Maria Mucci

Symptomatology and comorbidity of generalized anxiety disorder in children and adolescents

This study investigated the symptomatology and comorbidity of generalized anxiety disorder (GAD) in a clinically referred sample of Italian children and adolescents as a function of age and gender. The sample consisted of 58 subjects (19 children and 39 adolescents), 23 males and 35 females screened from consecutively referred children and adolescents. This sample was divided into two groups of younger children (19 subjects, eight males and 11 females aged 7 to 12 years; mean age, 9.6) and adolescents (39 subjects, 15 males and 24 females aged 12 to 18 years; mean age, 14.9). Feelings of tension, apprehension, the need for reassurance, irritability, negative self-image, and physical complaints were reported in more than 70% of the subjects. Differences in the symptomatic profile between males and females were not significant. Children and adolescents did not show significant differences in the number of symptoms. The need for reassurance was significantly more frequent in children, and brooding was more frequent in adolescents. Other anxiety disorders were commonly comorbid with GAD. More than half of the patients with GAD showed a concurrent depressive disorder; no differences were found for comorbidity between children and adolescents, except for higher rates of separation anxiety disorder in children.

Open trial of risperidone in 24 young children with pervasive developmental disorders

OBJECTIVE To describe tolerability and efficacy of risperidone in very young children with pervasive developmental disorders. METHOD Twenty-four children aged 3.6 to 6.6 years (mean 4.6 years +/- 8 months) enrolled during 1999 and 2000 participated in a 16-week open-label trial with risperidone monotherapy. Outcome measures included the Childrens Psychiatric Rating Scale (CPRS), Childhood Autism Rating Scale (CARS), Clinical Global Impression-Improvement (CGI-I), and Childrens Global Assessment Scale (C-GAS). RESULTS Two subjects did not complete the trial because of side effects. The optimal dose was 0.5 mg/day. After the treatment a 21% improvement in CPRS and a 14% improvement in CARS total scores was found. Items related to behavioral control (hyperactivity, fidgetiness, rhythmic motions) and affect regulation (lability of affect, angry affect) improved more than 25%. Based on improvement of at least 25% on the CPRS and a score of 1 or 2 on the CGI-I, eight subjects were considered responders. Functional impairment (C-GAS) improved more than 25%. Thirteen subjects (54%) were free of any side effects; in the other participants risperidone was well tolerated. Only three subjects had a weight gain greater than 10%. CONCLUSIONS Low-dose risperidone may positively affect symptoms in young autistic children, improving disruptive/hyperactive behavior and affective dysregulation. Further controlled studies in this age group are warranted.

Somatic Symptoms in Children and Adolescents Referred for Emotional and Behavioral Disorders

Medically unexplained physical symptoms are frequently endorsed by children and adolescents in both clinical and community samples. The aim of this exploratory study is to examine the prevalence of somatic symptoms in a sample of 162 Italian children and adolescents consecutively referred to a Division of Child Neurology and Psychiatry from emotional and/or behavioral disorders. The role of age, gender, and psychiatric status was considered as a variable. Each patient received a DSM-IV assessment, including a diagnostic structured interview (DICA-R). The sample was divided according to gender (96 males, 66 females), age (70 children younger and 92 adolescents older than 12 years), and psychiatric diagnosis (Anxiety, Depression, Depression/Anxiety, Other). The presence of medically unexplained somatic symptoms was based on the responses to the DICA-R. Somatic complaints were reported in 69.2% of the patients. Headache was the most frequent somatic symptom (50.6%). Younger children showed higher rates of abdominal complaints than adolescents. No gender differences in frequency of somatic complaints were reported. Subjects with anxiety and/or depression reported significantly higher rates of somatic complaints, namely headache, than subjects with other mental disorders. No differences in frequency of somatic symptoms were evident between patients with anxiety, depression, and comorbid anxiety-depression. Our data suggest that an unexplained somatic symptom can be often considered as indicative of a neglected anxiety and/or depressive disorder. A collaboration between primary care physicians, pediatricians, and child psychiatrists may promote early diagnoses and timely treatments and prevent negative social and scholastic consequences.

Anxiety disorders in children and adolescents with bipolar disorder: a neglected comorbidity

Objective: We describe a consecutive clinical sample of children and adolescents with bipolar disorder to define the pattern of comorbid anxiety and externalizing disorders (attention-deficit hyperactivity disorder [ADHD] and conduct disorder [CD]) and to explore the possible influence of such a comorbidity on their cross-sectional and longitudinal clinical characteristics. Methods: The sample comprised 43 outpatients, 26 boys and 17 girls, (mean age 14.9 years, SD 3.1; range 7 to 18), with bipolar disorder type I or II, according to DSM-IV diagnostic criteria. All patients were screened for psychiatric disorders using historical information and a clinical interview, the Diagnostic Interview for Children and Adolescents-Revised (DICA-R). To shed light on the possible influence of age at onset, we compared clinical features of subjects whose bipolar onset was prepubertal or in childhood (< 12 years) with those having adolescent onset. We also compared different subgroups with and without comorbid externalizing and anxiety disorders. Results: Bipolar disorder type I was slightly more represented than type II (55.8% vs 44.2%). Only 11.6% of patients did not have any other psychiatric disorder; importantly, 10 subjects (23.5%) did not show any comorbid anxiety disorder. Comorbid externalizing disorders were present in 12 (27.9%) patients; such comorbidity was related to the childhood onset of bipolar disorder type II. Compared with other subjects, patients with comorbid anxiety disorders more often reported pharmacologic (hypo)mania.

Clozapine in adolescent inpatients with acute mania.

Some bipolar patients with acute manic episodes can be refractory to conventional treatment with mood stabilizers. Clozapine, an atypical antipsychotic, has been reported to be effective in adults with treatment-resistant bipolar disorder. We describe the therapeutic effect of clozapine in 10 adolescent inpatients (12- to 17-year-olds) with severe acute manic or mixed episodes who did not improve after treatment with conventional drugs (mood stabilizers, antipsychotics). At hospital discharge, 15 to 28 days after clozapine treatment, all patients had responded positively according to the Clinical Global Impression-Improvement Scale scores. The mean changes in Mania Rating Scale, Brief Psychiatric Rating Scale, Childrens Global Assessment Scale, and Clinical Global Impression-Severity Scale were significant (p < 0.001). Clozapine dosage was 142.5 +/- 73.6 mg/day (range 75-300 mg/day). Side effects (increased appetite, sedation, enuresis, sialorrhea) were frequent but not severe enough to require reduction of dosage. Mean weight gain after 6 months was 6.96 +/- 3.08 kg (10.7%). Neither decrease of white cells nor epileptic seizures were reported during follow-up (12-24 months). These preliminary findings suggest that clozapine may improve the clinical picture in adolescents with treatment-refractory manic or mixed episodes. Controlled studies on larger samples are warranted.

Children with Schizophrenia Clinical Picture and Pharmacological Treatment

Awareness of childhood-onset schizophrenia is rapidly increasing, with a more precise definition now available of the clinical picture and early signs, the outcome and the treatment strategies. Premorbid developmental impairments, including language, motor and social deficits, are more frequent and more pronounced in earlier-than in later-onset forms of schizophrenia. This ‘pandysmaturation’ is reported from the first months of life in more than half of the children who will develop childhood-onset schizophrenia, and it suggests a more severe and early disruption of brain development compared with the adolescent- and adult-onset disorder. The insidious onset in at least 75% of children, the high rates of premorbid problems and the hesitancy on the part of clinicians to make a diagnosis of schizophrenia in a child usually delay the recognition of the syndrome. Elementary auditory hallucinations are the most frequent positive symptom, while visual and tactile hallucinations are rarer. Delusions are less complex than in adolescents and are usually related to childhood themes. Negative symptoms are largely predominant, namely flat or inappropriate affect. A marked deterioration from the previous level of functioning is present in all these children, and an impaired outcome is reported in approximately 50–60% of them.The main diagnostic challenges are with differentiating childhood-onset schizophrenia from affective disorders (both depression and bipolar disorder) with psychotic symptoms, pervasive developmental disorders and severe personality disorders. Post-traumatic stress disorder and obsessive-compulsive disorder without insight may also be misdiagnosed as schizophrenia. Furthermore, approximately 10% of children from the community report nonpsychotic hallucinations or delusions. Finally, children with atypical psychotic features that do not strictly fit diagnostic criteria for schizophrenia have been described, and new labels have been proposed to categorise these clinical patterns, such as multidimensionally impaired disorder and multiple complex developmental disorder.In the context of a multimodal approach, including behavioral, social, scholastic and familial interventions, a pharmacological treatment is usually the core treatment. Available experience from the few controlled studies, open studies and case reports on pharmacotherapy in children with schizophrenia aged <12 years is critically analysed in this review, with particular reference to the use of atypical antipsychotics in clinical practice. To date, the major evidence supports the efficacy of risperidone and olanzapine, while clozapine seems an effective option in treatment-refractory cases. Published experience with newer atypical antipsychotics (quetiapine, ziprasidone, aripiprazole) is still lacking in this age range. Safety data (namely extrapyramidal symptoms, weight gain, hyperprolactinaemia, haematological adverse effects, seizures, hepatotoxicity, metabolic effects, neuroleptic malignant syndrome and cardiovascular effects) are reviewed and discussed, along with strategies for management.

Separation anxiety disorder in children and adolescents: Epidemiology, diagnosis and management

This paper provides an overview of the phenomenology, longitudinal outcome data, assessment and management of separation anxiety disorder (SAD) in children and adolescents.SAD is qualitatively different from early worries, and is characterised by an abnormal reactivity to real or imagined separation from attachment figures, which significantly interferes with daily activities and developmental tasks. Different epidemiological studies indicate a prevalence of 4 to 5% in children and adolescents. In contrast to other anxiety disorders, 50 to 75% of children with SAD come from homes of low socioeconomic status. The severity of symptomatology ranges from anticipatory uneasiness to full-blown anxiety about separation, but children are usually brought to the clinician when SAD results in school refusal or somatic symptoms. School refusal is reported in about 75% of children with SAD, and SAD is reported to occur in up to 80% of children with school refusal. Longitudinal studies have suggested that childhood SAD may be a risk factor for other anxiety disorders, but whether this link is specific to, for example, panic disorder and agoraphobia, or whether SAD represents a general factor of vulnerability for a broad range of anxiety disorders is still debated.Most relevant data are reported on nonpharmacological treatments (psychoeducational, behavioural, cognitive-behavioural, family and psychodynamic), and these are the first choice approach in SAD. Controlled studies show efficacy of cognitive-behavioural therapy in children with anxiety disorders and specifically in SAD-school phobia, supporting this approach as the best proven treatment. Pharmacotherapy should be used in addition to behavioural or psychotherapeutic intervention when the child’s symptoms have failed to respond to those treatments, and he/she is significantly impaired by the symptoms. Selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRI) have a good adverse effect profile and may be considered as first choice drugs in SAD. When different SSRIs fail to improve symptomatology, a trial with a tricyclic antidepressant (TCA) is indicated, with careful monitoring of cardiac functioning. Because of the adverse effect profile and the potential for abuse and dependence, benzodiazepines should be used only when a rapid reduction of symptomatology is needed, until the SSRI or the TCA have begun to be effective (few weeks). Buspirone should be considered in children who have not responded to other treatments. Further research is needed to confirm efficacy of newer antidepressants (venlafaxine, mirtazapine, nefazodone) in childhood anxiety disorders.

A Naturalistic Exploratory Study of the Impact of Demographic, Phenotypic and Comorbid Features in Pediatric Obsessive-Compulsive Disorder

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.

Panic disorder in clinically referred children and adolescents.

Prevalence, phenomenology, comorbidity, functional impairment and familial correlates of juvenile panic disorder (PD) are described in this study. A clinical interview (Diagnostic Interview for Children and Adolescents-Revised) was administered to 220 children and adolescents consecutively referred to a Division of Child Neurology and Psychiatry. 23 subjects (10.4%), aged 7 to 18 years, fulfilled DSM-IV criteria for PD. Reported panic symptoms are described, according to gender and chronological age. High comorbidity with generalized anxiety disorder (74%) and depression (52%) was noted. Agoraphobia (56%) and other phobias (56%) were significantly more frequent than in two control groups of subjects with generalized anxiety disorder and with depression. Antecedent and/or associated separation anxiety disorder was reported in 73% of the patients. Functional impairment, assessed with a specific diagnostic instrument (Childrens Global Assessment Scale) was significantly greater in PD patients than in depressed or anxious patients. 90% of patients had at least one parent with an anxiety disorder, 52% had one parent with depressive disorder, 33% had one parent with drug treated PD.

Prolactin levels in young children with pervasive developmental disorders during risperidone treatment.

Although hyperprolactinemia is a common side effect during risperidone treatment in adult patients, no information is available on young children. The aim of this study is to report on serum prolactin levels in 25 young autistic children (22 males and 3 females, age range 3.9-7 years, mean age 4.10 years) during treatment with risperidone (dosage range 0.25-0.90 mg/day, mean dosage 0.52 mg/day). Prolactin levels were measured at baseline and after 10 weeks of treatment. The clinical outcome measure used was the Clinical Global Impression-Improvement. Serum prolactin was 9.77 +/- 3.94 ng/mL at baseline and 25.92 +/- 13.9 ng/mL during the 10th week of treatment (p < 0.001). Six children (24%) showed prolactin levels lower than 15 ng/mL, which is the upper normal level; eight children (28%) had prolactin levels higher than two times the upper limit (30 ng/mL). Hyperprolactinemia did not show significant correlations with age, weight, or risperidone dosage. There was no relation with clinical outcome. Dose reduction of risperidone resulted in a decrease of prolactin levels. None of the children showed clinical signs of hyperprolactinemia. Given the paucity of available data on potential effects of long-term hyperprolactinemia, a monitoring of prolactin during treatment with risperidone and other typical and atypical antipsychotics may be warranted.