Treatment of ADHD in adults – prevalence of discontinuation and associated factors – results from a cross-sectional analysis of Danish register data

BackgroundA growing number of adults are receiving pharmacological treatment for ADHD but a sizable proportion also discontinues or have gaps in treatment. The primary aims of this study were to identify how many patients treated for ADHD in adulthood, have at least one event of discontinuation in treatment and to identify possible associated variables.MethodsWithin the Danish population aged 18–60 years on the 1st of January 2013, we identified the number of individuals who had been prescribed ADHD-medication at least once during the 1st of January 2002–31st of December 2013 using Danish register data. Among those who filed more than one prescription, treatment discontinuation was defined as having more than 211 days between two prescriptions. In crude and adjusted logistic regression analysis, we explored potential associations to discontinuation for variables such as gender and age at treatment initiation.ResultsIn a population, if N = 3,165,844 individuals, n = 42,892 had received at least one prescription for ADHD medication. Among those with more than one prescription (N = 38,289), 29.4% had discontinued their treatment at least once, according to our definition of treatment discontinuation. ADHD treatment discontinuation was associated with being male, unemployment, lower educational attainment, receiving incapacity benefits and younger age at treatment initiation (p [less than] 0.001).ConclusionsA large proportion of individuals treated for ADHD had at least one discontinuation of treatment according to our definition. Although the present study does not allow for investigating the direction of these effects, nor whether some patients later resumed treatment, having at least one discontinuation was associated with a range of variables relating to e.g. age and gender, and provides an emerging profile for clinicians of patients more likely to discontinue

Is there evidence of a causal link between childhood maltreatment and attention deficit/hyperactivity disorder? A systematic review of prospective longitudinal studies using the Bradford-Hill criteria

Background: Studies report an elevated risk of maltreatment in children with attention deficit/hyperactivity disorder (ADHD), and elevated levels of ADHD in people who suffered childhood maltreatment (CM). However, the direction(s) of causality between CM and ADHD remain unclear—does ADHD create a context for CM, does CM cause ADHD, or both? Objective: This study systematically reviews and qualitatively synthesizes the research evidence relating to this question using Bradford-Hill criteria for establishing causality—strength, temporality, dose-response and plausibility. Methods: We conducted a systematic review, following PRISMA guidelines, of prospective longitudinal studies examining both CM and ADHD. We then used Bradford-Hill criteria to assess the quality of evidence for a causal link between CM and ADHD. Results: All 11 included studies demonstrated an association between CM and ADHD. Seven included evidence for temporality: five suggesting that CM precedes ADHD in the lifespan; two suggesting ADHD precedes CM. Four studies demonstrated a dose response relationship in which greater CM exposure was associated with elevated risk of ADHD. Studies presented a range of plausible mechanisms, including CM causing ADHD through biological programming, versus ADHD causing CM through parental stress. Conclusions: The high quality prospective longitudinal studies reviewed confirm the association between ADHD and CM, but present conflicting evidence about the direction of causality and mechanisms underpinning this association. To better understand the complex interplay between CM and ADHD, more studies using new research designs will be required that can partition effects by type of CM and account for bidirectional effects and other complexities

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline