Immediate-release methylphenidate for ADHD in children with comorbid chronic multiple tic disorder

OBJECTIVE: To examine the safety and efficacy of immediate-release methylphenidate (MPH-IR) for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children (ages 6-12 years) with Tourette's syndrome (96%) or chronic motor tic disorder (4%). METHOD: Two cohorts of prepubertal children (N = 71) received placebo and three doses of MPH (0.1, 0.3, and 0.5 mg/kg) twice daily for 2 weeks each, under double-blind conditions as part of their involvement in a long-term observation study (1989-2004). Treatment effects were assessed with an extensive battery of parent-, teacher-, child-, and physician-completed rating scales and laboratory tasks. RESULTS: MPH-IR effectively suppressed ADHD, oppositional defiant disorder, and peer aggression behaviors. There was no evidence that MPH-IR altered the overall severity of tic disorder or obsessive-compulsive disorder behaviors. Teacher ratings indicated that MPH-IR therapy decreased tic frequency and severity. CONCLUSIONS: MPH-IR appears to be a safe and effective short-term treatment for ADHD in the majority of children with chronic tic disorder; nevertheless, the possibility of tic exacerbation in susceptible individuals warrants careful monitoring of all patients.     

EEG coherence in children with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder.

OBJECTIVES: This study is the first to investigate EEG coherence differences between two groups of children with attention-deficit/hyperactivity disorder combined type (AD/HD), with or without comorbid oppositional defiant disorder (ODD), and normal control subjects. METHODS: Each group consisted of 20 males. All subjects were between the ages of 8 and 12 years, and groups were matched on age. EEG was recorded during an eyes-closed resting condition from 21 monopolar derivations. Wave-shape coherence was calculated for 8 intrahemispheric electrode pairs (4 in each hemisphere), and 8 interhemispheric electrode pairs, within each of the delta, theta, alpha, and beta bands. RESULTS: Children with comorbid AD/HD and ODD had intrahemispheric coherences at shorter inter-electrode distances significantly reduced from those apparent in children with AD/HD without comorbid ODD. Such reduced coherences in the comorbid group appeared to wash out coherence elevations previously noted in AD/HD studies. CONCLUSIONS: The present results suggest that, rather than suffering an additional deficit, children with AD/HD and comorbid ODD show significantly less CNS impairment than AD/HD patients without comorbid ODD. SIGNIFICANCE: These results have treatment implications, suggesting that behavioural training, perhaps using family-based cognitive behavioural therapy, could be useful for those children with AD/HD and comorbid ODD. This should focus on the ODD symptoms, in association with a medication regime focussed on the AD/HD symptoms.     

Atomoxetine treatment in children and adolescents with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder

OBJECTIVE: To examine (1) moderating effects of oppositional defiant disorder (ODD) on attention-deficit/hyperactivity disorder (ADHD) treatment response and (2) responses of ODD symptoms to atomoxetine. METHOD: Children and adolescents (ages 8-18) with ADHD were treated for approximately 8 weeks with placebo or atomoxetine (fixed dosing: 0.5, 1.2, or 1.8 mg/kg/day, b.i.d.) under randomized, double-blind conditions. Among patients with lifetime diagnostic information (n = 293), 39% were diagnosed with comorbid ODD and 61% were not. Treatment-group differences and differences between patients with and without comorbid ODD were examined post hoc for changes on the Attention-Deficit/Hyperactivity Disorder Rating Scale IV-Parent version, investigator-administered and -scored; Conners' Parent Rating Scale-Revised Short Form; Clinical Global Impressions Severity of ADHD Scale; and the parent-rated Child Health Questionnaire. RESULTS: Youths with ADHD and comorbid ODD showed statistically significant improvement in ADHD, ODD, and quality-of-life measures. Treatment response was similar in youths with and without ODD, except that the comorbid group showed improvement compared with placebo at 1.8 mg/kg/day but not 1.2 mg/kg/day. In contrast, youths without ODD showed improvement at 1.2 mg/kg/day and no incremental benefit at 1.8 mg/kg/day. CONCLUSIONS: Atomoxetine treatment improves ADHD and ODD symptoms in youths with ADHD and ODD, although the comorbid group may require higher doses.     

Differential stimulant response on attention in children with comorbid anxiety and oppositional defiant disorder

Attention-deficit hyperactivity disorder (ADHD) affects 3% to 7% of school-age children. Approximately 30% of the children with ADHD also have comorbid anxiety or oppositional defiant disorder. Methylphenidate is the drug of choice for the medical treatment of such cases. When compared with children with ADHD alone, children with comorbid anxiety or oppositional defiant disorder may show worsening of the global attention score in response to methylphenidate and not only a "reduced response," as reported in previous studies. This study included 1122 children diagnosed as ADHD, of which 174 were diagnosed with comorbid anxiety and 141 with comorbid oppositional defiant disorder. All patients performed the Test of Variables of Attention before and after methylphenidate administration. A normal distribution (Gaussian distribution) of reaction to methylphenidate, as measured by the global ADHD score in children diagnosed as pure ADHD, was found. These findings were in contrast to children with ADHD and comorbid anxiety or oppositional defiant disorder who showed a bimodal distribution and hence represent a distinct population. In both groups with comorbid disorders, there was a larger subgroup in which significant worsening of global ADHD score occurred after methylphenidate administration (P < .05). Children with ADHD and comorbid anxiety or oppositional defiant disorder might represent clinically distinct populations in which inattention is secondary to those disorders; therefore, methylphenidate may be an inappropriate treatment for such children.     

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/hyperactivity disorder and comorbid oppositional defiant disorder or conduct disorder

Comorbid oppositional defiant disorder (ODD) and conduct disorder (CD) are common in clinically referred children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Early recognition and treatment of co-occurring ADHD and ODD and/or CD is important because comorbidity influences symptom severity, prognosis, and treatment. Research on treatment supports the importance of behavior therapies for ODD and multimodal psychosocial interventions delivered simultaneously and intensively for CD with adjunctive medication for ADHD symptoms. Clinical trials are beginning to show that stimulants and atomoxetine are effective for ADHD and ODD symptoms when the disorders occur together. It is presently unclear if ODD in the absence of ADHD responds to pharmacotherapy. More research is needed examining the effects of commonly prescribed ADHD medications on CD symptoms. Research suggests a high prevalence of lifetime comorbidity with ODD in clinically referred patients with ADHD.     

Children with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder: an EEG analysis

This study investigated EEG differences between two groups of children with attention-deficit/hyperactivity disorder combined type (ADHD), with or without comorbid oppositional defiant disorder (ODD), and normal control subjects. Each group consisted of 20 males. All subjects were between the ages of 8 and 12 years, and groups were matched on age. EEG was recorded during an eyes-closed resting condition from 21 monopolar derivations, which were clustered into nine regions for analysis. The EEGs were Fourier transformed to provide absolute and relative power estimates for the delta, theta, alpha and beta bands. Values were also calculated for the theta/alpha and theta/beta ratios. The ADHD groups had more absolute and relative theta than the control group. Regionally, the ADHD groups had less relative alpha and more relative delta in posterior regions, and less relative beta in the frontal regions, than the control group. These differences were also apparent in both ratio measures. Only two significant topographic differences were found between the ADHD groups, with both of these being less deviant from normality in the ADHD+ODD group than the ADHD group. These results indicate that EEG correlates of ADHD are not clouded by the presence of comorbid ODD, which suggests possible applications in clinical practice.     

Comorbidity of internalizing disorders in children with oppositional defiant disorder

Oppositional defiant disorder (ODD) is often comorbid with other psychiatric disorders in childhood. Its association with attention deficit hyperactivity disorder and conduct disorder has been well studied. Recent studies suggest that children with ODD have substantial comorbidity with anxiety and depressive (internalizing) disorders, as well. Identifying the pattern of internalizing comorbidity with ODD in childhood and adolescence and how this varies across age and gender may help to identify mechanisms of such comorbidity. This systematic review presents evidence on the association of internalizing disorders with ODD across childhood and adolescence. Data from cross-sectional and longitudinal studies in clinic, community and epidemiologic samples are considered separately. Findings suggest that while internalizing comorbidity with ODD is present at all ages, the degree of comorbidity may vary over time in particular groups of children. Girls and boys appear to have different patterns of ODD comorbidity with either anxiety or depression, as well as ages of onset of ODD, however more large studies are required. Children with ODD in early life require further study as they may be a subgroup at increased risk for anxiety and affective disorders. This could have important implications for the treatment of these ODD children and the prevention of sequential comorbidity.     

Medication refusal in children with oppositional defiant disorder or conduct disorder and comorbid attention-deficit/hyperactivity disorder: medication history and clinical correlates

Abstract Objective: This study examines the characteristics of 96 children with attention-deficit/hyperactivity disorder (ADHD) and their families who refused a recommendation for medication as part of their treatment for disruptive disorders. Methods: The ADHD cases were taken from a sample of 139 youth (age 6-11) who were recruited for a clinical trial that compared the administration of a modular psychosocial treatment in an outpatient clinic or community settings. Medication management was an optional treatment module for children with ADHD in both conditions. Children who were (vs. were not) taking medication at intake, and children who accepted (vs. refused) medication recommendations during the study were compared on diagnostic and clinical measures related to child, school, parent, and family domains of functioning. Results: Parents of 30% of the children refused study medication for ADHD. Parental medication acceptability and intake correlated highly with both medication history and study refusal of medication. Increased parental self-efficacy and emotional support for their youth correlated with medication refusal. No demographics and few child or school factors were associated with medication refusal. Medication use was associated with reductions in some key ADHD symptoms, but did not affect disruptive behaviors as did the psychosocial interventions. Conclusion: Medication refusers remain poorly understood but certain correlates, such as parental self-efficacy, parental emotional support for their youth, and medication acceptability, warrant further evaluation.     

Altered brain morphology in boys with attention deficit hyperactivity disorder with and without comorbid conduct disorder/oppositional defiant disorder

About 50% of attention deficit hyperactivity disorder (ADHD) patients suffer from comorbidity with oppositional defiant disorder/conduct disorder (ODD/CD). Most previous studies on structural morphology did not differentiate between pure (ADHD‐only) and comorbid ADHD (ADHD+ODD/CD). Therefore, we aimed to investigate the structural profile of ADHD‐only versus ADHD+ODD/CD spanning the indices subcortical and cortical volume, cortical thickness, and surface area. We predicted a reduced total gray matter, striatal, and cerebellar volume in both patient groups and a reduced amygdalar and hippocampal volume for ADHD+ODD/CD. We also explored alterations in prefrontal volume, thickness, and surface area. We acquired structural images from an adolescent sample ranging from 11 to 17 years, matched with regard to age, pubertal status, and IQ—including 36 boys with ADHD‐only, 26 boys with ADHD+ODD/CD, and 30 typically developing (TD) boys. We analyzed structural data with FreeSurfer. We found reductions in total gray matter and total surface area for both patient groups. Boys with ADHD+ODD/CD had a thicker cortex than the other groups in a right rostral middle frontal cluster, which was related to stronger ODD/CD symptoms, even when controlling for ADHD symptoms. No group differences in local cortical volume or surface area emerged. We demonstrate the necessity to carefully differentiate between ADHD and ADHD+ODD/CD. The increased rostral middle frontal thickness might hint at a delayed adolescent cortical thinning in ADHD+ODD/CD. Patients with the double burden ADHD and ODD or CD seem to be even more affected than patients with pure ADHD.     

The influence of comorbid oppositional defiant disorder on white matter microstructure in attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) are highly comorbid disorders. ADHD has been associated with altered white matter (WM) microstructure, though the literature is inconsistent, which may be due to differences in the in- or exclusion of participants with comorbid ODD. WM abnormalities in ODD are still poorly understood, and it is unclear whether comorbid ODD in ADHD may have confounded the current ADHD literature. Diffusion Tensor Imaging (DTI) was used to compare fractional anisotropy (FA) and mean diffusivity (MD) between ADHD patients with (n = 42) and without (n = 117) comorbid ODD. All participants were between 8–25 years and groups did not differ in mean age or gender. Follow-up analyses were conducted to examine the role of antisocial behaviour (conduct problems) on FA and MD values in both groups. Comorbid ODD in ADHD was associated with lower FA in left frontotemporal WM, which appeared independent of ADHD symptoms. FA was negatively associated with antisocial behaviour in ADHD + ODD, but not in ADHD-only. Comorbid ODD is associated with WM abnormalities in individuals with ADHD, which appears to be independent of ADHD symptoms. Altered WM microstructure in comorbid ODD may play a role in inconsistencies in the current DTI literature in ADHD. Altered development of these tracts may contribute to social-emotional and cognitive problems in children with oppositional and antisocial behaviour.     

Attention-deficit-hyperactivity disorder with and without oppositional defiant disorder in 3- to 7-year-old children

Attention-deficit-hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with a high degree of associated behavioural problems. In order to study characteristics of ADHD with and without oppositional defiant disorder (ODD) in a representative group of young children with clinical impairment in Sweden, 131 children (101 males, 30 females) with ADHD (mean age 5 years, SD 1 year 5 months; range 3 to 7 years) were clinically examined, and their parents interviewed. Independent questionnaire data (Child Behavior Checklist, ADHD Rating Scale-IV, ODD Rating Scale-IV, Conners Hyperactivity Index) were collected. For comparison 131 children without ADHD were matched for sex, age, marital status, and socioeconomic status (115 males, 16 females; mean age 4 years 10 months, SD 1 year 5 months; range 3 to 7 years). Sixty percent of those with ADHD met full DSM-IV criteria for ODD. Only 10 of the 131 children with ADHD had no symptoms of ODD at all. The rate of children meeting full diagnostic criteria for ODD was similar across all age cohorts. Males were overrepresented in ODD, as were children of divorced parents and of mothers with low socioeconomic status. ADHD combined subtype was a stable independent factor influencing the diagnosis of ODD, regardless of psychosocial factors. Those with ADHD with ODD consistently showed higher rates of ADHD symptoms than did those with ADHD without ODD. The prevalent comorbidity of ADHD with ODD indicates that all children presenting with ADHD or ODD symptoms need to be assessed with a view to exploring both types of problem behaviours. The link between ODD and some psychosocial variables indicates the need to address these, possibly by measures such as parent training and network support.     

Psychosocial problems in attention-deficit hyperactivity disorder with oppositional defiant disorder

The purpose of this study is to clarify psychosocial characteristics of the comorbidity of attention-deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) in comparison with ADHD or ODD alone. Thirty-one patients with ADHD comorbid with ODD were compared with 23 ADHD alone and 10 with ODD alone, in terms of various examination items including objective assessment scales. The comorbid group demonstrated higher Children Depression Inventory score and State-Trait Anxiety Inventory for Children (state-anxiety) score than the ADHD or the ODD group, possessing more problems in the relationship with teachers than the ADHD group, with friends more than the ADHD or the ODD group, and with their mothers more than the ADHD group and less than the ODD group. School refusal occurred more frequently in the comorbid group than the ADHD group and less than the ODD group. The comorbid group had more psychosocial problems than the ADHD group and the ODD group. These problems could be classified into three types: (i) those derived from ODD, problems in the relationship with teachers; (ii) those derived from ODD but reduced by the coexistence of ADHD, problems in the relationship with their mothers; and (iii) those resulting from the comorbidity of ADHD and ODD, problems in the relationship with friends and anxious and depressive tendency. The difficulties in the relationship with teachers and friends observed in the comorbid group may lead to school refusal.     

Gene-environment interplay in oppositional defiant and conduct disorder

Oppositional defiant and conduct disorder is a disturbance in behavior that is characterized by aggressive and antisocial acts. At present, genetic research on conduct disorder has raised more questions than it has answered, and basic questions such as the heritability of childhood antisocial behavior cannot yet be answered with certainty. Current research, however, has consistently highlighted the importance of gene-environment interplay in antisocial behavior.     

Serotonergic functioning in children with oppositional defiant disorder: a sumatriptan challenge study.

BACKGROUND: Several studies support the notion that disturbances in the central serotonergic function are related to impulsive aggression. There is recent evidence from studies on 5-HT(1B) knock-out mice that this specific receptor is involved in impulsive aggressive behavior. The aim of the present study was to investigate 5-HT(1B/1D) receptor functioning in normal intelligent hospitalized children with oppositional defiant disorder (ODD). METHODS: The growth hormone (GH) response to a challenge with the 5-HT(1B/1D) agonist sumatriptan was examined in 20 children with an ODD, of whom 13 had an attention-deficit/hyperactivity disorder comorbidity, and 15 normal control subjects (NC). Blood samples for growth hormone were collected repeatedly between 8:30 and 12:00 AM. Sumatriptan was administered at 10 AM. The effect of stress due to this procedure was assessed by measuring salivary cortisol. RESULTS: The GH response was significantly stronger in the children with ODD. After sumatriptan injection NC children showed a significant increase in cortisol; no such pattern was present in the ODD group. CONCLUSIONS: The results suggest that the postsynaptic 5-HT(1B/1D) receptor is functionally more sensitive in children with ODD.     

Neuroanatomical correlates of attention‐deficit–hyperactivity disorder accounting for comorbid oppositional defiant disorder and conduct disorder

Aim: An increasing number of neuroimaging studies have been conducted to uncover the pathophysiology of attention‐deficit–hyperactivity disorder (ADHD). The findings are inconsistent, however, at least partially due to methodological differences. In the present study voxel‐based morphometry (VBM) was used to evaluate brain morphology in ADHD subjects after taking into account the confounding effect of oppositional defiant disorder (ODD) and conduct disorder (CD) comorbidity. Methods: Eighteen children with ADHD and 17 age‐ and gender‐matched typically developing subjects underwent high‐spatial resolution magnetic resonance imaging. The regional gray matter volume differences between the children with ADHD and controls were examined with and without accounting for comorbid ODD and CD in a voxel‐by‐voxel manner throughout the entire brain. Results: The VBM indicated significantly smaller regional gray matter volume in regions including the bilateral temporal polar and occipital cortices and the left amygdala in subjects with ADHD compared with controls. Significantly smaller regional gray matter volumes were demonstrated in more extensive regions including the bilateral temporal polar cortices, bilateral amygdala, right occipital cortex, right superior temporal sulcus, and left middle frontal gyrus after controlling for the confounding effect of comorbid ODD and CD. Conclusion: Morphological abnormalities in ADHD were seen not only in the regions associated with executive functioning but also in the regions associated with social cognition. When the effect of comorbid CD and ODD was taken into account, there were more extensive regions with significantly smaller volume in ADHD compared to controls.