[Duration of antidepressant drug treatment and its determinants in France]. / Étude sur la durée des traitements antidépresseurs en France et ses déterminants à partir des bases de données de l'Assurance maladie.

INTRODUCTION: Practice guidelines recommend maintaining antidepressant treatment for a long duration (at least six months) after symptomatic improvement. In practice, treatment effectiveness is often jeopardized by non-persistence. METHOD: A retrospective cohort study was conducted on a standard sample representative of the members of the French universal health insurance system database, in order to assess antidepressant treatment duration in a real-life setting. 35,053 outpatients who initiated an antidepressant treatment in 2005-2006 were followed up until 2007. Incident antidepressant treatment was defined as no delivery of antidepressant in the six months prior to treatment initiation. Persistence to treatment was defined as antidepressant treatment duration of six months or more. Multivariate analyses were conducted in order to identify characteristics associated with persistence to treatment. RESULTS: Most antidepressant treatments (n = 28,674; 81.8%) lasted for less than six months and more than half for 28 days at most (n = 20,377; 58.1%). Persistence to treatment was associated with older age (OR 1,13; 95% CI 1.11-1.15), female gender (1.22; 1.15-1.30), chronic disease (1.21; 1.13-1.31), not being on welfare (0.67; 0.60-0.74) and coprescription of anxiolytics (0.36; 0.33-0.38), antipsychotics (0.39; 0.35-0.43) or mood-stabilizers (0.45; 0.39-0.53). Prescribers' specialty was also associated with persistence. Treatments prescribed by general practitioners were less likely to be continued than those prescribed by psychiatrists (1.65; 1.47-1.86). CONCLUSION: Non-persistence to antidepressant treatment is very frequent in France. Intervention programs aimed at increasing persistence should target physicians' training and patients' education.

Impact of duration of antidepressant treatment on the risk of occurrence of a new sequence of antidepressant treatment.

INTRODUCTION: Despite the recommendation that antidepressant treatment should be continued for several months to reduce the risk of relapse/recurrence of depression, early discontinuation is frequent in naturalistic conditions. The study was aimed at exploring the impact of early discontinuation of antidepressant treatment on the risk of antidepressant re-initiation. METHODS: A follow-up study of persons (n=35,053) starting antidepressant treatment was performed using a representative sample of the French Social Security Insurance national database. RESULTS: The risk of re-initiation of antidepressant treatment was higher if the duration of the index episode of antidepressant treatment was ≥ 6 months [hazard ratio (HR)=2.35; 95% CI 2.25-2.45) or 2-5 months (HR=1.65; 95% CI 1.59-1.71) compared to ≤ 1 month. The other characteristics independently associated with re-initiation of treatment were older age, female gender, low income, serious chronic illness, index prescription by a specialist and co-prescription of other psychotropic drugs. CONCLUSIONS: The lower risk of re-initiation of antidepressant treatment in persons with shorter-than-recommended duration of antidepressant treatment might be explained by overprescription of antidepressants in persons with sub-threshold symptoms.

[Occupational outcome of patients with schizophrenia after first request for disability status: a 2-year follow-up study]. / Devenir professionnel de sujets souffrant de schizophrénie dans les deux ans suivant l'obtention du statut adulte handicapé.

OBJECTIVE: To assess occupational outcome of persons with schizophrenia over the 2 years following the first request of disability status. METHODS: This study was carried out in collaboration with the Commission Technique d'Orientation et de Reclassement Professionnel (COTOREP) (technical commission for occupational guidance and rehabilitation of the disabled) de la Gironde (Bordeaux region, South Western France). Persons with schizophrenia or schizoaffective disorder requesting for the first time in 2006 a disability allowance or the status of disabled worker were assessed using a standardized questionnaire collecting data on clinical, occupational and income history. Information on occupational outcome over the 2 years after the first request was collected at the end of the follow-up using multiple sources of information. We used a broad definition of work, including moonlighting and episodic activities (baby-sitting or grape-harvesting), as well as study periods. RESULTS: Of the 121 patients included at baseline, direct or indirect information was available for 108 (90%) at the 24-month assessment. Persons lost to follow-up were less likely to have worked before first request of disability status compared to persons with information available at the end of the follow-up, but did not differ regarding the other characteristics. Nearly half of the persons (41.7%) had worked over the follow-up, irrespective of the type and duration of the occupation. The working periods were of short duration (median duration 14.5 days, interquartile range 6.5-47.5) and most (98%) were done in low-qualified jobs. Nearly half of the persons reported that they had benefitted from support for starting or returning to work, mainly from recruitment agencies specialized in supporting disabled workers. Persons with the status of disabled worker (Reconnaissance de la qualité de travailleur handicapé) (RTH) were more likely to have worked over the follow-up period (66.7% vs 33.3%; OR=3.9; 95%IC 1.3-11.3; p<0.01) as well as persons who had benefitted from institutional support (61.1% vs 38.9%; OR=3.0; 95%IC 1.2-7.8; p=0.02). However, a noteworthy result was that most jobs were obtained by the patient's personal effort. Nearly one out of four patients (23.2%) was involved in vocational training over the follow-up period. CONCLUSION: This prospective study demonstrates that half of persons with schizophrenia who benefit from the disabled status remain actively engaged in vocational rehabilitation. Hence, giving access to disability status does not act as a disincentive regarding the return or access to work. However, the benefit of being kept involved in vocational rehabilitation has to be weighted against the fact that most patients only obtained low-qualified jobs of short-duration. This precarious situation may be stressful and may have a deleterious impact regarding self-esteem.

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.

The prognostic impact of psychotropic drugs in intentional drug overdose.

INTRODUCTION: Psychotropic drugs belong to the drugs most frequently involved in intentional drug overdose (IDO). Few studies have explored their prognostic impact during hospitalisation for IDO. METHODS: In order to assess which types of psychotropic drugs ingested during IDOs were associated with an increased morbidity, a cohort study included 1,974 patients consecutively hospitalised for IDO. IDOs were categorised as serious if associated with one of the following criteria: death, hospitalisation longer than 48 h, respiratory support, vasopressive drugs, cardiac massage or dialysis. RESULTS: Nearly all the patients ingested psychotropic medications during the IDO (88.4%), most often benzodiazepines (71.6%). Serious IDO was associated with tricyclics (OR 5.7; 95% CI 3.3-9.8), lithium (OR 4.3; 95% CI 1.6-11.6), carbamates (OR 2.7; 95% CI 1.8-4), anticonvulsants (OR 2.4: 95% CI 1.4-4.3), first-generation antipsychotics (OR 2.4; 95% CI 1.7-3.5) or selective serotonin reuptake inhibitors (SSRIs) (OR 1.6; 95% CI 1.1-2.3). DISCUSSION: Some drugs may be dangerous because of low toxic doses; hence, prescriptions of short duration may be recommended. Moreover, for safety reasons, prescribers may prefer SSRIs to tricyclics and benzodiazepines to carbamates or phenothiazines.

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.

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.

[Prescription practices of antipsychotic medication in early psychosis: a two-year follow-up survey of subjects admitted in two psychiatric hospitals of South-Western France]. / Pratiques de prescription des traitements antipsychotiques dans les premières hospitalisations pour épisode psychotique: étude sur une cohorte de patients hospitalisés dans deux hôpitaux girondins.

OBJECTIVES: The aims of this pharmacoepidemiological study were to describe the antipsychotic medication received during the first admission and over a two-year follow-up in subjects with a first episode of psychosis, and to assess whether the prescriptions in naturalistic conditions were in adequacy with guidelines. METHOD: All first-admitted patients, less than 50 years old, consecutively hospitalised in 10 acute wards of two psychiatric hospitals serving Bordeaux's catchment area were included over a period of one year, if they presented with at least one overt psychotic symptom during the last month. Information on psychotropic medication received during the first admission was collected in medical records, and that received after the first admission was collected at the end of a two-year follow-up using multiple sources of information. RESULTS: Of the 86 patients included in the cohort, 53 presented with broadly defined schizophrenia and 33 with psychotic mood disorder. All except two subjects were prescribed at least one neuroleptic drug. Antipsychotic drugs (amisulpride, olanzapine, risperidone, clozapine) were the most frequently prescribed drugs during the first admission and over the two-year follow-up. If sedative neuroleptics were excluded, antipsychotic drugs were the first prescribed neuroleptic drugs in a large proportion (80%) of patients. Although few patients were first prescribed a conventional neuroleptic, the proportion of subjects treated with these drugs increased over the next prescriptions, and one out of three patients was prescribed at least one of these drugs during the follow-up. The mean dose of antipsychotic drugs at first discharge was higher than that recommended in first episode patients (amisulpride 616 mg, olanzapine 13 mg, risperidone 7 mg). Coprescription of neuroleptic drugs, found in one third of patients at all times of assessment, was especially due to coprescription of a sedative neuroleptic to a conventional or an antipsychotic one. Nearly half of the patients did not take any psychotropic medication at the end of the follow-up. CONCLUSION: The main recommendation specifying that the first neuroleptic treatment in subjects with a first episode of psychosis should use antipsychotic drugs instead of conventional neuroleptics was generally respected in this cohort of first-admitted subjects with psychosis. However, conventional neuroleptics were found in first or second rank prescriptions, although they should not be used before at least the third rank. The recommendations that the initial neuroleptic dose should be lower in subjects with a first episode, and that coprescription of neuroleptics should be avoided, were frequently not respected. This study highlights the fact that international guidelines should be better applied in naturalistic conditions, and that clinicians have to be better informed about these recommendations.

Pattern of health service utilization and predictors of readmission after a first admission for psychosis: a 2-year follow-up study.

OBJECTIVE: To explore the pattern of health service utilization over 2 years following a first admission for psychosis and the baseline characteristics predicting readmission. METHOD: Patients included in a cohort of first-admitted subjects with psychosis (n = 84) were assessed at the end of a 2-year follow-up using multiple sources of information. RESULTS: At the end of the follow-up, one of three subjects had no contact with any mental health professional, and 38% of subjects had no contact with a psychiatrist. Half of the patients were readmitted over the 2-year follow-up. The baseline characteristics independently predicting psychiatric readmission were a high number of helping contacts before first admission and persistence of psychotic symptoms at discharge. CONCLUSION: Decreasing the frequency of readmission in the early course of psychosis is a public health priority. Development of psychotherapeutic programs for subjects with early psychosis who have enduring psychotic symptoms at first discharge should be promoted.

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.

Pathways to care of first-admitted subjects with psychosis in South-Western France.

BACKGROUND: A limited number of studies have assessed the pathways to care of patients with first-episode psychosis. The aim of the study was to describe the pathways to care of subjects with psychosis between onset of psychosis and first admission, and to examine the demographic and clinical factors influencing access to care. METHOD: Number and type of helping contacts since onset of first psychotic symptoms were assessed using multiple sources of information in 86 subjects with psychosis first-admitted in two hospitals of South-Western France. Characteristics independently associated with long delays between onset of symptoms and first helping contact, first treatment and first admission were explored using logistic regressions. RESULTS: Twelve per cent of subjects were first admitted without any previous helping contact. The patients were seen by a median of two helpers (maximum 7). For most patients (70%), the first helping contact was a health care professional, and the same proportion of patients had a first contact with a GP or a psychiatrist. The type of first contact was not predicted by demographic or clinical characteristics. Subjects with poor pre-morbid functioning or at-risk behaviour were more likely to have a delayed access to care. CONCLUSIONS: The delay in access to care may not be totally attributed to inadequate management by health professionals, but may be a characteristic of the disease itself, at least in part independent of the organization of the health system.

Accuracy of self-report and toxicological assays to detect substance misuse disorders in parasuicide patients.

OBJECTIVE: To assess the accuracy of self-reported substance use and toxicological assays in subjects admitted for Intentional Drug Overdose (IDO), using as a reference diagnosis of substance use disorder. METHOD: Self-reported substance use was collected and toxicological assays were carried out in urine samples in 507 patients with IDO. A standardized psychiatric evaluation was performed in 100 randomly selected subjects. RESULTS: In routine practice, the emergency department staff did not investigate substance use in nearly one of two patients. Patients' statements and toxicological assays were more specific than sensitive, with lower scores for toxicological assays. Patients' statements made it possible to detect nearly 80% of subjects with substance use disorder. CONCLUSION: Identification of substance use disorder in subjects with IDO has strong clinical consequences regarding treatment and prevention of suicidal behaviour. Thus, emergency department staff should be made aware of the value of more systematically exploring self-reported substance use.

[High levels of factor VIIIc and risk of venous thrombosis: critical analysis of case-control studies]. / Elévation du facteur VIIIc coagulant et risque de thrombose veineuse: analyse critique des études cas-témoins.

INTRODUCTION: Deep venous thrombosis is a frequent and potentially serious disease. Its causes are multifactorial, associating facilitating circumstances and genetic or acquired coagulation abnormalities. Genetic currently well known abnormalities are quantitative deficiencies of some natural anticoagulants (proteins C and S, antithrombin), and mutations of V and II (G20210-A) genes. The Leiden group has recently shown that the elevation of some coagulation factors level could also constitute a risk factor for deep venous thrombosis. CURRENT KNOWLEDGE AND KEY POINTS: Elevation of factor VIIIc is associated with a higher risk for thrombosis than in the general population but the threshold for normality of this factor is difficult to define. It is a probable constitutional abnormality whose prevalence in the general population vary from 6 to 36%. Risks of deep venous thrombosis associated to this factor elevation is more elevated in patients who have this anomaly (odds ratios vary from 2,2 to 10,3) (95% CI). FUTURE AND PROJECTS: The frequency of this anomaly and its association with a high risk for thrombosis are reasons to assess the potential usefulness of screening for these anomalies in patients who had thrombosis or in their family. The probable genetic origin of these anomalies has to be confirmed by other studies.