Evolution of the profiles of new psychotropic drug users before and during the COVID-19 crisis: an original longitudinal approach through multichannel sequence analysis using the French health-care database.

The COVID-19 pandemic has had a substantial impact on mental health. An increase in the use of anxiolytic, hypnotic, and antidepressant drugs has been highlighted in France, but with no information at the individual level (trajectories) or concerning patient characteristics. The objective of this study was to describe the profile of new psychotropic drug users since the beginning of the pandemic. We formed two historical cohorts using the Pays-de-la-Loire regional component of the National Health Data System (SNDS): a "COVID-19 crisis cohort" (2020-2021) and a "control cohort" (2018-2019). We analyzed reimbursements for psychotropic medications (anxiolytics, antidepressants, hypnotics, mood stabilizers, and antipsychotics) using a multichannel sequence analysis and performed clustering analysis of sequences. The proportion of new consumers of psychotropic drugs was higher in the COVID-19 crisis cohort (18.0%) than that in the control cohort (16.0%). In the COVID-19 cohort, three clusters of psychotropic drug users were identified, whereas four clusters were identified in the control cohort. A time lag in treatment initiation was observed in the COVID-19 crisis cohort (September) compared with the control cohort (July). This study is one of the first to analyze the profile of psychotropic treatment users during the COVID-19 crisis. Our analysis sheds light on changes in patterns of psychotropic drug use during the COVID-19 pandemic, possibly associated with changes in prescribing conditions and mental health conditions during the crisis. This study also provides an example of the application of an innovative longitudinal analysis methodology in the field of pharmacoepidemiology.

Characterization of antipsychotic utilization before clozapine initiation for individuals with schizophrenia: an innovative visualization of trajectories using French National Health Insurance data.

AIMS: Despite recommendations to initiate clozapine after two unsuccessful trials of antipsychotics, clozapine is underprescribed and initiated too late. The aim of this study was to describe different antipsychotic treatment sequences in the 36 months before the initiation of clozapine and to characterize clusters of treatment trajectories. METHODS: Using the French National Health Insurance database, a historical cohort study of the population in an area in western France was performed. The data from all new users of clozapine with a diagnosis of schizophrenia or schizoaffective disorder in the period of 2017-2018 were evaluated. All outpatient reimbursements for antipsychotics during the 36 months before clozapine initiation were analysed. Successive reimbursements for identical treatments were grouped into treatment trials (TTs), and different trajectories were clustered using a state sequence analysis. RESULTS: The results showed 1191 TTs for 287 individuals. The mean number of TTs per individual was 3.2. Risperidone, aripiprazole and haloperidol were the main treatments delivered. The frequencies of antipsychotics used differed between monotherapies and combination therapies. A three-cluster typology was identified: one cluster (n = 133) of 'less treated' younger individuals with fewer TTs and shorter TT durations; a second cluster (n = 53) of 'more treated' individuals with higher numbers of TTs and combinations of antipsychotics; and a third cluster (n = 103) of 'treatment-stable' older individuals with longer TT durations. CONCLUSIONS: The results indicate that the median number of TTs during the 36 months before clozapine prescription was higher than the two recommended. The different trajectories were associated with individual characteristics and treatment differences, suggesting that additional studies of clinical parameters are needed to understand barriers to clozapine prescription.

Expert consensus on monitoring antimicrobial stewardship in French nursing homes using assessed reimbursement database indicators.

Objectives: Monitoring the appropriateness of antibiotic prescriptions with indicators based on reimbursement data is required to guide antibiotic stewardship (AMS) interventions in nursing homes (NHs). Quantity metrics (QMs) monitor the volume of prescriptions while proxy indicators (PIs) reflect the appropriateness of antibiotic use. Our objectives were: (i) to provide a relevant consensual set of indicators to be used in French NHs; and (ii) to assess the feasibility of their implementation at the national and local scale. Methods: Nine French professional organizations implicated in AMS in NHs were asked to nominate at least one member to create a national expert panel of 20 physicians. Twenty-one recently published QMs and 11 PIs were assessed by the expert panel. Indicators were evaluated using a RAND-modified Delphi procedure comprising two online surveys and a videoconference meeting. Indicators were kept in the final list if >70% of stakeholders validated their relevance for estimating the volume (QMs) and appropriateness (PIs) of prescriptions. Results: Of the 21 QM indicators submitted to the panel, 14 were selected, describing the consumption of antibiotics overall (n = 3), broad-spectrum (n = 6) and second-line antibiotics (n = 2). The three remaining QMs evaluated the route of administration (n = 1) and urine culture prescriptions (n = 2). Ten PIs (six modified, two rejected, one new) were selected to assess the appropriateness of prescriptions for urinary tract infections (n = 2), seasonal variations in prescriptions (n = 2), repeated prescriptions of fluoroquinolones (n = 1), cephalosporins' route of administration (n = 1), duration of treatment (n = 1), rate of second-line antibiotics (n = 1), co-prescriptions with non-steroidal anti-inflammatory drugs (n = 1), and flu vaccine coverage (n = 1). The panel was in favour of using these indicators for regional and facility level AMS programmes (91%), feedback to NH prescribers (82%), benchmarking by health authorities (55%) and public reporting at the facility level (9%). Conclusions: This consensual list of indicators, covering a wide range of frequent clinical situations, may be used as part of the French national AMS strategy for monitoring antibiotic prescriptions in NHs at the national and local levels. Regional AMS networks might manage this selected list to guide personalized action plans with concrete objectives of reducing the quantity and improving the quality of antibiotic prescriptions.

(De)Prescribing of proton pump inhibitors: what has changed in recent years? an observational regional study from the French health insurance database.

BACKGROUND: Proton pump inhibitors (PPIs) are one of the most widely prescribed drug classes in the community and at hospital. The significant misuse of PPIs requires the implementation for a deprescribing strategy. Numerous studies aiming at evaluating the impact of deprescribing interventions have been set up, implying a precisely known evolution of consumption of PPIs in the population studied without intervention. The main objective of the study was to study overall changes in PPI prescribing and deprescribing in a regional population of chronic consumers without intervention, according to health insurance databases. METHODS: This historical cohort study was based on the French National Health Data System databases. All adult patients living in the Pays de la Loire area and covered by the French National Health Insurance and who had at least one reimbursement for a PPI dispensing between 01 October 2016 and 31 December 2020 were included. Only chronic consumer patients were included, defined as patients who has had PPI dispensed for 3 consecutive months with a temporal coverage of at least 80%. Patients under 18 years of age and patients who received parenteral PPIs only were excluded. RESULTS: The percentage of chronic treatment discontinuation in 2017 was 12.5% and remained stable to reach 12.4% in 2020. The number of new chronic patients increased from year to year to reach 77,222 patients in 2020, with an increasing rate of 1.2 to 2% between 2017 and 2020. The prevalent patient population increased from year to year to reach 167 751 patients in 2020, with an increasing rate of 4.2 to 4.4% between 2017 and 2020. Regarding the initiation of PPI therapy, in 2020, 87.1% of treatment initiations were done by general practitioners. They renewed 2,402,263 prescriptions (89.3%) between 2017 and 2020. CONCLUSIONS: This study shows a stagnation over the last 4 years in the deprescribing of chronic PPI treatments in a French region despite the information on their inappropriate use reported by national agencies and in the literature with increasing frequency. This reinforces the interest of setting up a deprescribing project.

Les pratiques des professionnels de santé assurant le suivi gynécologique en Pays de la Loire.

INTRODUCTION: In France, four health care categories ensure primary care gynecological follow-up: general practitioners (GP), medical gynecologists, obstetrician gynecologists and midwives. PURPOSE OF RESEARCH: To describe private health professionals’ ensuring gynecological follow-up in Pays de la Loire (France) in 2018, as well as their respective activities. RESULTS: Our study population was composed of 3764 health professionals, a majority of those being GP. Proportion of aged 60 or older GP in Loire-Atlantique was 25.5%, this proportion was higher in Sarthe (49%). 80% of medical gynecologists were at least 60 years of age and mainly settled in Loire-Atlantique and Maine-et-Loire. Obstetrician gynecologists were older in Mayenne, Sarthe and Vendée. Midwives were relatively younger: 71% were under 50 years of age.On a regional basis, 1 658 155 medical consultations, for any type of gynecological reasons, were identified. Among them, 41.3% were done by GP, 24.3% by gynecologists and 34.4% by midwives. GPs aged 60 or older who represented 30.5% of all GP in Pays de la Loire ensured 26.3% of GP gynecological follow-up, with wide departmental discrepancies. CONCLUSIONS: Medical gynecologist specialty is unequally distributed within the Pays de la Loire area and many professionals are aged 60 or older. Inadequate access to healthcare in this specific field due to the lack of healthcare professional will be soon problematic. Obstetrician gynecologist specialty is better spread, due to care facility locations. A larger volume of activities is taken on by midwives, whereas a wider range of activities is carried out by physicians, according to medical classification.

What about regular hematological monitoring during clozapine treatment? A compliance analysis using the French health insurance database.

BACKGROUND: The inherent risk of agranulocytosis associated with clozapine requires the realization of weekly white blood cell monitoring (WBCM) during the 18 first weeks of treatment. The aim of this study was to assess the compliance with WBCM during clozapine initiation for schizophrenia and Parkinson's disease (PD) subjects. RESEARCH DESIGN AND METHOD: The analysis was conducted using SNDS data on a cohort of new users of clozapine in 2018. We analyzed all reimbursements for WBCM from 2 weeks before the index date to 18 weeks after (optimal monitoring during hospitalization was assumed). The primary outcome was the proportion of good realization of WBCM according to different thresholds of completion (70%; 80%; 90%). Descriptive and comparative analyses with chi-squared test or Student's t-test were performed. RESULTS: Two hundred and ninety-six subjects were included. Rates of patients with WBCM realization over 70%, 80%, and 90% of WBCM expected were, respectively, 78.1%, 70.0%, and 56.9% for subjects with schizophrenia and 71.3%, 63.2%, and 47.8% for PD subjects. Only hospitalization during the follow-up period for schizophrenia subjects was significantly associated with good WBCM realization. CONCLUSIONS: We observed rather good results for compliance with clozapine initial monitoring. Other studies are needed to confirm our results.

Advocacy for better metabolic monitoring after antipsychotic initiation: based on data from a French health insurance database.

Background: Nearly 3% of the population is treated by antipsychotic. The aim of this study was to assess the conformity of monitoring with guidelines to prevent Metabolic Syndrome. Research design and method: The analysis was conducted using SNIIRAM data (2013 to 2017) on a cohort of patients who received at least eight antipsychotic dispensings in the first year. Glucose and lipid testings were recorded according to refunds at initiation [between -3 and 0.5 months], 3 months [between 2 and 4 months], and 12 months [between 11 and 13 months] after, and assuming optimal testing during hospitalization (exclusive of psychiatric unit). Descriptive and comparative analysis, «chi-squared test or Student's t-test¼, were performed as well as multivariate analysis with logistic regression. Results: 18 760 patients were selected, 14 421 were still alive and monitored at the end of the follow up. In the recommended period, only 2.89% of patients had three complete testings and 50.6% one or two complete testings Non-optimal testing was more likely to occur in children and adults (vs elderly), in patients with less than 3 prescribers, and with universal medical coverage. Conclusion: Monitoring remains dramatically insufficient. New actions involving patients, practitioners, and authorities are warranted.

Interaction between CYP2D6 inhibitor antidepressants and codeine: is this relevant?

INTRODUCTION: Co-occurring pain impairs depression's prognosis. Selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) are first-line pharmacotherapies for depression and inhibit many cytochrome 2D6 enzymes. Codeine is a first-line treatment for pain and needs to be metabolized into morphine by cytochrome 2D6 to exert its analgesic effect. Concomitant prescription of both pharmacotherapies leads to inadequate analgesia. Areas covered: We performed a systematic review of the literature to amalgamate the current knowledge regarding the clinical effect of this association and quantified its prevalence in clinical practice in the French Pays de la Loire area using a retrospective observational cohort study design. Expert opinion: The literature review highlighted that antidepressants with moderate-to-strong inhibition of CYP2D6 should be avoided in patients receiving codeine. However, 0.44% of the 12,296 sampled patients received concomitant codeine and CYP2D6 inhibitor between January 2015 and June 2015. Switching drugs in both painful and depressive patients depends on the pain and depression subtypes. Promising drugs that both show an effect on pain and depression are currently being studied but are not usable in clinical practice. Until then, tailored communication reinforcement toward health-care professionals is needed to prevent these problematic occurrences of concomitant prescription administration.

Influence of socioeconomic status on antipsychotic prescriptions among youth in France.

BACKGROUND: Recent studies analysing the trends in antipsychotic (AP) prescriptions for children and adolescents have raised concerns regarding the influence of socioeconomic status. Previous findings have also shown variable prescription rates for first-generation (FG) and second-generation (SG) APs. METHOD: Our objectives were to assess the proportion of patients from low-income families receiving APs and the most commonly prescribed APs in France. We conducted a descriptive analysis of AP drugs dispensed during a 1-year period (July 1, 2013-June 30, 2014) in a northwestern region of France with 941,857 subjects less than 18 years old. All data were extracted from an exhaustive, individual and anonymous social security database. We obtained each subject's socioeconomic status (by identifying their affiliation with a specific social security program) and also collected sociodemographic data, drug type, prescribing and dispensing dates and amount, and prescriber type (e.g., hospital physician, general practitioner, psychiatrist, paediatrician). RESULTS: There were two main novel findings. First, we found that the proportion of patients with AP prescriptions was nearly ten times higher in low-income families than in the general population: 35.9% of CMU-C patients compared to 3.7% in all of Pays de la Loire (X 2 = 7875.1, p < 0.001). Additionally, we found a higher rate of FGAP than SGAP prescriptions (65% vs. 57%). CONCLUSIONS: Our study suggests two types of AP misuse that could provide interesting targets for public healthcare interventions. First, our results strongly suggest an over-representation of patients from low-income families. Low-income families primarily resided in areas with low physician density and appeared to receive drugs to treat their conditions more frequently than other individuals. This increased prescription rate is a public health issue, potentially requiring political action. Second, the use of FGAPs did not adhere to the latest recommendations for drug use in this population, and this discrepancy should be addressed with informational campaigns targeted to medical practitioners.

Inclusion of populations at risk of advanced melanoma in an opportunistic targeted screening project involving general practitioners.

OBJECTIVE: The study objective was to measure the rates of inclusion of populations at risk of advanced melanoma in a pilot targeted screening project involving general practitioners. DESIGN: This cross-sectional database study compared the inclusion rates of patients who signed inclusion in a targeted screening project with those of patients who did not, during a period in which both groups of patients consulted investigators. SETTING: Data were extracted from the national healthcare insurance records in western France from 11 April to 30 October 2011. PATIENTS: Patients, older than 18, considered for the data extraction had consulted one of the 78 participating GPs during the study period, and were affiliated with the national healthcare insurance. MAIN OUTCOME MEASURES: Inclusion in the screening was the main outcome measure. Patients at risk of advanced melanoma were characterized by male gender, age over 50, low income, rural residence, farmer, and presence of chronic disease. RESULTS: A total of 57,279 patients consulted GPs during the inclusion period and 2711 (4.73%) were included in the targeted screening. Populations at risk of advanced melanoma were less included: men (OR = 0.67; 95%CI [0.61-0.73]; p < 0.001), older than 50 (OR = 0.67; 95%CI [0.60-0.74]; p < 0.001), low income (OR = 0.65; 95%CI [0.55-0.77]; p < 0.001), farmer (OR = 0.23; 95%CI [0.17-0.30]; p < 0.001) and presence of a chronic disease (OR = 0.87; 95%CI [0.77-0.98]; p < 0.028). CONCLUSION: This study demonstrated inequalities in the inclusion of patients in a melanoma screening. Patients at risk of advanced cancer were screened less often. Further studies should focus on GPs ability to identify and screen these patients. KEY POINTS Advanced melanoma is more frequently diagnosed in men, older patients and socioeconomically disadvantaged populations, which leads to survival inequalities. • Despite the involvement of general practitioners, the implementation of targeted melanoma screening did not avoid inclusion inequalities. • Men, older patients, patients suffering from chronic diseases, and low-income patients were less likely to benefit from screening. • The display of a conventional or an alarmist poster in the waiting room did not statistically reduce these inclusion inequalities.

Did the new French pay-for-performance system modify benzodiazepine prescribing practices?

BACKGROUND: French general practitioners (GPs) were enrolled in a new payment system in January 2012. As part of a national agreement with the French National Ministry of Health, GPs were asked to decrease the proportion of patients who continued their benzodiazepine treatment 12 weeks after its initiation and to decrease the proportion of patients older than 65 who were prescribed long half-life benzodiazepines. In return, GPs could expect an extra payment of up to 490 euros per year. This study reports the evolution of the corresponding prescribing practices of French GPs during that period regarding patients who were prescribed a benzodiazepine for the first time. METHODS: The national healthcare system's administrative database was used to report the longitudinal follow-up of two historical cohorts of French patients from the Pays de la Loire area. STUDY PATIENTS: The "2011" and "2012" cohorts included all patients who initiated benzodiazepine regimens from April 1 to June 30 in 2011 and 2012, respectively.The primary outcomes were the proportion of those study patients who continued benzodiazepine treatment after 12 weeks and the proportion of study patients >65 years who were prescribed long half-life benzodiazepines.Analyses were performed using a multi-level regression. RESULTS: In total, 41,436 and 42,042 patients initiated benzodiazepine treatment in 2011 and 2012, respectively. A total of 18.97% of patients continued treatment for more than 12 weeks in 2012, compared with 18.18% in 2011. In all, 27.43% and 28.06% of patients >65 years continued treatment beyond 12 weeks in 2011 and 2012, respectively. The proportion of patients >65 years who were prescribed long half-life benzodiazepines decreased from 53.5% to 48.8% (p < 0.005) due to an increase in short half-life benzodiazepine prescriptions. Patients >65 years who were prescribed short half-life benzodiazepines were more likely to continue treatment after 12 weeks (p < 0.005). CONCLUSIONS: Despite the pay-for-performance strategy, the number of short half-life benzodiazepine prescriptions increased between 2011 and 2012, and the number of long half-life benzodiazepine initiations remained unchanged. Reducing the proportion of long half-life benzodiazepine prescriptions might be counterproductive because prescribing short half-life benzodiazepines was associated with higher rates of continuation beyond the recommended duration.

Pharmacoepidemiological characterization of psychotropic drugs consumption using a latent class analysis.

France has one of the highest recorded rates of psychotropic use of drugs compared with other European countries, especially for anxiolytics, hypnotics and antidepressants. The aim of this study was to characterize the use of three psychotropic drugs among the most prescribed in France (bromazepam, paroxetine, zolpidem) using reimbursement databases in real-life conditions. Individuals from a region affiliated to the French General Health Insurance Scheme, who had received at least two dispensings of bromazepam, paroxetine or zolpidem reimbursed between 1 January and 30 June 2008, were included. We used a latent class analysis to identify different subgroups of users for these three psychotropic drugs. A total of 40,644 patients were included for bromazepam, 36,264 for zolpidem and 31,235 for paroxetine. Using latent class analysis, four clinical subtypes of users of bromazepam and zolpidem were identified: nonproblematic users, at-risk users, users with a probable mental disorder and compulsive users. Three subgroups were identified for paroxetine that differed rather by the prescription patterns. Users of anxiolytics and hypnotics with at-risk behaviours represented a significant proportion in the studied population. This original method could be extended to other prescription databases to identify populations at risk of abuse or dependence to psychotropic drugs.

Diuretic drug therapy monitoring in the elderly: a cohort study.

BACKGROUND: Because the elderly are often treated by multiple-drug regimens, their iatrogenic risks are considerably raised. However, despite the serious side-effects that diuretic agents may have in this population, SPCs (summary of product characteristics) do not specify how often serum chemistry should be monitored. This study of long-term diuretic therapy prescription and monitoring in elderly patients was conducted by the Department of Clinical Pharmacology of the Nantes teaching hospital in collaboration with the medical department of the French national health insurance scheme. METHODS: Data were extracted from the French national health insurance database. Patients were 75 years old or more and had been receiving a diuretic agent for 1 year or longer. The patients were classified into two groups: one group included those patients whose serum chemistry had been monitored at least once (electrolyte levels and/or urea and creatinine blood levels); the other group included the non-monitored patients. RESULTS: Mean patient age was 80+/-4.6 (SD) years. The non-monitored patients represented 22.8% of the cohort. The at-risk patients were mainly women suffering from no severe disease, treated by a single practitioner (often a general practitioner) and/or always receiving the same type of diuretic agent. CONCLUSION: Many elderly patients receiving diuretic agents do not benefit from regular serum chemistry monitoring. The prescription of serum chemistry assays is correlated to the presence of various patient-related risk factors. Recommendations should be made to help practitioners to ensure a minimal serum chemistry monitoring in all elderly patients receiving diuretics.

[Reactivity and communication of Health Authorities toward health professionals: a public health priority]. / Réactivité et communication des décisions de pharmacovigilance des autorités de santé vers les professionnels de santé: exemples du pergolide et du célécoxib.

OBJECTIVE: evaluate the impact of Health Authorities' communication on medical practices through 2 examples: celecoxib, taking into account the recent countra indication related to cardio vascular risks; pergolide, taking into account the risk of cardiac valvulopathy. MATERIAL AND METHOD: Use of the Pays de Loire Health Insurance Administration data base to monitor the number of cardio vascular patients at risk who receive celecoxib, and cardiac surveillance of pergolide exposed patients. RESULTS: Communication from Health Authorities resulted in a major decrease (71.9%) of the number of risking patients who take celecoxib, and a significant 14% decrease of pergolide treated patients needing cardiac monitoring CONCLUSION: Unlike the information related to pergolide, the information related to celecoxib was fully taken into account. The difference seems to come from the fact that one was widely relayed by medias, not the other.

Benzodiazepine use and risk of dementia: a nested case-control study.

The objective of this article was to examine the possible association between benzodiazepine use and the risk of dementia in the elderly. This was a nested case--control study set in community settings in Bordeaux area, France. The participants were a representative sample of 3,777 elderly persons (65 years of age and older) followed from 1989 to 1997. The main outcome measures were the use of benzodiazepines in incident cases of dementia versus nondemented controls. On the basis of medical and psychological data, 150 patients were diagnosed with dementia according to the criteria of the third revision of the Diagnostic and Statistical Manual of Mental Disorders. Information on benzodiazepine use was obtained by face-to-face interview and visual assessment of patient's medicine chest by a trained neuropsychologist. After controlling for age, gender, education level, living alone, wine consumption, psychiatric history, and depressive symptomatology, ever use of benzodiazepines was associated with a significantly increased risk of dementia [adjusted odds ratio (OR), 1.7; 95% confidence interval, 1.2-2.4]. Former use was associated with a significantly increased risk of dementia (adjusted OR, 2.3; 95% CI,1.2-4.5). No association was found between dementia and the current use of benzodiazepines (adjusted OR, 1.0; 95% CI, 0.6-1.6). Our finding suggest that former use of benzodiazepines could be a risk factor for dementia, but more detailed investigation are needed.