Methylphenidate: Gender trends in adult and pediatric populations over a 7year period.

OBJECTIVE: Methylphenidate (MPH) is a prescription-stimulant medication which is authorized in France for two indications: attention-deficit hyperactivity disorder in children (aged≥6years) and narcolepsy in cases where modafinil is ineffective (for children and adults). MPH use has increased worldwide in the past 2 decades in children and adults. Different pharmacoepidemiological Europeans studies have described MPH patterns of use. To our knowledge, few pharmacoepidemiological studies have described MPH patterns of use in France. METHODS: In this context, we have performed a study on regional reimbursement database (PACA-Corse area, covering approximately 4 millions inhabitants). The first part of the study analyzed the evolution of MPH users characteristic's yearly (grouped by age and gender) over a 7year period (2005-2011). In order to better characterize patterns of MPH use in adults, a specific analyze has been performed in the second part on MPH adult users in 2011 with a gender descriptive approach. RESULTS: During the 7year period, MPH dispensing grew from 0.28 to 0.68 patient per 1000. The proportion of adult patients rose from 14.8 to 25.7% (P<0.0001), with patients mainly aged 35-49years old. Gender differences in MPH users were noted between adults and children: the proportion of girls was less important in children than in adult (in 2011, 20.7% of girls among children vs 44.9% among adults). Moreover, the proportion of girls among children increased between 2005 to 2011 (15.1% of girls in 2005 versus 20.7% in 2011). Among adults, women were prescribed more antidepressants (41.5% versus 28.2%, P=0.003) and less opiate maintenance treatments (22.4% versus 31.9%, P=0.03) than men. Finally, 11% of men and 16.4% of women were over 50years old. CONCLUSION: MPH prescription greatly increased over7years, especially in adults. Moreover, in this population, patterns of MPH use differed with gender specificities. Such findings may increase clinical attention on monitoring MPH use in adults.

Patterns of Methylphenidate Use and Assessment of Its Abuse among the General Population and Individuals with Drug Dependence.

PURPOSE: The aim of this study was to describe the extent of methylphenidate (MPH) abuse and characterize its patterns by following several cases involving intravenous administration of crushed MPH tablets. METHODS: First, a drug reimbursement database (covering 4 million inhabitants) was explored to assess the magnitude of MPH abuse among the general population, and second, a specific study based on individuals with drug dependence was performed to describe abusers' characteristics (n = 64), patterns of abuse and clinical implications. RESULTS: From 2005 to 2011, the number of patients who were dispensed MPH at least once increased by 166%. The patients with 'deviant' patterns of MPH consumption were mainly male adults with opiate maintenance treatment reimbursements. MPH abusers had precarious living conditions. Half of them consumed MPH daily by intravenous route and reported amphetamine-like effects (cardiovascular events, weight loss, psychiatric adverse events). CONCLUSION: Given the increase of MPH use, it is important to warn the scientific community about possible MPH abuse, especially in individuals with drug dependence. This study has facilitated public health intervention and dissemination of information related to MPH abuse among health care professionals at local and national levels.

[Characteristics of subjects under opiate maintenance treatment in primary care using the OPEMA data 2013]. / Caractéristiques des sujets sous traitement de substitution vus en médecine générale d'après l'enquête nationale OPEMA 2013.

AIM: The objective of the study is to describe the characteristics of subjects under opiate maintenance treatment by general practionners (GPs). METHOD: Data analysis from observatory for pharmacodependency in ambulatory medicine survey (observation des pharmacodépendances en médecine ambulatoire [OPEMA]) program in 2013 of the subjects under high dosage buprenorphine (HDB) and methadone prescribed or obtained illegally reported by GPs in France. RESULTS: Survey concerned consumers with 862, 433 and 429 of high dosage buprenorphine and respectively methadone. The average age is 39±9 years respectively, and 36±8 years; over 70% are male; 55% have paid employment and over 30% report social benefits; 9% are in temporary housing. In both groups, more than 50% have anxiety and depression; over 25% have associated somatic disorders and digestive diseases, respiratory, pain is the most common. Almost 99% use oral route; nearly 100% have a daily consumption and about 20% of the alcohol concomitantly; 24% of HDB use benzodiazepines and 18% of the methadone group (P=0.06); 33% of the population using methadone consume illicit psychoactive substances and 21% for HDB population (P<0.0001), in particular cannabis (P<0.0001). Heroin and cocaine are also consumed. CONCLUSION: The population consuming opiate maintenance treatments shows social, somatic and psychiatric vulnerability. Misuse associated forms and consumption of other psychoactive substances and illegal drugs are observed. Despite the complexity of management of these patients, general practitioners have a major role to play.

Use of a multi-state model in a claims database: illustration with methadone.

PURPOSE: In pharmacoepidemiology, one of the main concerns is analysis of drug exposure time. However, in real-life settings, patient's behavior is complex and characterized by drug exposure dynamics. Multi-state models allow assessing the probabilities of various patterns, instead of just continuous use and/or discontinuation. The aim of this study was to illustrate with methadone, the use of multi-state model (MSM) in a large claims database. METHODS: This study is based on the French health insurance reimbursement database. Methadone exposure is defined using four states for each period of follow-up: syrup only, capsule only, syrup-capsule and no dispensing. The model considered 12 possible transitions (including reverse transitions) from one state to another. To describe these transitions a time-homogeneous Markov model was used. RESULTS: A total of 1265 methadone users were included. When patients belonged to the syrup-capsule state, they had a 61.8% chance of moving to capsules the following month and 20.9% of moving to syrup. The probability of moving from the syrup to the non-user state was 13.6% (11.7% from capsule state to non-user state). The average length of stay was 5.9 months (CI95%: [5.5-6.4]) in capsule state, 4.9 (CI95%: [4.6-5.2]) in syrup state and 5.9 (CI95%: [5.5-6.3]) in non user state. CONCLUSION: MSM provided a good description of methadone patterns of use. It outlined behaviors which have led to a rapid spread of capsule formulation among methadone users. Therefore, it illustrates the utility of MSM for modeling multiple sequences of drug use in a large claims database.

New methadone formulation in France: results from 5 years of utilization.

BACKGROUND: In France, methadone has historically been less accessible than buprenorphine. In 2008, a dry formulation (capsule) was introduced into the market, aimed in particular to improve methadone accessibility. OBJECTIVE: To describe the impact (prevalence of use, patient profiles and compliance with requirements) of the dry methadone formulation in France. METHOD: A retrospective cohort (from 2008 to 2012) was created from the data of the French General Health Insurance System which covers 80% of the French population. For each years, all subjects affiliated to this insurance system in southeast France (about 8.5 million inhabitants) with at least two reimbursements of methadone between 1st January and 31st December were selected. RESULTS: In 2012, the proportion of capsule users was almost the same as that of syrup users (40.0% versus 43.1%; p < 0.001). The rise in the number of methadone users has followed the rise in capsule users. Over the study period, the proportion of patients using benzodiazepines or antidepressants was 6-9% (p < 0.001) higher for capsule users than for syrup users. On average over the study period, 18% of subjects had at least one concurrent issue of the two forms. CONCLUSION: The study has shown the rapid spread of the capsule formulation among methadone users. This may suggest that the capsule is well accepted by patients and the medical community. However, the monitoring of methadone-related deaths should continue because of the pharmacodynamic properties of methadone and the context of relaxed regulations concerning access to methadone maintenance treatement (MMT).

[Use of generic high dose buprenorphine (HDB): about a qualitative survey]. / Utilisation des génériques de la buprénorphine haut dosage (BHD) : évaluation qualitative.

OBJECTIVE: Analyze the factors of the low use of buprenorphine (HDB) generic in France, studying heath care professionals' and patients' attitudes towards this substitution. METHODS: A qualitative method based on the realization of semi-directive conversations was held. 14 health care professionals and 10 patients were interviewed. RESULTS: Generic drug of HDB presents undeniable economic benefits and galenic advantages. Physicians suggest this generic at first prescription or with stabilized patients. The switch princeps/generic is more difficult with patients who diverted the product, or when they are accustomed to the brand product. Some patients prefer brand product because of its galenics, or of the perception of greater efficiency. CONCLUSION: There is a certain distrust compared to this generic. It is necessary to properly support the prescription of this drug in order to help health care professionals and patients (therapeutic education, medical information, creating a climate of trust).

[Antipsychotic use in the cohort PACA-Alz in patients with Alzheimer's disease and other dementia in 2010]. / Consommation d'antipsychotiques chez les sujets atteints de maladie d'Alzheimer et maladies apparentées de la cohorte PACA-Alz 2010.

AIM: The aim of the study was to identify and to characterize patients with Alzheimer's disease or related dementia describing antipsychotics and other psychotropic expositions. METHODS: The study was performed, in 2010, based on Provence-Alpes-Côte d'Azur region (PACA)-Corse Alz cohort included patients with dementia, with chronic condition 'Alzheimer disease or related disease' and/or had at least one delivery of Alzheimer's specific treatment, registered in the General Health Care System. Psychotropic drugs were extracted according anatomical, therapeutical and chemical code. Chronic exposure defined as more than 3 consecutive deliveries. RESULTS: Among 34 696 included patients, 26.9% were men and 68.8% were 80 years old and more. Among them, 26% received at least one antipsychotic medication, with a chronic exposition estimated around 61.3%. Antidepressant and anxiolytic were consumed respectively by 47% and 45.3% of patients. Risperidone was the most used antipsychotic (11.2%). The Health care use (hospitalizations, nurses and physicians visits) was significantly higher among patients with antipsychotics. CONCLUSION: Antipsychotics use in patients with dementia remains high. The follow up of this regional cohort would be helpful to identify the impact of guidelines on the prescription and the care of patients with dementia.

Misuse of buprenorphine maintenance treatment since introduction of its generic forms: OPPIDUM survey.

PURPOSE: The purpose of the study was to compare, using data from Observation of Illicit Psychotropic Substances or Non-medical Used Medications (OPPIDUM) surveys, first, the profile of buprenorphine users and their modalities of buprenorphine use from 2006 to 2008 and, second, two subgroups: brand-name and generic buprenorphine users in 2008. METHODS: OPPIDUM is an annual, nationwide, multicentric, cross-sectional survey, including buprenorphine users followed in specialised centres dedicated to drug dependence. The evolution of the profile during three consecutive years (2006, 2007 and 2008) was analysed using Cochran-Armitage test for trend. A multivariate regression analysis was used to identify the factors associated with the use of generic compared with brand-name buprenorphine in 2008. RESULTS: In OPPIDUM, 1311 individuals used buprenorphine in 2006, 1688 in 2007 and 1696 in 2008. The proportion of users of generic buprenorphine increased from 4.2% in 2006 to 31.7% in 2008. From 2006 to 2008, a decrease in intravenous use and higher than recommended dosage, with an increase in occupation, have been observed. According to the multivariate analysis, factors associated with being generic buprenorphine user compared with brand-name buprenorphine user in 2008 were younger age, more education, absence of use of alcohol with buprenorphine, absence of heroin and/or cocaine use and absence of nasal route for buprenorphine. CONCLUSION: Three years after the launch of the buprenorphine generic, the health professionals' and buprenorphine users' perception of generic can still change. Additionally, the long-term impact of generic medications with abuse potential has not yet been studied. Thus, continued monitoring of buprenorphine is needed.

[General Practitioners' Contribution to Dependence Assessment: the OPEMA Programme]. / Observation des pharmacodépendances en médecine ambulatoire : le programme OPEMA.

Aim. This study presents the OPEMA (Observation des pharmacodépendances en médecine ambulatoire) programme and the main results of its last annual survey (november 2010). Method. Collected data concern mainly subjects' sociodemographic situation, their state of health and their current consumption of psychoactive substance. Results. In 2010, 1394 subjects have been included, describing 2 450 consumptions of psychoactive susbtance. Their mean age is 38,2±12,7 years. Eighty-six per cent have a stable accomodation and 52% are in employment. Fifty-six percent of included subjects present a psychiatric comorbidity. Among included subjects, HIV and HVC prevalence is respectively 3% and 20%. Fourty-five percent of included subjects have been using intraveinous route, 6% of whom using it currently. Eighty-two percent consume opiate maintenance treatment and 29% benzodiazepines. Conclusion. The OPEMA programme supplement the french pharmacodependence assessment system with collecting data from general practitioners, and promotes a global knowledge of dependent subjects' state of health.

[Harm reduction centers ("CAARUD"): privileged places for warning signal detection in addictovigilance]. / Les CAARUD, lieux privilégiés d'émergence de signaux pour l'addictovigilance.

This study aims to describe profile and consumptions of subjects suffering a substance use disorder recruited in harm reduction centers (HRC, French "CAARUD", 156 included subjects in 7 centers) for the 2010 OPPIDUM survey, performed by the French CEIP-Addictovigilance network, in order to compare them to subjects included in ambulatory care centers (ACC, French "CSAPA", 3549 subjects included in 80 centers). Subjects recruited in HRC are younger and more precarious; they consume more illicit drugs, and prescription drugs known to be diverted (methylphenidate, morphine, ketamine,…). They consume less opiate maintenance treatment, antidepressants and psychotics. Obtaining and consumption modalities are also different (more illegal acquisitions for prescription drugs, more intravenous route use and less nasal route use in HRC). HRC are privileged places for watching substance use disorder (abuse, dependence) or prescription drugs diversions, and for early warning signal detection in addictovigilance.

Ascorbic acid treatment corrects the phenotype of a mouse model of Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease (CMT) is the most common hereditary peripheral neuropathy, affecting 1 in 2,500 people. The only treatment currently available is rehabilitation or corrective surgery. The most frequent form of the disease, CMT-1A, involves abnormal myelination of the peripheral nerves. Here we used a mouse model of CMT-1A to test the ability of ascorbic acid, a known promoter of myelination, to correct the CMT-1A phenotype. Ascorbic acid treatment resulted in substantial amelioration of the CMT-1A phenotype, and reduced the expression of PMP22 to a level below what is necessary to induce the disease phenotype. As ascorbic acid has already been approved by the FDA for other clinical indications, it offers an immediate therapeutic possibility for patients with the disease.

Evolution of opioids reimbursement since 2004 from the National Database of the General Health Insurance System.

OBJECTIVE: This study aims at evaluating trends in the consumption of opioids over the last years to assess the impact of public health measures on the management of pain and opiate addiction in France. METHODS: The evolution of opioids consumption was analysed by using the national database of the General Health Insurance System in France between 2004 and 2008. RESULTS: During the study period, the reimbursed quantities of opioids used for pain management have increased by 13%, except for dextropropoxyphene that has decreased by 9%. The reimbursed quantities of opioids used for substitution maintenance treatments for opioid dependence have increased by 34%, with a 116% increase for methadone. CONCLUSION: This study suggests that consumption of opioids is globally increasing in France and reveals discrepancies concerning the evolution of the different drugs. It allows to analyse switches of consumption between different opioids and constitutes the first step for further studies targetting signals of diversion and abuse.

[Post-marketing surveillance systems for psychoactive prescription drug abuse]. / Les systèmes d'évaluation de l'abus et de la dépendance des médicaments psychoactifs.

Drugs affecting the central nervous system form a unique group of products for surveillance because they could be misused, abused or diverted. Considering the characteristics of this behaviour that is often concealed, specific post-marketing surveillance systems have been developed to monitor abuse of prescription drugs in some countries. The purpose of this review is to list and to describe post-marketing surveillance systems, according their methodology, in France and in foreign countries. These programs are based on adverse effect notifications, medical or legal consequences of abuse, general or specific population-based survey, professional networks or medication databases. Some programs use simultaneously several information sources. In conclusion, the multifaceted nature, the diversity and the inventiveness of post-marketing surveillance systems reflects the complexity of the abuse issue.

Impact of a prescription monitoring program on doctor-shopping for high dosage buprenorphine.

PURPOSE: Doctor-shopping (simultaneous use of several physicians by a patient) is one of the most frequent ways of diversion for prescription drugs. A specific method was used to assess the evolution of doctor-shopping for High Dosage Buprenorphine (HDB) in a French region from 2000 to 2005 and the impact of a prescription monitoring program for HDB implemented in 2004. METHODS: Data from eight periods (semesters of years 2000, 2002, 2004, and 2005) were extracted from a prescription database. Three quantities (the delivered, the prescribed, and the doctor-shopping quantity) were computed for each patient. The total doctor-shopping quantity and the doctor-shopping ratio (percentage of buprenorphine obtained through doctor-shopping) were used to evaluate the diversion of HDB among the population. The total prescribed quantity and the number of patients treated regularly were used as indicators of the access to treatment. RESULTS: The doctor-shopping ratio increased from 1st semester 2000 to 1st semester 2004 (from 14.9 to 21.7%) and then decreased to 16.9% in 2nd semester 2005. The total doctor-shopping quantity followed the same evolution. The number of patients treated remained stable from 1st semester 2000 to 2nd semester 2005. The prescribed quantity increased from 1st semester 2000 to 2nd semester 2002, decreased in 1st semester 2004 (4163 g) and then remained stable. CONCLUSIONS: After a four-year increase of the diversion through doctor-shopping for buprenorphine the beginning of the prescription monitoring program was concomitant with a marked decrease of doctor-shopping indicators without notable impact on the access to treatment.

[Not Available]. / 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'Évaluation 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.

[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.

[Psychotropic drug addiction: consumption study of specific population by the survey OPPIDUM 2004 from the CEIP network]. / Abus et dépendances aux produits psychoactifs: étude de consommations à travers l'enquête OPPIDUM 2004 du réseau des CEIP.

The purpose of this study was to identify the characteristics of psychotropic drug use and abuse by drugs addicts. The results are based on data from OPPIDUM (Observation des Produits Psychotropes Illicites ou Détournés de leur Utilisation Médicamenteuse), an annual survey primarily concerned with the consumption of licit and illicit drugs. The study involved 3373 patients recruited during october 2004 from 109 health centers. The main trends observed were an increasing interest for opioid maintenance treatment by methadone versus buprenorphine high dosage (patients treated by methadone are mainly represented for the first year of the OPPIDUM program), some changes in illicit drugs uses (increase in sniff and decrease in intravenous injection) and changes in the grading of the most consumpted benzodiazepines (decrease in flunitrazepam consumption and increase in clonazepam consumption). Main warnings concern the buprenorphine illicit use leading to firstly dependence and the illicit use of some benzodiazepines, especially clonazepam.

[Not Available]. / Abus et dépendances aux produits psychoactifs : étude de consommations à travers l'enquête OPPIDUM 2004 du réseau des CEIP.

The purpose of this study was to identify the characteristics of psychotropic drug use and abuse by drugs addicts. The results are based on data from OPPIDUM (Observation des Produits Psychotropes Illicites ou Détournés de leur Utilisation Médicamenteuse), an annual survey primarily concerned with the consumption of licit and illicit drugs. The study involved 3373 patients recruited during october 2004 from 109 health centers. The main trends observed were an increasing interest for opioid maintenance treatment by methadone versus buprenorphine high dosage (patients treated by methadone are mainly represented for the first year of the OPPIDUM program), some changes in illicit drugs uses (increase in sniff and decrease in intravenous injection) and changes in the grading of the most consumpted benzodiazepines (decrease in flunitrazepam consumption and increase in clonazepam consumption). Main warnings concern the buprenorphine illicit use leading to firstly dependence and the illicit use of some benzodiazepines, especially clonazepam.

[Misuse of clonazepam (Rivotril): recent trends]. / Détournement d'usage du clonazépam (Rivotril): tendances récentes.

Recent observations suggest the existence of clonazepam abuse. In order to determine the importance of this practice and the characteristics of these consumers, a study has been carried out, based on data from the Provence-Alpes-Côte-d'Azur and Corsica health reimbursement system. Individuals from these regions affiliated to the French health reimbursement system, who have had a prescription of clonazepam reimbursed between January 1, 2001 and February 15, 2001, have been selected. The deliveries have been monitored over a 9 month-period. 9381 subjects have been selected. A sub-group of 1.5 per cent subjects with a deviant behaviour has been identified by factorial analysis and has been compared to the sub-group without deviant behaviour. The subjects with deviant behaviour are younger and mostly male. The dosage of clonazepam is higher (10.8 mg per day versus 2.1 mg per day) with a significantly higher proportion of benzodiazepine and high-dose buprenorphine. The number of deliveries is higher (19.4 versus 5.9) as well as the number of different physicians (4.5 versus 1.5) and pharmacies (5.9 versus 1.3). This study provides some arguments in favor of the potential of abuse and dependence of clonazepam and the necessity to reinforce its monitoring. This information requires to be relayed to health professionals.

Night shift decreases cognitive performance of ICU physicians.

BACKGROUND: The relationship between tiredness and the risk of medical errors is now commonly accepted. The main objective of this study was to assess the impact of an intensive care unit (ICU) night shift on the cognitive performance of a group of intensivists. The influence of professional experience and the amount of sleep on cognitive performance was also investigated. METHODS: A total of 51 intensivists from three ICUs (24 seniors and 27 residents) were included. The study participants were evaluated after a night of rest and after a night shift according to a randomized order. Four cognitive skills were tested according to the Wechsler Adult Intelligence Scale and the Wisconsin Card Sorting Test. RESULTS: All cognitive abilities worsened after a night shift: working memory capacity (11.3 ± 0.3 vs. 9.4 ± 0.3; p < 0.001), speed of processing information (13.5 ± 0.4 vs. 10.9 ± 0.3; p < 0.001), perceptual reasoning (10.6 ± 0.3 vs. 9.3 ± 0.3; p < 0.002), and cognitive flexibility (41.2 ± 1.2 vs. 44.2 ± 1.3; p = 0.063). There was no significant difference in terms of level of cognitive impairment between the residents and ICU physicians. Only cognitive flexibility appeared to be restored after 2 h of sleep. The other three cognitive skills were altered, regardless of the amount of sleep during the night shift. CONCLUSIONS: The cognitive abilities of intensivists were significantly altered following a night shift in the ICU, regardless of either the amount of professional experience or the duration of sleep during the shift. The consequences for patients' safety and physicians' health should be further evaluated.