Internet Gaming Disorder in Children and Adolescents with Attention Deficit Hyperactivity Disorder.

Although Attention Deficit Hyperactivity Disorder (ADHD) has been related to an increased risk for behavioral addictions, the relationship between ADHD and Internet Gaming Disorder (IGD) is still debated. The aim of this study is to address this topic by exploring the prevalence of IGD in a consecutive sample of ADHD youth, compared to a normal control group, and by assessing selected psychopathological and cognitive features in ADHD patients with and without IGD. One hundred and eight patients with ADHD (mean age 11.7 ± 2.6 years, 96 males) and 147 normal controls (NC) (mean age 13.9 ± 3.0 years, 114 males) were included in the study and received structured measures for IGD. In the ADHD group, 44% of the sample were above the IGD cut-off, compared to 9.5% in the NC group. ADHD patients with IGD presented with greater severity and impairment, more severe ADHD symptomatology, more internalizing symptoms, particularly withdrawal/depression and socialization problems, and more prominence of addiction and evasion dimensions. A binary logistic regression showed that the degree of inattention presented a greater weight in determining IGD. These findings may be helpful for identifying, among ADHD patients, those at higher risk for developing a superimposed IGD.

Acute Tolerability of Methylphenidate in Treatment-Naïve Children with ADHD: An Analysis of Naturalistically Collected Data from Clinical Practice.

OBJECTIVES: The acute tolerability of methylphenidate (MPH) in children with attention-deficit/hyperactivity disorder (ADHD) has been studied mainly in research samples. Taking advantage of the mandatory test-dose procedure required for starting MPH in Italy, this study aimed to assess the incidence of intolerable adverse events after initial exposure to MPH in routine clinical practice. METHODS: The medical records of 480 consecutively treated, previously drug-naïve children and adolescents with ADHD (90% male, mean age 10.6 ± 3.0 years) were retrospectively analyzed. All children received an initial single dose of MPH immediate release (5 or 10 mg) followed by a 4-hour direct medical observation. Heart rate and blood pressure were measured at dosing and 1, 2, and 3 hours afterwards. If the first dose was well tolerated, the child continued treatment with MPH 5-20 mg daily, and was reassessed a week later. RESULTS: Eleven patients (2.3%, 95% CI 1.1-4.1) interrupted treatment within a week of initiation because of the following adverse events: irritability (n = 3), tics worsening (n = 3), reduced appetite (n = 1), enuresis (n = 1), hallucinations (n = 1), hyperfocus (n = 1), and 'rebound' behavioral worsening (n = 1). The most common adverse events were reduced appetite (20%), irritability (14.2%), headache (10.6%), sleep problems (9.4%), stomachache (9.4%), and tics (5%). Intellectual disability increased the risk of any adverse event in general and of irritability in particular. No cardiovascular symptom was clinically reported. However, routine assessments of vital signs during the first 3 hours after the first dose of MPH showed that 9% of the children had a 20% increase in heart rate, 8.8% had a 20% increase in diastolic blood pressure and 4.5% had a 20% increase in systolic blood pressure. Of these, 25.2% still had an elevated heart rate 1 week later. CONCLUSIONS: Among stimulant-naïve children in clinical practice, the incidence of acute MPH intolerance can be estimated to be between 1.2 and 4.1%. An asymptomatic elevation in cardiovascular parameters can be observed in about 1 out of 10 children and warrants monitoring during ongoing treatment.

Auditory time thresholds in the range of milliseconds but not seconds are impaired in ADHD.

The literature on time perception in individuals with ADHD is extensive but inconsistent, probably reflecting the use of different tasks and performances indexes. A sample of 40 children/adolescents (20 with ADHD, 20 neurotypical) was engaged in two identical psychophysical tasks measuring auditory time thresholds in the milliseconds (0.25-1 s) and seconds (0.75-3 s) ranges. Results showed a severe impairment in ADHD for milliseconds thresholds (Log10BF = 1.9). The deficit remained strong even when non-verbal IQ was regressed out and correlation with age suggests a developmental delay. In the seconds range, thresholds were indistinguishable between the two groups (Log10BF = - 0.5) and not correlated with milliseconds thresholds. Our results largely confirm previous evidence suggesting partially separate mechanisms for time perception in the ranges of milliseconds and seconds. Moreover, since the evidence suggests that time perception of milliseconds stimuli might load relatively less on cognitive control and working memory, compared to longer durations, the current results are consistent with a pure timing deficit in individuals with ADHD.

Treatment with Methylphenidate Improves Affective but Not Cognitive Empathy in Youths with Attention-Deficit/Hyperactivity Disorder.

BACKGROUND: Beside the core symptoms, patients with attention-deficit/hyperactivity disorder (ADHD) frequently show relevant difficulty in developing relationships with peers. Although ADHD symptoms may account for social impairment, deficits in cognitive and/or affective empathy have also been involved. Our aim was to investigate the effect of methylphenidate (MPH) treatment on affective and cognitive empathy. METHODS: Sixty-one drug-naïve youths with ADHD (age range 6 to 17 years, mean 10.3 ± 2.8 years, 51 males) naturalistically treated with MPH monotherapy were followed up for 6 months for ADHD symptoms and empathy, measured with the Basic Empathy Scale. RESULTS: After being treated with MPH, the patients showed a significant improvement in affective and cognitive empathy scores. Linear regression models showed that changes in inattention symptoms predicted changes in affective but not in cognitive empathy, while changes in the hyperactivity/impulsivity symptoms did not predict changes in affective or cognitive empathy. CONCLUSIONS: Our study provides a further contribution for a better understanding of the possible effects of the MPH on youth's characteristics.

An Exploratory Study of Emotional Dysregulation Dimensions in Youth With Attention Deficit Hyperactivity Disorder and/or Bipolar Spectrum Disorders.

Emotional dysregulation (ED) is currently the most frequently used term to describe children with an impaired regulation of emotional states. Recent research studies speculate whether ED may be a neurodevelopmental disorder itself, a shared risk factor, or a common key feature of several psychiatric disorders, including, among others, attention deficit hyperactivity disorder (ADHD), and bipolar spectrum disorders (BSD). The association between ADHD and ED is one of the main reasons of misconceptions in the definition of boundaries between ADHD and BSD, leading to the frequent misdiagnosis of ADHD as BSD. Since ED is a multidimensional concept, a novel instrument-the Reactivity, Intensity, Polarity and Stability (RIPoSt) scale-was recently developed to assess the different dimensions of ED, which could help in detecting specific ED profiles in clinical youths. Our study included 154 patients, aged 13.8 ± 2.3 years, diagnosed with either ADHD, BSD, or comorbid condition, and a school-based sample of 40 healthy control (HC) adolescents, aged 12.5 ± 1.2 years. The RIPoSt scale and the Child Behavior Checklist were administered to both groups. Our results indicate that affective instability and negative emotionality subscales, as well as negative emotional dysregulation, are higher in BSD, both pure and comorbid with ADHD, while emotional impulsivity is higher in the comorbid condition and similar in the ADHD and BSD alone group; all clinical groups scored higher than HC. Conversely, positive emotionality is similar among clinical groups and within them and HC. Our findings also support the validity of the RIPoSt questionnaire, since the instrument proved to have good-to-excellent internal consistency, and strongly significant positive correlations were found with the CBCL-Dysregulation Profile, which is a commonly used, indirect measure of ED. Hence, the five subscales of the RIPoSt can be reliably used as an effective tool to study the emotional dysregulation in different clinical conditions, to help disentangle the complex relationship between ADHD and juvenile BSD and to provide clinicians with crucial evidence for better diagnostic characterization and therapeutic indications.

Autism Spectrum Disorder and Disruptive Behavior Disorders Comorbidities Delineate Clinical Phenotypes in Attention-Deficit Hyperactivity Disorder: Novel Insights from the Assessment of Psychopathological and Neuropsychological Profiles.

Although childhood-onset psychiatric disorders are often considered as distinct and separate from each other, they frequently co-occur, with partial overlapping symptomatology. Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) commonly co-occur with each other and with other mental disorders, particularly disruptive behavior disorders, oppositional defiant disorder/conduct disorder (ODD/CD). Whether these associated comorbidities represent a spectrum of distinct clinical phenotypes is matter of research. The aim of our study was to describe the clinical phenotypes of youths with ADHD with and without ASD and/or ODD/CD, based on neuropsychological and psychopathological variables. One-hundred fifty-one participants with ADHD were prospectively recruited and assigned to four clinical groups, and assessed by means of parent-reported questionnaires, the child behavior checklist and the behavior rating inventory of executive functions. The ADHD alone group presented a greater impairment in metacognitive executive functions, ADHD+ASD patients presented higher internalizing problems and deficits in Shifting tasks, and ADHD+ODD/CD subjects presented emotional-behavioral dysregulation. Moreover, ADHD+ASD+ODD/CD individuals exhibited greater internalizing and externalizing problems, and specific neuropsychological impairments in the domains of emotional regulation. Our study supports the need to implement the evaluation of the psychopathological and neuropsychological functioning profiles, and to characterize specific endophenotypes for a finely customized establishment of treatment strategies.

A Naturalistic Study of Youth Referred to a Tertiary Care Facility for Acute Hypomanic or Manic Episode.

BACKGROUND: Bipolar Disorders (BD) in youth are a heterogeneous condition with different phenomenology, patterns of comorbidity and outcomes. Our aim was to explore the effects of gender; age at onset (prepubertal- vs. adolescent-onset) of BD; and elements associated with attention deficit hyperactivity disorder (ADHD) and Substance Use Disorder (SUD) comorbidities, severe suicidal ideation or attempts, and poorer response to pharmacological treatments. METHOD: 117 youth (69 males and 57 females, age range 7 to 18 years, mean age 14.5 ± 2.6 years) consecutively referred for (hypo)manic episodes according to the Diagnostic and Statistical Manual of Mental Disorders, 54th ed (DSM 5) were included. RESULTS: Gender differences were not evident for any of the selected features. Prepubertal-onset BD was associated with higher rates of ADHD and externalizing disorders. SUD was higher in adolescent-onset BD and was associated with externalizing comorbidities and lower response to treatments. None of the selected measures differentiated patients with or without suicidality. At a 6-month follow up, 51.3% of the patients were responders to treatments, without difference between those receiving and not receiving a psychotherapy. Clinical severity at baseline and comorbidity with Conduct Disorder (CD) and SUD were associated with poorer response. Logistic regression indicated that baseline severity and number of externalizing disorders were associated with a poorer outcome. CONCLUSIONS: Disentangling broader clinical conditions in more specific phenotypes can help timely and focused preventative and therapeutic interventions.

The Role of Executive Functions in the Development of Empathy and Its Association with Externalizing Behaviors in Children with Neurodevelopmental Disorders and Other Psychiatric Comorbidities.

Executive functions have been previously shown to correlate with empathic attitudes and prosocial behaviors. People with higher levels of executive functions, as a whole, may better regulate their emotions and reduce perceived distress during the empathetic processes. Our goal was to explore the relationship between empathy and executive functioning in a sample of children and adolescents diagnosed with Attention Deficit and Hyperactivity Disorder alone or associated with comorbid Disruptive Behavior Disorders and/or Autism Spectrum Disorder. We also aimed to examine the role of empathic dimensions and executive skills in regulating externalizing behaviors. The 151 participants with ADHD were assigned to four groups according to their psychiatric comorbidity (either "pure" or with ASD and/or ODD/CD) and assessed by means of either parent- or self-reported questionnaires, namely the BRIEF-2, the BES, and the IRI. No questionnaire was found to discriminate between the four groups. Affective Empathy was found to positively correlate with Emotional and Behavioral Regulation competences. Furthermore, Aggressiveness and Oppositional Defiant Problems were positively associated with Executive Emotional and Behavioral Regulation competences. On the other hand, Rule-Breaking Behaviors and Conduct Problems were negatively associated with Affective Empathy and with Behavioral skills. Our study provides an additional contribution for a better understanding of the complex relationship between empathic competence and executive functions, showing that executive functioning and empathic attitudes interact with each other to regulate aggressive behaviors. This study further corroborates developmental models of empathy and their clinical implications, for which externalizing behaviors could be attenuated by enhancing executive functioning skills.

Emotional dysregulation and callous unemotional traits as possible predictors of short-term response to methylphenidate monotherapy in drug-naïve youth with ADHD.

BACKGROUND: Emotional dysregulation (ED) and callous unemotional (CU) traits can be associated with ADHD in youth, influencing its natural history and outcome, but their effect on medication efficacy is unexplored. We examined whether two measures of baseline ED and CU traits, the Child Behavior Checklist-Dysregulation Profile (CBCL-DP) and the Antisocial Process Screening Device (APSD), respectively, were predictors of change of ADHD-Rating Scale (ADHD-RS) after a 4-week methylphenidate (MPH) monotherapy. METHODS: 43 patients (37 males, 8-16 years, mean 9.9 ± 2.7 years) were included. Hierarchical linear regression models were used to explore whether CBCL-DP and APSD might predict ADHD-RS score, controlling for baseline severity. RESULTS: Baseline CBCL-DP predicted higher post-treatment ADHD-RS scores in total and hyperactivity-impulsivity, but not in inattention subscale. Baseline APSD was not significantly related to ADHD-RS scores at the follow-up. LIMITATIONS: Small sample size, lack of gender diversity, non-blind design and short period of observation. CONCLUSION: ED, assessed with that CBCL-DP, might be a negative predictor of change of hyperactive-impulsive symptoms after MPH treatment and should be systematically assessed at baseline.

Effects of melatonin in children with attention-deficit/hyperactivity disorder with sleep disorders after methylphenidate treatment.

PURPOSE: Methylphenidate (MPH), the first-line medication in children with attention-deficit/hyperactivity disorder (ADHD), is associated with increased risk of sleep disorders. Melatonin has both hypnotic and chronobiotic properties that influence circadian rhythm sleep disorders. This study explores the effectiveness of melatonin in children with ADHD who developed sleep problems after starting MPH. PATIENTS AND METHODS: This study, based on a clinical database, included 74 children (69 males, mean age 11.6±2.2 years) naturalistically treated with MPH (mean dosage 33.5±13.5 mg/d). The severity of sleep disorder (sleep onset delay) was recorded at baseline and after a follow-up of at least 4 weeks using a seven-point Likert scale according to the Clinical Global Impression Severity score. Effectiveness of melatonin on sleep (mean dosage 1.85±0.84 mg/d) after 4 weeks was assessed using a seven-point Likert scale according to the Clinical Global Impression Improvement (CGI-I) score, and patients who scored 1 (very much improved) or 2 (much improved) were considered responders. RESULTS: Clinical severity of sleep disorders was 3.41±0.70 at the baseline and 2.13±1.05 after the follow-up (P<0.001). According to the CGI-I score, 45 patients (60.8%) responded to the treatment with melatonin. Gender and age (children younger and older than 12 years) did not affect the response to melatonin on sleep. Patients with or without comorbidities did not differ according to sleep response. Specific comorbidities with disruptive behavior disorders (oppositional defiant disorder or conduct disorder), affective (mood and anxiety) disorders and learning disabilities did not affect the efficacy of melatonin on sleep. Treatment was well tolerated, and no side effects related to melatonin were reported. CONCLUSION: In children with ADHD with sleep problems after receiving MPH treatment, melatonin may be an effective and safe treatment, irrespective of gender, age and comorbidities.

A NATURALISTIC EXPLORATORY STUDY OF OBSESSIVE-COMPULSIVE BIPOLAR COMORBIDITY IN YOUTH.

BACKGROUND: Growing evidence supports the comorbidity between bipolar disorder (BD) and obsessive-compulsive disorder (OCD) in children and adolescents. Our aim is to further explore clinical and treatment implications of this comorbidity, as it appears in clinical practice. METHOD: The sample included 429 consecutive patients with BD and/or OCD as primary diagnoses, followed for a mean period of 6 months (range 4-9 months), 172 with BD (102 males, mean age 13.7±2.9 years), 169 with OCD (118 males, mean age of 13.2±2.7 years) and 88 with comorbid BD+OCD (56 males, mean age 14.2±2.6 years, 52 with BD as the primary diagnosis), followed for a mean period of 6 months (range 4-9 months). The comorbid group was compared to pure BD and OCD groups, to explore differential clinical and treatment features. RESULTS: The BD-OCD comorbidity was found in 33.8% of the BD patients and in 34.2% of the OCD patients. Age at onset of BD and OCD were not different in pure and "comorbid" groups. The comorbid group presented a higher occurrence of BD type II and hoarding symptoms, and more frequently received a psychotherapy and second generation antipsychotics, but it presented the poorest outcome in terms of response to treatments. Severity at baseline (clinical severity and functional impairment), hoarding obsessions and compulsions, and conduct disorder comorbidity were associated with a treatment non-response. LIMITATIONS: A selection bias may have increased the rate of comorbidity, as most of the patients were referred to our tertiary hospital for severe BD and/or OCD and pharmacological treatment. We have used CGI-I as an outcome measure, not a specific measure of BD or OCD symptoms' severity and improvement. The short duration of the follow-up may limit our conclusions. CONCLUSIONS: The timely identification of BD-OCD comorbidity may have relevant clinical implications in terms of symptomatology, course, treatment and outcome.

A Naturalistic Comparison of Methylphenidate and Risperidone Monotherapy in Drug-Naive Youth With Attention-Deficit/Hyperactivity Disorder Comorbid With Oppositional Defiant Disorder and Aggression.

BACKGROUND/PURPOSE: Attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) are frequently co-occurring in youth, but data about the pharmacological management of this comorbidity are scarce, especially when impulsive aggression is prominent. Although stimulants are the first-line medication for ADHD, second-generation antipsychotics, namely, risperidone, are frequently used. We aimed to assess effectiveness and safety of monotherapy with the stimulant methylphenidate (MPH) and risperidone in a consecutive sample of 40 drug-naive male youths diagnosed as having ADHD-combined presentation, comorbid with ODD and aggression, without psychiatric comorbidities, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria and a structured clinical interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version). METHODS: Twenty males treated with MPH (mean age, 8.95 ± 1.67 years) and 20 males treated with risperidone (mean age, 9.35 ± 2.72 years), followed up to 6 months, were assessed according to efficacy measures (Child Behavior Checklist [CBCL], Clinical Global Impression-Severity [CGI-S] and Improvement [CGI-I], Children Global Assessment Scale), and safety measures. At the end of the follow-up, both medications were similarly effective based on CBCL subscales of aggression and rule-breaking behaviors, on Diagnostic and Statistical Manual of Mental Disorders-oriented oppositional defiant problems and conduct problems, and on CGI-S, CGI-I, and Children Global Assessment Scale, but only MPH was effective on CBCL attention problems and attention-deficit/hyperactivity problems. Risperidone was associated with weight gain and elevated prolactin levels. IMPLICATIONS/CONCLUSIONS: Although the nonrandomized, nonblind design limits the conclusions of our exploratory study, our findings suggest that when ADHD is comorbid with ODD and aggression MPH and risperidone are both effective on aggressive behavior, but only stimulants are effective on ADHD symptoms.

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.

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% Children's 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 augmentation of selective serotonin reuptake inhibitors in resistant tic-related obsessive-compulsive disorder in children and adolescents: a naturalistic comparative study.

The aim of this study is to assess efficacy of augmentation of SSRIs with risperidone or aripiprazole in youths with tic-related Obsessive-Compulsive Disorder (OCD) non responders to an SSRI monotherapy. 120 consecutive patients (age range 7-18 years) were treated with an SSRI monotherapy for at least 12 weeks, 51 (42.5%) were responders, and the 69 non-responders (mean age 13.7 ± 2.4 years) were included in this study. 35 patients received an augmentation with risperidone (1.7 ± .8 mg/day), and 34 with aripiprazole (8.9 ± 3.1 mg/day) for 12 weeks. Regarding the OCD symptomatology, at the endpoint the Clinical Global Impression-Severity score (CGI-S) improved from 5.6 ± .8 (severely ill), to 3.2 ± .9 (mild to moderately ill) (p < .0001), and the Children-Global Assessment Scale (C-GAS) from 40.3 ± 5.2 to 53.8 ± 9.2 (p < .0001). Thirty-nine patients (56.5%) were responders in OCD symptomatology (CGI-I score 1 or 2, CGI-S score 3 or less and C-GAS score 50 or more during three consecutive months after a 12-week treatment). Compared to non responders, they were less impaired at the baseline in CGI-S (p < .0001) and C-GAS (p < .0001). Subtypes of OCD and comorbidity did not affect the response. No differences were found between risperidone and aripiprazole augmentation. 47 patients (68.1%) significantly improved tics, without differences between risperidone and aripiprazole. None discontinued medications because of side effects, but risperidone was associated with weight gain and sedation, and aripiprazole to mild/moderate agitation. In tic-related pediatric OCD, augmentation of SSRIs with risperidone or aripiprazole was tolerated and effective in about half of the patients non responding to an SSRI.

Pediatric social anxiety disorder: predictors of response to pharmacological treatment.

OBJECTIVE: Pediatric social anxiety disorder (SAD) is associated with an increased risk of comorbid mental disorders, with implications for prognosis and treatment strategy. The aim of this study is to explore predictors of treatment response, and the role of comorbidity in affecting refractoriness. METHODS: One hundred and forty consecutive youths (81 males, 57.9%), ages 7-18 years (mean age 13.7 ± 2.5 years, mean age at onset of SAD 10.6 ± 2.7 years) met American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for SAD as primary diagnosis, according to a structured clinical interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime Version [K-SADS-PL]). All received a pharmacological treatment with serotonin reuptake inhibitors (SSRIs) targeted to SAD, associated with additional medications for comorbidities (mood stabilizers in 27.1%, antipsychotics in 12.8%) and 57.9% received an additional psychotherapy. RESULTS: Eighty-nine patients (63.6%) responded to treatments after 3 months, namely 72.8% with psychotherapy plus medication and 50.8% with medication only. Nonresponders had more severe symptoms at baseline in terms of both clinical severity and functional impairment, and had more comorbid disruptive behavior disorders. The backward logistic regression indicated that clinical severity and functional impairment at baseline, comorbid disruptive behavior disorders, and bipolar disorders were predictors of nonresponse. CONCLUSION: Our data suggest that SSRIs can be effective in pediatric SAD, but that the more severe forms of the disorder and those with heavier comorbidity are associated with poorer prognosis.

Developmental pathways for different subtypes of early-onset bipolarity in youths.

OBJECTIVE: Two main patterns of comorbidity have been described in bipolar disorder in children and adolescents: the first including preexisting attention-deficit/hyperactivity disorder (ADHD) and related disruptive behavior disorders and the second including anxiety disorders, namely, the association of co-occurring multiple anxiety disorders, usually predating the onset of bipolarity. This study was aimed at exploring whether ADHD and multiple anxiety disorders may exhibit different pathways to specific bipolar phenotypes. METHOD: We compared 49 youths (7 to 18 years) with bipolar disorder + ADHD without anxiety, 76 youths with bipolar disorder + multiple anxiety disorders without ADHD, and 52 youths with bipolar disorder without ADHD or multiple anxiety disorders who were referred to a third-level hospital and diagnosed according to DSM-IV-TR in the period 2005-2011. Subjects were evaluated for current and lifetime Axis I psychiatric disorders by using a structured clinical interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime Version) and followed up for at least 6 months. RESULTS: Compared to both patients with bipolar disorder + multiple anxiety disorders and patients with bipolar disorder without ADHD and multiple anxiety disorders, patients with bipolar disorder + ADHD without anxiety were more frequently male, were younger, had an earlier onset of bipolar disorder, had a prevalent chronic course and irritable mood, were more likely to present with a bipolar disorder not otherwise specified diagnosis, had a greater clinical severity and functional impairment, had a manic/mixed index episode, had a higher risk of conduct disorder, and were more resistant to treatments, according to the CGI-Improvement scores (P < .0001). Patients with bipolar disorder + multiple anxiety disorders were similar to those with bipolar disorder without ADHD or multiple anxiety disorders, except for a higher rate of diagnosis of bipolar II disorder, more use of antidepressants, and less use of atypical antipsychotics. CONCLUSIONS: The presence of comorbid ADHD versus anxiety disorders is indicative of fundamental differences in the phenomenology of bipolar disorder in youth. While ADHD prior to bipolar disorder is associated with a specific bipolar phenotype, bipolar patients with multiple anxiety disorders are similar to "typical" bipolar patients.

Aripiprazole in children with Tourette's disorder and co-morbid attention-deficit/hyperactivity disorder: a 12-week, open-label, preliminary study.

Tourette's disorder (TD) in children and adolescents is frequently co-morbid with attention-deficit/hyperactivity disorder (ADHD). Dopamine-blockers are the first line treatment for TD, whereas dopamine-agonists, such as stimulants, are the gold-standard in the treatment of ADHD. These contrasting effects supported concerns about the risk that stimulants for treating ADHD may trigger or worsen co-morbid tics. Aripiprazole, a partial dopamine agonist, acts as an antagonist at dopamine D2 receptors in hyperdopaminergic conditions and displays agonist properties under hypodopaminergic conditions. The present study describes the use of aripiprazole (10.0 ± 4.8 mg/day) in a consecutive group of 28 patients with a primary diagnosis of TD and co-morbid ADHD, combined subtype. The Yale Global Tic Severity Scale (YGTSS) and the ADHD-Rating Scale (ADHD-RS-IV) were used as primary outcome measures and both significantly improved (p<0.001) after the treatment. Global measures of severity (Clinical Global Impressions-Severity) and of functional impairment (Children's Global Assessment Scale) also significantly improved during the treatment (p<0.001). At the YGTSS there was a reduction of 42.5%, in motor tics, of 47.9% in phonic tics (44.7% for the combined scores), and of 32.3% in tic impairment. Nineteen patients (67.9%) had a reduction of at least 50% of the YGTSS score (motor+phonic tics). The improvement at the ADHD-RS-IV score was 22.5%, 12 patients (42.8%) presented an improvement of 30%, but only 2 (7.1%) an improvement greater than 50%. Using a logistic regression model, a reduction of at least 30% in ADHD-RS-IV score was more likely to occur in the obsessive-compulsive disorder co-morbid group. Aripiprazole was well tolerated and none of the patients discontinued medication because of side effects. In summary, aripiprazole resulted in an effective treatment for TD, but it was only moderately effective on co-occurring ADHD symptomatology. Our preliminary data suggest that aripiprazole may represent a possible therapeutic option, among other possible monotherapies addressing both tics and ADHD.

Aripiprazole augmentation in 39 adolescents with medication-resistant obsessive-compulsive disorder.

The aim of this study was to assess efficacy of aripiprazole augmentation of serotonin reuptake inhibitor (SRI) treatment in adolescents with obsessive-compulsive disorder (OCD) who did not respond to 2 initial trials with SRI monotherapy. A consecutive series of 39 adolescents (28 males and 11 females; age range, 12 to 18 years; mean age, 14.6 ± 1.2 years), with OCD diagnosed based on a clinical interview and according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, were included. The mean final aripiprazole dosage was 12.2 ± 3.4 mg/d. At the endpoint, 27 patients (59.0%) had a Clinical Global Impression (CGI)-Improvement score 1 or 2 (very much or much improved) and a Clinical Global Impression-Severity (CGI-S) score 3 or below and were thus considered responders. The CGI-S improved from 6.0 ± 0.9 at the baseline (severely to extremely severely ill) to 3.5 ± 1.0 (mild to moderately ill) at the end of the follow-up (P < 0.0001), whereas the Children's Global Assessment Scale improved from 39.2 ± 5.8 to 49.8 ± 9.0 (P < 0.0001). Compared with nonresponders, responders were less impaired at the baseline in functional impairment (Children's Global Assessment Scale; P = 0.004) but not in clinical severity (CGI-S). Subtypes of OCD comorbidity and absence of insight did not affect clinical response. Mild transitory agitation (10.3%), mild sedation (10.3%), and sleep disorders (7.7%) were reported, but any of the patients discontinued medication because of adverse effects.In these severely impaired adolescents, aripiprazole augmentation of SRIs was well tolerated and effective in more than half of the patients.