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.

Descriptive analysis of sickle cell patients living in France: The PHEDRE cross-sectional study.

BACKGROUND: Sickle cell disease (SCD) induces chronic haemolytic anaemia and intermittent vaso-occlusion that results in tissue ischaemia causing acute, severe pain episodes that can lead to frequent hospitalizations. These consequences can have repercussions on family, social, school and/or professional life. Here, we present some of the results of the PHEDRE study (Pharmacodépendance Et DREpanocytose-drug dependence and sickle-cell disease), which is the largest study of patients with SCD in France. This paper intends to describe characteristics of the French SCD population. We also aimed to assess the impact of the disease on the lives of patients using objective and subjective variables. METHODS: The PHEDRE study was a national multicentric observational study. Adults, adolescents and children with a confirmed SCD diagnosis were included in the study by their referring doctor. Then, they were interviewed by phone about their socioeconomic status, about the impact of the disease on their lives and about their analgesic and psychoactive drug use. RESULTS: The study population consisted of 872 patients (28% were minors). Seventy-two percent of adults were active, and all minors were in school. Many patients presented criteria of severe SCD. Seventy-five percent were homozygous SS, 15% were double heterozygotes SC and 8% were heterozygotes Sßthal, 87% received specific treatment, 58% were hospitalized at least once for vaso-occlusive crisis in the past 12 months, and the number of analgesic drugs taken averaged 3.8. Seventy-five percent of patients reported academic or professional consequences related to their SCD, and 52% reported social consequences. CONCLUSIONS: The impact of SCD on patients' lives can be significant, nevertheless their social integration seems to be maintained. We highlighted respect of recommendations regarding analgesic treatments and only a few patients used tobacco, alcohol or cannabis. TRIAL REGISTRATION: Clinical Trials, NCT02580565; https://clinicaltrials.gov/ Registered 16 October 2015.

Medicated or not medicated hypnotic substance use: strategies in sleep disorders among patients of community pharmacy.

The principal outcome was to identify which hypnotics substances, medicated (benzodiazepines, antihistamine, antidepressant…) or not medicated (herbal medicine, homeopathy, melatonin…), were consumed by community pharmacy patients who reported taking something for sleep disorder, and which factors can influence the consumption of medicated substance rather than nonmedicated substance. Data were collected via a network of 73 partner pharmacies around Nantes, France. Patients who reported taking a substance to sleep completed a questionnaire that collected data relative to the different substances consumed by that person for sleep, and the desired effect. Substances were classified in Hypnotic Drug Substances and nonmedicated hypnotic substances. A logistical regression was done in order to highlight the factors associated with the consumption of Hypnotic Drug Substance rather than nonmedicated hypnotic substances. Six hundred and forty-seven patients were included, with an average age of 58 years and 74% female. The principal strategy employed to combat sleep disorder was the consumption of Hypnotic Drug Substance (54%), followed by herbal medicine (32%) and homeopathy (19%). The factors positively associated with the consumption of a Hypnotic Drug Substance are age, living alone, being out of work, or in the process of looking for a job and being a parent. In our survey, the use of Hypnotic Drug Substance to help patients with sleep is far from systematic. On the other hand, among patients who consume HDS, misuse is still significant, particularly in terms of the duration of consumption.

Cannabis and anticancer drugs: societal usage and expected pharmacological interactions - a review.

Cannabis is a plant that has been used for centuries to relieve a wide range of symptoms. Since the 1960s, interest in medical research into this plant has grown steadily. Already very popular for recreational use, a growing number of consumers not accustomed to using cannabis for psychoactive purposes have begun to use it as an alternative or complement to mainstream pharmaceutical medicines. The principal unsubstantiated or 'social' uses of cannabis are based mainly on data that is at best controversial, but usually not scientifically proven. The aim of this review was to identify the scientific basis and reasons that lead patients with cancer to consume cannabis, and also to identify whether there is a risk of interaction between cannabis and anticancer medicines through drug transporters (P-glycoprotein and other ATP-binding cassette superfamily members) Cytochromes P450 (3A, 1A, 2B, 2C, 2D families…) and glucuronyl transferases.

Psychiatric disorders, acne and systemic retinoids: comparison of risks.

BACKGROUND: The link between isotretinoin, treatment of a severe form of acne, and psychiatric disorders remains controversial, as acne itself could explain the occurrence of psychiatric disorders. This study aims at assessing the disproportionality of psychiatric adverse events reported with isotretinoin in the French National PharmacoVigilance Database, compared with other systemic acne treatments and systemic retinoids. MATERIALS AND METHODS: Data were extracted from the French National PharmacoVigilance Database for systemic acne treatments, systemic retinoids and drugs used as comparators. Each report was subjected to double-blind analysis by two psychiatric experts. A disproportionality analysis was performed, calculating the number of psychiatric ADRs divided by the total number of notifications for each drug of interest. RESULTS: Concerning acne systemic treatments: all 71 reports of severe psychiatric disorders involved isotretinoin, the highest proportion of mild/moderate psychiatric adverse events was reported with isotretinoin (14.1%). Among systemic retinoids, the highest proportion of severe and mild/moderate psychiatric events occurred with isotretinoin and alitretinoin. CONCLUSION: Our study raises the hypothesis that psychiatric disorders associated with isotretinoin are related to a class effect of retinoids, as a signal emerges for alitretinoin. Complementary studies are necessary to estimate the risk and further determine at-risk populations.

Management of cannabis use during pregnancy: an assessment of healthcare professionals' practices.

PURPOSE: Because of the increase of cannabis use, healthcare professionals are more and more confronted with pregnancies which have been exposed to this drug. There may be health consequences during the course of pregnancy and also for the babies throughout their development. We have made a study in order to evaluate practices of detection and care for pregnant women who use cannabis. METHODS: A questionnaire was sent to all gynaecologists (GYNs), obstetricians (OBs) and midwives (MWs) in the district of Loire-Atlantique and to a 20% randomized sample of general practitioners (GPs). RESULTS: The participation rate was 60.1%. Only 51.4% of healthcare professionals asked their patients about drugs use and 68.1% didn't feel informed enough about the risks of cannabis use during pregnancy. There was a significant difference between the healthcare professionals who deliver babies (OBs and MWs) and those who only do prenatal consultations (GYNs and GPs). The first group question their patients about the use of cannabis more often (69.1% versus 39.8%; p = 0.01), and also feel more informed about the risks of cannabis use during pregnancy (42.0% versus 24.4%; p = 0.025). CONCLUSIONS: Healthcare professionals who supervise childbirth have a more accurate perception of the risk related to the consumption of cannabis during pregnancy. But preventive action must be taken early on because the lack of early identification at the beginning of pregnancy represents a public health problem. After observing the results we feel there is a strong need for training for all practitioners.

[Consumption of cannabis among subjects with history of abuse/dependence or under an opiate maintenance therapy: OPPIDUM data in 2006 and main trends since 2004]. / La consommation de cannabis chez les sujets présentant un abus, une pharmacodépendance ou sous traitement de substitution de la dépendance aux opiacés: données OPPIDUM 2006 et principales tendances depuis 2004 du réseau des Centres d'Evaluation et d'Information sur la Pharmacodépendance (CEIP).

The data on consumption of cannabis in the young people are well documented on the other hand this consumption is less described in subjects presenting a drug dependency. The consumption of cannabis in 2006 and the principal tendencies since 2004 were studied from the OPPIDUM (Observation of Illegal Drugs and Misuse of Psychotropic Medications) program's. OPPIDUM is an annual transverse national study pharmaco-epidemiologic which recruits subjects presenting a drug dependency or benefiting of a maintenance treatment. In October 2006, 3743 subjects were included. Thirty eight per cent (n=1437) of them are consumers of cannabis, among them 27% announced consumed only cannabis and 73% consumed it with other psychoactive substances. The consumers of cannabis alone are younger, have better social-economical indicators and presented consumption of cannabis in term of abuse and dependence more important. This study underlines the problems of the polyconsommation. No change related to the characteristics of consumers of cannabis was observed between 2004 and 2006. This study underline the presence of two groups of consumers of cannabis presented in structures of care who are different on level of the social-economical indicators and its consumptions.

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.

[Impacts of the new flunitrazepam regulations on the consumption of hypnotics]. / Impacts de la nouvelle réglementation du flunitrazépam sur la consommation d'hypnotiques.

The frequent misuse of flunitrazepam has led the French drug agency (AFSSAPS [Agence française de sécurité sanitaire des produits de santé]) to subject this agent to the regulatory regime for drugs known to produce dependency; this drug may now be prescribed for no more than 14 days, is available only on an "ordonnance sécurisée" (prescribing and dispensing subject to stupefacient regulations), and pharmacists must dispense no more than 7 days' supply. We identified, in a French medical-care database, 738 patients who had received at least one flunitrazepam prescription in January 2001, and monitored the hypnotics delivered to this cohort over a period of 8 months. Sixty-nine percent of the patients had replaced flunitrazepam by another hypnotic without any further change. The most surprising result of our survey was the discovery that nearly half of the selected patients stopped using hypnotics during the review period. Although many hypotheses can be offered to account for this phenomenon, it seems that many consumers halted their consumption of flunitrazepam as a result of the new regulatory regime.