Paramala Santosh

Long-acting medications for the hyperkinetic disorders : A systematic review and European treatment guideline

A systematic review of published and unpublished data on the use of long-acting medications in ADHD and hyperkinetic disorder is reported, giving effect sizes and numbers-to-treat for extended-release stimulant preparations and atomoxetine (ATX). A panel of experts from several European countries used the review to make recommendations about the use of these drugs in practice, and conclusions are reported: (1) Long-acting preparations should be available and used; (2) They should not replace short-acting drugs (which will be the initial treatment for many children for reasons of cost and flexibility of dosing). Individual clinical choice is needed. (3) Both ATX and extended-release preparations of stimulants should be available. The choice will depend upon the circumstances, and detailed recommendations are made.

European guidelines on managing adverse effects of medication for ADHD

The safety of ADHD medications is not fully known. Concerns have arisen about both a lack of contemporary-standard information about medications first licensed several decades ago, and signals of possible harm arising from more recently developed medications. These relate to both relatively minor adverse effects and extremely serious issues such as sudden cardiac death and suicidality. A guidelines group of the European Network for Hyperkinetic Disorders (EUNETHYDIS) has therefore reviewed the literature, recruited renowned clinical subspecialists and consulted as a group to examine these concerns. Some of the effects examined appeared to be minimal in impact or difficult to distinguish from risk to untreated populations. However, several areas require further study to allow a more precise understanding of these risks.

The quality of life of children with attention deficit/ hyperactivity disorder: a systematic review

Quality of life (QoL) describes an individual’s subjective perception of their position in life as evidenced by their physical, psychological, and social functioning. QoL has become an increasingly important measure of outcome in child mental health clinical work and research. Here we provide a systematic review of QoL studies in children and young people with attention deficit hyperactivity disorder (ADHD) and address three main questions. (1) What is the impact of ADHD on QoL? (2) What are the relationships between ADHD symptoms, functional impairment and the mediators and moderators of QoL in ADHD? (3) Does the treatment of ADHD impact on QoL? Databases were systematically searched to identify research studies describing QoL in ADHD. Thirty six relevant articles were identified. Robust negative effects on QoL are reported by the parents of children with ADHD across a broad range of psycho-social, achievement and self evaluation domains. Children with ADHD rate their own QoL less negatively than their parents and do not always seeing themselves as functioning less well than healthy controls. ADHD has a comparable overall impact on QoL compared to other mental health conditions and severe physical disorders. Increased symptom level and impairment predicts poorer QoL. The presence of comorbid conditions or psychosocial stressors helps explain these effects. There is emerging evidence that QoL improves with effective treatment. In conclusion, ADHD seriously compromises QoL especially when seen from a parents’ perspective. QoL outcomes should be included as a matter of course in future treatment studies.

Evidence-based guidelines for management of attention-deficit/hyperactivity disorder in adolescents in transition to adult services and in adults: recommendations from the British Association for Psychopharmacology.

Attention-deficit/hyperactivity disorder (ADHD) is an established diagnosis in children, associated with a large body of evidence on the benefits of treatment. Adolescents with ADHD are now leaving children’s services often with no readily identifiable adult service to support them, which presents problems as local pharmacy regulations often preclude the prescription of stimulant drugs by general practitioners (GPs). In addition, adults with ADHD symptoms are now starting to present to primary care and psychiatry services requesting assessment and treatment. For these reasons, the British Association for Psychopharmacology (BAP) thought it timely to hold a consensus conference to review the body of evidence on childhood ADHD and the growing literature on ADHD in older age groups. Much of this initial guidance on managing ADHD in adolescents in transition and in adults is based on expert opinion derived from childhood evidence. We hope that, by the time these guidelines are updated, much evidence will be available to address the many directions for future research that are detailed here.

Cognitive Training for Attention-Deficit/Hyperactivity Disorder: Meta-Analysis of Clinical and Neuropsychological Outcomes From Randomized Controlled Trials

Objective The authors performed meta-analyses of randomized controlled trials to examine the effects of cognitive training on attention-deficit/hyperactivity disorder (ADHD) symptoms, neuropsychological deficits, and academic skills in children/adolescents with ADHD. Method The authors searched Pubmed, Ovid, Web of Science, ERIC, and CINAHAL databases through May 18, 2014. Data were aggregated using random-effects models. Studies were evaluated with the Cochrane risk of bias tool. Results Sixteen of 695 nonduplicate records were analyzed (759 children with ADHD). When all types of training were considered together, there were significant effects on total ADHD (standardized mean difference [SMD] = 0.37, 95% CI = 0.09–0.66) and inattentive symptoms (SMD = 0.47, 95% CI = 0.14–0.80) for reports by raters most proximal to the treatment setting (i.e., typically unblinded). These figures decreased substantially when the outcomes were provided by probably blinded raters (ADHD total: SMD = 0.20, 95% CI = 0.01–0.40; inattention: SMD = 0.32, 95% CI = −0.01 to 0.66). Effects on hyperactivity/impulsivity symptoms were not significant. There were significant effects on laboratory tests of working memory (verbal: SMD = 0.52, 95% CI = 0.24–0.80; visual: SMD = 0.47, 95% CI = 0.23–0.70) and parent ratings of executive function (SMD = 0.35, 95% CI = 0.08–0.61). Effects on academic performance were not statistically significant. There were no effects of working memory training, specifically on ADHD symptoms. Interventions targeting multiple neuropsychological deficits had large effects on ADHD symptoms rated by most proximal assessors (SMD = 0.79, 95% CI = 0.46–1.12). Conclusion Despite improving working memory performance, cognitive training had limited effects on ADHD symptoms according to assessments based on blinded measures. Approaches targeting multiple neuropsychological processes may optimize the transfer of effects from cognitive deficits to clinical symptoms.

Psychopharmacotherapy in children and adults with intellectual disability

The prevalence of psychiatric disorders is increased in children and adults with intellectual disability. Brain damage or dysfunction interact with social and family factors to increase susceptibility to mental illness. Psychiatric disorders in the context of genetic syndromes are commonly overlooked, and there is substantial underdiagnosis of mental disorders because of the atypical and non-specific clinical presentations, and the frequent assumption that psychiatric symptoms are an inherent part of the underlying intellectual disability. There is a strong need for evidence-based practice in the prescribing and monitoring of drugs in this population, especially since many of the drugs are unlicensed for use in children. There is an urgent need to understand and establish the pharmacokinetics, pharmacodynamics, and side-effect profiles of psychotropic medication in this population. Positive trends in pharmacotherapy include the use of atypical antipsychotics instead of the classic antipsychotics, serotonin-specific reuptake inhibitors (SSRIs) rather than tricyclic antidepressants, and newer antiepileptic drugs. Another welcome trend is the use of SSRIs instead of antipsychotics in the long-term management of challenging behaviour in this population.

Social impairment in hyperkinetic disorder: Relationship to psychopathology and environmental stressors

Abstract.Background:There is paucity of information concerning social impairment in children and adolescents referred to mental health services.Aims:The aim of this study was to assess the association of social impairment, psychopathology and environmental stressors in Hyperkinetic Disorder (HKD) and to determine the frequency of pervasive developmental disorder (PDD) symptoms in HKD.Method:‘Item sheets’ about children and adolescents seen in child and adolescent mental health between 1992 and 2001 (n = 3644) were used to extract nine psychopathology domains, two social impairment subtypes and nine environmental stressors. The two social impairment subtypes were relationship difficulty (RD) and social communication difficulty (SCD) (i. e. autistic-like social impairment). The association of SCD/RD, psychopathology domains and environmental stressors was investigated in HKD cases and compared to a psychiatric control group.Results:In children and adolescents with HKD, SCD was associated with speech and language difficulties, repetitive behaviour, developmental difficulties (all symptoms of PDD), affective symptoms, conduct problems and ADHD symptoms. Relationship difficulty was linked to conduct problems, affective symptoms and environmental stressors. Unlike SCD, RD was associated with all of the environmental stressors studied. There were significantly more children with PDD symptoms in the HKD group than in the control group.Conclusion:This study highlights the importance of subtyping social impairment in HKD and its association with psychopathology and environmental stressors. In HKD, SCD reflecting autistic social impairment is associated with other autistic symptoms, such as speech and language problems and repetitive behaviour. A small subgroup of HKD cases may have a milder form of autistic spectrum disorder.

Youth meeting symptom and impairment criteria for mania‐like episodes lasting less than four days: an epidemiological enquiry

BACKGROUND Little is known about short-duration episodes of mania-like symptoms in youth. Here we determine the prevalence, morbid associations, and contribution to social impairment of a phenotype characterised by episodes during which symptom and impairment criteria for mania are met, but DSM-IV duration criteria are not (bipolar not otherwise specified; BP-NOS). METHODS A cross-sectional national survey of a sample (N = 5,326) of 8-19-year-olds from the general population using information from parents and youth. Outcome measures were prevalence rates and morbid associations assessed by the Developmental and Well-Being Assessment, and social impairment assessed by the impact scale of the Strengths and Difficulties Questionnaire. RESULTS While only seven individuals (.1%) met definite or probable DSM-IV criteria for BPI or BPII, the prevalence of BP-NOS was 10-fold higher, 1.1% by parent report and 1.5% by youth report. Parent-youth agreement was very low: kappa = .02, p > .05 for BP-NOS. Prevalence and episode duration for BP-NOS did not vary by age. BP-NOS showed strong associations with externalising disorders. After adjusting for a dimensional measure of general psychopathology, self-reported (but not parent-reported) BP-NOS remained associated with overall social impairment. CONCLUSIONS BP meeting full DSM-IV criteria is rare in youth. BP-NOS, defined by episodes shorter than those required by DSM-IV, but during which DSM-IV symptom and impairment criteria are met, is commoner and may be associated with social impairment that is beyond what can be accounted for by other psychopathology. These findings support the importance of research into these short episodes during which manic symptoms are met in youth but they also call into question the extent to which BP-NOS in youth is a variant of DSM-IV BP - superficially similar symptoms may not necessarily imply deeper similarities in aetiology or treatment response.

Effects of the committee on safety of medicines advice on antidepressant prescribing to children and adolescents in the UK

AbstractBackground: Psychotropic medication prescribing for children and adolescents rose significantly between 2000 and 2002, including antidepressant prescribing. In 2003, the Committee on Safety of Medicines (CSM) advised against using venlafaxine or any selective serotonin receptor inhibitor (SSRI), with the exception of fluoxetine, for childhood and adolescent depression. The aim of this study was to compare the prevalence and incidence of children and adolescents who were prescribed antidepressants in UK primary care, before and after the CSM advice on antidepressant prescribing. We also compared paediatric antidepressant prescribing trends from Mediplus data with national antidepressant prescribing trends in England from the Prescription Pricing Authority (PPA). Methods: The Disease Analyzer-Mediplus database contains anonymised primary care records for about 3 million patients. Eligible patients were aged ≤18 years and received ≥1 antidepressant prescription between 2000 and 2004. Antidepressants were grouped according to the CSM advice and the British National Formulary. Prevalence and incidence were calculated. The prevalences of 2000, 2002 and 2004 were compared using a Chi-squared test. PPA data on antidepressant prescribing rates were compared with paediatric antidepressant prescribing rates from Mediplus. Results: 5718 children and adolescents received a total of 25 542 prescriptions between 2000 and 2004. The median number of prescriptions per patient was two (interquartile range 1–5). Common indications included depression and anxiety. Antidepressant prevalence increased from 2000 to 2002 (from 5.4 to 6.6 patients per 1000 people), with a rise in the number of patients prescribed venlafaxine and SSRIs. However, between 2002 and 2004 there was a decrease in antidepressant prevalence (from 6.6 to 5.7 per 1000). The prevalence of CSM-contraindicated antidepressants (citalopram, escitalopram, fluvoxamine, paroxetine, sertraline and venlafaxine) declined by a third (from 3.1 to 2.0 per 1000), but there was no change in fluoxetine prevalence (from 2.1 to 2.3 per 1000). The number of patients prescribed tricyclic antidepressants dropped marginally (from 2.0 to 1.7 per 1000). Incidences followed the same trends as the prevalences, but there was a 48% reduction in the incidence of CSM-contraindicated antidepressants between 2002 and 2004. National antidepressant prescribing trends increased; paediatric prescribing trends were similar to national trends between 2000 and 2003; however, there was a 27% reduction in the paediatric prescribing rate of CSM-contraindicated antidepressants between 2002 and 2004. Conclusion: Since 2003, fewer children and adolescents have been prescribed antidepressants in primary care. However, fluoxetine and non-SSRI antidepressant prevalences have not risen, implying that they are not prescribed as alternative treatments. This study shows that the CSM advice has had a significant effect in reversing the rising prevalence of antidepressant prescribing to children and adolescents in primary care.

Efficacy and Tolerability of Pharmacotherapies for Attention-Deficit Hyperactivity Disorder in Adults

This review examines the evidence regarding the efficacy and tolerability of long- and short-acting stimulant medications, as well as the non-stimulant medications atomoxetine and bupropion in the treatment of adult attention-deficit hyperactivity disorder (ADHD). Effect sizes in adults appear to be of almost the same magnitude as in school-age children when robust doses are used. There are adequate data demonstrating short-term efficacy and safety of medication in ADHD during adulthood but long-term studies are lacking, particularly in view of concerns regarding cardiovascular adverse events. There is some evidence that stimulant medication can improve driving performance in adults with ADHD. The extent to which medication may improve academic, occupational and social functioning in adults with ADHD is unclear, and future research should investigate these outcomes. Medication treatment of adults with ADHD in sports is controversial.Both stimulant and non-stimulant medications seem to be well tolerated. Monitoring of pulse and blood pressure is recommended with these drugs because of their cardiovascular effects. There have been extremely rare case reports of sudden death in adults and children treated with stimulants and atomoxetine, but it is difficult to clearly establish causality. In view of reports of treatment-related suicide-related behaviour with atomoxetine, it is recommended that adults should be observed for agitation, irritability, suicidal thinking, self-harming or unusual behaviour, particularly in the first months of treatment, or after a change of dose.ADHD in adults continues to remain an under-recognized disorder in many parts of the world and there is a lack of specialist clinics for assessment and treatment of adult ADHD. Studies to date have failed to show efficacy of medications in the treatment of ADHD in the substance misuse population. There is little evidence so far to suggest an increased misuse of stimulants or diversion amongst substance misusers; however, data are insufficient to draw firm conclusions. Further work is necessary to evaluate effective treatments in subgroups such as the substance misuse population, those with multiple comorbidities and different ADHD subtypes.