Treating children with attention-deficit/hyperactivity disorder and comorbid epilepsy

Attention-deficit/hyperactivity disorder (ADHD) is one of common neurodevelopmental disorder often comorbid with epilepsy. There are no existing guidelines on how to manage these two conditions when they are comorbid. To identify relationship between epilepsy and ADHD and to know role of antiepileptics and safety of stimulant like methylphenidate in such conditions from existing literature, we searched articles published in clinical journals available online between 1990-2010, with these key words in medline:children, epilepsy, seizure, comorbid, ADHD, treatment. Relevant abstracts were further selected for their focus on current topic. Cross references were extracted. Finally relevant articles that included original research articles, reviews and abstracts of non-english literature were used. Children with epilepsy may manifest with symptoms of ADHD. Children with ADHD may develop epilepsy. Some antiepileptics like phenobarbitone, gabapentin, topiramate may not be helpful in controlling behavioral symptoms of ADHD. Stimulants are the main stay of pharmacotherapy for ADHD but there is risk of decreasing seizure threshold in children with comorbid epilepsy especially when their epilepsy is not well controlled. Existing evidence is not in favor of screening children with ADHD for EEG abnormality before starting stimulant therapy.     

Medication patterns for attention-deficit/hyperactivity disorder and comorbid psychiatric conditions in a low-income population

The aims of this study were two-fold: (1) to describe the patterns of comorbid psychiatric diagnosis and psychotropic drug therapy for children enrolled in a Medicaid-managed care program and diagnosed with attention-deficit/hyperactivity disorder (ADHD) in 2000 and (2) to examine child and provider characteristics associated with psychotropic medication patterns for this population. Multivariate logistic regression models were used to examine correlates of stimulant and seven nonstimulant psychotropic medication classes (alpha-agonists, mood stabilizer/anticonvulsant, antianxiety, standard antipsychotic, atypical antipsychotic, and tricyclic antidepressant (TCA)/other antidepressant and selective serotonin reuptake inhibitor (SSRI) antidepressant). With the exception of conduct disorders (odds ratio, 1.22; 95% confidence interval, 1.06-1.40), comorbid disorders had a significant protective effect (odds ratio less than 1) on dispensing stimulants. After adjusting for covariates, stimulant dispensing was strongly correlated with the interactions of geographic region with race/ethnicity and provider type. Children residing in the upstate New York region had an approximately ten-fold greater chance of being dispensed a stimulant compared to similar children in New York City. Utilizing a mental health provider increased the chance of being dispensed a stimulant by factor of two for children from New York City of any race/ethnicity group. Models predicting nonstimulant drug dispensing were distinct from the stimulant model. After adjusting for covariates, nonstimulant psychotropic medication dispensing was correlated with clinical factors, including comorbid disorder category and use of a mental health provider, as well as notable sociodemographic factors. Complex psychotropic medication and comorbid psychiatric disorder patterns were evident for this low-income population of children with ADHD. The roles of clinical, patient, and provider factors need to be better understood to explain these patterns of stimulant and nonstimulant psychotropic medications dispensed.     

Atomoxetine treatment for pediatric patients with attention-deficit/hyperactivity disorder with comorbid anxiety disorder

OBJECTIVE: Research suggests 25% to 35% of children with attention-deficit/hyperactivity disorder (ADHD) have comorbid anxiety disorders. This double-blind study compared atomoxetine with placebo for treating pediatric ADHD with comorbid anxiety, as measured by the ADHD Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-PI) and the Pediatric Anxiety Rating Scale (PARS). METHOD: Patients (ages 8-17 years) meeting DSM-IV criteria for ADHD and generalized anxiety disorder, separation anxiety disorder, and/or social phobia were randomized to 12 weeks of atomoxetine (n = 87) or placebo (n = 89). ADHDRS-IV-PI and PARS total scores were analyzed using analysis of covariance last observation carried forward and repeated-measures analyses. RESULTS: Sixty-six patients in each group completed the study. Mean ADHDRS-IV-PI total score improved significantly for atomoxetine (n = 55; -10.5, SD 10.6) relative to placebo (n = 58; -1.4, SD 8.3; p < .001). Mean PARS total score also improved significantly for atomoxetine (n = 55; -5.5, SD 4.8) relative to placebo (n = 58; -3.2, SD 5.0; p = .011). CONCLUSIONS: Atomoxetine was efficacious in reducing ADHD symptoms in patients who have ADHD with comorbid anxiety and was well tolerated. There was also a significant reduction in independently assessed anxiety symptoms using both clinician-rated and self-rated measures, which merits further investigation. Results support consideration of atomoxetine for the treatment of ADHD in youths who have ADHD with comorbid anxiety disorder. CLINICAL TRIAL REGISTRATION INFORMATION: The LYBP study, on which this article is based, was not registered at clinicaltrials.gov because the last patient visit occurred before July 1, 2005. Results, however, are publicly posted at lillytrials.com and clinicalstudyresults.org. The unique study ID at both sites is 6477a.     

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.     

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.     

Bupropion sustained release in adolescents with comorbid attention-deficit/hyperactivity disorder and depression

OBJECTIVE: To determine whether bupropion sustained release (SR) is effective and well-tolerated in adolescents with comorbid attention-deficit/hyperactivity disorder (ADHD) and depression. METHOD: Subjects were 24 adolescents (aged 11-16 years old) with ADHD and either major depressive disorder or dysthymic disorder. After a 2-week, single-blind placebo lead-in, subjects were treated for 8+ weeks with bupropion SR at doses flexibly titrated up to 3 mg/kg b.i.d. (mean final doses: 2.2 mg/kg q A.M. and 1.7 mg/kg q P.M.). Outcomes were global improvement in ADHD and depression (clinician-rated), along with changes in depressive symptomatology (parent- and child-rated), ADHD symptomatology (parent- and teacher-rated), and functional impairment (parent-rated). RESULTS: Clinicians rated 14 subjects (58%) responders in both depression and ADHD, 7 (29%) responders in depression only, and 1 (4%) a responder in ADHD only. Compared with post-placebo ratings, final parents' (p < .0005) and children's (p = .016) ratings of depressive symptomatology improved significantly, as did parents' (p < .0005) but not teachers' (p = .080) ratings of ADHD symptomatology. Final ratings of functional impairment improved significantly from enrollment (p < .0005). No subject discontinued medication because of side effects. CONCLUSIONS: Bupropion SR may be effective and well-tolerated in adolescents with comorbid ADHD and depressive disorders. However, randomized, placebo-controlled studies are needed.     

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.     

Parent-reported problematic sleep behaviors in children with comorbid autism spectrum disorder and attention-deficit/hyperactivity disorder

BackgroundSleep problems are frequent and well documented in children with Autism Spectrum Disorders (ASD), children with Attention Deficit/Hyperactivity Disorder (ADHD) and children with internalizing problems, however limited work has examined sleep problems in children presenting with comorbid ASD/ADHD. In healthy children, sleep problems negatively impact social, emotional, and academic functioning. The current study sought to examine diagnostic severity as predictors of sleep problems in children with comorbid ASD/ADHD. Additionally, the association between sleep and “real-life” functional domains (i.e., intellectual functioning, academic achievement, and executive functioning) were assessed.MethodSleep, internalizing difficulties, intellectual functioning, academic achievement and executive functioning were assessed in 85 children with who carried the dual diagnoses of ASD and ADHD.ResultsInternalizing difficulties, rather than ASD or ADHD symptom severity, was the most consistent predictor of problematic sleep behaviors (i.e., nightmares overtiredness, sleeping less than other children, trouble sleeping, and Total Problematic Sleep Behaviors) in this sample. Further, parent report of problematic sleep behaviors was significantly associated with functional domains after controlling for ASD, ADHD, and internalizing symptoms.ConclusionsResults suggest that internalizing symptoms are associated with problematic sleep behaviors in children with comorbid ASD/ADHD and may have implications for the “real-life” functioning among children with comorbid ASD/ADHD.     

Neurochemical alterations in women with borderline personality disorder and comorbid attention-deficit hyperactivity disorder

Background. Borderline personality disorder (BPD) is associated with structural and functional brain changes. Recent models and findings refer to alterations of glutamate and total N-acetylaspartate (tNAA) in this condition. Methods. Absolute quantities of tNAA, creatine, glutamate, glutamine, myoinositol and total choline were measured using 3 Tesla magnetic resonance spectroscopy of the left anterior cingulate cortex and the left cerebellum in 14 unmedicated women with BPD and comorbid attention-deficit hyperactivity disorder (ADHD) and 18 healthy women. Both groups were matched with respect to age, education and premorbid intelligence. Results. In the anterior cingulate, we found significantly higher tNAA and glutamate concentrations and a trend for lower glutamine levels in women with BPD and comorbid ADHD as compared to healthy women. There were no significant group differences in cerebellar metabolite concentrations. Conclusions. Glutamatergic changes in the anterior cingulate may be associated with BPD and comorbid ADHD. Increased anterior cingulate tNAA may indicate disturbed energy metabolism or impaired frontal maturation.     

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.     

Inattention symptoms and the diagnosis of comorbid attention-deficit/hyperactivity disorder among youth with generalized anxiety disorder

Generalized anxiety disorder (GAD) and attention-deficit/hyperactivity disorder (ADHD) commonly co-occur in childhood. Inattention symptoms can be hallmarks of both conditions, however assessment tools of inattention may not effectively distinguish between the two conditions. The present study used receiver operating characteristic (ROC) analyses to examine the high-end specificity of the Attention Problems Scale of the Child Behavior Checklist (CBCL) for detecting comorbid ADHD among youth with GAD (N = 46). Results support the utility of the Attention Problems Scale for accurately distinguishing between the two groups (AUC = .84, SE = .06). Specifically, a cut score of 63 achieved the most favorable values across diagnostic utility indices; 74% of GAD youth with ADHD scored above this cutoff and 91% of GAD youth without ADHD scored below this cutoff. Findings provide support for the use of the CBCL Attention Problems Scale to supplement diagnostic interviews and identify inattention associated with ADHD among GAD youth.     

Attentional functions in children and adolescents with attention-deficit/hyperactivity disorder with and without comorbid tic disorder

Summary Although the coexistence of attention-deficit/hyperactivity disorder (ADHD) and tic disorder (TD) is common, the nature of association is yet not fully understood. Thus, the aim of the present study was to explore attentional dysfunction in children with pure ADHD compared to children with comorbid ADHD + TD. Three groups of 20 children each, aged 8–15 years with either ADHD, ADHD + chronic tic disorder or Tourette syndrome (ADHD + TD) and a healthy control group were compared in their performance on three computerized attention tasks. Tasks of sustained attention, selective attention and interference control were employed. In addition, parental ratings of ADHD symptom severity and behaviour problems were obtained. Both clinical groups were rated as equally inattentive, however, externalising symptoms were more severe in the ADHD group. Objective measures of attentional performance revealed differences between the groups: whereas the ADHD group was markedly impaired in sustaining attention and selective attention/inhibitory control, the ADHD + TD group only showed marginal deficits in selective attention/inhibitory control. Possible explanations for the superior performance of the comorbid group are discussed: In particular, the results may indicate that in some patients, the tic disorder produces behavioural symptoms of ADHD, but not the broad neurocognitive deficits that usually are associated with ADHD. Alternatively, compensatory neural mechanisms of TD patients may result in a better neuropsychological performance of comorbid patients relative to patients suffering from pure ADHD. Correspondence: Ellen Greimel, Child Neuropsychology Section, Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital Aachen, 52074 Aachen, Germany     

Corpus callosum abnormalities in women with borderline personality disorder and comorbid attention-deficit hyperactivity disorder

OBJECTIVE: Decreased brain volumes in prefrontal, limbic and parietal areas have been found in women with borderline personality disorder (BPD). Recent models suggest impaired structural and functional connectivity in this condition. To investigate this, we studied the thickness of the corpus callosum, the largest connecting fibre bundle in the human brain. METHODS: We acquired magnetic resonance imaging scans from 20 healthy women and 20 women with BPD and comorbid attention-deficit hyperactivity disorder. A novel computational mesh-based method was applied to measure callosal thickness at high spatial resolution. RESULTS: Women with BPD had a thinner isthmus of the corpus callosum, compared with healthy women. In the patient group, a history of childhood sexual abuse was associated with a thinner posterior body of the corpus callosum. CONCLUSION: Interhemispheric structural connectivity involving parietal and temporal areas may be impaired in women with BPD and comorbid attention-deficit hyperactivity disorder.     

Children with attention-deficit/hyperactivity disorder and autistic features: EEG evidence for comorbid disorders

Attention-deficit/hyperactivity disorder (AD/HD) is the most common psychiatric disorder of childhood, although AD/HD is rarely the only diagnosis given to these children. Within the literature there is some debate as to whether it is valid to diagnose AD/HD with autism as a comorbid disorder, since the present diagnostic systems exclude the diagnosis of both disorders in the same child. The aim of this study was to determine whether electroencephalography (EEG) differences exist between two groups of children diagnosed with AD/HD, one scoring high (AD/HD+) and one scoring low (AD/HD?) on a measure of autism. The EEG was recorded during an eyes-closed resting condition from 19 electrodes, and Fourier transformed to provide absolute and relative power estimates in delta, theta, alpha and beta bands. Compared to age- and sex-matched controls, the AD/HD? group had increased absolute power in all frequency bands, somewhat higher relative theta activity and decreased relative delta. In comparison to the AD/HD? group, patients with autistic features (AD/HD+) had a number of qualitative differences in the beta and theta bands. These results indicate the presence of two comorbid conditions in the AD/HD+ group, which suggests that AD/HD and autism can occur in the same individual.     

Zinc in attention-deficit/hyperactivity disorder

OBJECTIVE: The aim of this study was to review the published evidence for a role of zinc nutrition in attention-deficit/hyperactivity disorder (ADHD). METHOD: A computer literature search was supplemented by the authors' knowledge. RESULTS: Numerous controlled studies report cross-sectional evidence of lower zinc tissue levels (serum, red cells, hair, urine, nails) in children who have ADHD, compared to normal controls and population norms. A few studies show correlations of zinc level with either clinical severity or a change thereof in response to stimulant or chemical challenge. Two placebo-controlled trials--one of zinc monotherapy, the other of zinc supplementation of methylphenidate--reported significant benefit. However, diagnostic procedures and sample representativeness were often not clear, and most such reports have come from countries and cultures with different diets and/or socioeconomic realities than are found in the United States (only one American sample in nine published reports). In particular, both positive clinical trials of zinc supplementation came from the Mid-East (Turkey and Iran), an area with suspected endemic zinc deficiency. The largest of these trials used zinc doses above the recommended upper tolerable limit and had a 2 in 3 dropout rate. CONCLUSION: It is not clear how well the accumulating evidence for a possible role of zinc in ADHD applies to middle-class American children. However, the evidence appears strong enough to warrant further controlled study in well-diagnosed samples representative of the socioeconomic spectrum. Hypothesis-testing clinical trials are needed of this potential treatment that, if found effective, might become a relatively safe, cheap substitute for, or adjunct to, current treatments in some patients. At present, it should remain an investigational treatment.     

Sleep disorders and attention-deficit/hyperactivity disorder

The relationship between attention-deficit/hyperactivity disorder (ADHD) and sleep is complex and poses many challenges in clinical practice. Recent studies have helped to elucidate the nature of the neuromodulator systems underlying the associations among sleepiness, arousal, and attention. Studies of sleep disturbances in children with academic and behavioral problems have also underscored the role that primary sleep disorders play in the clinical presentation of symptoms of inattention and behavioral dysregulation. Recent research has shed further light on the prevalence, type, risk factors for, and impact of sleep disturbances on children with ADHD. The following discussion of the multilevel and bidirectional relationships among sleep, neurobehavioral functioning, and the clinical syndrome of ADHD synthesizes current knowledge about the interaction of sleep and attention/arousal in these children. Guidelines are provided to outline a clinical approach to evaluating and managing children with ADHD and sleep problems.     

Inattentiveness in attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a long-term impact on functioning, productivity and quality of life of patients. This impact is largely due to the symptoms of inattentiveness. However, despite its impairing role in the lives of ADHD patients, inattentiveness has been studied relatively less frequently than have symptoms of impulsivity/hyperactivity and problems with executive function. This review therefore seeks to integrate the neuropsychological theories and current findings in the research fields of neuropsychology, neurophysiology, and neuroimaging, in an attempt to gain a more complete understanding of the role that inattentiveness plays in ADHD, as well as to suggest directions for future studies. The need for a more comprehensive understanding of inattentiveness and ADHD, which integrates findings from each of the three disciplines mentioned above, is emphasized.