[Use and misuse of benzodiazepines out of France]. / Usages et mésusages de benzodiazépines hors France.

Among 8 countries included in the report of ANSM, France is second behind Spain, when defined daily doses (DDD) are considered. Few studies, recent and based on representative samples of population, investigated the use of benzodiazepines in other countries and data are limited to compare France and other countries. In most countries, the use of benzodiazepines increases with age and is more frequent in women than in men. Variations of benzodiazepines use that were observed in other countries are similar to those observed in France, with a slight decrease but persistent high levels of use. In most countries, the long-term use of benzodiazepines is stable over time even though simple use decreases.

[Exception drugs status: specific characteristics and the role in the proper use of drugs]. / Les médicaments d'exception: spécificité et rôle dans le cadre du bon usage des médicaments.

BACKGROUND: In 1994, the French health care system established a special status for certain costly drugs reimbursed for ambulatory use: exception drugs. Drugs with this status are reimbursed only when prescribed for specified indications. The purpose of this study was to identify the specific characteristics of drugs with the exception status, and to understand the role of this status in proper use of drugs. METHODS: Drugs included in the study were analyzed using three types of data: administrative, clinical and economic. RESULTS: For most of the drugs, prescription was restrictive. For five of them, the sickness fund accepted reimbursements for fewer indications than mentioned in the marketing authorisation. For the majority, reimbursement was 100%. The exception drugs were indicated for the treatment of 15 diseases. Eighty percent of expenditures for exception drugs concerned ten drugs. CONCLUSION: The characteristics considered in the study did not enable a specific description of the inherent features of exception drugs. This special status was established for the purpose of economic efficiency. Currently, its role in ensuring proper use of drugs is questionable.

Characteristics associated with use of homeopathic drugs for psychiatric symptoms in the general population.

OBJECTIVE: To explore which patient characteristics are associated in naturalistic conditions with the lifetime use of homeopathic treatment for psychiatric symptoms. METHOD: Lifetime use of psychotropic treatment was explored in a sample of 36,785 persons, participating in the Mental Health Survey in the General Population. Characteristics associated with use of homeopathic treatments, associated or not with conventional psychotropic drugs, were explored using multivariate analyses. RESULTS: Use of homeopathic treatment for psychiatric symptoms was reported by 1.3% of persons. Younger age, female gender and high educational level were associated with use of homeopathy. Half of homeopathy users presented at least one Mini International Neuropsychiatric Interview (MINI) diagnosis, most frequently anxiety disorders. Their diagnostic profile was similar to that of persons reporting use of anxiolytics or hypnotics. Compared to persons with no lifetime use of psychotropic drugs, persons using homeopathy were more likely to present with a diagnosis of mood disorder or anxiety disorder. Compared to those using conventional psychotropic drugs, they presented less frequently with psychiatric disorders, with the exception of anxiety disorders. CONCLUSION: Homeopathic treatment for psychiatric symptoms appears to be used mainly to reduce anxiety symptoms in the general population.

Pharmacovigilance data mining with methods based on false discovery rates: a comparative simulation study.

The early detection of adverse reactions caused by drugs that are already on the market is the prime concern of pharmacovigilance efforts; the methods in use for postmarketing surveillance are aimed at detecting signals pointing to potential safety concerns, on the basis of reports from health-care providers and from information available in various databases. Signal detection methods based on the estimation of false discovery rate (FDR) have recently been proposed. They address the limitation of arbitrary detection thresholds of the automatic methods in current use, including those last updated by the US Food and Drug Administration and the World Health Organization's Uppsala Monitoring Centre. We used two simulation procedures to compare the false-positive performances for three current methods: the reporting odds ratio (ROR), the information component (IC), the gamma Poisson shrinkage (GPS), and also for two FDR-based methods derived from the GPS model and Fisher's test. Large differences in FDR rates were associated with the signal-detection methods currently in use. These differences ranged from 0.01 to 12% in an analysis that was restricted to signals with at least three reports. The numbers of signals generated were also highly variable. Among fixed-size lists of signals, the FDR was lowered when the FDR-based approaches were used. Overall, the outcomes in both simulation studies suggest that improvement in effectiveness can be expected from use of the FDR-based GPS method.

When patients report diseases that prescribers seem unaware of: discordance between patient and physician reporting of risk-related previous history in NSAID users from the CADEUS study.

Prescribers are often unaware of possibly dangerous previous medical histories (PMHs) of their patients. Data from a study of nonsteroidal anti-inflammatory drug (NSAID) users served to identify factors associated with this lack of awareness. In this study, we analyzed the factors that may have led prescribers to report the absence of some PMHs that the patients reported as being present. Of 26,618 patients prescribed an NSAID, 469 (1.7%) reported a PMH of unstable angina, 648 (2.4%) reported heart failure, 2,244 (8.4%) reported gastric or duodenal ulcer, 489 (1.8%) reported upper gastrointestinal tract bleeding (UGIB), 5,343 (20.0%) reported gastroesophageal reflux disease (GERD), and 7,832 (29.4%) reported dyspepsia. Between 64 (GERD) and 92% (UGIB) of these patient-reported PMHs were absent in the corresponding prescribers' reports. This discordance was associated with the following factors: patients of younger age, female patients, less frequent patient-prescriber contact, prescription of NSAID by a specialist, no recent specialist consultation, hospitalization or surgery related to the PMH, and no dispensation of proton-pump inhibitors (PPIs) for digestive disorder-related PMHs. The study showed that a substantial proportion of prescribers seemed unaware of the presence of risk-related PMHs that the patient reported when asked.

Are generic drugs really inferior medicines?

In this issue Gagne et al. report an elegant case-crossover study of seizures in patients on antiepileptic drugs. They found that a dispensation episode approximately triples the risk of having a seizure within 21 days, but the risk is not statistically different whether the dispensation was of the same brand-name or generic drug as previously used or a switch from brand-name to a generic or from a generic to a brand name. The cause of the seizure might be a delay in taking medication or late redispensation, among others, but apparently the nature of the product dispensed is not relevant in this study; this may alleviate some of the concerns about generic drugs and epilepsy.

Antipsychotic use patterns in persons initially treated with mood stabilizers: a naturalistic study.

INTRODUCTION: Little information is available on the pattern of use of antipsychotics in naturalistic conditions in persons initially treated with "conventional" mood stabilizers (lithium and anticonvulsants). METHODS: Data on community prescriptions were extracted from the 2004-2006 claims database of a French health care insurance fund for self-employed workers. Patients included were those continuously exposed to mood stabilizers without concomitant dispensing of antipsychotics over at least a 3-month period. RESULTS: Of the 3 958 persons included, 17.8% had at least one addition/switch to antipsychotics over the follow-up period. The most frequent pattern was addition of second-generation antipsychotics (SGAPs) (41%) or first-generation antipsychotics (FGAPs) (23%) to the mood stabilizer for a relatively short period of time. A switch from mood stabilizer to SGAPs (20%) or FGAPs (15%) was less frequent. Mood stabilizers alone were prescribed again in most patients with the addition of FGAPs (72%) or SGAPs (61%) to mood stabilizers. Conversely, the majority of patients with a switch from mood stabilizers to FGAPs (55%) or SGAPs (58%) went on with these latter treatments over the follow-up. CONCLUSIONS: SGAPs are preferentially prescribed in combination with mood stabilizers and their pattern of use is similar to that of FGAPs.

Antipsychotic prescribing trends: a review of pharmaco-epidemiological studies.

OBJECTIVE: To review findings from pharmaco-epidemiological studies exploring antipsychotic (AP) drugs prescribing trends. METHOD: We retrieved original studies that explored AP prescribing trends in general population samples since 2000. For each study, we extracted information on sampling method, period, assessment of AP use and corresponding estimates (incidence rates, prevalence rates, pharmacy sales, prescription data) and diagnostic assessment. RESULTS: Nearly all studies meeting the inclusion criteria (n = 17) showed an increase in AP prescriptions, mainly because of a dramatic rise in second-generation antipsychotics (SGAP) prescriptions. APs are often prescribed for non-psychotic disorders in adults as well as in children and adolescents. CONCLUSION: Considering the growing number of persons from the general population exposed to APs, population studies assessing the risk/benefit ratio of SGAP use in disorders other than psychosis are necessary, particularly in children and adolescents.

Impact of antidepressants on the risk of suicide in patients with depression in real-life conditions: a decision analysis model.

BACKGROUND: The impact of antidepressant drug treatment (ADT) on the risk of suicide is uncertain. The aim of this study was to determine in a real-life setting whether ADT is associated with an increased or a reduced risk of suicide compared to absence of ADT (no-ADT) in patients with depression. METHOD: A decision analysis method was used to estimate the number of suicides prevented or induced by ADT in children and adolescents (10-19 years old), adults (20-64 years old) and the elderly (65 years) diagnosed with major depression. The impact of gender and parasuicide history on the findings was explored within each age group. Sensitivity analyses were used to assess the robustness of the models. RESULTS: Prescribing ADT to all patients diagnosed with depression would prevent more than one out of three suicide deaths compared to the no-ADT strategy, irrespective of age, gender or parasuicide history. Sensitivity analyses showed that persistence in taking ADT would be the main characteristic influencing the effectiveness of ADT on suicide risk. CONCLUSIONS: Public health decisions that contribute directly or indirectly to reducing the number of patients with depression who are effectively administered ADT may paradoxically induce a rise in the number of suicides.

[Psychotropic drug use and correspondence with psychiatric diagnoses in the mental health in the general population survey]. / Usage et congruence diagnostique des traitements à visée psychotrope: résultats de l'enquête santé mentale en population générale en France métropolitaine.

OBJECTIVES: The aims of this study were to assess the lifetime prevalence rate of psychotropic drugs use in the French general population and the correspondence between psychotropic drug use and psychiatric diagnoses. METHODS: Data were derived from the multicentric survey mental health in the general population, carried out in 47 French public sites between 1999 and 2003. A face-to-face questionnaire was used to interview a representative sample of French metropolitan subjects, aged 18 and over, noninstitutionalized or homeless. These subjects were recruited using quota sampling for age, sex, socioprofessional and education levels, according to data from the 1999 national French population census. Lifetime use of psychotropic drugs was explored by an open question. Psychiatric diagnoses were identified using the mini international neuropsychiatric interview (MINI). A national database was then constituted by pooling data from all sites, weighted for age, sex, level of education, socioprofessional level and work status, to be representative of the French general population. RESULTS: Of the 36785 individuals included in this study, more than one out of three subjects reported having used at least one psychotropic drug during their life. Anxiolytics were the most commonly used drugs, reported by 19.4% of the sample. The other frequently used psychotropic drugs were antidepressants (11.6%) and hypnotics (9.2%). Nearly half of the subjects with a MINI diagnosis reported no lifetime psychotropic drug use. Among the subjects meeting criteria for a diagnosis of mood disorder, 66.3% used psychotropic drugs. However, less than one out of three subjects with a diagnosis of major depressive disorder used antidepressants while 37.2% reported having used anxiolytics. Less than one out of four subjects with a diagnosis of anxiety disorder used antidepressants while 34.3% used anxiolytics. Among subjects with a diagnosis of anxiety disorder, antidepressants and anxiolytics were the most commonly used drugs for subjects with a diagnosis of panic disorder with agoraphobia (46.4 and 58.1%, respectively). Conversely, these were the treatments used the least by subjects with a diagnosis of generalized anxiety disorder (21.9 and 31.5%, respectively). Only 14.9% of subjects with a psychotic syndrome reported having used neuroleptics. Lastly, the highest proportion of subjects with at least one psychiatric diagnosis was found in mood stabilizer and neuroleptic users. However, one third of mood stabilizer users, a quarter of neuroleptic users and less than half of antidepressant and anxiolytic users presented no psychiatric disorder identified by the MINI. CONCLUSION: This study highlights the high frequency of exposure to psychotropic drugs in the general French population, and the marked inadequacy between the presence or absence of a psychiatric diagnosis and the lifetime presence or absence of a psychotropic drug treatment.

[One-year follow-up in real clinical practice conditions of type 2 diabetic patients treated with rosiglitazone: the Avantage study]. / Suivi sur un an dans les conditions de pratique courante d'une cohorte de patients diabétiques de type 2 traités par rosiglitazone: l'étude Avantage.

The Avandia, tolérance à grande échelle (Avantage) study was an observational study conducted in a large cohort of type 2 diabetic patients (T2D) followed for 12 months. Its aim was to assess in real clinical practice conditions, the tolerability of rosiglitazone, an oral antidiabetic agent of the new thiazolidinedione ("glitazone") class, available in France since May 2002. Study was carried out from December 2002 to January 2005. To be included, T2D seen during the inclusion period should start the rosiglitazone treatment (within eight days prior to 15 days after) in agreement with therapeutic indications and drug datasheet information in force at that time. Patient characteristics, clinical and biological data and adverse events (AE) during the 12-month follow-up were recorded. Among the 3845 T2D enrolled from January to November 2003, 3580 constituted the analyzed population (at least one documented rosiglitazone intake). At inclusion, mean age (+/-S.D.) was 62+/-11 years, 52% were male, mean BMI was 29.9+/-5.3kg/m2 and mean HbA1c was 8.5+/-1.4%. Ongoing antidiabetic treatments were mainly a monotherapy (46% of patients, metformin or a sulfonylurea) or a bitherapy (in 47%). Main reasons to prescribe rosiglitazone were insufficient control of diabetes (91% of patients), associated or not with a poor tolerance to the ongoing oral antidiabetic treatment at inclusion (in 29%) and/or with a contraindication to metformin (in 4%). Two thousand four hundred and twenty-four patients (71%) completed the 12-month follow-up. Along the study, 514 T2D (14%) experienced at least one AE, judged related to the treatment in the physician's opinion for 377 patients (11%). Two hundred and fifteen patients dropped out from the study due to AE. AE notified in more than 1% of patients were: weight gain (n=100 patients; 3% of the cohort), nausea (n=57; 2%), edema (n=55; 2%) and anemia (n=40; 1%). A seriousness criteria was reported for 105 patients (3% of the cohort), including 18 (<1%) heart failure. Mean HbA1c level decreased from 8.5+/-1.4% at inclusion to 7.8+/-1.6% at study end. Mean value of the main lipid parameters remained stable. Mean systolic blood pressure (BP) decreased from 137+/-13 to 135+/-12mmHg and diastolic BP from 79+/-8 to 78+/-8mmHg. Mean weight was 82+/-15kg at inclusion and 83+/-17kg at study end (NS), mean waist circumference was not significantly modified. In conclusion, the observational Avantage study, conducted in a large cohort of type 2 diabetic patients treated with rosiglitazone in clinical practice conditions and followed-up for 12 months, confirmed the results of controlled double blind clincal studies, with a clinical and biological tolerability in accordance with the known AE profile and a beneficial effect on metabolic control and arterial blood pressure.

Congruence between diagnosis of recurrent major depressive disorder and psychotropic treatment in the general population.

OBJECTIVE: We explored in a sample representative of the French general population the congruence between lifetime use of psychotropic drugs and diagnosis of recurrent major depressive disorder (rMDD). METHOD: A total of 2111 (5.6%) subjects with rMDD were identified in the sample of 36 785 subjects assessed in the Mental Health survey in the General Population. A treatment congruent with a diagnosis of rMDD was defined as lifetime use of antidepressants or mood stabilizers. RESULTS: Only one-third of subjects with rMDD reported having ever used a congruent treatment. Female gender, higher income and presence of anxiety disorder were associated with a higher probability of having used a congruent treatment. CONCLUSION: Although these findings indicate that a large proportion of subjects with rMMD do not benefit from adequate treatment, community surveys not primarily designed to assess utilization and adequacy of psychotropic treatment in the community may overestimate the frequency of unmet need for care.

Channelling of COX-2 inhibitors to patients at higher gastrointestinal risk but not at lower cardiovascular risk: the Cox2 inhibitors and tNSAIDs description of users (CADEUS) study.

PURPOSE: To describe the characteristics of users of cyclo-oxygenase (COX)-2 inhibitors and traditional nonselective non-steroidal anti-inflammatory drugs (tNSAIDs) in France. METHODS: Between 1 August 2003 and 31 July 2004, patients who received at least one dispensing of celecoxib, rofecoxib or tNSAIDs were randomly sampled with a 1:1:2 target ratio within the French National Healthcare Insurance database. Patients and prescribers were asked to fill a questionnaire on socio-demographic characteristics, NSAID indication and use and previous medical history. For each respondent, healthcare resources used in the 6 months before inclusion were extracted from the database. Multivariate logistic regression was used to study the determinants of a first COX-2 inhibitor dispensing. RESULTS: Of the 45 217 patients included, 13 065 COX-2 inhibitors and 13 553 tNSAID users had prescriber data. Ninety seven per cent of COX-2 inhibitor prescriptions were for 'rheumatological' indications, whereas 37% of tNSAIDs use was for benign diseases (n = 2643) or analgesia (n = 2318). Among patients with rheumatological indications (n = 4730) and a first COX-2 inhibitor (n = 2427) or tNSAID (n = 2303) dispensing, multivariate analysis of factors associated with COX-2 inhibitors dispensing showed that, compared to new tNSAID users, new COX-2 inhibitor users were older, more often female, on sick leave or unemployed. COX-2 use was also associated with previous gastrointestinal history and previous gastroprotective agent dispensing, but not with previous cardiovascular (CV) history. CONCLUSION: The choice of NSAID depended largely on indication and on previous gastrointestinal history, in line with the recommendations of the French health authorities. Possible knowledge of CV risk associated with COX-2 inhibitors did not influence prescribing.

The CADEUS study: methods and logistics.

PURPOSE: At the request of the French Health authorities, a study called CADEUS (COX-2 inhibitors and NSAIDs: description of users) aimed to describe the users of cyclo-oxygenase (COX)-2 inhibitors and traditional non-selective non-steroidal anti-inflammatory drugs (tNSAIDs). We report here the methodology, logistics and study design performances. METHODS: CADEUS is a cohort study designed to include 40,000 patients randomly sampled monthly in the French National Healthcare Insurance database, who received at least one dispensation of celecoxib, rofecoxib or tNSAIDs (1:1:2), from September 2003 to August 2004. Patients and prescribers were asked to fill a questionnaire on indication, medical history, risk factors and hospitalizations since drug acquisition. There was no reminder. For each respondent, healthcare resources used for the 6 months before and after inclusion were extracted from the database. Response rate, response delay, responders and non-responders characteristics were assessed. RESULTS: Of the 222,879 patients and their prescribers contacted, 20.8% patients and 32.6% prescribers responded. Median response delay was 16 days for patients and 17 days for physicians. Factors associated with patient response were age, cohort, type of prescriber and period of inclusion. CONCLUSION: This is the first study of this design in France, combining data from a claims database and direct patient and prescriber questionnaires.

[Cardiac tolerance of moxifloxacin: Clinical experience from a large observational French study in usual medical practice (IMMEDIAT study)]. / Tolérance cardiaque de la moxifloxacine: expérience clinique issue d'une large étude observationnelle française en pratique médicale usuelle (étude IMMEDIAT).

BACKGROUND: Moxifloxacin (Izilox) is prescribed for bacterial respiratory tract infections. ECG analysis done in clinical trials showed a mean QT prolongation at 6 ms that could lead to Torsades de Pointe. However, Izilox was well tolerated during clinical trials. To confirm the correct safety profile of Izilox in a large sample of patients, a French PMS study - MMEDIAT - was carried out in usual medical practice. METHODS: This prospective observational uncontrolled and monitored study was conducted in 13,578 patients with respiratory tract infection and treated with moxifloxacin 400 mg daily (duration: 5 to 10 days in accordance to the Market Authorization). Any clinical event being potentially a surrogate of a ventricular rhythm disorder ("critical event") were collected and analyzed by a Scientific Committee in charge to determine the potential cardiac origin of the reported event and to establish a causal relationship with the treatment. RESULTS: Among 13,578 patients, 1046 adverse events (678 patients [5%]) were reported, including 854 drug related events (564 patients [4.15%]). Of these 1046 adverse events, 95 (62 patients [0.46%]) were serious. A total of 189 critical adverse events (159 patients [1.2%]) were reviewed by the Scientific Committee. After analysis, 34 adverse events (28 patients [0.21%]) were assessed from potential cardiac origin. Of these 34 adverse events, 25 (19 patients [0.14%]) were assessed as drug-related: palpitations [13 patients], tachycardia [4 patients], malaise [4 patients], vertigo [3 patients] and pallor [1 patient]. All adverse events were transient and had favourable outcome. CONCLUSION: This PMS study confirmed that Izilox is well-tolerated in usual medical practice, in adequation with the safety data obtained in clinical trials.

Prognostic impact of psychoactive substances use during hospitalization for intentional drug overdose.

OBJECTIVE: To assess whether current use of psychoactive substance(s) is a prognostic factor during hospitalization for intentional drug overdose (IDO). METHOD: Current intoxication with psychoactive substance(s) [cannabis, opiate, buprenorphine, amphetamine/ecstasy, cocaine, lysergic acid diethylamide (LSD)] was identified using toxicological urinalysis in 671 patients with IDO. An IDO was a priori defined as serious if associated with one of the following events: death, hospitalization in intensive care unit longer than 48 h, respiratory support, use of vasopressive drugs, cardiac massage or dialysis. RESULTS: Subjects positive for toxicological assays were twice as likely to present with serious IDO (OR = 1.9, 95% CI: 1.3-2.8, P = 0.001), independently from a large range of confounding factors. The risk of serious IDO was especially marked in subjects using LSD, buprenorphine or opiates. CONCLUSION: Systematic investigation of substance use could be important to adapt medical management of subjects with IDO in general hospital, but also in primary care and psychiatric settings.

[A case of Parkinsonian syndrome, cognitive impairment and hyperammonemia induced by divalproate sodium prescribed for bipolar disorder]. / Troubles cognitifs, syndrome extrapyramidal et hyperammoniémie sous traitement thymorégulateur par divalproate de sodium: a propos d'un cas.

Several cases of Parkinsonian syndrome, cognitive impairment or hyperammonemia induced by sodium valproate have been described in the literature. We report the first case presenting an association of the three adverse effects occurring with divalproate sodium prescribed for bipolar disorder: a 58-year-old man with a history of bipolar type I disorder presented with Parkinsonian syndrome and cognitive impairment of insidious onset. This patient had been treated for several years with lithium carbonate, with a successful effect on mood swings, but with distressing adverse effects such as hand tremor and diarrhoea. Lithium therapy was progressively withdrawn while sodium divalproate was initiated. Associated medications, unchanged for several years, were amisulpride (daily dose: 100 mg), liothyronine, ciprofibrate and benfluorex. The patient was treated with sodium divalproate for seven months (daily dose: 1,000 mg), and with trihexyphenidyle for one month for extrapyramidal symptoms. At hospital admission, he presented with temporal disorientation, slowed thinking, severe anterograde memory deficits, and Parkinsonian syndrome. The minimal mental state (MMS) score was 16 (maximum: 30). The patient was anxious but did no present with mood symptoms. He also developed hyperammonemia (124 micromol/liter, normal range: 15 to 60 micromol/liter) without signs or biochemical evidence of hepatic failure. Valproate concentrations were within the therapeutic ranges (79 mg/l, normal range: 50 to 100 mg/l). The CT-scan showed cerebral and cerebellar atrophy with enlarged ventricles. The electroencephalogram showed generalized slowing waves. All the symptoms resolved within one month after the withdrawal of divalproate: the extrapyramidal hypertonia resolved, the MMS score was 29. The CT-scan and the electroencephalogram returned to normal. The divalproate was replaced by lithium. After a one-year follow-up, the cognitive and neurological symptomatology did not reappear at the exception of the pre-existing hand tremor. The pathophysiology of valproate induced hyperammonemic encephalopathy remains unclear. A possible mechanism is neuronal toxicity induced by increased intracellular concentrations of glutamate and ammonium in astrocytes. Indeed, these abnormal intracellular concentrations increase the intracellular osmolarity and thus induce rise in intracranial pressure and cerebral oedema. Reversible dementia could be due to a direct toxic effect of valproate on the central nervous system or to an indirect effect mediated through valproate-induced hyperammonemia. It has been suggested that the occurrence of extrapyramidal syndrome could be explained by a disturbance in the GABAergic pathways inducing reversible dopamine inhibition. A drug adverse reaction should always be considered when a patient treated with valproate presents with extrapyramidal symptoms and cognitive disorders even when valproate concentrations are within standard therapeutic ranges.

Effectiveness and safety profile of leflunomide in rheumatoid arthritis: actual practice compared with clinical trials.

OBJECTIVE: Leflunomide, an immunosuppressant agent for treating rheumatoid arthritis, was first marketed in France in 2000. Three years after its launch, we sought to assess its prescription patterns in the real world of prescription and use, and to see if its efficacy and safety profiles observed during clinical trials were confirmed. METHODS: All patients treated with leflunomide from May 2000 to April 2003 in the Department of Rheumatology of the Bordeaux University Hospital were identified, and their treatment patterns and outcome ascertained. This was compared to data from clinical trials. RESULTS: 116 were included (mean age = 55 years, 70% women). Almost 21.7% stopped treatment for lack of efficacy (after a mean delay of 3.6 months), 16% for secondary loss of efficacy (median = 7 months), and 32% for the occurrence of an adverse event (half within 4 months). Over a similar time frame in clinical trials, in patients of about the same age and sex but with less severe disease, the corresponding figures were 7-17% for lack or loss of efficacy, and 14-22% for adverse effects. At one year of follow-up, the discontinuation rate was 70% in the cohort compared to 28-47% in clinical trials. DISCUSSION: The differences between the two populations confirm the need to conduct post-marketing studies in order to obtain better knowledge on the effectiveness and safety of a new drug. In many cases, a simple drug utilization study can provide relevant information on the degree of shift between populations included in clinical trials and those treated in real life.