Use of sodium-glucose cotransporter-2 inhibitors in France: Analysis of French nationwide health insurance database.

AIM: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have been commercialized in France for type 2 diabetes since April 2020 and later for heart and renal diseases. Given the recent developments in treating diabetes and the widening of SGLT-2i indications, we aimed to study changes in the use of glucose-lowering drugs in France and to characterize SGLT-2i new users. METHODS: We performed a nationwide utilization study using the French health insurance database. Trends in incidence and prevalence of glucose-lowering drug use were assessed by a repeated cross-sectional study in 2019 and 2021. A cohort study of incident SGLT-2i users was then conducted to describe patient characteristics and the strategy for treating diabetes. RESULTS: The prevalence of SGLT-2i use gradually reached 0.1% in the third quarter of 2021 and increased more significantly to 0.2% thereafter. SGLT-2i became the second most prescribed glucose-lowering drug class after metformin at the end of 2021 (0.1%). Among the cohort of 125 387 SGLT-2i new users (mean age 65.0 years; 60.1% of men), 87.6% presented a diabetic comorbidity. The patient profile changed over the study period with an increasing proportion of patients with cardiovascular (28.7% in 2020 vs. 40.2% in 2021) or renal (7.7% in 2020 vs. 11.8% in 2021) comorbidities at initiation. The main combinations used at SGLT-2i initiation were metformin (12.5%) and metformin plus dipeptidyl peptidase-4 inhibitors (8.1%). One-year probability of SGLT-2i persistence was estimated to be 55%. CONCLUSION: The expansion of indications for SGLT-2i and the broadening of the target population make it essential to assess the reasons for discontinuation and review their safety profile.

Invasive fungal infection incidence and risk factors in patients receiving ibrutinib in real-life settings: A nationwide population-based cohort study.

BACKGROUND: Data on the risk of invasive fungal infections (IFI) with ibrutinib treatment are scarce. OBJECTIVES: This study aimed to determine IFI incidence and risk factors in ibrutinib-treated patients in real-life settings. METHODS: We constituted a cohort of ibrutinib incident users in the French National Healthcare Database. All patients ≥18 years with a first dispensing of ibrutinib between 21 November 2014 and 31 December 2019 were included. Patients were followed from the cohort entry date until IFI, ibrutinib discontinuation, death, or 31 December 2020, whichever came first. The cumulative incidence function method was used to estimate the probability of IFI accounting for competing risk of death. A multivariate cause-specific Cox proportional hazards model was used to assess independent IFI risk factors. RESULTS: Among 6937 ibrutinib-treated patients, 1-year IFI cumulative incidence was 1.3%, with invasive aspergillosis being the most frequent. Allogenic or autologous stem cell transplantation (ASCT) (hazard ratio [HR] 3.59, 95% confidence interval [1.74; 7.41]), previous anticancer treatment (HR 2.12, CI 95% [1.34; 3.35]) and chronic respiratory disease (HR 1.66, [1.03; 2.67]) were associated with higher risk of IFI. Besides neutropenia and corticosteroids, use of anti-CD20 agents was significantly more frequent in patients having experienced IFI (HR 3.68, [1.82; 7.45]). CONCLUSIONS: In addition to patients with ASCT history, severe neutropenia or treated with corticosteroids, our findings support active surveillance of IFIs in those with chronic respiratory disease, previously treated, or treated with anti-CD20 agents in combination with ibrutinib. Further studies are needed to optimise IFI prophylaxis in these patient subgroups.

Bleeding risk with concurrent use of anticoagulants and ibrutinib: A population-based nested case-control study.

Data regarding the safety of co-administration of ibrutinib with anticoagulants in real-life settings are scarce. Using a nationwide database, we conducted a nested case-control study in a cohort of new users of ibrutinib to assess the risk of clinically relevant bleeding (CRB) associated with anticoagulation. Cases were patients with a diagnosis of CRB, defined as hospitalization with a diagnosis of bleeding. The date of CRB constituted the index date. Up to four controls were matched on sex, age at index date and duration of follow-up. The risk of CRB associated with anticoagulation in patients receiving ibrutinib was estimated using conditional logistic regression models, providing odds ratios (OR) adjusted for risk factors of bleeding. Among 614 cases and 2407 matched controls, the risk of CRB was significantly higher in patients receiving both ibrutinib and anticoagulants (adjusted OR [aOR] 2.54, confidence interval [CI] 95% [1.94; 3.32]). When considering anticoagulant class, aOR was 1.99 (CI 95% [1.19; 3.33]) for VKA, 2.48 (CI 95% [1.76; 3.47]) for direct oral anticoagulants and 3.40 (CI 95% [2.01; 5.75]) for parenteral anticoagulants. In conclusion, this study found a 2.5-fold increased risk of CRB in patients receiving both ibrutinib and anticoagulants in real-life settings, and similar aOR among oral anticoagulants.

Pathways between Risk/Protective Factors and Maternal Postnatal Depressive Symptoms: The ELFE Cohort.

OBJECTIVE: The risk factors for postnatal depressive symptoms (PNDS) are numerous, but little is known about the protective factors or the interactions between different exposures. The present study explored the pathways between maternal, infant and parenthood vulnerabilities or risk/protective factors and PNDS at 2 months postpartum (PP) in a large sample of women from the general population. METHODS: We used data from the French ELFE cohort, a nationally representative cohort of children followed-up from birth. The available information about vulnerabilities or risk/protective factors for PNDS was collected during the maternity ward stay (mother or medical records) and at 2 months PP (mother by phone). PNDS were evaluated with the Edinburgh Postnatal Depression Scale (EPDS) at 2 months. A measurement model was built based on the psychosocial model for PNDS of Milgrom and colleagues using exploratory factor analysis. The Structural Equation Model was used to investigate the pathways between vulnerability, risk/protective factors and PNDS at 2 months PP. RESULTS: In the study sample (n = 11,583), a lack of a partner's perceived antenatal emotional support, consultation with a mental health specialist before pregnancy, family financial difficulties, prenatal psychological distress and a difficult pregnancy experience were directly associated with the severity of maternal PNDS at 2 months PP, as well as lack of perceived postnatal support. Family financial difficulties and consultation with a mental health specialist before pregnancy were also indirectly associated with the intensity of PNDS through a lack of perceived antenatal emotional support, a difficult pregnancy experience, prenatal psychological distress and a lack of perceived postnatal support. Regarding infant and parenthood characteristics, infant self-regulation difficulties, maternal difficulty in understanding infant crying and infant hospitalisation were directly associated with PNDS severity at 2 months PP, while maternal difficulty in understanding an infant's cries was also indirectly associated with infant self-regulation difficulties. CONCLUSIONS: Perinatal professional support should begin antenatally and target the couple's prenatal functioning, with particular attention to women presenting a history of psychiatric disorders, especially those of low socioeconomic status. After delivery, addressing infant and parenthood characteristics is also recommended.

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.

Since 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. ß-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.

The risk of dementia in patients using psychotropic drugs: Antidepressants, mood stabilizers or antipsychotics.

OBJECTIVE: The risk of dementia associated with the use of psychotropic drugs is not fully understood. A nested case-control study was carried out to assess the risk of dementia broadly defined or Alzheimer's disease associated with antidepressants, mood stabilizers or antipsychotics. METHODS: A cohort was formed from healthcare claim databases including all patients aged 50 and over with a first dispensing of the psychotropic drugs concerned between 2006 and 2017. Patients who developed dementia over the study period were considered as cases. The association between drug exposure prior to a five-year lag time and diagnosis of dementia was assessed by conditional logistic regression models. RESULTS: No association was found between dementia, either broadly defined or Alzheimer disease, and antidepressant or mood stabilizers. Findings were conflicting with regard to antipsychotics. First- and second-generation antipsychotics (FGA and SGA) were not associated with Alzheimer disease. SGA treatments of more than 3 months were associated with a higher risk of dementia broadly defined than no use of antipsychotics (Odds ratio [OR] 2.00; 95%CI 1.06-3.79; p = 0.03). In a sensitivity analysis using a lag time of 3 years, ever use of SGA and SGA treatments of more than 3 months were associated with a higher risk of dementia broadly defined than no use of antipsychotics (OR 1.71; 1.10-2.67; p = 0.02 and OR 1.84; 1.03-3.32; p = 0.04, respectively). CONCLUSION: The association between antipsychotics and dementia should be further investigated to establish patients, specific drugs, and patterns of treatment at risk. Prescribers should remain cautious when prescribing them.

Impact of pregnancy on antidepressant treatment course: a population-based comparative cohort study in France.

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.

Conventional mood stabilizers and/or second-generation antipsychotic drugs in bipolar disorders: A population-based comparison of risk of treatment failure.

BACKGROUND: The study compared treatment failure when using three therapeutic strategies in bipolar disorders: (i) mood stabilizers (MSs: lithium, valpromide, divalproate, carbamazepine, lamotrigine) without second-generation antipsychotic (SGAP); (ii) SGAPs (aripiprazole, olanzapine, risperidone, quetiapine) without MS; (iii) combination of MSs and SGAPs. METHODS: A historical cohort study was conducted using the French national healthcare databases in 20,086 outpatients aged 21+, newly treated with one of the three treatment strategies in 2011-2012, and diagnosed with a bipolar disorder. A composite outcome was based on indicators of treatment failure identified over 12 months: treatment discontinuation, switch or addition, psychiatric hospitalisation, suicide attempt, and death. For each strategy, the cumulative incidence of treatment failure was calculated while adjusting for covariates by propensity score weighting. RESULTS: A total of 8,225 patients (40.9%) were newly dispensed MSs, 9,342 (46.5%) SGAPs, and 2,519 (12.5%) both MSs and SGAPs. The one-year adjusted cumulative incidence of treatment failure was 75.7% (95%CI 74.9;76.3) in patients using MSs, 75.3% (74.6;76.0) in patients using SGAPs, and 60.5% (58.3;62.6) in patients with the combination. The adjusted difference in incidence for SGAPs compared with MSs was -0.40% (-1.4;0.6 p = 0.4) in the whole population, -2.2% (-3.3; -1.2 p < 0.002) in patients under 65 years and +6.7% (4.1;9.1 p < 0.002) in patients 65 years and over. LIMITATIONS: Combinations of MSs and SGAPs could not be directly compared with MS or SGAP monotherapies. CONCLUSIONS: One-year treatment failure was high. Overall, no difference in treatment failure was observed between MS or SGAP strategy but differences might exist depending on age.

Trajectories of Antipsychotic Drug Use Over 10 Years in a French Community-Based Sample of Persons Aged 50 and Older.

OBJECTIVE: To identify the temporal prescribing patterns of antipsychotics among persons aged 50 and older and to explore the demographic and clinical characteristics associated with each trajectory of antipsychotic drug use. METHODS: This was a historical fixed cohort study on a community-based sample of persons affiliated with the French Insurance Healthcare system. Data from community drug reimbursement claims were collected by the French Insurance Healthcare system over the period 2006-2015. The study included 160,853 persons aged 50 and older. Trajectories of antipsychotic drug use were identified by examining the distribution of antipsychotic use within consecutive 3-month periods over the entire follow-up period. Latent class analyses were used to identify distinct trajectories. Multivariate polynomial logistic regression models were used to explore the characteristics independently associated with trajectories. RESULTS: Five trajectories of antipsychotic use were identified: null or very low use (93.8%), occasional use (2%), decreasing use (1.6%), chronic use (1.5%), and increasing use (1.1%). Occasional users were older and had a lower use of other psychotropic drugs and a high use of health resources. Chronic users had the highest frequency of chronic psychiatric diseases and were less likely to present with dementia or Parkinson disease. Persons with increasing use of antipsychotics were more frequently males and had a high frequency of dementia; half of them died over the follow-up period compared with 20% in the total sample. CONCLUSION: Further studies should explore whether the benefit-risk ratio of antipsychotic drugs in older adults differs according to trajectories of use.

Patterns of antidepressant use during pregnancy: a nationwide population-based cohort study.

AIMS: We explored the patterns of antidepressant use during pregnancy. METHODS: A cohort of women who started a pregnancy in 2014 was identified using data from the French reimbursement healthcare system (covering approximately 99% of the population). Antidepressant usage (initiated before or during pregnancy) was assessed. Explored changes in antidepressant treatment were: associations, switches, discontinuation and resumption of antidepressants during pregnancy. RESULTS: The cohort included 766 508 pregnancies (755 519 women). Antidepressant use during pregnancy was 25.7 per 1000 [95% CI: 25.3-26.0]. New use concerned 3.9 per 1000 [95% CI: 3.7-4.0]; the most initiated class during pregnancy was selective serotonin reuptake inhibitors (SSRIs), while the most prescribed individual drug in second and third trimesters was amitriptyline, a tricyclic. Most changes were observed before pregnancy and during the first trimester: 63% of ongoing treatments in the year before pregnancy were discontinued before conception; 68% of treatments maintained after conception were discontinued during the first trimester; switches or antidepressant associations mostly occurred during the periconceptional period or during the first trimester. Regardless of initial antidepressant, switches to sertraline were the most frequent. Associations mainly consisted of a prescription of tri-/tetracyclic or mirtazapine/mianserin in addition to an SSRI. Discontinuation during pregnancy led to treatment resumption in 22% of pregnancies. CONCLUSIONS: These results suggest that pregnancy was planned or the treatment especially adapted in accordance with existing recommendations in a large proportion of women under antidepressants or in whom such treatments have been initiated after starting a pregnancy.

Antipsychotics use: 2006-2013 trends in prevalence and incidence and characterization of users.

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 Généraliste de Bénéficiaires, 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.

Prevalence and prescription patterns of oral glucocorticoids in adults: a retrospective cross-sectional and cohort analysis in France.

OBJECTIVES: To study trends in use of oral glucocorticoids (GCs) among adults, characteristics of oral GC initiators and prescriptions for the prevention of potential adverse effects associated with GC therapy. DESIGN: First, a cross-sectional study repeated yearly was performed from 2007 to 2014 in a nationwide representative sample. Second, characteristics of initiators and patterns of GC therapy during the year following treatment initiation were described in a cohort of patients who began GC between 2007 and 2013. SETTING: Population-based study using data from the French reimbursement healthcare system (covering approximately 90% of the population) in patients aged ≥18 years. RESULTS: Over the study period, the prevalence of oral GC use ranged from 14.7% to 17.1% (95% CI 17.0%-17.2%) with a significant increase of 14.1% (95% CI +13.5% to +14.8%). The 2007-2013 cohort of oral GC initiators comprised 206 759 individuals. Oral GC use was mostly short-term (68% of unique reimbursement) and more than half of short-term users took concurrent antibiotics or respiratory/otological drugs. Chronic users (≥6 reimbursements/year) represented 1.8% (n=3789) of the cohort. The proportion of chronic users with comorbidities likely to be worsened by GC use (diabetes, psychotic disorders, osteoporosis) was 25%. Among patients at increased risk of osteoporosis, 62% received specific prevention/monitoring measures and only 27% had a bisphosphonate. Half of chronic oral GC users had a concurrent reimbursement of a proton pump inhibitor in the absence of non-steroidal anti-inflammatory drug use. CONCLUSIONS: Oral GC use was highly widespread and increased among adults from 2007 to 2014. The overwhelming short-term use could mainly concern a growing use of unjustified prescriptions rather than situations with a favourable benefit/risk ratio. For chronic users, our findings plead for the development of interventions designed to improve monitoring with regard to the frequent comorbidities at risk and inappropriate prescribing of preventive therapeutic measures.

Trends in patterns of antidepressant use in older general population between 2006 and 2012 following publication of practice guidelines.

OBJECTIVE: The French regulatory agency published in 2006 practice guidelines related to the management of depressive and anxiety disorders. The main objective of the study was to assess their impact regarding use and monitoring of antidepressant drug treatment in older patients. The secondary objective was to identify factors associated with compliance with practice guidelines. METHODS: A historical fixed cohort study with dynamic follow-up time was conducted in 16,144 subjects aged 65 years and over, initiating antidepressant treatment and registered in the National Health Insurance Database between 2006 and 2012. Compliance with guidelines was assessed from year to year using segmented regression analysis. Multiple logistic regressions were used to identify factors associated with compliance with guidelines. RESULTS: Duration of antidepressant treatment was compliant with guidelines in 13.0% of patients aged 65-74 years and 18.5% of patients aged 75 years and over. Biological monitoring was performed in 12.6% of patients aged 65-74 years and 18.5% of patients aged 75 years and over. No significant change of rate of compliance with guidelines was observed over the study period. Compliance of prescriptions with guidelines was associated with patient's age, specialty of the prescriber, presence of chronic disease, year of treatment initiation, and presence of a university hospital in the area of residence. CONCLUSION: While treatment duration and biological monitoring were often inadequate in older patients, the publication of guidelines by the French health regulatory authorities did not lead to any significant and sustained improvement in their patterns of antidepressant use. Copyright © 2016 John Wiley & Sons, Ltd.

Comparison of pharmacy-based and diagnosis-based comorbidity measures from medical administrative data.

PURPOSE: Health status is sometimes quantified by chronic condition (CC) scores calculated from medical administrative data. We sought to modify two pharmacy-based comorbidity measures and compare their performance in predicting hospitalization and/or death. The reference was a diagnosis-based score. METHODS: One of the two measures applied an updated approach linking specific ATC codes of dispensed drugs to 22 CCs; the other used a list of 37 drug categories, without linking them to specific CCs. Using logistic regressions that took repeated measures into account and hospitalization and/or death the following year as the outcome, we assigned weights to each CC/drug category. Comorbidity scores were calculated as the weighted sum of the 22 CCs/37 drug categories. We compared the performance of both measures in predicting hospitalization and/or death with that of a diagnosis-based score based on 30 groups of long-term illnesses (LTIs), a status granted in France to exempt beneficiaries with chronic diseases from copayments. We assessed the predictive performance of the scores with the quasi-likelihood under the independence model criterion (QIC), the c statistic and the Brier score. RESULTS: The two pharmacy-based scores performed better than the LTI score, with lower QIC and Brier scores and higher c statistics. Their predictive performance was very similar. CONCLUSIONS: While there is no clear consensus or recommendations about the optimal choice of comorbidity measure, both pharmacy-based scores may be useful for limiting confounding in observational studies among general populations of adults from health insurance databases. Copyright © 2016 John Wiley & Sons, Ltd.

Trends in incident use of benzodiazepines and Z-drugs in France from 2006 to 2012: a population-based study.

PURPOSE: To study trends in incident use of benzodiazepines in France between 2006 and 2012. METHODS: A cross-sectional study repeated yearly was conducted using data from the French national healthcare insurance system. New benzodiazepine users were defined as users without any benzodiazepine dispensing in the year prior to the first dispensing of benzodiazepine in each year. Relative changes in incidence of use were calculated with the year 2006 as reference; confidence intervals for changes were estimated using the bootstrap method. RESULTS: Over the study period, the incident use of benzodiazepines decreased from 6.2% to 5.9%; this corresponded to a 5.1% decrease (95%CI: -6.8% to -4.2%) for 2012 compared to 2006. The decrease mainly concerned hypnotics (-15.5%; -21.2% to -15.3%) and appeared more pronounced in people aged 18-44 years. Incident use of anxiolytics remained stable overall during the period (4.0% of the population). Within anxiolytics, incident use of long half-life benzodiazepines (bromazepam, prazepam) decreased in favor of short half-life benzodiazepines (alprazolam, oxazepam). This change concerned patients aged 65-79 and patients aged 80 years and over. Nevertheless, in 2012, nearly one third of incident users aged 65 years and over started a treatment with a long half-life benzodiazepine, mostly bromazepam. CONCLUSIONS: A limited decrease in incident benzodiazepine use was observed in France between 2006 and 2012 that concerned only hypnotics. Although congruent with recommendations, this improvement appears insufficient with regard to the level of exposure to these drugs in France. New actions especially targeting anxiolytic benzodiazepine use should be undertaken to consolidate these results. Copyright © 2016 John Wiley & Sons, Ltd.

Antipsychotic long-acting injections: A community-based study from 2007 to 2014 of prescribing trends and characteristics associated with initiation.

OBJECTIVE: To explore the impact of the introduction of newer antipsychotic long-acting injections (LAIs) on trends in LAI prescribing and characteristics associated with initiation of LAIs in naturalistic conditions. METHODS: The study was performed using reimbursement data from the French Insurance Healthcare system. Prescribing trends were investigated from 2007 to 2014 in 382,572 persons aged 18years and over. Characteristics associated with delay in transition from oral antipsychotic to LAIs were explored in a cohort of 6904 persons newly treated with an oral antipsychotic using multivariate survival analyses. RESULTS: LAI prescribing rates slightly increased over the study period. The likelihood of being prescribed LAIs was stable for FGA LAIs (around 1.8 per 1000) (aOR=0.99, 95%CI 0.98-1.00) and increased for SGA LAIs from 0.5 to 1 per 1000 (aOR=1.11, 95%CI 1.08-1.14). In persons initiating an LAI (n=288), shorter transition from oral antipsychotic to LAI was independently predicted by male gender, younger age, dispensing of an oral SGA and a higher number of oral antipsychotics dispensed over the follow-up. Transition was longer in persons dispensed antidepressants or mood-stabilizers over the follow-up. Male gender, low income and higher number of antipsychotics were associated only with shorter transition to FGA LAIs, while initial prescription by a public practitioner, no mood-stabilizer dispensing and lack of somatic severe chronic condition were associated only with SGA LAIs dispensing. CONCLUSIONS: It is of interest to explore whether similar prescribing trends are observed in other countries and to further assess the effectiveness of new LAIs in real-life conditions.

Comorbidities and concurrent medications increasing the risk of adverse drug reactions: prevalence in French benzodiazepine users.

PURPOSE: To estimate benzodiazepine prevalence of use and to quantify, in benzodiazepine users, the prevalence of comorbidities and concurrent medications increasing the risk of adverse drug reactions (ADRs). METHODS: Cross-sectional study performed using data from the French national healthcare insurance system. The prevalence of use was estimated by considering as users, patients who had at least one benzodiazepine reimbursement during the year 2013. Patients at increased risk for benzodiazepine ADRs were those who had (i) drug-drug interactions at risk for central nervous system and respiratory depression and (ii) comorbidities at risk for adverse respiratory effects, or for falls or fractures. RESULTS: Overall, the prevalence of benzodiazepine use in 2013 was estimated to be 13.8 %; it was higher among women and increased with age. This prevalence was 10.6 % for anxiolytic benzodiazepines, and 6.1 % for hypnotic benzodiazepines. Approximately half of the benzodiazepine users (48.1 %) were at increased risk for benzodiazepine ADRs; this proportion increased with age. Drug-drug interactions represented the most prevalent condition (39.3 % of benzodiazepine users). The drugs most frequently involved were opioids: analgesics (15.9 %) and antitussives (6.8 %). Overall, 11.3 % of benzodiazepine users had comorbidities at increased risk for adverse respiratory effects (13.9 % in those aged 65-79), and 7.0 % comorbidities at increased risk for falls or fractures (13.4 % in those aged ≥80). CONCLUSIONS: This study found that benzodiazepine use remained high in France, and that roughly half of the users presented with comorbidities and concurrent medications increasing the risk of ADRs. These findings are of concern, given that benzodiazepines are frequently used, and especially among the elderly.

Compliance of psychotropic drug prescription with clinical practice guidelines in older inpatients.

Several practice guidelines were published by French regulatory agencies between 2006 and 2009 to improve psychotropic drug use in older patients. The objectives of the study were to assess compliance with these guidelines in older patients hospitalized in psychiatric units and to identify characteristics associated with compliance. A cross-sectional study was conducted in 117 patients aged 65 years and older hospitalized in two psychiatric departments of a public hospital, at three dates randomly chosen between January and May 2014. Medical and sociodemographic characteristics were collected from electronic medical records. In all, 8% of psychotropic prescriptions were compliant with guidelines. A total of 98% of antidepressant prescriptions complied with guidelines for product selection (no tricyclics) and 72% for initial dosage (half of that recommended for younger adults). Regarding benzodiazepines, short half-life drugs were chosen in 73% of treatments, low maintenance dosage was found in 64% of treatments, and a discontinuous administration rhythm was noted in 33% of treatments. Regarding antipsychotics, initial dosage was a quarter of the allowed initial dosage for younger adults in 39% of prescriptions and metabolic blood testing was performed in 17% of prescriptions. Neurological and cognitive tolerance was monitored in 41% and 61% of prescriptions, respectively. Few clinical factors were found to be associated with compliance or noncompliance with guidelines in older psychiatric inpatients. Practice guidelines on psychotropic drug prescription were partially respected in older inpatients. Practitioners should take into account the risks associated with non-recommended patterns of psychotropic drug use in this vulnerable population.

Impact of prenatal exposure to psychotropic drugs on neonatal outcome in infants of mothers with serious psychiatric illnesses.

OBJECTIVE: To assess whether prenatal exposure to 4 major classes of psychotropic drugs compared with no exposure differed with respect to neonatal outcome. METHOD: We used the database collected from 13 mother-baby units (MBUs) by the French Network of MBUs. The Marcé Clinical Checklist was used to collect data from maternal interview and clinical record with respect to maternal demographic and clinical characteristics, prenatal exposure to psychotropic drugs, and neonatal outcome (birth weight, preterm birth, neonatal hospitalization). Multivariate logistic regression was used to explore the independent impact of each therapeutic class of psychotropic drug (antipsychotics, antidepressants, mood stabilizers, and anxiolytics/hypnotics) on infant outcomes. All the models were adjusted for maternal confounding factors. RESULTS: The sample included 1,071 women and their infants. Nearly half (40.2%) used at least 1 psychotropic drug during pregnancy. The risk of low birth weight was increased by antenatal exposure to mood stabilizers (adjusted odds ratio [aOR] = 2.04, 95% confidence interval [CI] = 1.03-4.04, P = .04). The risk of neonatal hospitalization was increased by prenatal exposure to antipsychotics (aOR = 1.74, 95% CI = 1.19-2.54, P = .004), antidepressants (aOR = 1.59, 95% CI = 1.05-2.41, P = .03) or anxiolytics/hypnotics (aOR = 1.89, 95% CI = 1.30-2.75, P = .001), independent of birth weight and term delivery status. CONCLUSIONS: Infants exposed to psychotropic drugs during pregnancy have less optimal neonatal outcome than unexposed infants and should be considered as a high-risk population.