• Effects of long-term methylphenidate use on growth and blood pressure: results of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS)

      Hollis, Chris P.; Liddle, Elizabeth B. (2018)
      BACKGROUND: Concerns have been raised over the safety of methylphenidate (MPH), with regard to adverse effects on growth and blood pressure. Our study investigates whether, and to what extent, methylphenidate use in boys with ADHD is associated with having low body mass index (BMI), having low height, and increased systolic and diastolic blood pressure. METHODS: Data used for this study stem from the German KiGGS dataset. Three different groups of boys aged 6-15 years were included in the analysis: ADHD patients who used MPH for less than 12 months; ADHD patients who used MPH for 12 months or more; and ADHD patients without current MPH treatment. Each of these three groups was compared to a non-ADHD control group regarding low weight (BMI </= 3rd percentile), low height (</=3rd percentile) and raised systolic and diastolic blood pressure. For growth outcomes, boys were categorized according to age (< 11 years/>/=11 years, to account for pubertal maturation). Multivariable logistic regression was conducted to test for associations. RESULTS: 4244 boys were included in the study; MPH < 12 months: n = 65 (n = 36 < 11 years), MPH >/= 12 months: n = 53 (n = 22 < 11 years), ADHD controls: n = 320 (n = 132 < 11 years), non-ADHD controls: n = 3806 (n = 2003 < 11 years). Pre-pubertal boys with MPH use less than 12 months and pubertal/postpubertal boys with MPH use of 12 months or greater were significantly more likely to have a BMI </= 3rd percentile compared to non-ADHD controls. Boys from the ADHD control group were significantly less likely to have a raised systolic blood pressure compared to non-ADHD controls. Beyond that, no significant between group differences were observed for any other growth and BP parameter. CONCLUSION: The analyses of the KiGGS dataset showed that MPH use in boys with ADHD is associated with low BMI. However, this effect was only observed in certain groups. Furthermore, our analysis was unable to confirm that MPH use is also associated with low height (</=3rd percentile) and changes in blood pressure.
    • Lateralization of attention in adults with ADHD: evidence of pseudoneglect

      Liddle, Elizabeth B. (2020)
      Objective: To investigate whether adults with ADHD show pseudoneglect - preferential allocation of attention to the left visual field (LVF) and a resulting slowing of mean reaction times (MRT) in the right visual field (RVF), characteristic of neurotypical individuals (NT) - and whether lateralization of attention is modulated by presentation speed and incentives. Method: Fast Task, a 4-choice reaction-time task where stimuli were presented in LVF or RVF, was used to investigate differences in MRT and reaction time variability (RTV) in adults with ADHD (n = 43) and NT (n = 46) between a slow/no-incentive and fast/incentive condition. In the lateralization analyses pseudoneglect was assessed based on MRT, which was calculated separately for the LVF and RVF for each condition and each study participant. Results: Adults with ADHD had overall slower MRT and increased RTV relative to NT. MRT and RTV improved under the fast/incentive condition. Both groups showed RVF-slowing with no between-group or between-conditions differences in RVF-slowing. Conclusions: Adults with ADHD exhibited pseudoneglect, a neurotypical pattern of lateralization of attention, which was not attenuated by presentation speed and incentives.
    • Long term methylphenidate exposure and growth in children and adolescents with ADHD. A systematic review and meta-analysis

      Hollis, Chris P.; Liddle, Elizabeth B. (2020)
      BACKGROUNDMethylphenidate (MPH) is an efficacious treatment for ADHD but concerns have been raised about potential adverse effects of extended treatment on growth.OBJECTIVESTo systematically review the literature, up to December 2018, conducting a meta-analysis of association of long-term (> six months) MPH exposure with height, weight and timing of puberty.RESULTSEighteen studies (ADHD n = 4868) were included in the meta-analysis. MPH was associated with consistent statistically significant pre-post difference for both height (SMD = 0.27, 95% CI 0.16-0.38, p < 0.0001) and weight (SMD = 0.33, 95% CI 0.22-0.44, p < 0.0001) Z scores, with prominent impact on weight during the first 12 months and on height within the first 24-30 months. No significant effects of dose, formulation, age and drug-naïve condition as clinical moderators were found. Data on timing of puberty are currently limited.CONCLUSIONSLong-term treatment with MPH can result in reduction in height and weight. However, effect sizes are small with possible minimal clinical impact. Long-term prospective studies may help to clarify the underlying biological drivers and specific mediators and moderators.
    • Morphological abnormalities in prefrontal surface area and thalamic volume in attention deficit/hyperactivity disorder

      Batty, Martin J.; Palaniyappan, Lena; Groom, Madeleine J.; Liddle, Elizabeth B.; Liddle, Peter F.; Hollis, Chris P. (2015)
      Although previous morphological studies have demonstrated abnormalities in prefrontal cortical thickness in children with attention deficit/hyperactivity disorder (ADHD), studies investigating cortical surface area are lacking. As the development of cortical surface is closely linked to the establishment of thalam-ocortical connections, any abnormalities in the structure of the thalamus are likely to relate to altered cortical surface area. Using a clinically well-defined sample of children with ADHD (n = 25, 1 female) and typically developing controls (n = 24, 1 female), we studied surface area across the cortex to determine whether children with ADHD had reduced thalamic volume that related to prefrontal cortical surface area. Relative to controls, children with ADHD had a significant reduction in thalamic volume and dorsolateral prefrontal cortical area in both hemispheres. Furthermore, children with ADHD with smaller thalamic volumes were found to have greater reductions in surface area, a pattern not evident in the control children. Our results are further evidence of reduced lateral prefrontal cortical area in ADHD. Moreover, for the first time, we have also shown a direct association between thalamic anatomy and frontal anatomy in ADHD, suggesting the pathophysiological process that alters surface area maturation is likely to be linked to the development of the thalamus.Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
    • Motivational incentives and methylphenidate enhance electrophysiological correlates of error monitoring in children with attention deficit/hyperactivity disorder

      Groom, Madeleine J.; Liddle, Elizabeth B.; Liddle, Peter F.; Batty, Martin J.; Hollis, Chris P. (2013)
      BACKGROUND: Children with attention deficit hyperactivity disorder (ADHD) are characterised by developmentally inappropriate levels of hyperactivity, impulsivity and/or inattention and are particularly impaired when performing tasks that require a high level of cognitive control. Methylphenidate (MPH) and motivational incentives may help improve cognitive control by enhancing the ability to monitor response accuracy and regulate performance accordingly.
    • Neurological and psychiatric adverse effects of long-term methylphenidate treatment in ADHD: A map of the current evidence

      Hall, Charlotte L.; Groom, Madeleine J.; Kochhar, Puja; Roberts, Samantha; Sayal, Kapil; Xia, Jun; Hollis, Chris P.; Liddle, Elizabeth B. (2019)
      Methylphenidate (MPH), the most common medication for children with Attention Deficit/Hyperactivity Disorder (ADHD) in many countries, is often prescribed for long periods of time. Any long-term psychotropic treatment in childhood raises concerns about possible adverse neurological and psychiatric outcomes. We aimed to map current evidence regarding neurological and psychiatric outcomes, adverse or beneficial, of long-term MPH (> 1 year) treatment in ADHD. We coded studies using a "traffic light" system: Green: safe/favours MPH; Amber: warrants caution; Red: not safe/not well-tolerated. Un-categorisable study findings were coded as "Unclear". Although some evidence suggests an elevated risk of psychosis and tics, case reports describe remission on discontinuation. Several studies suggest that long-term MPH may reduce depression and suicide in ADHD. Evidence suggests caution in specific groups including pre-school children, those with tics, and adolescents at risk for substance misuse. We identified a need for more studies that make use of large longitudinal databases, focus on specific neuropsychiatric outcomes, and compare outcomes from long-term MPH treatment with outcomes following shorter or no pharmacological intervention.
    • Reports of perceived adverse events of stimulant medication on cognition, motivation, and mood: Qualitative investigation and the generation of items for the medication and cognition rating scale

      Hollis, Chris P.; Liddle, Elizabeth B. (2016)
      There is no questionnaire to specifically monitor perceived adverse events of methylphenidate (MPH) on cognition, motivation, and mood. The current study therefore had two goals. First, to harvest accounts of such putative events from transcripts of interviews in samples enriched for such potential experiences. Second, to use the derived data to generate items for a new questionnaire that can be used for monitoring such events in medication trials or routine clinical care. Following a literature search aimed at identifying associations between MPH and cognition and/or motivation, a qualitative semistructured interview was designed to focus specifically on the domains of cognition (i.e., reasoning, depth/breadth of thinking, intellectual capacity, and creativity) and motivation (i.e., drive, effort, and attitudes toward rewards/incentives). Interviews were conducted with 45 participants drawn from the following four groups: (a) clinicians, child and adolescent psychiatrists, and pediatricians specializing in attention-deficit/hyperactivity disorder (ADHD) (n = 15); (2) teachers, with experience of teaching at least 10 medicated children with ADHD (n = 10); (3) parents of children with ADHD (n = 8) treated with MPH; and (4) adolescents/adults with ADHD (n = 12). Purposeful sampling was used to selectively recruit ADHD participants whose histories suggested a degree of vulnerability to MPH adverse events. Data were analyzed using a deductive approach to content analysis. While we probed purposefully for cognitive and motivational adverse events, a third domain, related to mood, emerged from the reports. Therefore, three domains, each with a number of subdomains, were identified from the interview accounts: (i) Cognition (six subdomains; attention/concentration, changes in thinking, reduced creativity, sensory overload, memory, slower processing speed); (ii) motivation (four subdomains; loss of intrinsic motivation for goal-directed activities, external locus of control, lack of effort/engagement in daily tasks, increased focus on incentives); and (iii) mood (three subdomains; dampening of spontaneity/flat affect, mood dysregulation, increased anxiety/edginess). On the basis of these reports, 34 items were specified and incorporated into a prototype questionnaire, which was piloted and refined on the basis of field-testing. Items were identified that capture potential/perceived cognitive, motivational, and mood-related adverse events of MPH. The items generated will allow us to further develop and psychometrically examine their prevalence, and the extent to which they are associated with medication adherence, treatment outcome, impairment, and other reported adverse events (e.g., loss of appetite/cardiovascular effects).