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Objective: To assess the one-year period prevalence of stimulant combination therapy and switching in children/ adolescents with attention deficit/hyperactivity disorder (ADHD) in Quebec, Canada. Method: Patients aged 6-17 years, with at least two ADHD diagnosis codes documented in different visits and at least 30 days' supply of a stimulant during their most recent one-year observation period were selected from the Regie de l'assurance maladie du Quebec database (03/2007-02/2012). Combination therapy was defined as at least 30 consecutive days of concomitant use of multiple stimulants with different active moieties, or use of a stimulant and another psychotropic medication. Therapy switching was defined as a prescription claim for a new psychotropic medication less than 30 days before or after the end of supply of a stimulant. The one-year period prevalence of therapy combination and switching was calculated. Results: The one-year period prevalence of combination therapy and switching among 9,431 children and adolescents with ADHD treated with stimulants was 19.8% and 18.7%, respectively. The most frequent combination categories were atypical antipsychotics (AAP: 10.8%), atomoxetine (ATX: 5.5%) and clonidine (5.3%). The most frequent switched-to categories were other stimulants (7.9%), AAP (5.5%) and ATX (4.7%). Conclusions: Approximately one in five children/adolescents with ADHD on a stimulant experienced combination therapy or therapy switching; however, the majority of the medications used in combination or switching were not label-indicated for the treatment of ADHD in Canada. These results highlight the need for further research to evaluate the risk-benefit of stimulant combination and switching in children and adolescents with ADHD. [ABSTRACT FROM AUTHOR]

Objectives: Genetic and nonshared environmental factors (experienced by 1 family member to the exclusion of the others) have been strongly implicated in the causes of attention-deficit hyperactivity disorder (ADHD). Pregnancy, labour/delivery and neonatal complications (PLDNC) have often been associated with ADHD; however, no investigations aimed at delineating the shared or nonshared nature of these factors have been reported. We aimed to identify those elements of the PLDNC that are more likely to be of a nonshared nature. Methods: We used an intrafamily study design, comparing the history of PLDNC between children diagnosed with ADHD, according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), and their unaffected siblings. Children with ADHD were recruited from the outpatient, day-treatment program of the Child Psychiatry Department, Douglas Hospital, Montréal. The unaffected sibling closest in age to the child with ADHD was used as a control. The history of PLDNC was assessed using the Kinney Medical and Gynecological Questionnaire and the McNeil--Sjöstrom Scale for both children with ADHD and their siblings. Seventy children with ADHD along with 50 of their unaffected siblings agreed to participate in the study. Child Behavior Checklist (CBCL), Continuous Performance Test (CPT) and Restricted Academic Situation Scale (RASS) scores were also used as measures of ADHD symptoms in children with ADHD. Results: The children with ADHD had significantly higher rates of neonatal complications compared with their unaffected siblings (F4,196 = 3.67, p < 0.006). Furthermore, neonatal complications in the children with ADHD were associated with worse CBCL total and externalizing scores and with poorer performance on the CPT. Conclusions: These results suggest that neonatal complications are probably a nonshared environmental risk factor that may be pathogenic in children with ADHD. [ABSTRACT FROM AUTHOR]

Objective: Sleep disturbances appear as a comorbid condition in children with attention-deficit/hyperactivity disorder. The aim of this study was to investigate the relationship of activity levels during sleep and therapeutic response to methylphenidate (MPH). Method: Nightly sleep actigraphic recordings during a double-blind, placebo-controlled, cross- over clinical study (1-week of 0.5 mg/kg MPH; 1-week of placebo) were obtained on 44 children, 6 to 12 years old, diagnosed with attention-deficit/hyperactivity disorder (DSM-IV). Results: Significant (p c .005) differences between the conditions were found in several software-computed parameters: sleep onset latency (MPH, 39.3 minutes; placebo, 28.2 minutes), sleep efficiency (MPH, 78.0%; placebo, 80.4%), total sleep time (MPH, 7 hours; 57 minutes; placebo, 8 hours, 16 minutes). No significant differences on any of these measures were found among the 26 subjects who showed a moderate or large global improvement on MPH over placebo compared with 18 subjects who showed mild or no clinical improvement. Conclusions: MPH, given twice daily, induces a slight but significant sleep disturbance. Motor activity levels during sleep did not differentiate children who responded to MPH from those who did not respond. This suggests that responders to MPH treatment do not experience greater sleep disturbances than nonresponders, at least at the dose studied. [ABSTRACT FROM AUTHOR]

Objective: To compare the pattern of familial aggregation of psychopathology in children who are good responders (GR) to methylphenidate (MPH) versus those who are poor responders (PR).Method: A total of 118 clinically referred children ages 6 to 12 years, diagnosed with ADHD participated in a double-blind, placebo-controlled, randomized 2-week crossover trial of MPH from 1999 to 2004. A low dose of 0.5 mg/kg of body weight of MPH divided in two equal doses was used. Family history was obtained by interviewing at least one key historian relative of each subject using Family Interview for Genetic Studies. Information was collected on 342 first-degree and 1,151 second-degree relatives of children with attention-deficit/hyperactivity disorder.Results: Forty-four subjects showed mild or no improvement (PR) and 74 showed moderate or very much improvement (GR) on MPH over placebo. First-degree relatives of GR subjects were at significantly higher risk of attention-deficit/hyperactivity disorder than the relatives of PR subjects (p<.05). Second-degree relatives of the GR were at significantly higher risk of antisocial personality disorder compared to the relatives of PR subjects (p<.05).Conclusions: The significantly higher presence of attention-deficit/hyperactivity disorder in the first-degree relatives and of antisocial personality disorder in the second-degree relatives of GR children suggests that this group may, at least partially, be distinct from the PR group on the basis of genetic determinants. [ABSTRACT FROM AUTHOR]

Background: An association has been observed between the catechol-O-methyltransferase (COMT) gene, the predominant means of catecholamine catabolism within the prefrontal cortex (PFC), and neuropsychological task performance in healthy and schizophrenic adults. Since several of the cognitive functions typically deficient in children with Attention Deficit Hyperactivity Disorder (ADHD) are mediated by prefrontal dopamine (DA) mechanisms, we investigated the relationship between a functional polymorphism of the COMT gene and neuropsychological task performance in these children. Methods: The Val108/158 Met polymorphism of the COMT gene was genotyped in 118 children with ADHD (DSM-IV). The Wisconsin Card Sorting Test (WCST), Tower of London (TOL), and Self-Ordered Pointing Task (SOPT) were employed to evaluate executive functions. Neuropsychological task performance was compared across genotype groups using analysis of variance. Results: ADHD children with the Val/Val, Val/Met and Met/Met genotypes were similar with regard to demographic and clinical characteristics. No genotype effects were observed for WCST standardized perseverative error scores [F2,97 = 0.67; p > 0.05], TOL standardized scores [F2,99 = 0.97; p > 0.05], and SOPT error scores [F2,108 = 0.62; p > 0.05]. Conclusions: Contrary to the observed association between WCST performance and the Val108/ 158 Met polymorphism of the COMT gene in both healthy and schizophrenic adults, this polymorphism does not appear to modulate executive functions in children with ADHD. [ABSTRACT FROM AUTHOR]

Objective: To compare weight and glucose changes of long-term second-generation antipsychotic (SGA) monotherapy versus polytherapy (switching or combining SGAs) in children and adolescents.Methods: This is a 24-month retrospective study conducted between November 2005 and June 2013. From 147 antipsychotic-naive patients selected (mean age, 12.8 years; 95% confidence interval [CI], 9.8-15.9), 116 (78.9%) received SGA monotherapy and 31 (21.1%) SGA polytherapy for up to 24 months. Height, weight, and fasting glucose (FG) were measured at baseline and 1, 3, 6, 12, and 24 months. Linear mixed-model analysis was used to compare weight, body mass index z score (BMI z score), and glucose changes between the 2 SGA treatment groups, with the repeated factor being the time relative to baseline at 1, 3, 6, 12, and 24 months.Results: Overall, after 24 months of SGA treatment, mean weight increased significantly by 12.8 kg (95% CI, 10.4-15.0), BMI z score by 0.44 (95% CI, 0.21-0.68), and FG levels by 0.29 mmol/L (95% CI, 0.11-0.47). Incidence of overweight/obesity was 22.6%, BMI z score increase over 0.5 was 9.4%, impaired fasting glucose was 9.4%, and type 2 diabetes mellitus was 3.1%. Regarding metabolic effects, no significant difference was found between the subjects taking a single SGA and those exposed to an SGA polytherapy.Conclusion: Our study confirms the significant increase of metabolic complications during 24 months of SGA treatment without excluding or confirming a difference between the 2 groups of treatment (mono vs. poly). [ABSTRACT FROM AUTHOR]

Objectives: To assess treatment patterns, health care resource utilization (HRU), and costs among previously stimulant-treated children and adolescents with attention-deficit hyperactivity disorder (ADHD) receiving atypical antipsychotic (AAP) prescriptions in Quebec. Methods: Health care claims data extracted from Quebec's provincial health plan database between March 2007 and February 2012 were analyzed. Children and adolescents (6 to 17 years) with ADHD who were taking a stimulant and either switched to, or augmented with, an AAP (with the first AAP defined as the index AAP) without a documented diagnosis for which AAPs are Health Canada-approved were included. Discontinuation, augmentation, and switching of the index AAP during the 12-month, follow-up period were estimated using Kaplan-Meier survival analysis. HRU and costs for the 6 months before (baseline period) and after initiation of the index AAP were compared. Results: A total of 453 children and adolescents with ADHD, mostly male (74.6%) and aged 6 to 12 years (73.7%), met the inclusion criteria. The 12-month discontinuation, augmentation, and switching rates were 45.5%, 68.2%, and 80.7%, respectively. Patients had, on average, more all-cause prescription fills (22.2, compared with 13.3) and incurred more all-cause pharmacy ($889, compared with $710), total medical ($1096, compared with $644), and total health care ($1985, compared with $1354) costs during the 6-month study period than during the 6-month baseline period (all P < 0.05). Similarly, ADHD-related total health care costs were higher during the study period ($1269, compared with $835; P < 0.05); all-cause and ADHD-related total health care costs increased by 46.6% and 52.0%, respectively. Conclusions: Use of an AAP among stimulant-treated children and adolescents with ADHD in Quebec was associated with high rates of therapy changes and increased HRU and costs. [ABSTRACT FROM AUTHOR]

We sought to test the hypothesis that the variable number of tandem repeat (VNTR) polymorphism in the 3′-untranslated region (3′-UTR) of the SLC6A3 gene modulates behavior in children with ADHD and/or behavioral response to methylphenidate (MPH). One hundred and fifty-nine children with AHDH (6–12 years) were assessed with regard to the Conners’ Global Index for parents (CGI-Parents) and teachers (CGI-Teachers) and the response of these behaviors to MPH (0.5 mg/kg/day) using a 2-week prospective within-subject (crossover) trial. Based on CGI-Parents, the profile of behavioral response to MPH as compared to placebo was not parallel in the three groups of children separated according to their genotype in the 3′-UTR VNTR polymorphism of SLC6A3, as indicated by a significant (p=0.017) genotype by treatment two-way interaction. Individuals having the 9/10 and 10/10 genotypes displayed a significant positive response to MPH as opposed to those homozygous for the 9-repeat allele. No genotype or genotype by treatment interaction was observed for CGI-Teachers. These findings support a role for the DAT gene 3′-UTR VNTR polymorphism in modulating the response of some behavioral dimensions to MPH in children with ADHD. They also suggest the presence of genetic heterogeneity that could be indexed by the quality of behavioral response to MPH.Neuropsychopharmacology (2007) 32, 1370–1376. doi:10.1038/sj.npp.1301240; published online 25 October 2006 [ABSTRACT FROM AUTHOR]

Objective: In a recent study, Thapar and colleagues reported that COMT "gene variant and birth weight predict early-onset antisocial behavior in children" with attention-deficit/hyperactivity disorder. We have attempted to replicate these findings in a group of ADHD children using a similar research design.Method: Children (n=191) between 6 and 12 years of age who were diagnosed with ADHD were included in the study. Conduct disorder was diagnosed according to DSM-IV criteria based on clinical evaluation and a structured interview (Diagnostic Interview Schedule for Children-IV). The mother's report on the child's birth weight was used in the analysis. Logistic regression analysis, with genotype and birth weight as independent variables and DSM-IV conduct disorder as the dependent variable, was conducted.Results: No significant main effects of genotype and birth weight or interaction effects on conduct disorder were observed.Conclusion: In this sample of children diagnosed with ADHD, we find no association between the COMT ValMet gene variant, birth weight, and conduct disorder. Further investigations are required before using birth weight and COMT genotype as predictors of conduct disorder in children with attention-deficit/hyperactivity disorder, especially given the societal and legal ramifications of conduct disorder. [ABSTRACT FROM AUTHOR]

Objective: To examine whether COMT (catechol-O-methyltransferase) polymorphism modulates aspects of sleep in children diagnosed with attention-deficit/hyperactivity disorder (ADHD).Method: Nightly sleep actigraphic recordings during a double-blind, placebo-controlled, crossover clinical study (1 week of 0.5 mg/kg MPH; 1 week of placebo) were obtained for 34 children, 7.4 to 12 years old, diagnosed with ADHD (DSM-IV). Diagnosis was generated by the Diagnostic Interview Schedule for Children and was confirmed by multidisciplinary consensus.Results: Children who were Val allele carriers had poorer sleep continuity compared with children with the Met-Met genotype while receiving a placebo and while receiving methylphenidate.Conclusions: The findings of the present study support the hypothesis that sleep disturbances in children with ADHD are related to the underlying pathophysiology of the disorder. [ABSTRACT FROM AUTHOR]