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Child behaviour checklist emotional dysregulation profiles in youth with disruptive behaviour disorders: clinical correlates and treatment implications

Two Child Behaviour Checklist (CBCL) profiles were correlated to poor self-regulation, Deficient Emotional Self-Regulation (DESR) (elevation between 1 and 2 Standard Deviations (SD) in Anxiety/Depression, Aggression, Attention subscales), and Dysregulation Profile (DP) (elevation of 2 Standard Deviations or more). We explored youths with Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD) whether these profiles are associated with specific clinical features. The sample included 57 patients with DESR profile and 41 with DP profile, ages 9 to 15 years, all assigned to a non-pharmacological Multimodal Treatment Program. No differences resulted between groups in demographic features, diagnosis ratio, and comorbidities with Attention Deficit Hyperactivity Disorder (ADHD), Bipolar Disorder (BD), and Anxiety Disorder. The DP group was associated with higher scores in Withdrawn, Social Problem, Thought, Rule Breaking, and Somatic CBCL subscales, and higher scores in Narcissism and Impulsivity (but not Callous-Unemotional (CU)), according to the Antisocial Process Screening Device (APSD). After treatment, patients with DESR improved their personality traits (Narcissistic and Callous-Unemotional, but not Impulsivity), while changes in CBCL scales were modest. Patients with DP improved scales of Attention, Aggression, Anxiety-Depression, Rule Breaking, Withdrawal, Social Problem and Thought, while personality features did not change. These results suggest diagnostic implications of CBCL profiles, and indications for targeted treatment strategies.

Callous unemotional traits in children with disruptive behavior disorder: predictors of developmental trajectories and adolescent outcomes

The present study investigated trajectories of Callous Unemotional (CU) traits in youth with Disruptive Behavior Disorder diagnosis followed-up from childhood to adolescence, to explore possible predictors of these trajectories, and to individuate adolescent clinical outcomes. A sample of 59 Italian referred children with Disruptive Behavior Disorder (53 boys and 6 girls, 21 with Conduct Disorder) was followed up from childhood to adolescence. CU traits were assessed with CU-scale of the Antisocial Process Screening Device-parent report. Latent growth curve models showed that CU traits are likely to decrease linearly from 9 to 15 years old, with a deceleration in adolescence (from 12 to 15). There was substantial individual variability in the rate of change of CU traits over time: patients with a minor decrease of CU symptoms during childhood were at increased risk for severe behavioral problems and substance use into adolescence. Although lower level of socio-economic status and lower level of parenting involvement were associated to elevated levels of CU traits at baseline evaluation, none of the considered clinical and environmental factors predicted the levels of CU traits. The current longitudinal research suggests that adolescent outcomes of Disruptive Behavior Disorder be influenced by CU traits trajectories during childhood.

Efficacy and Safety of Risperidone and Quetiapine in Adolescents With Bipolar II Disorder Comorbid With Conduct Disorder.

Abstract Although a frequent co-occurrence between bipolar disorder (BD) and conduct disorder (CD) in youth has been frequently reported, data about pharmacological management are scarce and focused on BD type I. Second generation antipsychotics are frequently used in clinical practice, but no comparative studies are available. The aim of this exploratory study was to compare efficacy and safety of risperidone and quetiapine in a sample of adolescents presenting a BD type II comorbid with CD. Twenty-two patients diagnosed with a structured interview according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (male/female ratio, 12/10; mean (SD) age 15.0 (1.4) years) were randomized in 2 treatment groups (quetiapine [n = 12] vs risperidone [n = 10]), treated with flexible doses, and followed up for 12 weeks. Efficacy measures assessed manic symptoms, aggression, anxiety, depression, global clinical severity, and impairment. Safety measures included body mass index, serum prolactin, extrapyramidal adverse effects, and electrocardiogram. At the end of the study, all patients improved in all efficacy measures. Both treatments showed similar efficacy in reducing manic symptoms and aggression. Quetiapine was more effective in improving anxiety and depressive symptoms. A change in body mass index was found, and in a post hoc analysis, it was significant only in the risperidone group. Prolactin significantly increased only in the risperidone group. In BD type II, CD comorbidity, quetiapine, or risperidone monotherapy may be effective and relatively safe, although the small sample size, the limited duration of the study, and the design (lack of a blind assessments and of a placebo group) make it difficult to draw definitive conclusions.

Mozart's music in children with drug-refractory epileptic encephalopathies

Mozarts sonata for two pianos in D major, K448, has been shown to decrease interictal EEG discharges and recurrence of clinical seizures in both adults and young patients. In this prospective, open-label study, we evaluated the effect of listening to a set of Mozarts compositions, according to the Tomatis method, on sleep quality and behavioral disorders, including auto-/hetero-aggression, irritability, and hyperactivity, in a group of children and adolescents with drug-resistant epilepsy. The study group was composed of 11 outpatients (7 males and 4 females), between 1.5years and 21years of age (mean age: 11.9years), all suffering from drug-resistant epileptic encephalopathy (n=11). All of them had a severe/profound intellectual disability associated with cerebral palsy. During the study period, each patient had to listen to a set of Mozarts compositions 2h per day for fifteen days for a total of 30h, which could be distributed over the day depending on the habits and compliance of each patient. The music was filtered by a device preferably delivering higher sound frequencies (>3000Hz) according to the Tomatis principles. The antiepileptic drug therapy remained unchanged throughout the study period. During the 15-day music therapy, 2 out of 11 patients had a reduction of 50-75% in seizure recurrence, and 3 out of 12 patients had a reduction of 75-89%. Overall, 5 (45.4%) out of 11 patients had a ≥50% reduction in the total number of seizures, while the percentage decrease of the total seizure number (11/11) compared with baseline was -51.5% during the 15-day music therapy and -20.7% in the two weeks after the end of treatment. All responders also had an improvement in nighttime sleep and daytime behavior.

Update on the safety of second generation antipsychotics in youths: a call for collaboration among paediatricians and child psychiatrists

During the past decade, a substantial increase in the use of second generation antipsychotics (SGAs) has occurred for a number of juvenile psychiatric disorders, often as off-label prescriptions. Although they were thought to be safer than older, first generation antipsychotics, mainly due to a lower risk of neurological adverse reactions, recent studies have raised significant concerns regarding their safety regarding metabolic, endocrinological and cardiovascular side effects. Aim of this paper is to update with a narrative review, the latest findings on safety of SGAs in youths. Results suggest that different SGAs may present different safety profiles. Metabolic adverse events are the most frequent and troublesome, with increasing evidences of heightened risk for type II diabetes mellitus. Results are discussed with specific emphasis on possible strategies of an active monitoring, which could enable both paediatricians and child psychiatrists to a possible prevention, early detection, and a timely management of such effects.

Second generation antipsychotics in ‘real-life’ paediatric patients. Adverse drug reactions and clinical outcomes of drug switch

ABSTRACT Objective: Gap in knowledge on benefit/risk ratio of second generation antipsychotics (SGA) in the paediatric population represents a challenge for the scientific community. This study aims to analyse all suspected adverse drug reactions (ADRs) to SGA observed during the study period; compare the safety profiles of risperidone and aripiprazole; evaluate the effect of switching from risperidone to aripiprazole or to a first generation antipsychotic (FGA). Methods: Prospective analysis of spontaneously reported ADRs concerning 184 paediatric outpatients between 2012 and 2014.; clinical outcomes of drug switch were evaluated. Results: Out of the 184 patients, 130 experienced at least one ADR; ADRs were usually not serious and more frequently associated with aripiprazole. Switching to aripiprazole was associated with better results than switching to FGAs in the Clinical Global Impression scale- Efficacy (CGI-E) scores (p = 0.018), Disturbed behaviour checklist-parents (DBC-P) self-absorption subscale (p = 0.010); only a trend for difference between changing to aripiprazole vs FGAs in the DBC-P total score (p = 0.054) and social relating subscale (p = 0.053) was observed. Conclusions: SGAs safety data were consistent with the ones already known; however, there is still a need to improve the knowledge in pharmacovigilance field among clinicians. Switching to aripiprazole may be a valid alternative to risperidone.

Use of Quetiapine in Children and Adolescents

The atypical antipsychotic quetiapine has been used in different psychotic and non-psychotic disorders in children and adolescents in randomized clinical trials, open-label studies and chart reviews. Most of these studies suggest that quetiapine may be a promising agent with a potential for use in young patients. The aim of this paper is to critically review available literature on quetiapine in the treatment of children and adolescents with a variety of psychiatric disorders, including psychotic disorders, bipolar disorders (manic and depressive episodes), conduct disorder, autism spectrum disorder, Tourette’s syndrome and personality disorders. Furthermore, we report on possible neurochemical pathways involved during treatment with quetiapine, and discuss some issues that are clinically relevant in daily practice, such as titration strategies, safety and tolerability, and monitoring possible side effects. Controlled studies support the short-term efficacy for treating psychosis, mania, and aggression within certain diagnostic categories. However, although quetiapine seems well tolerated in various pediatric populations during acute and intermediate treatments, and hyper-prolactinemia and extra-pyramidal side effects are consistently low among studies, weight gain and alterations in lipid profile need to be closely monitored. Furthermore, the distal benefit/risk ratio during long-term treatment remains to be determined.

Emotional reactivity in referred youth with disruptive behavior disorders: The role of the callous-unemotional traits

Deficits in emotional reactivity are frequently reported in Disruptive Behavior Disorders (DBDs). A deficit in prosocial emotions, namely the callous unemotional traits (CU), may be a mediator of emotional reactivity. Our aim is to investigate subjective emotional reactivity towards visual stimuli with different affective valence in youths with DBDs and healthy controls. The clinical sample included 62 youths with DBDs (51 males, 8 to 16 years, mean 11.3±2.1 years), the control group 53 subjects (36 males, 8 to 16 years, mean 10.8±1.5 years). The groups were compared using the Child Behavior Checklist (CBCL), the Inventory of Callous-Unemotional Traits (ICU), and the International Affective Picture System (IAPS), which explores the affective (pleasant/unpleasant emotional reaction) and arousal (low/high intensity of emotion) dimensions. The DBD group presented higher scores in externalizing and internalizing CBCL scores, and in ICU callous and indifferent subscales. At the IAPS, DBD patients differed from controls in the affective valence of the images, rating less unpleasant neutral and negative images. The CU traits were the only predictor of emotional reactivity in the DBD sample. A less aversive way to interpret neutral and negative stimuli may explain why DBD patients are less responsive to negative reinforcements.

Quetiapine Monotherapy in Adolescents with Bipolar Disorder Comorbid with Conduct Disorder

Bipolar Disorders (BD) are often comorbid with disruptive behaviour disorders (DBDs) (oppositional-defiant disorder or conduct disorder), with negative implications on treatment strategy and outcome. The aim of this study was to assess the efficacy of quetiapine monotherapy in adolescents with BD comorbid with conduct disorder (CD). A consecutive series of 40 adolescents (24 males and 16 females, age range 12-18 years, mean age 14.9 ± 2.0 years), diagnosed with a clinical interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime Version [K-SADS-PL]) according to American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria were included. All the patients were treated with quetiapine monotherapy (mean final dose 258 ± 124 mg/day, range 100-600 mg/day). At the end-point (3 months), 22 patients (55.0%) were responders (Clinical Global Impressions-Improvement [CGI-I] score of 1 or 2 and CGI-Severity [CGI-S] ≤ 3 and improvement of at least 30% Childrens Global Assessment Scale [C-GAS] during 3 consecutive months). Both CGI-S and C-GAS significantly improved (p<0.0001). Nine out of the 16 patients with suicidality (56.3%) had a reduction in this severe symptom during the follow-up. Nonresponders were more frequently males, and more frequently had an attention-deficit/hyperactivity disorder (ADHD) comorbidity. Eight patients (20.0%) experienced moderate to severe sedation and eight (20.0%) experienced increased appetite and weight gain. In these severely impaired adolescents, quetiapine monotherapy was well tolerated and effective in>50% of the patients.

Antipsychotic-Induced Dyslipidemia Treated with Omega 3 Fatty Acid Supplement in an 11-Year-Old Psychotic Child: A 1-Year Follow-up

Antipsychotic-induced weight gain and dyslipidemia are hard-to-fight threats that can arise during treatment with second generation antipsychotic drugs (De Hert et al. 2011). The youth population is probably at higher risk than adults for antipsychotic-induced metabolic adverse events, because they are more likely drug naı̈ve (Correll et al. 2009; Roy et al. 2010, De Hert et al. 2011). The concern about metabolic complications in youth derives from evidence that metabolic abnormalities and weight gain during childhood strongly predict obesity, metabolic syndrome, hypertension, cardiovascular morbidity, sleep apnea, osteoarthritis, and malignancy risk in adulthood (De Hert et al. 2011; Maayan and Correll 2011). The mechanism of action that lead to metabolic abnormalities is still poorly understood (Roerig et al. 2011), as is what to do to prevent or to treat these adverse events. Guidelines published in 2009 and in August 2011 suggest strictly monitoring patients receiving atypical antipsychotics (De Hert et al. 2009; Ho et al. 2011). Common strategies currently implemented to moderate weight gain and other metabolic changes consist in encouraging a healthy lifestyle and switching to a lower metabolic impact drug (Correll et al. 2011; De Hert et al. 2011). Concomitant metformin administration is used in adults, but data regarding children and adolescents are limited (Newall et al. 2012). Many other psychopharmacological interventions have been suggested, but, although promising, none of those drugs have been demonstrated to be able to entirely reverse weight gain or reduce cholesterol and triglycerides (TG) (Maayan et al. 2010). Omega 3 fatty acids are becoming more frequently used in all fields of medicine, including child psychiatry (e.g., Gabbay et al. 2012). Use of well-timed controls of bleeding time are encouraged, but, generally, omega 3 use is considered safe (Emsley et al. 2008). In general medicine, the effects on lowering triglyceride levels are described, as well as small evidences of reducing obesity and metabolic syndrome symptoms (Balk et al. 2006; Buckley and Howe 2010; Poudyal et al. 2011). The use of omega 3 in antipsychotic-induced metabolic syndrome is only suggested, but no controlled or naturalistic studies are known by authors at the time of this report. An urgent need for evidence-based strategies to reduce metabolic symptoms in children and adolescents taking antipsychotic drugs is an opinion shared among experts (Correll et al. 2009; De Hert et al. 2011; Maayan and Correll 2011).