P]27-57) generates animals that exhibit a high level of offensive aggression. This study examined whether risperidone exerts selective aggression-suppressing effects by using this pharmacologic animal model of highly escalated offensive aggression. METHODS: Experimental hamsters were tested for offensive aggression after the acute administration of risperidone (.05-1.0 mg/kg, intraperitoneally). RESULTS: Risperidone dose-dependently reduced the highly aggressive phenotype, with a significant reduction observed at .1-.2 mg/kg for most aggressive responses measured. Experimental animals treated with higher doses of risperidone (.3-1.0 mg/kg) showed significant reductions in aggression and social interest toward intruders, indicating more general behavioral inhibition. CONCLUSIONS: These studies provide evidence that risperidone exerts specific aggression-suppressing effects in a developmentally immature animal model of escalated aggression.