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PubMed1995

School observations of children with attention-deficit hyperactivity disorder and comorbid tic disorder: effects of methylphenidate treatment.

Although the findings from recent controlled studies suggest that methylphenidate is a safe and effective treatment for many children with attention-deficit hyperactivity disorder (ADHD) and comorbid tic disorder, relatively little is known about drug effects on school behavior. Thirty-four prepubertal children with ADHD and tic disorder received placebo and 3 doses of methylphenidate (0.1, 0.3, and 0.5 mg/kg) twice daily for 2 weeks each under double-blind conditions. Treatment effects were assessed using direct observations of child behavior in classroom, lunchroom, and playground settings. Treatment with methylphenidate resulted in marked reductions of hyperactive, disruptive, and aggressive behavior, which was evident even for the 0.1 mg/kg dose. There were no "nonresponders." The only observed changes in tics were a small but statistically significant increase in the frequency of motor tics (classroom, 0.1 mg/kg dose) and a tendency for fewer vocal tics (lunchroom). However, these changes in motor tic frequency were not perceived by care providers as a worsening in the severity of the child's tic disorder. Most dose-response relationships were linear, but the mean (operationally defined) minimal effective dose (MED) was 0.3 mg/kg. In summary, the findings support the conclusions that (1) methylphenidate suppresses ADHD behaviors in the classroom and aggressive behavior in all settings and that (2) a low dose may have a weak exacerbation effect on the frequency of motor tics; but, in general, the majority of youngsters do not experience clinically significant tic worsening with a MED.

Aggression↗
PubMed2001

The familial phenotype of obsessive-compulsive disorder in relation to tic disorders: the Hopkins OCD family study.

BACKGROUND: Obsessive-compulsive disorder (OCD) and tic disorders have phenomenological and familial-genetic overlaps. An OCD family study sample that excludes Tourette's syndrome in probands is used to examine whether tic disorders are part of the familial phenotype of OCD. METHODS: Eighty case and 73 control probands and their first-degree relatives were examined by experienced clinicians using the Schedule for Affective Disorders and Schizophrenia-Lifetime Anxiety version. DSM-IV psychiatric diagnoses were ascertained by a best-estimate consensus procedure. The prevalence and severity of tic disorders, age-at-onset of OCD symptoms, and transmission of OCD and tic disorders by characteristics and type of proband (OCD + tic disorder, OCD - tic disorder) were examined in relatives. RESULTS: Case probands and case relatives had a greater lifetime prevalence of tic disorders compared to control subjects. Tic disorders spanning a wide severity range were seen in case relatives; only mild severity was seen in control relatives. Younger age-at-onset of OCD symptoms and possibly male gender in case probands were associated with increased tic disorders in relatives. Although relatives of OCD + tic disorder and OCD - tic disorder probands had similar prevalences of tic disorders, this result is not conclusive. CONCLUSIONS: Tic disorders constitute an alternate expression of the familial OCD phenotype.

Adolescent↗
PubMed2022

Phenotypic Impact of Rare Potentially Damaging Copy Number Variation in Obsessive-Compulsive Disorder and Chronic Tic Disorders.

BACKGROUND: Recent studies report an important-and previously underestimated-role of rare variation in risk of obsessive-compulsive disorder (OCD) and chronic tic disorders (CTD). Using data from a large epidemiological study, we evaluate the distribution of potentially damaging copy number variation (pdCNV) in OCD and CTD, examining associations between pdCNV and the phenotypes of probands, including a consideration of early- vs. late-diagnoses. METHOD: The Obsessive-Compulsive Inventory-Revised (OCI-R) questionnaire was used to ascertain psychometric profiles of OCD probands. CNV were identified genome-wide using chromosomal microarray data. RESULTS: For 993 OCD cases, 86 (9%) were identified as pdCNV carriers. The most frequent pdCNV found was at the 16p13.11 region. There was no significant association between pdCNV and the OCI-R total score. However, pdCNV was associated with Obsessing and Checking subscores. There was no significant difference in pdCNV frequency between early- vs. late-diagnosed OCD probands. Of the 217 CTD cases, 18 (8%) were identified as pdCNV carriers. CTD probands with pdCNV were significantly more likely to have co-occurring autism spectrum disorder (ASD). CONCLUSIONS: pdCNV represents part of the risk architecture for OCD and CTD. If replicated, our findings suggest pdCNV impact some OCD symptoms. Genes within the 16p13.11 region are potential OCD risk genes.

Humans↗
PubMed1995

Efficacy of methylphenidate for attention-deficit hyperactivity disorder in children with tic disorder.

BACKGROUND: The findings from case reports and patient questionnaire surveys have been interpreted as indicating that administration of stimulants is ill-advised for the treatment of attention-deficit hyperactivity disorder in children with tic disorder. METHODS: Thirty-four prepubertal children with attention-deficit hyperactivity disorder and tic disorder received placebo and three dosages of methylphenidate hydrochloride (0.1, 0.3, and 0.5 mg/kg) twice daily for 2 weeks each, under double-blind conditions. Treatment effects were assessed using direct observations of child behavior in a simulated (clinic-based) classroom and using rating scales completed by the parents, teachers, and physician. RESULTS: Methylphenidate effectively suppressed hyperactive, disruptive, and aggressive behavior. There was no evidence that methylphenidate altered the severity of tic disorder, but it may have a weak effect on the frequency of motor (increase) and vocal (decrease) tics. CONCLUSION: Methylphenidate appears to be a safe and effective treatment for attention-deficit hyperactivity disorder in the majority of children with comorbid tic disorder.

Attention Deficit Disorder with Hyperactivity↗
PubMed2001

Progress toward analysis of D8/17 binding to B cells in children with obsessive compulsive disorder and/or chronic tic disorder.

BACKGROUND: Previous research has suggested that a subgroup of children with obsessive compulsive disorder (OCD) have neuropsychiatric sequelae of streptococcal pharyngitis, similar to that seen in the neurological manifestation of rheumatic fever (RF). Monoclonal antibody D8/17 demonstrates increased binding to B cells in patients with RF and in patients with neuropsychiatric disorders using immunofluorescent microscopy. OBJECTIVE: The aim of this study was to determine if an earlier immunofluorescent microscopy study of monoclonal antibody D8/17 in childhood-onset OCD and/or chronic tic disorder (CTD) could be replicated using the more objective method of flow cytometric analysis. METHOD: D8/17 binding to B cells was determined in patients with OCD and or CTD (N=32), and healthy controls (N=12) by flow cytometric analysis. RESULTS: Subjects with OCD/CTD showed increased mean cell binding (26.0%) of monoclonal antibody compared with healthy controls (9.1%) (p<0.001). When using the threshold of greater than 19% binding (95% upper confidence interval) as a measure of positivity, 65.6% of patients compared with 8.3% of controls showed increased antibody binding to B cells (p=0.01). CONCLUSIONS: Although this study reports positive results, many methodological issues will need to be addressed before generalized use of assay for diagnostic purposes.

Adolescent↗
PubMed1999

Comparison of internalizing and externalizing symptoms in children with attention-deficit hyperactivity disorder with and without comorbid tic disorder.

This study examined the relation between internalizing and externalizing symptoms in two groups of prepubertal boys (with and without multiple chronic tic disorder) with diagnosed attention-deficit hyperactivity disorder (ADHD). Parents and teachers completed the Child Behavior Checklist (CBCL) and Teacher's Report Form (TRF), respectively. Children were carefully evaluated for the absence of a chronic tic disorder. Boys with ADHD and chronic multiple tic disorder (ADHD/+tics) received significantly higher (p = .0032, Bonferroni correction) scores for the Anxious/Depressed, Thought Problems, and Attention Problem scales of the CBCL and the Delinquent Behavior, Thought Problems, and Somatic Complaints scales of the TRF than did boys without chronic tic disorder (ADHD/-tics). Although many of the individual items that differentiated (p < .05) the two groups of boys pertained to behaviors that characterize motor tics, obsessions, or compulsions, the ADHD/+tics group exhibited higher rates of anxious behavior (CBCL) and obscene language (TRF) than did the ADHD/-tics group. Anxiety/depressive symptoms were associated with aggressive/oppositional behavior in both samples. Children with mild tic disorder were more similar (CBCL) to ADHD/-tics boys than they were to children with more severe tic disorder. The relatively higher rate of comorbidity in the ADHD/+tics group suggests that tics may be a marker for more severe symptomatology in clinic-referred samples of children with ADHD. Furthermore, these data suggest that it is not the presence, per se, but rather the severity of tic disorder that is associated with higher rates of emotional and behavioral disturbances.

Anxiety Disorders↗
PubMed1993

Comparison of clonidine response in the treatment of attention-deficit hyperactivity disorder with and without comorbid tic disorders.

OBJECTIVE: Clonidine has been suggested as an alternative pharmacotherapy for patients with attention-deficit hyperactivity disorder (ADHD) and comorbid tic disorders. To examine the efficacy of clonidine in this population of children, the use of clonidine in the treatment of children with ADHD with and without comorbid tic disorders was examined in a retrospective chart review of 54 children over a 4-year period. METHOD: Treatment was administered openly to these patients in a Pediatric Psychopharmacology Clinic, and response was assessed using clinical global improvement measures. RESULTS: Clonidine treatment resulted in improvement in both the ADHD (39/54; 72%) and tic symptoms (18/24; 75%) groups. The findings suggested that the children with ADHD with comorbid tic disorders (23/24; 96%) have a more frequent positive behavioral response to clonidine than children with ADHD without comorbid tic disorders (16/30; 53%). CONCLUSIONS: This report provides further support of a role for clonidine in the treatment of children with ADHD, particularly for those with comorbid tic disorders.

Adolescent↗
PubMed2000

Quantitative and qualitative aspects of obsessive-compulsive behaviour in children with attention-deficit hyperactivity disorder compared with tic disorder.

OBJECTIVE: Within the framework of associated psychopathology in child psychiatric disorders, this study focused on quantitative and qualitative aspects of obsessive-compulsive behaviour (OCB) in both attention-deficit hyperactivity disorder (ADHD) and chronic tic disorder/Tourette's disorder (TD). METHOD: Forty-two healthy controls, 41 children with ADHD and 38 children with TD, aged 9-13 years, were investigated using the Leyton Obsessional Inventory--Child Version (LOI-CV), the Child Behaviour Checklist (CBCL) and an expert-rated structured parent interview to reflect a cross-informant view of OCB. RESULTS: Unexpectedly, self-reports of children with ADHD rather than children with TD showed the highest OCB scores in the LOI-CV. Qualitatively, ADHD-related OCB focused on the item subsets concerning 'dirt and contamination', 'repetition', 'overconscientiousness', and 'hoarding'. In the parent-rated CBCL, similar levels of OCB were reported for ADHD and TD patients. In contrast, only children with TD showed clinically relevant OCB according to expert ratings. CONCLUSION: Not only young TD patients but also children with ADHD should be investigated and monitored carefully for quantitative and qualitative aspects of OCB comorbidity.

Adolescent↗
PubMed1999

Long-term methylphenidate therapy in children with comorbid attention-deficit hyperactivity disorder and chronic multiple tic disorder.

BACKGROUND: This study examined changes in attention-deficit hyperactivity (ADHD) behaviors and motor and vocal tics during long-term treatment with methylphenidate. METHODS: Thirty-four prepubertal children with ADHD and chronic multiple tic disorder (who had participated in an 8-week, double-blind, placebo-controlled methylphenidate evaluation) were evaluated at 6-month intervals for 2 years as part of a prospective, nonblind, follow-up study. Treatment effects were assessed using direct observations of child behavior in a simulated (clinic-based) classroom and behavior rating scales completed by parents and physician. Videotapes of the simulated classroom were scored by coders who were blind to treatment status. RESULTS: There was no evidence (group data) that motor tics or vocal tics changed in frequency or severity during maintenance therapy compared with diagnostic or initial double-blind placebo evaluations. Behavioral improvements demonstrated during the acute drug trial were maintained during follow-up. There was no evidence (group data) of clinically significant adverse drug effects on cardiovascular function or growth at the end of 2 years of treatment. CONCLUSIONS: Long-term treatment with methylphenidate seems to be safe and effective for the management of ADHD behaviors in many (but not necessarily all) children with mild to moderate tic disorder. Nevertheless, careful clinical monitoring is mandatory to rule out the possibility of drug-induced tic exacerbation in individual patients.

Attention Deficit Disorder with Hyperactivity↗
PubMed1993

The efficacy of fluvoxamine in obsessive-compulsive disorder: effects of comorbid chronic tic disorder.

This retrospective case-controlled analysis evaluated treatment response to the serotonin reuptake inhibitor fluvoxamine in patients with obsessive-compulsive disorder (OCD), with or without a comorbid chronic tic disorder. Thirty-three fluvoxamine-treated OCD patients with a concurrent chronic tic disorder were compared with 33 age- and sex-matched OCD patients without chronic tics who had received fluvoxamine treatment in the same setting during the same period of time and in a similar manner. Although both groups of patients demonstrated statistically significant reductions in obsessive-compulsive, depressive, and anxiety symptoms with fluvoxamine treatment, the frequency and magnitude of response of obsessive-compulsive symptoms was significantly different between the two groups. A clinically meaningful improvement in obsessive-compulsive symptoms occurred in only 21% of OCD patients with comorbid chronic tics compared with a 52% response rate in OCD patients without chronic tics. Moreover, OCD patients with a concurrent chronic tic disorder showed only a 17% reduction in Yale-Brown Obsessive-Compulsive Scale scores compared with a 32% decrease in the severity of obsessive-compulsive symptoms in those OCD patients without chronic tics. These results suggest that serotonin reuptake inhibitor monotherapy may be less efficacious for improving obsessive-compulsive symptoms in OCD patients with than without tics. Combined with differences in the clinical phenomenology between these two groups, these treatment response data support the hypothesis that OCD patients with a comorbid chronic tic disorder may be a clinically meaningful subtype.

Adult↗
PubMed2005

Association between streptococcal infection and obsessive-compulsive disorder, Tourette's syndrome, and tic disorder.

OBJECTIVE: Reports have suggested that streptococcal infection may be etiologically related to pediatric autoimmune neuropsychiatric disorders (PANDAS), but there are few good epidemiologic studies to support this theory. Using population-based data from a large West-Coast health maintenance organization, we assessed whether streptococcal infection was associated with increased risk for obsessive-compulsive disorder (OCD), Tourette's syndrome (TS), or tic disorder. METHODS: This is a case-control study of children 4 to 13 years old receiving their first diagnosis of OCD, TS, or tic disorder between January 1992 and December 1999 at Group Health Cooperative outpatient facilities. Cases were matched to controls by birth date, gender, primary physician, and propensity to seek health care. RESULTS: Patients with OCD, TS, or tic disorder were more likely than controls to have had prior streptococcal infection (OR: 2.22; 95% CI: 1.05, 4.69) in the 3 months before onset date. The risk was higher among children with multiple streptococcal infections within 12 months (OR: 3.10; 95% CI: 1.77, 8.96). Having multiple infections with group A beta-hemolytic streptococcus within a 12-month period was associated with an increased risk for TS (OR: 13.6; 95% CI: 1.93, 51.0). These associations did not change appreciably when limited to cases with a clear date of onset of symptoms or with tighter matching on health care behavior. CONCLUSION: These findings lend epidemiologic evidence that PANDAS may arise as a result of a postinfectious autoimmune phenomenon induced by childhood streptococcal infection.

Adolescent↗
PubMed1999

The 4-year course of tic disorders in boys with attention-deficit/hyperactivity disorder.

BACKGROUND: Despite long-standing clinical concerns, relatively little is known about the comorbidity between attention-deficit/hyperactivity disorder (ADHD) and tic disorders. Therefore, we examined tic disorders in an ongoing prospective follow-up study of male subjects with ADHD, a sample unselected for any comorbid disorder. METHODS: One hundred twenty-eight male children and adolescents with ADHD and 110 male controls were comprehensively evaluated at baseline and 4 years later. We characterized tic disorders along with a wide range of neuropsychiatric correlates, including other comorbid disorders and indices of psychosocial function in multiple domains (school, cognitive, social, and family). RESULTS: Compared with controls, subjects with ADHD showed more tic disorders at baseline and more new onsets were reported at follow-up. Attention-deficit/hyperactivity disorder and tic disorders appeared to be independent in course: in contrast to low rates of ADHD remission, tic disorders mostly remitted. The age-adjusted rate of ADHD remission was 20% and that of tic remission, 65%. Tic disorders had little effect on the psychosocial functioning of subjects with ADHD. CONCLUSIONS: These findings suggest that comorbidity with a tic disorder has a limited effect on ADHD outcome. However, because of the relatively small sample of subjects with tic disorders, our conclusions should be considered preliminary until confirmed in larger studies of medicated and unmedicated children with ADHD with and without tic disorders.

Adolescent↗
PubMed1988

Tic disorders of childhood.

Tic disorders may be classified as simple tics, chronic motor tics or Tourette syndrome, the most severe of the three types. Tourette syndrome is rather uncommon and is often misdiagnosed. Tic disorders of childhood probably have an organic etiology and a genetic component. An increased incidence of obsessive-compulsive behavior, attention deficit disorder and other abnormalities have been reported in Tourette patients. Haloperidol is often useful in controlling severe tic symptoms, while stimulant drugs may worsen the symptoms.

Attention Deficit Disorder with Hyperactivity↗
PubMed1989

Tic disorders: an overview.

Tics are purposeless and repetitive involuntary movements and vocalizations with variable and complex means of expression. Since up to 24 per cent of children can manifest tics at some point in their lives, growing interest has developed in the genetics, etiology, course, diagnosis, and treatment of the tic disorders. This article is a review of the current knowledge about tics and tic disorders.

Diagnosis, Differential↗
PubMed2005

An open-label, prospective study of guanfacine in children with ADHD and tic disorders.

OBJECTIVES: To evaluate the efficacy and safety of guanfacine in children with attention-deficit hyperactivity disorder (ADHD) and tic disorders. MATERIAL AND METHOD: Twenty-five medication-free subjects (23 males and 2 females), aged 7-16 (mean = 10.6 +/- 2.0) years participated in an 8-week open-label guanfacine study. Subjects were recruited from a specialty clinic for children with tic disorders over a four-year period. Eligibility criteria included presence of ADHD (any type), a tic disorder (any type), and being medication free for two weeks. Outcome measures included the Hyperactivity Index of the Conners Parent Questionnaire, the teacher-rated ADHD Rating Scale, and the Yale Global Tic Severity Scale (YGTSS). RESULTS: All subjects met criteria for ADHD (combined type N = 22; predominantly inattentive type N = 3) and a tic disorder (Tourette's Disorder N = 20; chronic motor tic disorder N = 5). At an average dose of 2.0 +/- 0.6 mg/ day, guanfacine was associated with mean improvement of 27% on the Hyperactivity Index (N = 25; t = 4.61; p < 0.001), 32% on the total score of the teacher-rated ADHD Scale (N = 19; t = 5.27; p < 0.001), and 39% on the total tic severity scale (N = 19; t = 4.17; p < 0.001). Mild and statistically insignificant decreases in blood pressure and pulse were observed in the sample as a whole. Five subjects had endpoint systolic blood pressure below 1 SD from their age and gender norms. CONCLUSION: Results of this open-label study add to the growing data base on the safety and efficacy of guanfacine in children with ADHD and tic disorders.

Adolescent↗
PubMed1999

Stimulant medication withdrawal during long-term therapy in children with comorbid attention-deficit hyperactivity disorder and chronic multiple tic disorder.

OBJECTIVES: In this study we examined changes in attention-deficit hyperactivity disorder behaviors and motor and vocal tics during withdrawal from long-term maintenance therapy with stimulant medication. METHODS: Subjects were 19 children with attention-deficit hyperactivity disorder and chronic tic disorder who had received methylphenidate (n = 17) or dextroamphetamine (n = 2) for a minimum of 1 year. Children were switched to placebo under double-blind conditions. Treatment effects were assessed by using direct observations of child behavior in a simulated (clinic-based) classroom and behavior rating scales completed by parents and clinician. RESULTS: There was no change (group data) in the frequency or severity of motor tics or vocal tics during the placebo condition compared with maintenance dose of stimulant medication (ie, no evidence of tic exacerbation while receiving medication or of a withdrawal reaction). There was no evidence of tic exacerbation in the evening as a rebound effect. Treatment with the maintenance dose was also associated with behavioral improvement in attention-deficit hyperactivity disorder behaviors, indicating continued efficacy. CONCLUSIONS: Abrupt withdrawal of stimulant medication in children receiving long-term maintenance therapy does not appear to result in worsening of tic frequency or severity. Nevertheless, these findings do not preclude the possibility of drug withdrawal reactions in susceptible individuals.

Adolescent↗
PubMed2001

Quetiapine for tic disorder: a case report.

UNLABELLED: Tic disorders happen in nearly 20 per cent of children. There is no "best drug" to treat this illness. Potent antipsychotics e.g. haloperidol and pimozide, are the most effective drugs but their limitations are their extrapyramidal side effects (EPS). Risperidone has been proved on efficacy for tic disorders but EPS still remain, even though it was claimed to be less. Thus, quetiapine, a newer atypical neuroleptic with the same action as risperidone and produces fewer EPS, was included in this study. OBJECTIVE: To study the efficacy and side effects of quetiapine in tic disorders. METHOD: A case report of a 19-year-old female patient with tic disorder who had taken haloperidol 2 mg/d with benzhexol HCl 2-4 mg/d, then switched to risperidone 1.5 mg/d with benzhexol HCl 4 mg/d because of acute dystonia and oculogyric. She was then prescribed quetiapine, 50 mg/d as a starting dose without benzhexol HCI, because of the remaining symptoms and EPS. The severity of the symptoms was assessed monthly using the Behavior Rating Scale. The dose was increased by 50 mg/d weekly for a better outcome. RESULTS: The tic was improved after the first week and disappeared for three weeks with 150 mg/d of quetiapine. However, the tic returned again, but less frequently (20%). Thus, the dose was stepped up to 200 mg/d. One week later, the patient reported that the tic has disappeared. CONCLUSION: Quetiapine showed the efficacy and fewest EPS in this patient. However, a further clinically controlled trial must be carried out before quetiapine can become the first-line treatment for tic disorders.

Adult↗