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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.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.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.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.

Background. The literature on time perception in individuals with ADHD is extensive but inconsistent, probably reflecting the use of different tasks and performances indexes. Methods. A sample of 40 children/adolescents (20 with ADHD, 20 neurotypical) was engaged in two identical psychophysical tasks measuring auditory time thresholds for both subsecond (0.5-1s) and suprasecond (0.75-3s) stimuli. Results. Results showed a severe impairment in ADHD for subsecond thresholds (Log10BF=1.9). The deficit remained strong even when non-verbal IQ was regressed out and correlation with age suggests a developmental delay. Suprasecond thresholds were indistinguishable between the two groups (Log10BF = –0.5) and not correlated with subsecond thresholds. Conclusions. Since much evidence suggest that perception of subsecond stimuli does not load on cognitive control and working memory, the current results are consistent with a pure timing deficit in individuals with ADHD.

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

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.

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.

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).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.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.

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 (p0.0001). 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 in50% of the patients.

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.

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.

This study reports on the naturalistic pharmacotherapy of 266 youths with bipolar disorder (BP), manic or hypomanic episode (158 males and 108 females, 13.8±2.8 years), first treated with monotherapy on valproic acid (VPA) ( n =158, 59.4%), lithium ( n =90, 33.8%) or atypical antipsychotics ( n =18, 6.8%). Among the patients receiving mood stabilizers, 59.5% of those treated with VPA and 47.8% of those receiving lithium did not need other antimanic agents (mood stabilizers and/or atypical antipsychotics). Lower severity was associated with a greater persistence of both VPA and lithium monotherapy. Factors associated with greater persistence of VPA monotherapy were BP II and co-occurring generalized anxiety disorder, separation anxiety disorder and simple phobias. On the contrary, BP I and co-occurring psychotic symptoms and/or conduct disorder were associated with a lower persistence of VPA monotherapy. Factors associated with lower persistence of lithium monotherapy were younger age and the association with attention deficit hyper-activity disorder (ADHD). Type of BP and presence of psychotic symptoms and conduct disorder did not affect the lithium monotherapy. Overall, predictors of non-response (multiple stepwise logistic regression) in both VPA and lithium groups were baseline Clinical Global Impression (CGI) Severity score and comorbid conduct disorder; while psychotic symptoms and absence of comorbid generalized anxiety disorder were predictors of poorer treatment response only in the VPA group, and chronic course, comorbid ADHD and absence of comorbid panic disorder were predictors only in the lithium group. Such naturalistic data from an ordinary clinical setting have relevance to clinical practice.

Introduction: The high percentage (between 40% and 60%) of resistance to first-line drugs, such as clomipramine or selective serotonin reuptake inhibitors, is a major problem in the pharmacologic management of obsessive-compulsive disorder (OCD). In these cases, different strategies have been employed with controversial outcomes. The meager information available on the association of two serotonergic drugs prompted us to explore the possible effectiveness and tolerability of citalopram+clomipramine in resistant OCD patients.Methods: Twenty outpatients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of OCD, who had failed to respond to at least two trials with a selective serotonin reuptake inhibitor and were currently taking clomipramine at different doses, were administered citalopram at a maximum dose of 60 mg/day. The clinical assessment was carried out at baseline (t0) and at the 4th (t1), 12th (t2), 24th (t3), 36th (t4), and 48th (t5) week by means of the Yale-Brown Obsessive Compulsive Scale, Hamilton Rating Scale for Depression, Clinical Global Impression scale, and the Dosage Record and Treatment Emergent Symptom Scale. The response was defined as a 35% decrease of the Yale-Brown Obsessive Compulsive Scale total score.Results: The results showed that ∼50% of the patients improved significantly after 1 month of this regimen and after 1 year of treatment.Conclusion: This study, although carried out in a small sample and in an open fashion, represents one of the few experiences with the association of two serotonergic compounds in resistant OCD and confirms its potential usefulness and good tolerability profile. Controlled research on this association in OCD is recommended.

This paper reports on implications of bipolar disorder (BD) co-morbidity in 120 children and adolescents with obsessive-compulsive disorder (OCD) (84 males, 36 females, age 13.7 +/- 2.8 years), diagnosed using a clinical interview according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria, and naturalistically followed-up for 12 +/- 6 months. The aim of this naturalistic, retrospective study was to explore the effect of BD co-morbidity, disentangling it from other co-occurring variables, namely the co-morbidity with disruptive behavior disorders. Forty three patients (35.8%) had a bipolar co-morbidity. Compared with OCD patients without BD, they had an earlier onset of OCD, a greater severity and functional impairment, more frequent hoarding obsessions and compulsions, and a poorer response to treatments. They had a higher co-morbidity with attention-deficit/hyperactivity disorder (ADHD) and oppositional-defiant disorder (ODD), and a lower co-morbidity with generalized anxiety disorder (GAD). Finally, they received more mood stabilizers, and 30.2% of them did not receive serotonin-selective reuptake inhibitors (SSRIs) because of pharmacological (hypo)mania. When all the OCD responders and nonresponders were compared, nonresponders (n = 42, 35%) were more severe at baseline and at end of the follow-up, had more frequently hoarding obsessions and compulsions, and had more frequent BD, ODD, and conduct disorder (CD) and less GAD and panic disorder. In the final regression model, hoarding obsessions and compulsions, co-morbidity with ODD, and CD were negative predictors of treatment outcome. This study suggests that even though bipolar co-morbidity is frequent and affects phenomenology and co-morbidity in pediatric OCD, its effect on treatment response seems prevalently accounted for by co-morbidity with disruptive behavior disorders. The significance of the hoarding subtype deserves further research on larger samples of pediatric patients.

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.

Objective: A substantial portion of juvenile bipolar disorder (BD) has a comorbid attention-deficit hyperactivity disorder (ADHD). The aim of our study was to analyze the cross-sectional and longitudinal implications of such comorbidity in children and adolescents with BD. Methods: Ninety-eight refereed patients (mean age 13.7 ± 3.0 years) with a diagnosis of BD by the Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifetime version (K-SADS-PL) were followed for 6 months. Results: Thirty-seven BD patients (37.8%) presented a lifetime diagnosis of comorbid ADHD. The mean age of onset of ADHD was 3.7 ± 1.1 years, and the mean age of onset of BD was 10.0 ± 3.2 years. Bipolar subjects with comorbid ADHD were predominantly male, younger, and had an earlier onset of BD (8.1 ± 2.8 versus 11.1 ± 2.9 years). Bipolar-ADHD patients presented more frequently a chronic rather than an episodic course of BD, with an irritable rather than an elated mood. They showed higher rates of oppositional defiant disorder/conduct disorder, lower rates of panic disorder, and less frequently received antidepressant medications. Finally, ADHD comorbidity was associated with a greater psychosocial impairment. Conclusions: ADHD comorbidity is frequent in juvenile BD and can influence age of onset, phenomenology, comorbidity, and course of BD. A timely diagnosis should improve our efforts regarding the outcome of these subjects.

Objective The aim of this study was to explore whether comorbid attention-deficit/hyperactivity disorder (ADHD) affects the clinical expression and outcome of obsessive-compulsive disorder (OCD) in a clinical sample. Method A consecutive series of 94 children and adolescents (mean age, 13.6 ± 2.8 years) with current diagnosis of OCD were included in the study. Twenty-four (25.5%) patients were diagnosed as having a comorbid ADHD. Subjects with OCD plus ADHD were compared with subjects with OCD but without ADHD. Results Comorbid ADHD with OCD was significantly associated with a higher rate of males, an earlier onset of OCD, a greater psychosocial impairment, and a heavier comorbidity, namely, with bipolar disorder, tic disorder, and oppositional defiant disorder/conduct disorder. Phenomenology of obsessions and compulsions and outcome were not affected by ADHD comorbidity. Conclusions A screening for ADHD should be performed in patients with OCD, as these patients and their parents are frequently not aware that the impairment may be partly due to a comorbid ADHD.

ResumenEl insight es un fenómeno complejo que se puede interpretar según un modelo dimensional. Dados los polémicos datos del insight en el trastorno obsesivo-compulsivo (TOC), nuestro estudio tenía el propósito de investigar este fenómeno en una muestra italiana de pacientes con TOC por medio del elemento específico en la Escala de Obsesión-Compulsión de Yale-Brown (Y-BOCS) y explorar las posibles correlaciones entre el insight y los rasgos clínicos. Se incluyó en el estudio a 117 pacientes ambulatorios con un diagnóstico del DSM IV de TOC y diferentes trastornos psiquiátricos comórbidos y se los evaluó por medio de la Y-BOCS, la Escala de Depresión de Hamilton (HRSD) y la Impresión Clínica Global. Los resultados mostraron que casi el 50% de los pacientes tenía un nivel excelente de insight y el 15% tenía poco o ningún insight. No se observó correlación entre los niveles de insight y los rasgos clínicos, excepto una tendencia negativa con la presencia de obsesiones somáticas. Además, se observó una tendencia hacia un nivel inferior de insight en los pacientes bipolares con antecedentes positivos de episodios maníacos o hipomaníacos repetidos. Parecen necesarios estudios adicionales para establecer si los pacientes de TOC con mal insight representan o no un subgrupo distinto de pacientes.

Obsessive-compulsive disorder (OCD) is a common psychiatric condition during childhood and adolescence, which continues to be underestimated and undertreated. For these reasons, it constitutes a primary cause of major disabilities in those ages and, sometimes, of permanent impairments later on. In these last few years, childhood and adolescence OCD has attracted an increasing focus which has promoted a deeper awareness of this illness, a better recognition with earlier interventions, as well as the set-up of more tailored and specific strategies, including psychotropic drugs. The aim of this paper is to present a critical review of paediatric OCD, with a special attention towards the most compelling reports available up to now and towards the most interesting areas for future research.

Different findings suggest that the serotonin (5-HT) system may be involved in both the regulation of aggression and the pathophysiology of obsessive-compulsive disorder (OCD). Our study aimed to evaluate the aggressive features of a group of OCD patients and to explore possible correlations with a serotonergic marker, namely platelet 5-HT transporter. Psychopathological and biological patterns were compared with those of a group of healthy controls and those of patients with major depression. Twenty-one patients affected by OCD, 21 by depression and 21 healthy controls were included in the study. Aggressive features were measured by means of the Buss and Durkee Hostility Inventory (BDHI). The platelet 5-HT transporter was evaluated by means of the 3H-paroxetine binding parameters (maximum binding capacity, Bmax and dissociation constant, Kd). The OCD patients showed a total score on the BDHI not significantly different from that of healthy controls and lower than that of depressed patients. The factor profile was similar in the 3 groups, but higher in the depressed patients. The irritability, resentment, guilt, negativism and suspiciousness factors were significantly more pronounced in depressed patients. Some sex-related difference in single factors were also observed. The Bmax of 3H-paroxetine binding was lower in OCD patients than in depressives or healthy controls. OCD patients were more similar to healthy controls than to depressed patients with regard to aggressive features measured by means of the BDHI. This suggests that aggression in OCD is a complex phenomenon that probably requires specific instruments of evaluation.

The course of obsessive-compulsive disorder (OCD) is variable, ranging from episodic to chronic. We hypothesised that the former course is more likely to be related to bipolar mood disorders. With the use of a specially constructed OCD questionnaire, we studied 135 patients fulfilling DSM-III-R criteria for OCD with an illness duration of at least 10 years and divided by course: 27.4% were episodic and 72.6% chronic. We compared clinical and familial characteristics and comorbidity. Univariate analyses showed that episodic OCD had a significantly lower rate of checking rituals and a significantly higher rate of a positive family history for mood disorder. Multivariate stepwise discriminant analysis revealed a positive and significant relationship between episodic course, family history for mood disorders, lifetime comorbidity for panic and bipolar-II disorders, late age at onset and negative correlation with generalized anxiety disorder. These data suggest that the episodic course of OCD has important clinical correlates which are related to cyclic mood disorders. This correlation has implications for treatment and research strategies on the aetiology within a subpopulation of OCD.

The present study reports the results of an open-label trial on the use of the combination of olanzapine (an atypical antipsychotic) serotonin reuptake inhibitors (SRIs) in 26 resistant outpatients affected by resistant obsessive-compulsive disorder (OCD). All patients had been suffering from OCD, according to DSM IV criteria, for at least 2 years and had different comorbid disorders; they had been treated with an SRI at adequate dosages for at least 6 months, or had tried different augmentation strategies with no or poor response. As a result, olanzapine was added and continued for 1 year. After 12 weeks of this regimen, most of the patients (17) had shown a reduction in OC symptoms, as assessed by a decrease in the Yale-Brown Obsessive Compulsive Scale total score, which continued throughout subsequent months. Only mild side-effects were recorded and no patient halted the treatment. The addition of olanzapine would appear to be a useful short- and long-term strategy for augmenting SRI effectiveness in resistant OCD patients, especially in those presenting comorbidity with bipolar disorders.

The similarities between the serotonin (5-HT) transporter in both human platelets and human brain permit us to investigate this structure in patients with different psychiatric disorders. Several reports have shown abnormalities of the 5-HT transporter, by means of the measurement of the 5-HT uptake or of the 3H-imipramine binding, in platelets of patients with obsessive-compulsive disorder (OCD). The availability of the ligand 3H-paroxetine, a selective 5-HT reuptake inhibitor, to label the 5-HT transporter, promoted us to evaluate the binding of 3H-paroxetine in platelets of 18 drug-free patients with OCD. The results, showing that the patients had a lower number of 3H-paroxetine sites, which is inversely correlated with the Yale Brown Obsessive-Compulsive Scale total score, than a similar group of controls, add supporting evidence to the involvement of 5-HT in OCD. In addition, the decreased functionality of the 5-HT transporter seems to be linked to the severity of OC symptoms.

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 (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.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.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.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.

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

Background: Few studies have examined the impact of gender, age at onset, phenotype and comorbidity in pediatric obsessive-compulsive disorder (OCD) in children. In this naturalistic study we consider these characteristics of OCD in the framework of the 4 OCD phenotypes (contamination/cleaning, order/symmetry, obsessions/checking and hoarding) proposed by Leckman et al. Sampling and Methods: A consecutive series of 257 patients aged 13.6 ± 2.8 years, diagnosed using a DSM-IV-based clinical interview (Schedule for Affective Disorders and Schizophrenia for School Age Children – Present and Lifetime Version), were included. Results: Patients with OCD onset before 12 years of age presented a higher frequency of comorbid tic disorder and disruptive behavior disorders. The type of obsession varied with gender: order/symmetry was more frequent in males, contamination/cleaning in females. Order/symmetry had the highest comorbidity with tics, contamination/cleaning was the least severe according to the Clinical Global Impression Severity, and was associated with a high rate of comorbid anxiety and depression, similarly to sexual-religious obsessions. Hoarding was the severest according to the Clinical Global Impression Severity, and was associated with a high comorbidity with social phobia and bipolar disorder. Tic comorbidity was more prevalent in males, had an earlier onset, and a heavier comorbidity with attention deficit hyperactivity disorder and other disruptive behavior disorders. A comorbid attention deficit hyperactivity disorder was associated with an earlier onset of OCD and a poorer response to treatments. Conclusions: OCD phenotypes and comorbidities may have marked clinical and prognostic implications. Tertiary care population results may not generalize to less impaired juvenile populations.

Background: Pediatric obsessive-compulsive disorder (OCD) can cause substantial impairment in academic, social and family functioning. Even though cognitive-behavioural therapy (CBT) is an effective treatment, the pharmacological option has to be taken into consideration. Effectiveness of serotonin reuptake inhibitors (SRIs) has been supported by several double-blind, placebo-controlled studies. Objective: To report the response to pharmacotherapy in children and adolescents with OCD naturalistically followed up and treated with SRIs. Methods: From a consecutive series of 257 patients (174 males and 83 females; mean age 13.6 ± 2.7 years) diagnosed with OCD following a clinical interview according to DSM-IV criteria, 37 children improved significantly after psychotherapy and were excluded. The remaining 220 patients were included in the study. Results: Eighty-nine patients (40.5%) were managed with SRI monotherapy and 131 with an SRI in combination with another medication. Compared with those who needed polypharmacy, patients managed with SRI mono-therapy were younger at the time of the first consultation, had less severe symptoms at baseline, and more frequently presented with co-occurring anxiety and depressive disorders, while patients receiving polypharmacy presented with higher rates of bipolar disorder, tic disorder and disruptive behaviour disorders. 135 patients (61.4%) achieved a positive clinical response and were considered responders. When differences between responders and nonresponders at the end of follow-up were considered, irrespective of the pharmacological treatment (monotherapy or polypharmacy), responders had less severe disease at baseline, were younger at the time of the first consultation, more frequently presented with the contamination/cleaning phenotype and less frequently presented with the hoarding phenotype. Treatment refractoriness was associated with higher rates of conduct disorder and bipolar disorder, and lower rates of generalized anxiety disorder and panic disorder. Forty-three children received therapy with an atypical anti-psychotic as an augmenting strategy, and 25 of these children (58.1%) became responders. Responders to augmentation were less severely impaired at baseline, while different subtypes of OCD were similar between responders and nonresponders, as were patterns of co-morbidity. Conclusion: Our study suggests that putative variables associated with response to pharmacological treatment of paediatric OCD can be defined, and can help improve treatment strategies.

This study on a large sample of unselected, consecutive children and adolescents referred to a third-level hospital who received a diagnosis of bipolar disorder (BD) was aimed at exploring whether childhood-onset BD, as compared with adolescent-onset BD, presents specific clinical features in terms of severity, functional impairment, course, prevalent mood, pattern of co-morbidity, and treatment outcome.A total of 136 patients, 81 males (59.6%) and 55 females (40.4%), mean age 13.5 +/- 2.9 years, meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of BD according to a structured clinical interview Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (KSADS-PL), were included in the study.Eighty patients (58.8%) had a childhood-onset BD (before 12 years of age) and 56 (41.2%) had an adolescents-onset BD. Compared with the adolescent-onset BD, patients with childhood-onset were more frequently males and had a more frequent co-morbidity with attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). An episodic course was found in only 42.5% of bipolar children, but 76.8% of youngsters with adolescent-onset BD. Severity, 6-month treatment outcome, prevalent mood (elated versus irritable), and co-morbid anxiety did not differentiate the two groups.Our findings suggest that a very early age at onset may identify a form of BD with a more frequent subcontinuous course and a heavy co-morbidity with ADHD.

Objective According to DSM-IV , bipolar disorders (BDs) include four subtypes, BD I, BD II, cyclothymic disorder, and BD not otherwise specified (NOS). We explore the clinical implications of this subtyping in a naturalistic sample of referred youths with BD I, BD II, and BD-NOS. Method The sample consisted of 217 patients, 135 males and 82 females, ages between 8 and 18 years (mean age, 13.6 ± 2.9 years), diagnosed according to historical information, prolonged observations, and a structured clinical interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version). The location of the study was the Stella Maris Scientific Institute of Child Neurology and Psychiatry of Pisa (Italy). Results Seventy-eight patients (35.9%) had BD I, 97 (44.7%) had BD II, and 42 (19.4%) had BD-NOS. Patients with BD I presented more frequently psychotic symptoms and elated rather than irritable mood. Patients with BD II were less severely impaired, presented more frequently depression as the intake affective episode, and had the highest comorbidity with anxiety disorders. Patients with BD-NOS presented an earlier onset of the disorder, a chronic rather than episodic course, an irritable rather than an elated mood, and a more frequent comorbidity with attention-deficit/hyperactivity disorder and oppositional defiant disorder. Conclusions DSM-IV categorization of BD may have meaningful implications in youths, but needs to be detailed further.

Introduction: The aim of this study was to compare the level of insight in patients with body dysmorphic disorder (BDD) with and without comorbid obsessive-compulsive disorder (OCD), and to measure its possible relationships with clinical features.Methods: Thirty outpatients affected by BDD, according to Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition criteria, of whom 18 were also suffering from OCD, were included in the study. Clinical assessment was carried out by means of the Yale-Brown Obsessive-Compulsive Scale modified for BDD and a specially designed OCD Questionnaire. The level of insight was measured by means of the score at item 11 of the Yale-Brown Obsessive-Compulsive Scale modified for BDD.Results: The insight resulted to be excellent in four cases, good in four, fair in five, poor in 15 and absent in two. Significant and positive correlations were observed between the level of insight and the following items: resistance to thoughts and to activities as well as to time spent on activities and control on activities related to the defect. The insight was significantly lower in patients affected by both BDD and OCD.Conclusion: The findings indicate that the majority of BDD patients in this study, and especially those with comorbid OCD, have a low degree of insight that is significantly correlated to symptoms specific of the disorder.

This paper aims to critically review currently available data on kleptomania and to analyze the possible future evolution of clinical research and therapeutic strategies.

SummaryInsight is a complex phenomenon that can be interpreted according to a dimensional model. Given the controversial data of insight in obsessive–compulsive disorder (OCD), our study aimed to investigate insight in an Italian sample of patients with OCD by means of the specific item on the Yale–Brown obsessive–compulsive scale (Y-BOCS) and to explore the possible correlations between it and clinical features. One hundred and seventeen out-patients with a DSM-IV diagnosis of OCD and different comorbid psychiatric disorders were included in the study and assessed by means of the Y-BOCS, Hamilton rating scale for depression (HRSD) and the global clinical impression. The results showed that almost 50% of the patients had an excellent level of insight and 15% had a little or no insight. No correlation between levels of insight and clinical features was observed, except for a negative trend with the presence of somatic obsessions. In addition, a trend towards a lower level of insight was observed in those bipolar patients with a positive history of repeated manic or hypomanic episodes. Further studies seem to be necessary in order to establish whether or not OCD patients with poor insight represent a distinct sub-group of patients.

Risperidone, an atypical neuroleptic, has been proposed for augmentation strategies in resistant obsessive-compulsive disorder (OCD). We report the results of an open-label trial on the use of the combination of serotonin reuptake inhibitors (SRIs) with risperidone in 20 refractory OCD outpatients. All patients had been suffering from OCD, according to DSM-IV criteria, for at least 2 years and had various comorbid disorders. All had been treated with a SRI at adequate dosages for at least 6 months, but had failed to respond. Therefore, risperidone was added and the dosage titrated up to the mean dose of 3 mg/day over 8 weeks. After 2 months of this regimen, all patients had shown a reduction in obsessive-compulsive symptoms, as assessed by the decrease in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) total score, particularly those with a lifetime comorbidity with bipolar disorder; only three patients reported mild sedation and postural hypotension, two mild extrapyramidal side-effects (tremors and akatysia) and two an increased appetite. All these effects were well tolerated and no patient halted the treatment. The addition of risperidone would appear to be a useful strategy for augmenting SRI effectiveness in refractory OCD patients.

This paper reports on the psychometric properties of the Structured Clinical Interview for Obsessive-Compulsive Spectrum (SCI-OBS) and the Structured Clinical Interview for Social Phobia Spectrum (SCI-SHY). Interviews were administered to 135 patients with psychiatric disorders and 119 controls. During the same session, subjects were given the Mini International Neuropsychiatric Interview (MINI), the Liebowitz Social Anxiety Scale (LSAS), the Checklist for Obsessions and Compulsions and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Patients and raters also answered specific questions on acceptability and usefulness of the interviews. Inter-rater reliability was assessed by administering the interviews to 36 patients with psychiatric disorders and 12 controls. The internal consistency of all domains of the interviews was from moderate to substantial (Kuder-Richardson coefficient >0.60). Discriminant validity was excellent. The concurrent validity of the SCI-SHY versus the LSAS and of the SCI-OBS versus the Checklist for Obsessions and Compulsions was satisfactory. However, no association was found between Y-BOCS and the SCI-OBS domains. Inter-rater reliability was substantial. Both interviews were rated as meaningful and clear by most subjects. Raters' attitudes toward the utility of these interviews for understanding patients and their foreseeable use in their practice varied, but most were in favour of administering them as self-report instruments. Copyright © 2000 Whurr Publishers Ltd.

Background: Some recent findings suggest the involvement of autoimmune mechanisms in childhood onset of obsessive-compulsive disorder (OCD), on the basis of a parallel drawn with Sydenham's chorea, a manifestation of rheumatic fever. A monoclonal antibody called D8/D17 characterizing a B-lymphocyte antigen, present in almost all patients with rheumatic fever, has been found also in children affected by OCD, Tourette syndrome, and chronic tics to a greater degree than in healthy control subjects. The few observations of disturbances of some immunologic parameters in adult OCD patients, prompted the authors to investigate and compare subsets of peripheral immunological cells for differences in adult patients with OCD and healthy control subjects. Methods: Twenty patients suffering from OCD, with no comorbidity for other psychiatric disorders, were compared with a similar group of healthy control subjects. The immune subsets were measured by flow cytometry. Results: The CD8 + lymphocytes were significantly increased and CD4 + lymphocytes significantly decreased in OCD patients, while the other cells did not differ between the two groups. No correlation was found between immunologic and clinical parameters. Conclusions: These data indicate that patients with adult OCD showed increased CD8 + , i.e., suppressor T lymphocytes, and decreased CD4 + , which identify helper T lymphocytes, as compared with a similar group of healthy control subjects. The findings appear peculiar to patients with OCD and are suggestive of an immunologic imbalance, which might be related to the stress deriving from the frustrating situation determined by the disorder itself.

The recently introduced notion of clinical conditions being related one to another, the spectrum concept, permits the testing of the involvement of serotonergic systems in a broad range of disorders tentatively linked to obsessive-compulsive disorder (OCD) for which no pathophysiological hypotheses yet exist. We therefore compared the binding of [3H]paroxetine ([3H]Par), a ligand that specifically labels the serotonin (5-HT) transporter, in platelets of drug-free outpatients suffering from various OCD-related disorders with binding in platelets of OCD patients and healthy subjects. Diagnoses were made according to DSM-IV criteria. The most frequent diagnosis was that of body dysmorphic disorder, followed by impulse control disorder, kleptomania, Tourette's syndrome and trichotillomania. Platelet membranes and [3H]Par binding were studied according to standardized protocols. The results, showing a similarly decreased density of [3H]Par binding sites in both patient groups as compared with healthy subjects, suggest the presence of a shared abnormality at the level of the presynaptic 5-HT transporter, probably linked to a common dimension yet to be identified.

Previous studies on the comorbidity of Obsessive-Compulsive Disorder (OCD) have largely focused on comorbidity with major depressive and anxiety disorders. The present investigation deals with a more complex pattern of comorbidity involving bipolarity. Indeed, in a consecutive series of 315 OCD outpatients, 15.7% had such comorbidity (mostly with bipolar II disorder). Unlike non-bipolar OCD patients, these had a more gradual onset of their OCD which, nonetheless, pursued a more episodic course with a greater number of concurrent major depressive episodes. These bipolar OCD patients had a significantly higher rate of sexual and religious obsessions, and a significantly lower rate of checking rituals. OCD probands with non-bipolar major depressive comorbidity (34.8%) were then compared with the remainder of OCD. These 'unipolar' OCD were older, had a more chronic course with hospitalizations and suicide attempts, had greater comorbidity with generalized anxiety disorder and caffeine abuse; finally, they were more likely to have aggressive obsessions and those with a philosophical, superstitious or bizarre content. Our data suggest that when comorbidity occurs with bipolar and unipolar affective disorders it has a differential impact on the clinical characteristics, comorbidity and course of OCD. We submit that the presence of major depression in OCD is incidental, as OCD in such cases dominates the course and dictates treatment choice. By contrast, when bipolar and obsessive-compulsive disorders co-exist, bipolarity should take precedence in diagnosis, course and treatment considerations.