Kapil Sayal

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.

Prenatal Alcohol Exposure and Gender Differences in Childhood Mental Health Problems: A Longitudinal Population-Based Study

OBJECTIVES. High levels of alcohol use during pregnancy can lead to adverse physical and neurodevelopmental outcomes in children. It remains uncertain whether there is a safe level of drinking during pregnancy. In this study we investigate whether very low levels of alcohol consumption (<1 drink per week) are independently associated with childhood mental health problems (assessed at 3 time points between ages 4 and 8 years) and whether these effects are moderated by gender. We expected that only higher levels of alcohol consumption would be associated with later mental health problems and that any associations might be more readily detectable in boys. METHODS. This prospective, population-based study used data from the Avon Longitudinal Study of Parents and Children. We investigated the relationship between self-reports of the amount and frequency of alcohol use in the first trimester and the presence of clinically significant mental health (behavioral and emotional) problems at 47 and 81 months (parental report: n = 9086 and 8046, respectively) and at 93 to 108 months (teacher report: n = 5648). RESULTS. After controlling for a range of prenatal and postnatal factors, the consumption of <1 drink per week during the first trimester was independently associated with clinically significant mental health problems in girls at 47 months. This gender-specific association persisted at 81 months and was confirmed by later teacher ratings. CONCLUSIONS. Very low levels of alcohol consumption during early pregnancy may have a negative and persistent effect on mental health outcomes. Given the lack of a clear dose-response relationship and unexpected gender effects, these findings should be considered preliminary and need additional investigation.

Evidence-based guidelines for the pharmacological management of attention deficit hyperactivity disorder: Update on recommendations from the British Association for Psychopharmacology

Attention deficit hyperactivity disorder (ADHD) is a common condition with a high societal burden. The present guidelines summarise current literature, generating expert consensus recommendations for the treatment of ADHD in children and adults. These guidelines also provide a review of recent research in the fields of neuroimaging, neuropsychology and genetics of ADHD. Novel discoveries in these areas have informed physiological models for the disease. Since the publication of the previous British Association for Psychopharmacology guidelines in 2008, new drugs have been licensed and further compounds are being investigated. The publication of randomised controlled trials of psychological interventions has contributed to the range of treatment options for ADHD. As the disorder has been diagnosed more frequently there has been greater focus on comorbid conditions and how they impact treatment. Services have continued to develop for the treatment of ADHD in adults and care agreements have been introduced to facilitate access to treatment.

Binge Pattern of Alcohol Consumption During Pregnancy and Childhood Mental Health Outcomes: Longitudinal Population-Based Study

OBJECTIVE. Patterns of alcohol consumption during pregnancy such as episodes of binge drinking may be as important as average levels of consumption in conferring risk for later childhood mental health and learning problems. However, it can be difficult to distinguish risk resulting from episodic or regular background levels of drinking. This large study investigates whether patterns of alcohol consumption are independently associated with child mental health and cognitive outcomes, whether there are gender differences in risk, and whether occasional episodes of higher levels of drinking carry any risk in the absence of regular daily drinking during pregnancy. METHODS. This prospective, population-based study used data from the Avon Longitudinal Study of Parents and Children. We investigated the relationships between a binge pattern of alcohol use (consumption of ≥4 drinks in a day) in the second and third trimesters of pregnancy and childhood mental health problems at 47 and 81 months of age (n = 6355 and 5599, respectively). In a subgroup, we also investigated these relationships with child IQ at 49 months of age (n = 924). RESULTS. After controlling for a range of prenatal and postnatal factors, any episodes of consuming ≥4 drinks in a day were independently associated with higher risks for mental health problems (especially hyperactivity/inattention) in girls at the age of 47 months and in both genders at 81 months. There was no association with IQ scores at 49 months after adjustment for confounders. The consumption of ≥4 drinks in a day continued to carry risk for mental health problems (especially hyperactivity/inattention) in the absence of regular daily drinking. CONCLUSIONS. The consumption of ≥4 drinks in a day on an occasional basis during pregnancy may increase risk for child mental health problems in the absence of moderate daily levels of drinking. The main risks seem to relate to hyperactivity and inattention problems.

Classroom based cognitive behavioural therapy in reducing symptoms of depression in high risk adolescents: pragmatic cluster randomised controlled trial.

Objective To compare the effectiveness of classroom based cognitive behavioural therapy with attention control and usual school provision for adolescents at high risk of depression. Design Three arm parallel cluster randomised controlled trial. Setting Eight UK secondary schools. Participants Adolescents (n=5030) aged 12-16 years in school year groups 8-11. Year groups were randomly assigned on a 1:1:1 ratio to cognitive behavioural therapy, attention control, or usual school provision. Allocation was balanced by school, year, number of students and classes, frequency of lessons, and timetabling. Participants were not blinded to treatment allocation. Interventions Cognitive behavioural therapy, attention control, and usual school provision provided in classes to all eligible participants. Main outcome measures Outcomes were collected by self completed questionnaire administered by researchers. The primary outcome was symptoms of depression assessed at 12 months by the short mood and feelings questionnaire among those identified at baseline as being at high risk of depression. Secondary outcomes included negative thinking, self worth, and anxiety. Analyses were undertaken on an intention to treat basis and accounted for the clustered nature of the design. Results 1064 (21.2%) adolescents were identified at high risk of depression: 392 in the classroom based cognitive behavioural therapy arm, 374 in the attention control arm, and 298 in the usual school provision arm. At 12 months adjusted mean scores on the short mood and feelings questionnaire did not differ for cognitive behavioural therapy versus attention control (−0.63, 95% confidence interval −1.85 to 0.58, P=0.41) or for cognitive behavioural therapy versus usual school provision (0.97, −0.20 to 2.15, P=0.12). Conclusion In adolescents with depressive symptoms, outcomes were similar for attention control, usual school provision, and cognitive behavioural therapy. Classroom based cognitive behavioural therapy programmes may result in increased self awareness and reporting of depressive symptoms but should not be undertaken without further evaluation and research. Trial registration Current Controlled Trials ISRCTN19083628.

Parental help-seeking in primary care for child and adolescent mental health concerns: qualitative study

BACKGROUND Child and adolescent mental health problems are common in primary care. However, few parents of children with mental health problems express concerns about these problems during consultations. AIMS To explore the factors influencing parental help-seeking for children with emotional or behavioural difficulties. METHOD Focus group discussions with 34 parents from non-specialist community settings who had concerns about their childs mental health. All groups were followed by validation groups or semi-structured interviews. RESULTS Most children had clinically significant mental health symptoms or associated impairment in function. Appointment systems were a key barrier, as many parents felt that short appointments did not allow sufficient time to address their childs difficulties. Continuity of care and trusting relationships with general practitioners (GPs) who validated their concerns were perceived to facilitate help-seeking. Parents valued GPs who showed an interest in their child and family situation. Barriers to seeking help included embarrassment, stigma of mental health problems, and concerns about being labelled or receiving a diagnosis. Some parents were concerned about being judged a poor parent and their child being removed from the family should they seek help. CONCLUSIONS Primary healthcare is a key resource for children and young people with emotional and behavioural difficulties and their families. Primary care services should be able to provide ready access to health professionals with an interest in children and families and appointments of sufficient length so that parents feel able to discuss their mental health concerns.

Fetal Alcohol Exposure and IQ at Age 8: Evidence from a Population-Based Birth-Cohort Study

Background Observational studies have generated conflicting evidence on the effects of moderate maternal alcohol consumption during pregnancy on offspring cognition mainly reflecting problems of confounding. Among mothers who drink during pregnancy fetal alcohol exposure is influenced not only by mother’s intake but also by genetic variants carried by both the mother and the fetus. Associations between children’s cognitive function and both maternal and child genotype at these loci can shed light on the effects of maternal alcohol consumption on offspring cognitive development. Methods We used a large population based study of women recruited during pregnancy to determine whether genetic variants in alcohol metabolising genes in this cohort of women and their children were related to the child’s cognitive score (measured by the Weschler Intelligence Scale) at age 8. Findings We found that four genetic variants in alcohol metabolising genes in 4167 children were strongly related to lower IQ at age 8, as was a risk allele score based on these 4 variants. This effect was only seen amongst the offspring of mothers who were moderate drinkers (1–6 units alcohol per week during pregnancy (per allele effect estimates were −1.80 (95% CI = −2.63 to −0.97) p = 0.00002, with no effect among children whose mothers abstained during pregnancy (0.16 (95%CI = −1.05 to 1.36) p = 0.80), p-value for interaction  = 0.009). A further genetic variant associated with alcohol metabolism in mothers was associated with their child’s IQ, but again only among mothers who drank during pregnancy.

Psychotropic interactions with warfarin

Objective: Improving knowledge about the cytochrome p450 system means that potential drug interactions can be predicted. Interactions involving warfarin may be thus avoidable. As many patients who have suffered from a stroke or other thromboembolic events may also develop psychiatric disorder, knowledge about possible interactions with psychotropics is essential for prescribers.

Pregnant women's attitudes towards alcohol consumption

BackgroundThere is uncertainty as to whether there is a safe threshold for drinking alcohol during pregnancy. We explored pregnant womens attitudes towards drinking alcohol in pregnancy and their attitudes towards sources of information about drinking in pregnancy following recent changes in UK government guidance.MethodsA qualitative study involving individual, semi-structured interviews with 20 pregnant women recruited from community organisations in the UK. Interview transcripts were analysed qualitatively using thematic analysis.ResultsMost women found information and advice about safe levels of drinking in pregnancy confusing and lacking in evidence and detail. Although most women considered that there were risks involved with drinking in pregnancy and these perceptions influenced their behaviour, only six women reported abstinence. Women reported being influenced by advice from family and friends and their experiences of previous pregnancies. Many had received no individual advice from general practitioners or midwives relating to drinking during pregnancy.ConclusionPregnant women wished to take responsibility for their own health and make choices based on informed advice. In order to do so, they require clear and consistent advice about safe levels of drinking from policy makers and health professionals. This is an important issue as women might drink socially during their pregnancy.