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.

Hypnotic prescription without face to face contact: a report from French family medicine.

BACKGROUND: Guidelines suggest a review of hypnotic prescriptions every four weeks for zopiclone, zolpidem and zaleplon ('Z-drugs'). The lack of face-to-face consultation between the physician and the patient increases the potential of misuse and resultant dependence. OBJECTIVES: To determine the proportion of long-term hypnotic Z-drug prescription issued without face-to-face consultation, and factors associated with such practice. METHOD: Audit based on an extract of data from the French health insurance database in two French departments. Long-term Z-drug prescriptions by general practitioners (GPs) were analysed over a one-year period, regardless of the association of the prescription with a reimbursed consultation. Main factors considered were patient characteristics (gender, age, socioeconomic status, suffering from a chronic disease) and physician characteristics (gender, age, location of the practice, patient list size). RESULTS: Overall, 67 256 long-term Z-drug prescriptions were reviewed. Of these, 23 107 (34.4%) were not associated with a consultation. Only 17% (95%CI: 16-18%) of long-term hypnotic consumers attended a consultation on all the dates noted on the prescription. Z-drug prescriptions were more likely to be prescribed in a consultation if the patient had a chronic illness (P < 0.0001), a low socioeconomic status (P < 0.0001), was less than 45 or over 65 years old (P < 0.0001), or visited a psychiatrist during the same year (P < 0.0001). Having a longer patient list or practising in a rural area were physician characteristics associated with non-adherent Z-drug prescription (P < 0.0001). CONCLUSION: Prescribing Z-drug hypnotics without a face-to-face consultation was frequent, especially in middle-aged patients without co-morbidity who were not seen by a psychiatrist.

Epidemiological characterization of drug overconsumption: the example of antidepressants.

The authors present a pharmaco-epidemiological method for the characterization of drug overconsumption. Using the database of a French regional health insurance office, a comparison was made between patients receiving doses higher than recommended and all patients receiving normal doses of two antidepressant drugs (tianeptine and milnacipran). Logistic regression models were used to identify the variables related to overconsumption. The selected variables were different for each antidepressant and provided a good characterization of overconsumption features: insufficient effectiveness and severity of the condition for milnacipran and abuse/misuse for tianeptine. Characterization of overconsumption of antidepressants can be performed using logistic regression models. This method of analysis, which is seldom used in the context of pharmacodependence, makes it possible to explain posology increase.

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.

[Creating and validating a tool able to detect fraud by prescription falsification from health insurance administration databases]. / Création et validation d'un outil de détection de la fraude par falsification d'ordonnance à partir des bases de données de l'Assurance Maladie.

GOAL: Make it possible to spot falsified prescriptions which were delivered and reimbursed. METHOD: 1- Use health insurance administration data bases to single patients liable to suspicion of fraud (repeated presentations of the same prescription to several pharmacies the same day) 2- Attribution of a diagnosis of fraud, by the CEIP (Center of Evaluation and Information about Pharmacodependence) based on transferred data, and by the medical department analysis of the complete file, and convocation when applicable 3- Calculation of quantitative performance of the tool. RESULTS: We have singled 2030 patients. Among them 25 were able to get 553 deliveries out of 288 pharmacies from 114 prescriptions in one year. Our tool specificity is 99.5% and its sensitivity 69.4%. CONCLUSION: Creating this tool which can become automatic and used on a large scale, brings a new light in the evaluation, by making hindsight fraud detection possible.

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.