A European community pharmacy-based survey to investigate patterns of prescription fraud through identification of falsified prescriptions.

AIM: To identify prescription drugs involved in falsified prescriptions in community pharmacies in 6 European countries. METHODS: A cross-sectional survey among 2,105 community pharmacies in Belgium, France, Italy, the Netherlands, Spain and Sweden was carried out to collect all suspect prescription forms. For each reported drug, the number of reported falsified prescriptions per thousand inhabitants was estimated. A falsification ratio was calculated by dividing the number of reports by the number of defined daily doses per 1,000 inhabitants per day for this drug, computed from national sale or reimbursement data. RESULTS: On 862 prescription forms, benzodiazepines (zolpidem, bromazepam, alprazolam), buprenorphine (as an opioid maintenance drug) and tramadol were the most frequently reported. Depending on their level of use in each country, methylphenidate, morphine and flunitrazepam presented the highest falsification ratios, particularly in Spain, Belgium and France. CONCLUSIONS: Stimulants, opioids and some benzodiazepines were the most frequently reported drugs in this survey on falsified prescriptions, but differences between countries were observed.

[Could we improve notification of adverse drugs reactions in hospital? Assessment of 5 years of network PharmacoMIP's activities]. / Peut-on améliorer la notification des effets indésirables dans les établissements hospitaliers ? Bilan de 5 ans d'activité du réseau PharmacoMIP.

BACKGROUND: Spontaneous reporting of adverse drug reactions (ADR) is fundamental to drug safety surveillance (pharmacovigilance) and assessment of benefit/risk ratio. However, under-reporting remains the limit of the system. OBJECTIVE: The aim of this study was to assess the effect of regular visits of an Assistant in Clinical Research (CRA) on the improvement of ADR reporting in non-university hospitals. METHODS: We set up an ADR report collecting system that involved regular visits in non-university hospitals, We began the visits in 2006 in 2 areas (Haute Garonne and Gers), extended to 4 other areas in 2009. We compared the reporting rate (number of reports/number of beds) of total ADRs reported by non-university hospitals in these areas before (one year) and after the start of CRA visits. RESULTS: A total 2831 of reports were collected by the CRA: 40% were "serious" including two deaths. The results suggest an increase of 100% of the rate of reporting of ADRs. CONCLUSION: This study shows that regular visits increases the number of ADRs reported by non-university hospitals. Further assessment of this procedure is necessary for long term evaluation of its effectiveness.

Lacosamide-induced personality changes: An unexpected adverse effect.

OBJECTIVES: To describe an 'unexpected' case of abrupt personality following the introduction of lacosamide. METHODS: A description of an 82-year-old male receiving neurological follow-up since 2010 due to epilepsy secondary to haemorrhagic stroke. We report a case of abrupt personality change in an 82-year-old male following the introduction of lacosamide with a return to the previous state after its discontinuation. We explored possible mechanisms and pharmacokinetic concerns explaining this personality change. RESULTS: In fact, a few days after introducing lacosamide, the patient was described as 'gentle', 'calm' and apologetic for his past aggressions against his family and caregivers which was in complete contrast to his usual personality. There was also marked insistence and the use of sexualised language towards women in his close circle, especially his home nurses. In view of his insistent behaviour towards his nurses and unusual sexualised language, lacosamide was withdrawn. A few days later, the patient displayed his usual, vindictive, aggressive and forceful character. He no longer made any sexualised remarks to his home nurses. CONCLUSION: To our knowledge, this is the first case of a sudden behavioural and personality change reported by family, friends and carers following the introduction of lacosamide.

Coxibs: evolution of prescription's behaviour in France.

The aim of the present study was, first to characterize profiles of coxibs' prescribers [general practitioners (GPs) and rheumatologists] in 2002 in France and, secondly, to identify factors associated with modification of this profile 1 year later. All GPs and rheumatologists from Midi-Pyrenees, Aquitaine, Languedoc-Roussillon and Pays de Loire areas (South of France: 11 050 000 inhabitants) were included in the study. For each practitioner, we used data concerning all non-steroidal anti-inflammatory drugs (NSAIDs) including coxibs reimbursed during period 1 (P1; January-March 2002) and period 2 (P2; January-March 2003). The ratio between the number of coxibs' prescriptions and the total number of NSAIDs' prescriptions (including coxibs) was used to define the two profiles of prescribers, one with a low level of coxibs' prescriptions and another one with a high level of coxibs' prescriptions. Characteristics of practitioners and characteristics of their practices were compared according to this profile. In the second step, we investigated the characteristics (of practitioners and practices) associated with an increase in the level of coxibs' prescriptions in P2 for practitioners with a low level of coxibs' prescriptions in P1. Results are expressed as odds ratio with their 95% confidence intervals. A positive statistical link was found between a high level of coxibs' prescriptions, the speciality of rheumatologist or extra costs for consultation. In contrast, a negative association was observed with female gender or age below 44 years. No relationship was found with the status of referent. Concerning practices' characteristics of practitioners, there was a positive statistical link between a high ratio of coxibs' prescriptions and high co-prescriptions of gastroprotective agents and a negative association with a high number of acts, a high proportion of patients with chronic disabling diseases (CDD) or a high number of patients between 15 and 64 years. There was no statistical link with proportion of patients covered by Universal Medical Coverage (UMC) or aged more than 65 years. Among the factors involved in the increase in the ratio (between P1 and P2), no relationship was found with practitioners' characteristics. In contrast, some factors related to practices (level of gastroprotective co-prescriptions, number of acts, number of CDD patients) were related to a change in coxibs' prescriptions between P1 and P2. This study allowed to discuss some relationships between coxibs' prescription and practitioners' (age, gender, medical speciality or extra costs for consultation) or practices' (level of medical practice, patients' age, number of CDD patients or level of gastroprotective prescriptions) characteristics. In contrast, some other factors like the referent status or the number of patients with UMC are not related. Physicians, initially low prescribers of coxibs and increasing their coxibs' prescriptions during the period of our study, were those with a high level of gastroprotective prescriptions, a low number of acts or a small proportion of CDD patients.

[Drugs, Parkinson's disease and parkinsonian syndroms: recent advances in pharmacovigilance]. / Medicaments, maladie de Parkinson et syndromes parkinsoniens: actualités de pharmacovigilance.

This paper reviews recent data on the pharmacovigilance of antiparkinsonian drugs and drugs inducing parkinsonian syndroms. Sudden sleep attacks were first described in 1999 with dopamine agonists. In fact, they can be induced by all the dopaminergic antiparkinsonian drugs. Favorising factors are duration of the disease, dose of dopaminergic drugs, daytime somnolence or dysautonomia. This adverse drug reaction can be serious leading, for example, to road accidents. Cardiac valvulopathies were more recently (end of 2002) described with pergolide. Thus, this dopamine agonist should now be prescribed as a last choice among dopamine agonists. Dopamine drugs (levodopa as well as dopamine agonists) can induce hypersexual behaviours or pathological gambling. Among the long list of drugs inducing parkinsonian syndroms, recent data suggest the involvement of serotoninergic antidepressants, valproic acid and trimetazidine. Finally, these data on pharmacovigilance allow to precise the physiological role of dopamine: beside its motor and psychic effects, dopamine is also involved in the sleep-arousal control. It is also an important mediator for pleasure, hedonic regulations and sexual behaviour. This review also underlines the major role of spontaneous reports to the pharmacovigilance systems to identify new adverse drug reactions.

[Meningococcal serogroup C vaccine: a pharmacovigilance point of view]. / A propos d'une campagne de vaccination contre la méningite C dans les Hautes-Pyrénées: réflexions de pharmacovigilance.

BACKGROUND: In October 2002, the Midi-Pyrenees centre of pharmacovigilance (Southwest of France) was in charge of an extensive pharmacovigilance follow-up of a campaign of meningococcal serogroup C vaccination performed in the Hautes-Pyrénées area. OBJECTIVE: The purpose of this study was to evaluate the incidence, nature and seriousness of adverse drug reactions (ADRs) occurring during the 15 days after vaccination. METHODS: 'Immediate' and 'late' ADRs were recorded. RESULTS: Local immediate ADRs were mainly nonserious local or inflammatory responses with a favourable evolution. General immediate ADRs occurred in 198 subjects and were principally neurological in nature (54%, mainly headache). Moreover, 1529 subjects suffered from general late ADRs (i.e. general health status or neurological [headache] ADRs [41%]). The incidence of ADRs leading to hospitalisation or medical consultation was defined as 'very rare' (0.1% led to consultation and 0.03% to hospitalisation). CONCLUSION: These results underline that most of the ADRs occurring during the 15 days after meningococcal serogroup C vaccination were benign. This study shows that the methods used in France for pharmacovigilance studies of drugs can also be used for vaccines, especially for an intensive and prospective survey. Further pharmacoepidemiological studies could be used after the pharmacovigilance survey to investigate the benefit/risk ratio in large populations.

Risk of serious extrapyramidal symptoms in patients with Parkinson's disease receiving antidepressant drugs: a pharmacoepidemiologic study comparing serotonin reuptake inhibitors and other antidepressant drugs.

To compare the risk of occurrence of "serious" extrapyramidal symptoms (EPS) between selective serotonin reuptake inhibitors and other antidepressant drugs in patients with Parkinson's disease (PD), the authors performed a retrospective study using the French Pharmacovigilance Database (i.e., the database recording all serious adverse drug reactions reported in France by physicians to the National French Pharmacovigilance Network). Patients with PD were identified from the case reports including at least one antiparkinsonian drug (except anticholinergics). The authors studied patients with PD exposed to at least one antidepressant (classified as imipraminics, selective serotonin reuptake inhibitors, or "other") drug. EPS were defined as aggravation of the parkinsonian symptoms. Of the76,640 case reports registered in the database between January 1, 1995, and December 31, 2000, 916 were identified as patients treated with at least one antiparkinsonian drug, including 199 treated with antidepressant drugs. Among them the authors found nine case reports of EPS (i.e., 4.5% of the patients with PD treated with at least one antidepressant). The odds ratio for EPS was 2.18 (0.47-11.35) for selective serotonin reuptake inhibitors, 1.17 (0.22-5.50) for imipraminics, and 0.74 (0.10-4.06) for other antidepressants. This study failed to find any significant difference in the occurrence of serious EPS according to the different classes of antidepressant drugs in patients with PD treated with dopaminergic antiparkinsonian drugs.

[Coxibs, which real therapeutic advance?: Recent pharmacoepidemiological data]. / Coxibs, quel réel progrès thérapeutique?: données pharmacoépidémiologiques récentes.

Therapeutic advance is defined by an improvement in effectiveness, safety and/or convenience. In this article, these three criteria were applied to currently marketed coxibs (celecoxib, rofecoxib), using data from clinical trials and pharmacoepidemiological studies. Risk of adverse drug reactions to coxibs, as evaluated by clinical trials, differs from that observed in real medical practice. Rofecoxib and celecoxib exhibit the same profile of adverse drug reactions as the other classical nonsteroidal anti-inflammatory drugs. Coxibs are currently prescribed and too often used outside the studied and approved indications, which clearly increases their cost (already high for society). Currently marketed coxibs do not appear to meet the previously defined criteria for therapeutic advance.

Improving adverse drug reaction reporting in hospitals: results of the French Pharmacovigilance in Midi-Pyrénées region (PharmacoMIP) network 2-year pilot study.

BACKGROUND: Spontaneous reporting of adverse drug reactions (ADRs) is fundamental to drug safety surveillance (pharmacovigilance); however, substantial under-reporting exists and is the main limitation of the system. Several factors could favour under-reporting. OBJECTIVE: The aim of this pilot study was to assess the effect of regular visits of a Clinical Research Assistant (CRA) on the improvement of ADR reporting in non-university hospitals. METHODS: We set up an ADR report collecting system that involved regular visits by a CRA to non-university hospitals, which was similar to a system that already existed in university hospitals in Toulouse, France. Two areas in our region were chosen: Haute Garonne and Gers. We compared firstly the reporting rate (number of reports/number of beds) of total ADRs (i.e. spontaneously reported ADRs plus solicited ADRs collected by the CRA) and secondly, the percentage of serious ADRs reported by non-university hospitals in these two areas, in 2005 (the year prior to CRA visits) and after the start of CRA visits (2006 until the end of December 2008). We also compared the reporting rate of total ADRs in Haute Garonne and Gers non-university hospitals with those reported during the same period with a control group (the Ariège area, which has a similar number of beds to Gers and that was not visited by the CRA). The characteristics of ADRs collected by the CRA were also described. RESULTS: A total of 687 reports were collected by the CRA: 40% were classified as serious, including two deaths. The number of ADRs and the reporting rate increased significantly between 2005 and 2008 in non-university hospitals of Haute-Garonne and Gers, but not in Ariège. In Gers, the reporting rate was 3% in 2005 and 25% in 2008. In Haute-Garonne, the reporting rate was 11% in 2005 and 40% in 2008. The difference between the number of spontaneous and solicited reports also increased. CONCLUSIONS: This study shows that regular visits by a CRA increases the number of ADRs collected by a Regional Pharmacovigilance Centre. Another interesting consequence was the rise in spontaneous reporting by healthcare professionals following the set-up of this system. Further assessment of this procedure is necessary for the long-term evaluation of its effectiveness.