M. C. H. de Groot

Evaluation of patients’ experiences with antidepressants reported by means of a medicine reporting system

ObjectiveTo assess experiences related to antidepressant use reported to an internet-based medicine reporting system and to compare the nature of the side effects reported by patients with those reported by health care professionals (HCPs).MethodsAll reports submitted from May 2004 to May 2005 to an internet-based medicine reporting system in The Netherlands related to the use of antidepressants were analysed. Spontaneous reports of adverse drug reactions on antidepressants from HCPs received by The Netherlands Pharmacovigilance Centre Lareb from May 2004 to May 2005 were included for comparison.ResultsOf the 2232 individuals who submitted a report to the internet-based medicine reporting system, 258 submitted a report on antidepressants. Of these, 92 individuals (36%) reported on effectiveness, 40 (16%) of whom reported on ineffectiveness, and 217 (84%) submitted a report on side effects, with 202 (78%) reporting a total of 630 side effects that were experienced as negative. Fourteen individuals (5%) reported a practical issue and four (2%) reported a reimbursement issue. Of all 630 side effects reported, 48% resulted in the patient discontinuing the antidepressant therapy; of these 29% did not inform their HCP. Of all the side effects reported, 52% were perceived as “very negative”. In comparison to the side effects reported by HCPs, patients more often reported apathy, excessive sweating, ineffectiveness, somnolence, insomnia, sexual problems and weight increase.ConclusionPatients report the ineffectiveness and side effects of antidepressant therapy as negative and leading to discontinuation of the therapy. Patients and HCPs differ in the nature of the reported side effects. Patient experiences should be included in the evaluation of antidepressant treatment in clinical practice.

[Accepted Manuscript] Case-only designs for studying the association of antidepressants and hip or femur fracture.

The purpose of this study is to evaluate the performance and validity of the case‐crossover (CCO) and self‐controlled case‐series (SCCS) designs when studying the association between hip/femur fracture (HF) and antidepressant (AD) use in general practitioner databases. In addition, comparability with cohort and case–control designs is discussed.

Association of polymorphisms in the beta-2 adrenergic receptor gene with fracture risk and bone mineral density

SummarySignaling through the beta-2 adrenergic receptor (B2AR) on the osteoblast influences bone remodeling in rodents. In the B2AR gene, three polymorphisms influence receptor function. We show that these polymorphisms are not associated with fracture risk or bone mineral density in the UCP, Rotterdam Study, and GEFOS cohorts.IntroductionSignaling through the beta-2 adrenergic receptor (B2AR) on the osteoblast influences bone remodeling in rodents. In the B2AR gene, three polymorphisms are known to influence receptor function in vitro and in vivo (rs1042713, rs1042714, and rs1800888). We examined the role of these polymorphisms in the B2AR gene on human bone metabolism.MethodsWe performed nested case–control studies to determine the association of these polymorphisms with fracture risk in the Utrecht Cardiovascular Pharmacogenetics (UCP) cohort and in three cohorts of the Rotterdam Study. We also determined the association of these polymorphisms with bone mineral density (BMD) in the GEFOS Consortium. UCP contains drug-dispensing histories from community pharmacies linked to national registrations of hospital discharges in the Netherlands. The Rotterdam Study is a prospective cohort study investigating demographics and risk factors of chronic diseases. GEFOS is a large international collaboration studying the genetics of osteoporosis. Fractures were defined by ICD-9 codes 800–829 in the UCP cohort (158 cases and 2617 unmatched controls) and by regular X-ray examinations, general practitioner, and hospital records in the Rotterdam Study (2209 cases and 8559 unmatched controls). BMD was measured at the femoral neck and lumbar spine using dual-energy X-ray absorptiometry in GEFOS (N = 32,961).ResultsMeta-analysis of the two nested case–control studies showed pooled odds ratios of 0.98 (0.91–1.05, p = 0.52), 1.04 (0.97–1.12, p = 0.28), and 1.16 (0.83–1.62, p = 0.38) for the associations between rs1042713, rs1042714, and rs1800888 per minor allele and fractures, respectively. There were no significant associations of the polymorphisms and BMD in GEFOS.ConclusionIn conclusion, polymorphisms in the beta-2 adrenergic receptor gene are not associated with fracture risk or BMD.

Seasonal changes in prescribing of long-acting beta-2-agonists-containing drugs.

BACKGROUND For patients with asthma, COPD, or asthma-COPD overlap syndrome (ACOS), inter-country comparisons of seasonal changes in drug prescriptions are scarce or missing. Hence, we aimed to compare seasonal changes in prescription rates of long-acting beta-2-agonist (LABA) in four European countries. METHODS A common study protocol was applied to six health care databases (Germany, Spain, the Netherlands (2), and the UK (2)) to calculate age- and sex-standardized point prevalence rates (PPRs) of LABA-containing prescriptions by the 1st of March, June, September, and December of each year during the study period 2002-2009. Seasonal variation of PPRs was quantified using seasonal indexes (SIs; based on the ratio-to-moving-average-method) and SIs averaged over the study period (aSI) stratified by sex, age, and indication (asthma, COPD, or ACOS). RESULTS There was a moderate seasonal change in LABA-containing prescriptions which was more pronounced in asthma or COPD patients compared to ACOS patients. For asthma and ACOS patients, highest seasonal variation was found for patients living in Spain (aSI: 87.3-110.7, aSI: 93.2-103.1) whereas for COPD highest seasonal variation was revealed for the NPCRD database (the Netherlands) (aSI: 92.2-105.6). Regarding age and sex, highest seasonal variation was found in Spanish boys under 10 years of age having a diagnosis of asthma. CONCLUSIONS By applying a common analysis in six databases, we could observe moderate overall seasonal changes in LABA-containing prescription rates in patients with asthma, COPD, or ACOS.

Risk of acute myocardial infarction after discontinuation of antihypertensive agents: a case–control study

We performed a nested case–control study in a cohort of antihypertensive drug users to assess the association between discontinuation of different antihypertensive agents and the risk of acute myocardial infarction (AMI). Cases and controls were drawn from the Utrecht Cardiovascular Pharmacogenetics database. Patients who were hospitalised for their first AMI were considered cases and controls were not hospitalised for AMI. Antihypertensive users were defined as current users if the index date (date of AMI) fell within the prescribed duration or as discontinuers if this date fell outside the prescribed duration. According to the recency of discontinuation, discontinuers were divided into the following: recent discontinuers (⩽90 days), intermediate-term discontinuers (91–180 days) and long-term discontinuers (>180 days). We found that the risk of AMI was significantly increased in discontinuers, regardless of time since discontinuation, of beta-blockers (adjusted odds ratio (OR) 1.54; 95% confidence interval (CI; 1.25–1.91), P-value<0.0005), calcium channel blockers (CCBs; adjusted OR 2.25; 95% CI (1.53–3.30), P-value<0.0005) and diuretics (adjusted OR 1.76; 95% CI (1.24–2.48), P-value=0.002) compared to current users of these drugs. Moreover, the risk of AMI was significantly increased in long-term discontinuers (beta-blockers, CCBs, angiotensin-converting enzyme inhibitors and diuretics) and intermediate-term discontinuers (beta-blockers and CCBs) versus current users of these drugs. There was no difference in AMI risk between recent discontinuers of antihypertensive drugs versus current users of these drugs. In conclusion, discontinuation of antihypertensive drugs increases the risk of AMI after >90 days of discontinuation. This further underlines the importance of persistence to antihypertensive drug therapy to reduce the risk of AMI in patients with hypertension.