Ian C. K. Wong

Nonpharmacological interventions for ADHD: systematic review and meta-analyses of randomized controlled trials of dietary and psychological treatments

OBJECTIVE Nonpharmacological treatments are available for attention deficit hyperactivity disorder (ADHD), although their efficacy remains uncertain. The authors undertook meta-analyses of the efficacy of dietary (restricted elimination diets, artificial food color exclusions, and free fatty acid supplementation) and psychological (cognitive training, neurofeedback, and behavioral interventions) ADHD treatments. METHOD Using a common systematic search and a rigorous coding and data extraction strategy across domains, the authors searched electronic databases to identify published randomized controlled trials that involved individuals who were diagnosed with ADHD (or who met a validated cutoff on a recognized rating scale) and that included an ADHD outcome. RESULTS Fifty-four of the 2,904 nonduplicate screened records were included in the analyses. Two different analyses were performed. When the outcome measure was based on ADHD assessments by raters closest to the therapeutic setting, all dietary (standardized mean differences=0.21-0.48) and psychological (standardized mean differences=0.40-0.64) treatments produced statistically significant effects. However, when the best probably blinded assessment was employed, effects remained significant for free fatty acid supplementation (standardized mean difference=0.16) and artificial food color exclusion (standardized mean difference=0.42) but were substantially attenuated to nonsignificant levels for other treatments. CONCLUSIONS Free fatty acid supplementation produced small but significant reductions in ADHD symptoms even with probably blinded assessments, although the clinical significance of these effects remains to be determined. Artificial food color exclusion produced larger effects but often in individuals selected for food sensitivities. Better evidence for efficacy from blinded assessments is required for behavioral interventions, neurofeedback, cognitive training, and restricted elimination diets before they can be supported as treatments for core ADHD symptoms.

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.

Incidence and nature of dosing errors in paediatric medications : a systematic review

In paediatric medicine, drug doses are usually calculated individually based on the patient’s age, weight and clinical condition. Therefore, there are increased opportunities for, and a relatively high risk of, dosing errors in this setting. Consequently, a systematic literature review using several databases was conducted to investigate the incidence and nature of dosing errors in children; 16 studies were found to be relevant.Eleven of the 16 studies found that dosing errors are the most common type of medication error, three of the remaining studies found it to be the second most common type. This review of published research on medication errors therefore suggests that dosing errors are probably the most common type of error in the paediatric population. In addition, there was a great variation in the error rates reported; this is likely to be due to the differences in the medication error definitions and methodologies employed. For example, the dosing error rate determined using spontaneous reporting ranges from 0.03 per 100 admissions in the UK to 2 per 100 admissions in the US. Extrapolating this, if the under-reporting rate is about 1 in 100, then the true incidence would be around 50 000 paediatric dosing errors per year in England.The information available shows that dosing errors are not uncommon and that 10-fold overdoses caused by calculation errors have led to serious consequences. There is an urgent need to develop methods to reduce medication errors in children and dosing errors should be the first priority.

Systematic Review of Medication Errors in Pediatric Patients

Objective: To systematically locate and review studies that have investigated the incidence of medication errors (MEs) in pediatric inpatients and identify common errors. Methods: A systematic search of studies related to MEs in children was performed using the following databases: MEDLINE (1951–April 2006), EMBASE (1966–April 2006), Pharm-line (1978–April 2006), International Pharmaceutical Abstracts (1970–April 2006), Cumulative Index to Nursing and Allied Health Literature (1982–April 2006), and British Nursing Index (1994–April 2006). Studies of the incidence and nature of MEs in pediatrics were included. The title, abstract, or full article was reviewed for relevance; any study not related to MEs in children was excluded. Results: Three methods were used to detect MEs in the studies reviewed: spontaneous reporting (n = 10), medication order or chart review (n = 14), or observation (n = 8). There was great variation in the definitions of ME used and the error rates reported. The most common type of ME was dosing error, often involving 10 times the actual dose required. Antibiotics and sedatives were the most common classes of drugs associated with MEs; these are probably among the most common drugs prescribed. Conclusions: Interpretation of the literature was hindered by variation in definitions employed by different researchers, varying research methods and setting, and a lack of theory-based research. Overall, it would appear that our initial concern about MEs in pediatrics has been validated; however, we do not know the actual size of the problem. Further work to determine the incidence and causes of MEs in pediatrics is urgently needed, as well as evaluation of the best interventions to reduce them.

The incidence and nature of prescribing and medication administration errors in paediatric inpatients

Objectives To determine the incidence and nature of prescribing and medication administration errors in paediatric inpatients. Design Prospective review of drug charts to identify prescribing errors and prospective observation of nurses preparing and administering drugs to identify medication administration errors. In addition, incident reports were collected for each ward studied. Participants Paediatric patients admitted to hospitals and nurses administering medications to these patients. Setting 11 wards (prescribing errors) and 10 wards (medication administration errors) across five hospitals (one specialist children’s teaching hospital, one nonteaching hospital and three teaching hospitals) in the London area (UK). Main outcome measures Number, types and incidence of prescribing and medication administration errors, using practitioner-based definitions. Results 391 prescribing errors were identified, giving an overall prescribing error rate of 13.2% of medication orders (95% CI 12.0 to 14.5). There was great variation in prescribing error rates between wards. Incomplete prescriptions were the most common type of prescribing error, and dosing errors the third most common. 429 medication administration errors were identified; giving an overall incidence of 19.1% (95% CI 17.5% to 20.7%) erroneous administrations. Errors in drug preparation were the most common, followed by incorrect rates of intravenous administration. Conclusions Prescribing and medication administration errors are not uncommon in paediatrics, partly as a result of the extra challenges in prescribing and administering medication to this patient group. The causes and extent of these errors need to be explored locally and improvement strategies pursued.

Attention-deficit hyperactivity disorder: treatment discontinuation in adolescents and young adults

BACKGROUND Symptoms of attention-deficit hyperactivity disorder (ADHD) are known to persist into adulthood in the majority of cases. AIMS To determine the prevalence of methylphenidate, dexamfetamine and atomoxetine prescribing and treatment discontinuation in adolescents and young adults. METHOD A descriptive cohort study using the UK General Practice Research Database included patients aged 15-21 years from 1999 to 2006 with a prescription for a study drug. RESULTS Prevalence of prescribing averaged across all ages increased 6.23-fold over the study period. Overall, prevalence decreased with age: in 2006, prevalence in males dropped 95% from 12.77 per 1000 in 15-year-olds to 0.64 per 1000 in 21-year-olds. A longitudinal analysis of a cohort of 44 patients aged 15 years in 1999 demonstrated that no patient received treatment after the age of 21 years. CONCLUSIONS The prevalence of prescribing by general practitioners to patients with ADHD drops significantly from age 15 to age 21 years. The fall in prescribing is greater than the reported age-related decrease in symptoms, raising the possibility that treatment is prematurely discontinued in some young adults in whom symptoms persist.

Epidemiologic features of antipsychotic prescribing to children and adolescents in primary care in the United Kingdom

OBJECTIVE. The goal was to investigate the epidemiologic features of antipsychotic prescribing to children and adolescents in general practice in the United Kingdom. METHODS. A total of 384 participating general practices from the United Kingdom General Practice Research Database were used to identify patients 0 to 18 years of age who were prescribed ≥1 antipsychotic medication between January 1, 1992, and December 31, 2005. Annual age-specific prevalences and incidences of antipsychotic prescribing were calculated. RESULTS. The overall prevalence of use of all antipsychotics increased from 1992 (0.39 users per 1000 patient-years) to 2005 (0.77 users per 1000 patient-years). The prescribing prevalence for patients 7 to 12 years of age almost tripled between 1992 (0.23 users per 1000 patient-years) and 2005 (0.61 users per 1000 patient-years). Atypical antipsychotic prescribing increased 60-fold from 1994 (0.01 users per 1000 patient-years) to 2005 (0.61 users per 1000 patient-years). However, typical antipsychotic prescribing decreased significantly from 2000 (0.44 users per 1000 patient-years) to 2005 (0.18 users per 1000 patient-years). The incidences for typical and atypical antipsychotics showed trends similar to those of the respective prevalences. However, the overall incidence (number of new starters) for all antipsychotics was relatively stable between 1992 and 2005, which suggests that patients remain on treatment longer. CONCLUSIONS. The overall prevalence of antipsychotics almost doubled between 1992 and 2005; however, the rate of increase was much lower than the reported figures in the United States. The prescribing of atypical antipsychotic drugs has increased despite the lack of conclusive evidence showing their superiority over older conventional antipsychotics. Additional investigation is required to evaluate their efficacy and safety in children and adolescents.

Drug use in children: Cohort study in three European countries

Objective To provide an overview of drug use in children in three European countries. Design Retrospective cohort study, 2000-5. Setting Primary care research databases in the Netherlands (IPCI), United Kingdom (IMS-DA), and Italy (Pedianet). Participants 675 868 children aged up to 14 (Italy) or 18 (UK and Netherlands). Main outcome measure Prevalence of use per year calculated by drug class (anatomical and therapeutic). Prevalence of “recurrent/chronic” use (three or more prescriptions a year) and “non-recurrent” or “acute” use (less than three prescriptions a year) within each therapeutic class. Descriptions of the top five most commonly used drugs evaluated for off label status within each anatomical class. Results Three levels of drug use could be distinguished in the study population: high (>10/100 children per year), moderate (1-10/100 children per year), and low (<1/100 children per year). For all age categories, anti-infective, dermatological, and respiratory drugs were in the high use group, whereas cardiovascular and antineoplastic drugs were always in the low use group. Emollients, topical steroids, and asthma drugs had the highest prevalence of recurrent use, but relative use of low prevalence drugs was more often recurrent than acute. In the top five highest prevalence drugs topical inhaled and systemic steroids, oral contraceptives, and topical or systemic antifungal drugs were most commonly used off label. Conclusion This overview of outpatient paediatric prescription patterns in a large European population could provide information to prioritise paediatric therapeutic research needs.

The epidemiology of pharmacologically treated attention deficit hyperactivity disorder (ADHD) in children, adolescents and adults in UK primary care

BackgroundAttention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder characterised by the symptoms of inattention, impulsivity and hyperactivity. ADHD was once perceived as a condition of childhood only; however increasing evidence has highlighted the existence of ADHD in older adolescents and adults. Estimates for the prevalence of ADHD in adults range from 2.5–4%. Few data exist on the prescribing trends of the stimulants methylphenidate and dexamfetamine, and the non-stimulant atomoxetine in the UK. The aim of this study was to investigate the annual prevalence and incidence of pharmacologically treated ADHD in children, adolescents and adults in UK primary care.MethodsThe Health Improvement Network (THIN) database was used to identify all patients aged over 6 years with a diagnosis of ADHD/hyperkinetic disorder and a prescription for methylphenidate, dexamfetamine or atomoxetine from 2003–2008. Annual prevalence and incidence of pharmacologically treated ADHD were calculated by age category and sex.ResultsThe source population comprised 3,529,615 patients (48.9% male). A total of 118,929 prescriptions were recorded for the 4,530 patients in the pharmacologically treated ADHD cohort during the 6-year study. Prevalence (per 1000 persons in the mid-year THIN population) increased within each age category from 2003 to 2008 [6–12 years: from 4.8 (95% CI: 4.5–5.1) to 9.2 (95% CI: 8.8–9.6); 13–17 years: from 3.6 (95% CI: 3.3–3.9) to 7.4 (95% CI: 7.0–7.8); 18–24 years: from 0.3 (95% CI: 0.2–0.3) to 1.1 (95% CI: 1.0–1.3); 25–45 years: from 0.02 (95% CI: 0.01–0.03) to 0.08 (95% CI: 0.06–0.10); >45 years: from 0.01 (95% CI: 0.00–0.01) to 0.02 (95% CI: 0.01–0.03). Whilst male patients aged 6-12 years had the highest prevalence; the relative increase in prescribing was higher amongst female patients of the same age - the increase in prevalence in females aged 6–12 years was 2.1 fold compared to an increase of 1.9 fold for their male counterparts. Prevalence of treated ADHD decreased with increasing age. Incidence (per 1000 persons at risk in the mid-year THIN population) was highest for children aged 6–12 years.ConclusionsA trend of increasing prescribing prevalence of ADHD drug treatment was observed over the period 2003–2008. Prevalence of prescribing to adult patients increased; however the numbers treated are much lower than published estimates of the prevalence of ADHD. This study has added to the limited knowledge on ADHD prescribing in primary care, particularly in the area of drug treatment in adulthood.

Minitablets: New Modality to Deliver Medicines to Preschool-Aged Children

OBJECTIVE. The goal was to assess the acceptability and suitability of placebo minitablets for preschool-aged children. METHODS. One hundred children 2 to 6 years of age were recruited from a major London hospital. How to swallow the minitablet was discussed with the child, and chewing was discouraged. The parents were asked to administer 1 minitablet (placebo, 3-mm diameter) to the child. The outcomes were recorded as (1) swallowed, (2) chewed, (3) spat out, or (4) refused to take. RESULTS. Of the youngest children (2 years of age), almost one half (46%) swallowed the minitablet. The proportion increased to 53% for children 3 years of age. Children ≥4 years of age were more likely to swallow the minitablet than not to swallow the minitablet, with 85% of 5-year-old children swallowing the minitablet. The ability to swallow the minitablet was not affected by gender. CONCLUSIONS. This study demonstrated the potential to use minitablets for the treatment of preschool-aged children and suggests that minitablets can be used as a potential new formulation for children in this age range.