Suzanne McCarthy

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.

Cessation of attention deficit hyperactivity disorder drugs in the young (CADDY)--a pharmacoepidemiological and qualitative study.

OBJECTIVES To estimate the prevalence of attention deficit hyperactivity disorder (ADHD) pharmacological treatment, and its demographic and clinical details, and to estimate the proportion of patients in the target group who stopped ADHD treatment and investigate possible factors for continuation or cessation of treatment. DESIGN A pharmacoepidemiological study using an automated database and a qualititative study using patient interviews. Part 1 was a pharmacoepidemiological study that provided accurate data on use and cessation of ADHD drugs. Part 2 was an in-depth interview study to investigate the reasons, processes and outcomes of treatment cessation. SETTING Part 1: primary care using the General Practice Research Database (GPRD). Part 2: secondary and tertiary care paediatric clinics, child and adolescent mental health and adult mental health clinics in London, Nottingham, Dundee and Liverpool. PARTICIPANTS Part 1: patients were 15-21 years old during the study period (1 January 2001 and 31 December 2004), had at least one prescription for methylphenidate, dexamfetamine or atomoxetine and had at least 1 year of research-standard data available in the GPRD. Part 2: patients fulfilled Part 1 criteria, had a diagnosis of ADHD as detected by a predefined algorithm and had been treated with methylphenidate, dexamfetamine or atomoxetine for at least 1 year. Child and adolescent psychiatrists, adult psychiatrists and paediatricians involved in the treatment of young people with ADHD were also interviewed as part of the study. RESULTS Part 1: prevalence of prescribing averaged across all ages increased eightfold, from 0.26 per 1000 patients in 1999 to 2.07 per 1000 patients in 2006. The increase in prevalence in the younger patients was less evident in the older patients. Prevalence in 15-year-old males receiving a study drug prescription increased from 1.32 per 1000 patients in 1999 to 8.31 per 1000 patients in 2006, whereas the prevalence in 21-year-olds rose from 0 per 1000 patients in 1999 to 0.43 per 1000 patients in 2006. Survival analysis showed that the rate of treatment cessation largely exceeded the estimated rate of persistence of ADHD. The reduction in prescribing was most noticeable between 16 and 17 years of age. Kaplan-Meier analysis showed that approximately 18% of patients restarted treatment if they had stopped treatment after the age of 15. Patients who restarted treatment were more likely to restart within the first year following treatment cessation. Part 2: the Child Health and Illness Profile (CHIP) was chosen as the quality of life questionnaire for the Part 2 study because the CHIP-CE scale has been validated in children with ADHD in the UK. Because of the age range of participants, the adolescent version (CHIP-AE) was administered to patients after interview. Of the 15, a total of nine patients finished the questionnaire. Interviews showed that although some young people felt able to cope after stopping medication, others felt the need to restart to control symptoms. Some patients had difficulty re-engaging with services and clinicians recognised the lack of services for young adults. Patients continuing on treatment considered cessation as an option for the future, but were concerned about the process of stopping and its impact on behaviour. CONCLUSIONS Part 1 study demonstrated that the prevalence of prescribing by GPs to patients with ADHD dropped significantly from age 15 to 21. The fall in prescribing was greater than the reported age-related decrease in symptoms, raising the possibility that treatment is prematurely discontinued in some young adults where ADHD symptoms persist. Part 2 of the study identified that some young adults had difficulty in obtaining treatment after discharge from paediatric services. Future work should include randomised placebo-controlled trials into long-term treatment with stimulants, particularly methylphenidate.OBJECTIVE(S) To investigate the clinical and cost-effectiveness of epoprostenol, iloprost, bosentan, sitaxentan and sildenafil for the treatment of adults with pulmonary arterial hypertension (PAH) within their licensed indications. DATA SOURCES Major electronic databases (including the Cochrane Library, MEDLINE and EMBASE) were searched up to February 2007. Further data were obtained from dossiers submitted to NICE by the manufacturers of the technologies. REVIEW METHODS The systematic clinical and economic reviews were conducted according to accepted procedures. Model-based economic evaluations of the cost-effectiveness of the technologies from the perspective of the UK NHS and personal social services were carried out. RESULTS In total, 20 randomised controlled trials (RCTs) were included in this assessment, mostly of 12-18 weeks duration and comparing one of the technologies added to supportive treatment with supportive treatment alone. Four published economic evaluations were identified. None produced results generalisable to the NHS. There was no consensus in the industry submissions on the most appropriate model structure for the technology assessment. Improvement in 6-minute walk distance (6MWD) was seen with intravenous epoprostenol in primary pulmonary hypertension (PPH) patients with mixed functional class (FC) (mainly III and IV, licensed indication) compared with supportive care (58 metres; 95% CI 6-110). For bosentan compared with supportive care, the pooled result for improvement in 6MWD for FCIII patients with mixed PAH (licensed indication) was 59 metres (95% CI 20-99). For inhaled iloprost, sitaxentan and sildenafil no stratified data for improvement in 6MWD were available. The odds ratio (OR) for FC deterioration at 12 weeks was 0.40 (95% CI 0.13-1.20) for intravenous epoprostenol compared with supportive care. The corresponding values for inhaled iloprost (FCIII PPH patients; licensed indication), bosentan, sitaxentan (FCIII patients with mixed PAH; licensed indication) and sildenafil (FCIII patients with mixed PAH; licensed indication) were 0.29 (95% CI 0.07-1.18), 0.21 (95% CI 0.03-1.76), 0.18 (95% CI 0.02-1.64) and [Commercial-in-confidence information has been removed] respectively. The incremental cost-effectiveness ratios (ICERs) for the technologies plus supportive care compared with supportive care alone, determined by independent economic evaluation, were 277,000 pounds/quality-adjusted life-year (QALY) for FCIII and 343,000 pounds/QALY for FCIV patients for epoprostenol, 101,000 pounds/QALY for iloprost, 27,000 pounds/QALY for bosentan and 25,000 pounds/QALY for sitaxentan. For the most part sildenafil plus supportive care was more effective and less costly than supportive care alone and therefore dominated supportive care. In the case of epoprostenol the ICERs were sensitive to the price of epoprostenol and for bosentan and sitaxentan the ICERs were sensitive to running the model over a shorter time horizon and with a lower cost of epoprostenol. Two RCTs directly compared the technologies against each other with no significant differences observed between the technologies. Combinations of technologies were investigated in four RCTs, with some showing conflicting results. CONCLUSION(S) All five technologies when added to supportive treatment and used at licensed dose(s) were more effective than supportive treatment alone in RCTs that included patients of mixed FC and types of PAH. Current evidence does not allow adequate comparisons between the technologies nor for the use of combinations of the technologies. Independent economic evaluation suggests that bosentan, sitaxentan and sildenafil may be cost-effective by standard thresholds and that iloprost and epoprostenol may not. If confirmed, the use of the most cost-effective treatment would result in a reduction in costs for the NHS. Long-term, double-blind RCTs of sufficient sample size that directly compare bosentan, sitaxentan and sildenafil, and evaluate outcomes including survival, quality of life, maintenance on treatment and impact on the use of resources for NHS and personal social services are needed.

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.

Mortality associated with attention-deficit hyperactivity disorder (ADHD) drug treatment: a retrospective cohort study of children, adolescents and young adults using the general practice research database

AbstractBackground: Following reports of sudden death in patients taking medication to treat attention-deficit hyperactivity disorder (ADHD), this study aimed to identify cases of death in patients prescribed stimulants and atomoxetine and to determine any association between these and sudden death. Method: The UK General Practice Research Database (GPRD) was used to identify patients aged 2–21 years from 1 January 1993 to 30 June 2006 with a prescription for methylphenidate, dexamfetamine or atomoxetine. Patients were followed from the date of first prescription until whichever came first: date of death, transferred-out date, age >21 years or end of the study period. Results: From a cohort of 18 637 patient-years, seven patients died. Cause of death was obtained for six of the patients. None were deemed to be cases of sudden death. Compared with a general population rate of sudden death in the literature, the worst-case scenario of one case of sudden death gave an incident rate ratio of 1.63 (95% CI 0.04, 9.71). Although it was not the primary outcome of the study, following reports of suicide in the cohort the standardized mortality ratio (SMR) of suicide was calculated. Due to differences in the definition of suicide used for children and adults, patients were categorized into two age groups: 11–14 years and 15–21 years. The SMR for suicide for patients aged 11–14 years was 161.91 (95% CI 19.61, 584.88). The SMR for suicide for patients aged 15–21 years was 1.84 (95% CI 0.05, 10.25). Conclusion: This study demonstrated no increase in the risk of sudden death associated with stimulants or atomoxetine. However, an increased risk of suicide was seen. Although we cannot exclude that the medications may contribute to the increased risk of suicide, there are other factors such as depression and antisocial behaviour that frequently co-exist with ADHD, which can also predispose to teenage suicide. Clinicians should identify patients at increased risk of cardiovascular events and identify those patients at increased risk of suicide, particularly males with co-morbid conditions, and monitor them appropriately.

The Pharmacology and Clinical Outcomes of Amphetamines to Treat ADHD Does Composition Matter

Attention-deficit hyperactivity disorder (ADHD) treatment options include pharmacological and nonpharmacological approaches. In North America, psychostimulants (amphetamine and methylphenidate) are considered first-line pharmacological treatments for patients (children, adolescents and adults) with ADHD. However, in the UK, National Institute for Health and Clinical Excellence (NICE) guidelines have placed short-acting d-amphetamine as a third-line treatment option due to a lack of contemporary, published clinical trials on its efficacy and the concerns from clinical and patient experts regarding the potential for increased abuse and/or misuse compared with methylphenidate. These guidelines do not account for some of the more recent amphetamine products that have been developed to alleviate some of these concerns, but that are not currently approved in the UK or other European countries. The purpose of this review is to describe the pharmacology and clinical efficacy of various amphetamine compositions, as well as to explore the apparent differences in these compositions and their associated risks and benefits. A PubMed literature search was conducted to investigate amphetamine pharmacology, clinical efficacy and safety and ADHD outcomes in the published literature from 1980 through March 2011. Search terms included the keywords ‘ADHD’ or ‘ADD’ or ‘hyperkinetic disorder’ and any of the following keywords combined with ‘or’: ‘amphetamine’, ‘dexamphetamine’, ‘mixed amphetamine salts’, ‘lisdexamfetamine’ and ‘methamphetamine’. The search included English-language primary research articles and review articles but excluded editorial articles and commentaries. The literature search resulted in 330 articles. Pertinent articles relating to amphetamine pharmacology, compositions, clinical efficacy and safety, effectiveness and tolerability, ADHD outcomes and abuse liability were included in this review. The different delivery profiles of amphetamine compositions result in pharmacological and pharmacokinetic differences that contribute to varying effects in the clinical treatment of ADHD, ADHD outcomes and abuse liability. The efficacy and safety of amphetamine compositions for the treatment of ADHD have been demonstrated in clinical trials and meta-analyses, and the long-acting amphetamine compositions have been widely studied and found efficacious without increased adverse effects. Long-acting amphetamine compositions offer the obvious advantage of enhanced duration of action over short-acting amphetamine compositions, and lisdexamfetamine has been shown to have reduced abuse liability compared with short-acting amphetamine.

Cost-outcome description of clinical pharmacist interventions in a university teaching hospital

BackgroundPharmacist interventions are one of the pivotal parts of a clinical pharmacy service within a hospital. This study estimates the cost avoidance generated by pharmacist interventions due to the prevention of adverse drug events (ADE). The types of interventions identified are also analysed.MethodsInterventions recorded by a team of hospital pharmacists over a one year time period were included in the study. Interventions were assigned a rating score, determined by the probability that an ADE would have occurred in the absence of an intervention. These scores were then used to calculate cost avoidance. Net cost benefit and cost benefit ratio were the primary outcomes. Categories of interventions were also analysed.ResultsA total cost avoidance of €708,221 was generated. Input costs were calculated at €81,942. This resulted in a net cost benefit of €626,279 and a cost benefit ratio of 8.64: 1. The most common type of intervention was the identification of medication omissions, followed by dosage adjustments and requests to review therapies.ConclusionThis study provides further evidence that pharmacist interventions provide substantial cost avoidance to the healthcare payer. There is a serious issue of patient’s regular medication being omitted on transfer to an inpatient setting in Irish hospitals.

Persistence of pharmacological treatment into adulthood, in UK primary care, for ADHD patients who started treatment in childhood or adolescence

BackgroundADHD guidelines in the UK suggest that children and adults who respond to pharmacological treatment should continue for as long as remains clinically effective, subject to regular review. To what extent patients persist with treatment from childhood and adolescence into adulthood is not clear. This study aims to describe, in UK primary care, the persistence of pharmacological treatment for patients with ADHD who started treatment aged 6–17 years and to estimate the percentage of patients who continued treatment from childhood and adolescence into adulthood.MethodsThe Health Improvement Network (THIN) database was used to identify patients with ADHD who received their first prescription for methylphenidate/ dexamfetamine/atomoxetine, aged 6–17 years. Patients were monitored until their ‘censored date’ (the earliest of the following dates: date the last prescription coded in the database ended, end of the study period (31st December 2008), date at which they transferred out of their practice, date of death, the last date the practice contributed data to the database). Persistence of treatment into adulthood was estimated using Kaplan Meier analysis.Results610 patients had follow-up data into adulthood. 213 patients (93.4% male) started treatment between 6–12 years; median treatment duration 5.9 years. 131 (61.5%) stopped before 18 years, 82 (38.5%) were still on treatment age ≥18 years. 397 patients (86.4% male) started treatment between 13–17 years; median treatment duration was 1.6 years. 227 (57.2%) stopped before 18 years, 170 (42.8%) were still on treatment age ≥18 years. The number of females in both age categories was too small to formally test for differences between genders in persistence of treatment.ConclusionPersistence of treatment into adulthood is lower (~40%) compared with published rates of persistence of the condition (~65% when symptomatic definition of remission used). Due to the limited number of patients with data past 18 years, it is important that ongoing monitoring of prescribing into later adulthood is undertaken, particularly to observe the effects of recommendations in new guidelines.

Prevalence of Limited Health Literacy Among Irish Adults

The authors conducted 2 health literacy investigations in Cork, Ireland. Study 1 was undertaken in 5 community pharmacies and the outpatient department of 2 urban hospitals and assessed patients’ health literacy skills using the Rapid Estimate of Adult Literacy in Medicine (REALM) and the Newest Vital Sign (NVS). Study 2 took place in 1 outpatient department and evaluated health literacy using the REALM and the short form of the Test of Functional Health Literacy.in Adults (S-TOFHLA). The authors collected data relating to age, gender, ethnicity, and educational level achieved. All subjects were asked items relating to their ability to use health-specific materials. A total of 1,759 people (61.2% female) completed either Study 1 (n = 1,339) or Study 2 (n = 420). Limited health literacy ranged from 18.4% (REALM) and 57.2% (NVS) in Study 1, and 21.9% (REALM) and 14.1% (S-TOFHLA) in Study 2 and was associated with increased age and lower educational attainment across all three tools (p < .001). Patients with limited health literacy were significantly more likely to report problems with using health materials received from a doctor or pharmacist. At minimum, 1 in 7 Irish adults were found to have limited health literacy, which may affect their ability to promote, protect, and manage health. As in the United States and in the United Kingdom, improving health literacy should be a public health objective for Ireland.

Determining the frequency and preventability of adverse drug reaction-related admissions to an Irish University Hospital: a cross-sectional study

Background Adverse drug reactions (ADR) cause considerable morbidity and mortality. Methods This 4-week study was undertaken in Cork University Hospital, Ireland, for all admissions from the emergency department (ED). A panel independently reviewed patients with suspected ADRs. Causality assessment was performed using the Naranjo ADR probability scale and the Hallas criteria was used to assess preventability of the ADRs. Results During the study period, 1258 patients were admitted from the ED; of these, 856 patients were included in the study; 75 patients (8.8%) had an ADR-related admission. Over half were deemed to be ‘possibly’ or ‘definitely’ avoidable. The level of agreement between reviewers using the Naranjo and Hallas criteria was very low. In the ADR group (n=75), 50.7% were men compared with 53.1% in the non-ADR group (n=781). The median age for patients in the ADR group was 73 years compared with 45 years in the non-ADR group. The average number of prescribed drugs per patient in the ADR group was 7.5 (SD±3.8) compared with 2.4 (SD±3.6) in the non-ADR group. Classified by drug type, 74.2% of the ADRs were attributed to cardiovascular and central nervous system drugs. Conclusions This study estimated the incidence of ADR-related admissions to an Irish hospital at 8.8%, with 57.3% of these deemed to have been potentially avoidable. Older patients were more likely to have an ADR-related admission. Prescribers must be aware of this increased likelihood of an ADR when prescribing new drugs to this patient population, and regularly review treatment.

Management of adult attention deficit hyperactivity disorder in UK primary care: a survey of general practitioners

BackgroundCompared to existing literature on childhood attention deficit hyperactivity disorder (ADHD), little published adult data are available, particularly outside of the United States. Using General Practitioner (GP) questionnaires from the United Kingdom, this study aimed to examine a number of issues related to ADHD in adults, across three cohorts of patients, adults who received ADHD drug treatment in childhood/adolescence but stopped prior to adulthood; adults who received ADHD drug treatment in childhood/adolescence and continued treatment into adulthood and adults who started ADHD drug treatment in adulthood.MethodsPatients with a diagnosis of ADHD and prescribed methylphenidate, dexamfetamine or atomoxetine were identified using data from The Health Improvement Network (THIN). Dates when these drugs started and stopped were used to classify patients into the three cohorts. From each cohort, 50 patients were randomly selected and questionnaires were sent via THIN to their GPs.GPs returned completed questionnaires to THIN who forwarded anonymised copies to the researchers. Datasets were analysed using descriptive statistics.ResultsOverall response rate was 89% (133/150). GPs stated that in 19 cases, the patient did not meet the criteria of that group; the number of valid questionnaires returned was 114 (76%). The following broad trends were observed: 1) GPs were not aware of the reason for treatment cessation in 43% of cases, 2) patient choice was the most common reason for discontinuation (56%), 3) 7% of patients who stopped pharmacological treatment subsequently reported experiencing ADHD symptoms, 4) 58% of patients who started pharmacological treatment for ADHD in adulthood received pharmacological treatment for other mental health conditions prior to the ADHD being diagnosed.ConclusionThis study presents some key findings relating to ADHD; GPs were often not aware of the reason for patients stopping ADHD treatment in childhood or adolescence. Patient choice was identified as the most common reason for treatment cessation. For patients who started pharmacological treatment in adulthood, many patients received pharmacological treatment for comorbidities before a diagnosis of ADHD was made.