Risk of first ischaemic stroke and use of antidopaminergic antiemetics: nationwide case-time-control study

OBJECTIVE: To estimate the risk of ischaemic stroke associated with antidopaminergic antiemetic (ADA) use. DESIGN: Case-time-control study. SETTING: Data from the nationwide French reimbursement healthcare system database Système National des Données de Santé (SNDS). PARTICIPANTS: Eligible participants were ≥18 years with a first ischaemic stroke between 2012 and 2016 and at least one reimbursement for any ADA in the 70 days before stroke. Frequencies of ADA reimbursements were compared for a risk period (days -14 to -1 before stroke) and three matched reference periods (days -70 to -57, -56 to -43, and -42 to -29) for each patient. Time trend of ADA use was controlled by using a control group of 21 859 randomly selected people free of the event who were individually matched to patients with stroke according to age, sex, and risk factors of ischaemic stroke. MAIN OUTCOME MEASURES: Association between ADA use and risk of ischaemic stroke was assessed by estimating the ratio of the odds ratios of exposure evaluated in patients with stroke and in controls. Analyses were adjusted for time varying confounders (anticoagulants, antiplatelets, and prothrombotic or vasoconstrictive drugs). RESULTS: Among the 2612 patients identified with incident stroke, 1250 received an ADA in the risk period and 1060 in the reference periods. The comparison with the 5128 and 13 165 controls who received an ADA in the same periods yielded a ratio of adjusted odds ratios of 3.12 (95% confidence interval 2.85 to 3.42). Analyses stratified by age, sex, and history of dementia showed similar results. Ratio of adjusted odds ratios for analyses stratified by ADA was 2.51 (2.18 to 2.88) for domperidone, 3.62 (3.11 to 4.23) for metopimazine, and 3.53 (2.62 to 4.76) for metoclopramide. Sensitivity analyses suggested the risk would be higher in the first days of use. CONCLUSIONS: Using French nationwide exhaustive reimbursement data, this self-controlled study reported an increased risk of ischaemic stroke with recent ADA use. The highest increase was found for metopimazine and metoclopramide

Presse Med

Benzodiazepine use remains high in France in 2015, especially among the elders. However, encouraging trend is observed regarding hypnotic benzodiazepines initiation: between 2008 and 2015, incident use of hypnotics, including that of Z-drugs, decreased while incident use of anxiolytics remained stable. Most of new benzodiazepine users (86 %) had treatment duration that complies with guidelines. Owing to the high number of user initiating a treatment each year and associated risks, the remaining 14 % of long-term users is of concern. Roughly half of benzodiazepine users presented with comorbidities and concurrent medications increasing the risk of adverse drug reactions, especially central nervous system depressant effects

Presse Med

Among 8 countries included in the report of ANSM, France is second behind Spain, when defined daily doses (DDD) are considered. Few studies, recent and based on representative samples of population, investigated the use of benzodiazepines in other countries and data are limited to compare France and other countries. In most countries, the use of benzodiazepines increases with age and is more frequent in women than in men. Variations of benzodiazepines use that were observed in other countries are similar to those observed in France, with a slight decrease but persistent high levels of use. In most countries, the long-term use of benzodiazepines is stable over time even though simple use decreases

Risk of first ischemic stroke and use of antidopaminergic antiemetics: A nationwide case-time-control study

International audienceIntroduction: Antidopaminergic antipsychotics have been associated with an increased risk of ischemic stroke. So far, this risk has not been assessed for antidopaminergic antiemetics (ADAs). This study aimed at estimating the risk of ischemic stroke associated with ADA use. Material and methods: Case-time-control study, based on data from the French reimbursement healthcare system (SNDS). Participants: Patients ≥18y with a first ischemic stroke between 2012 and 2016, and at least one ADA reimbursement in the 70 days before stroke. ADA use was self-compared between a risk-period (days [−14, −1] before stroke) and 3 reference periods (days [−70, −57], [−56, −43], and [−42, −29]). Time-trend of ADA use was controlled using a control group of 21,859 randomly selected patients free of the event, individually matched to cases according to age, sex, and risk factors of ischemic stroke. Association between ADA use and the risk of stroke was assessed by estimating the ratio of the odds ratios (OR) of exposure evaluated in i) stroke cases and ii) in controls. Analyses were adjusted for time-varying confounders (anticoagulants, antiplatelets, prothrombotic and vasoconstrictive drugs). Results: Among the 2,612 patients identified with incident stroke, 1,250 were exposed to ADA in the risk-period and 1,060 in the reference ones. The comparison with the 5,128 and 13,165 controls exposed to ADA in the same periods yielded a ratio of adjusted ORs (aORs) of 3.12 (2.85–3.42). Analyses stratified on age, sex, and dementia showed similar results. Ratio of aORs for analyses stratified on drug was 2.51 (2.18–2.88) for domperidone, 3.62 (3.11–4.23) for metopimazine and 3.53 (2.62–4.76) for metoclopramide. Sensitivity analyses suggested the risk would be especially increased in the first days of use. Discussion/Conclusion: This nationwide self-controlled study reported an increased risk of ischemic stroke with recent ADA use. The highest increase was highlighted for metopimazine and metoclopramide use. Conclusions Using French nationwide exhaustive reimbursement data, this self-controlled study reported an increased risk of ischaemic stroke with recent ADA use. The highest increase was found for metopimazine and metoclopramide

Road traffic crash risk associated with prescription of hydroxyzine and other sedating H1-antihistamines: A responsibility and case-crossover study

Background H1 antihistamines differ from each other by their ability to cross the blood-brain barrier. The resulting sedating effect can be sought in therapy but may be a driving hazard. The aim of this study was to estimate the impact of sedating H1-antihistamines on the risk of road traffic crash, with a particular focus on hydroxyzine which is also indicated as an anxiolytic in France. Methods The study consisted in extracting and matching data from three French nationwide databases: the national healthcare insurance database, police reports and the police national database of injurious crashes. All sedating H1-antihistamines, including hydroxyzine, were considered in the study. A case-control analysis, in which responsible drivers were cases and non-responsible were controls was performed. A case-crossover analysis, comparing for the same subject exposure during a period immediately before the crash with exposure during an earlier period, was also conducted. Results The extraction and matching procedures over the July 2005-December 2011 period led to the inclusion of 142,771 drivers involved in an injurious road traffic crash. The responsibility study found an increased risk of being responsible for an injurious road traffic crash in hydroxyzine users who were registered with a long-term chronic disease (mostly psychiatric disorders) on the day of the crash (OR=1.67 [1.22-2.30]). Among them, the risk was even higher in drivers with highest exposure levels (OR=2.60 [1.23-5.50]). There was no impact of sedating H1 antihistamine treatment initiation on the risk of crash. Conclusion Even if it is difficult to disentangle the part of the increased risk that would be causally related to hydroxyzine and the part related to behaviours of patients with a heavy psychiatric disorder, our study raises the alarm on the crash risk linked to hydroxyzine utilization in countries in which the anxiolytic indication is widespread

Impact of the COVID-19 pandemic and its control measures on cardiovascular and antidiabetic drugs use in France in 2020: a nationwide repeated cohort study

International audienceSince pandemic start, patients may have faced difficulties in accessing to care and treatment. This study aimed at assessing the impact of COVID-19 pandemic and its control measures on the use of drugs indicated in cardiovascular prevention and diabetes mellitus in France. From 09/17/2018 to 09/20/2020, a repeated cohort analysis was performed using the French nationwide health insurance databases. The pandemic impact was assessed using time-series analyses and unobserved components model for the weekly number of patients with (i) drug dispensing, (ii) ongoing treatment, (iii) treatment initiation, (iv) treatment disruption. Overall, 14,822,132 patients with cardiovascular drug dispensings and 3,231,618 with antidiabetic ones were identified. After a sharp spike in the amount of dispensings in the week the first national lockdown was announced, the period was marked by decreased levels and trends. Altogether, the estimated impact of the pandemic on dispensings appeared limited over the lockdown period (1-3% lack in dispensings). During lockdown, the weekly numbers of treatment disruptions remained stable whereas a significant decrease in treatment initiations was observed for almost all drug classes (e.g. β-blockers initiations: - 8.9%). Conversely, the post-lockdown period showed increases in treatment disruptions especially for antihypertensive and lipid lowering drugs (e.g. statins disruptions: + 4.9%). The pandemic and associated measures had a significant impact on cardiovascular and antidiabetic drugs use in France, mostly consisting in decreases of treatment initiations over lockdown and increases in treatment disruptions afterwards. Both could result in increased morbimortality that remains to be assessed

Eur Arch Psychiatry Clin Neurosci

BACKGROUND: Previous studies have suggested that exposure to some antidepressants (AD) during pregnancy could be associated with an increased risk of congenital malformations and neurodevelopment disorders for the child. We conducted a study to describe the use of AD during pregnancy in France. METHODS: We performed a drug utilisation study in EFEMERIS, a French cohort of pregnant women. At the time of the present study, 89,170 pregnant women, who were pregnant from 2005 to 2014 in Haute-Garonne were included. Prevalence and incidence of AD prescriptions during pregnancy, characteristics of AD users, and trends in AD use over the 10-year period were studied. RESULTS: During the 10-year study period, 1620 women registered in EFEMERIS (1.8%) received at least one prescription and dispensation for AD during pregnancy: 1363 during the first (1.5%), 591 during the second (0.7%), and 412 during the third (0.5%) trimester. A total of 2874 women (3.2%) got a prescription for an AD during the 3 months before and/or during pregnancy; 2187 of them (76.1%) stopped AD before pregnancy or during the first trimester. Selective serotonin reuptake inhibitors represented the most prescribed class during pregnancy (1.3%). A very slight decrease in the prevalence of AD prescriptions in pregnant women over time (1.7% in 2014 vs 2% in 2005) and some variations within classes were observed. CONCLUSIONS: Nearly, 2% of women received antidepressant drugs during pregnancy. This assessment encourages following research on these drugs including the potential risk of neurodevelopmental disorders in children after an exposure to antidepressants during pregnancy

Arch Womens Ment Health

The prevention of relapses and the treatment of depression during pregnancy are difficult challenges. The maintenance of antidepressants in pregnancy with its concomitant risks to mother and child needs to be weighed against those associated with not treating the disease. This study aimed at quantifying the impact of the occurrence of pregnancy on the course of antidepressant treatment among newly treated women (< 6 months). We performed a comparative observational cohort study using the nationwide French reimbursement healthcare system database. Women who conceived in 2014 and initiated an antidepressant at any time in the 6 months before pregnancy were compared with nonpregnant women newly exposed to antidepressants with matching on age, antidepressant exposure, history of psychiatric disorders, and area of residence. The primary outcome was a composite of antidepressant discontinuation, switch to another antidepressant, and concomitant use of antidepressants. The secondary outcome was the resumption of antidepressant during follow-up. We used Cox marginal proportional hazards models to compare time to outcomes between pregnant and nonpregnant women. The pregnant cohort included 6593 women, and the comparison cohort 29,347 nonpregnant women. In the period following the first month of treatment, pregnant women were more likely to experience treatment modification, and especially to stop receiving it, compared with nonpregnant women (adjusted hazard ratio (aHR) 1.58; 95%CI, 1.51–1.62). Pregnant women who discontinued treatment had a 41% decreased incidence of antidepressant resumption compared with nonpregnant women (aHR 0.59; 95%CI, 0.56–0.62). Pregnancy was a determinant of antidepressant treatment modification, and especially of discontinuation

Eur J Clin Pharmacol

PURPOSE: The present study was conducted to describe antipsychotic (AP) prevalent and incident use, characteristics of AP users, and their trends in the French population. METHODS: A cross-sectional study was repeated yearly from January 1, 2007 to December 31, 2013 (for prevalence analysis) or to December 31, 2012 (for incidence analysis) using the French Health Insurance reimbursement database (Echantillon Generaliste de Beneficiaires, EGB). For each year studied, prevalent and incident AP users were described in terms of age and gender overall, and according to the type of AP (FGAPs or SGAPs) used at index date. In addition, concurrent medications and comorbidities that a priori contraindicate the use of drugs having atropinic properties were researched. RESULTS: Prevalence and incidence remained relatively stable along the 2007-2013 period. Trends slightly decreased, from 2.07% (n = 10,252) to 2.05% (n = 11,015) for prevalence, and from 0.73% (n = 3461) to 0.66% (n = 3363) for incidence, especially in elderly, in contrast of children and adolescents (+ 39% for prevalence, from 184 to 271). The number of coprescribed drugs was found high (median = 5) and remained constant over time. In 2013, about 7% of prevalent AP users presented with a comorbidity increasing the risk of atropinic ADRs, and 36% used at least one concurrent atropinic drug. In incident AP users, these numbers were of 8 and 29%, respectively. CONCLUSIONS: The present study highlighted a marked shift from FGAPs toward SGAPs, as well as an increase in AP use in children and adolescents in France