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The European Clozapine Task Force is a group of psychiatrists and pharmacologists practicing in 18 countries under European Medicines Agency (EMA) regulation, who are deeply concerned about the underuse of clozapine in European countries. Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia, a large proportion of them do not have access to this treatment. Concerns about clozapine-induced agranulocytosis and stringent blood monitoring rules are major barriers to clozapine prescribing and use. There is a growing body of evidence that the incidence of clozapine-induced agranulocytosis is very low after the first year of treatment. Maintaining lifelong monthly blood monitoring after this period contributes to unjustified discontinuation of clozapine. We leverage recent and replicated evidence on the long-term safety of clozapine to call for the revision and updating of the EMA’s blood monitoring rules, thus aiming to overcome this major barrier to clozapine prescribing and use. We believe the time has come for relaxing the rules without increasing the risks for people using clozapine in Europe.
Stigma resistance (SR) is defined as one's ability to deflect or challenge stigmatizing beliefs. SR is positively associated with patient's outcomes in serious mental illness (SMI). SR appears as a promising target for psychiatric rehabilitation as it might facilitate personal recovery.
Objectives
The objectives of the present study are: (i) to assess the frequency of SR in a multicentric non-selected psychiatric rehabilitation SMI sample; (ii) to investigate the correlates of high SR
Methods
A total of 693 outpatients with SMI were recruited from the French National Centers of Reference for Psychiatric Rehabilitation cohort (REHABase). Evaluation included standardized scales for clinical severity, quality of life, satisfaction with life, wellbeing, and personal recovery and a large cognitive battery. SR was measured using internalized stigma of mental illness – SR subscale.
Results
Elevated SR was associated with a preserved executive functioning, a lower insight into illness and all recovery-related outcomes in the univariate analyses. In the multivariate analysis adjusted by age, gender and self-stigma, elevated SR was best predicted by the later stages of personal recovery [rebuilding; p = 0.004, OR = 2.89 (1.36–4.88); growth; p = 0.005, OR = 2.79 (1.30–4.43)). No moderating effects of age and education were found.
Conclusion
The present study has indicated the importance of addressing SR in patients enrolled in psychiatric rehabilitation. Recovery-oriented psychoeducation, metacognitive therapies and family interventions might improve SR and protect against insight-related depression. The effectiveness of psychiatric rehabilitation on SR and the potential mediating effects of changes in SR on treatment outcomes should be further investigated in longitudinal studies.
We studied the relation between individual and neighborhood socioeconomic characteristics and the probability of:
– new long-duration antidepressant treatment;
– early antidepressant discontinuation.
Methods
We followed two cohorts of inhabitants of Marseille (aged 18–64 years) covered by the National Health Insurance Fund (NHIF) for 2.5 years. In the first cohort (316,412 individuals in 2008), we studied new long-duration antidepressant treatments (≥ 4 antidepressants prescription claims within 6 months after the index claim, and none in the 6 months before). The second cohort was restricted to the 14,518 individuals with a new episode of antidepressant treatment prescribed by a private GP in 2008–2009 to study early treatment discontinuation: < 4 antidepressant prescription claims in the 6 months following the index claim. We developed a deprivation index at the neighborhood level (census block) and used multivariate multilevel logistic models adjusted for consultations with GPs and psychiatrists. In the second cohort, analyses were further adjusted on GPs characteristics.
results
First cohort: the probability of new long-duration antidepressant treatments was negatively associated with both individual low income and neighborhood deprivation. Second cohort: low income, and prescribers’ clientele composition (high proportion of disadvantaged patients) were independently associated with an increased risk of early discontinuation. A significant interaction was found between low income and gender.
Conclusions
Our results add further evidence supporting the existence of inequalities in antidepressant treatment at both the individual, GP and neighborhood levels, and that these inequalities occur principally during the processes of care. Inequalities in antidepressant continuation are more pronounced among women. Further research is warranted to improve our understanding of their mechanisms.
The case reports of two DSM III-R schizophrenic patients with a family history of bipolar disorder are presented. The two patients had a history of severe obstetric complications (OCs). These cases are discussed in the light of neurodevelopmental theories of schizophrenia and in the continuum view of psychosis.
To assess the metabolic impact of adding an antipsychotic to a mood stabilizer or switching a mood stabilizer to an antipsychotic in patients with bipolar disorder.
Methods:
A retrospective fixed cohort study was conducted through the claims database of the French health care program for the self-employed workers. The study population consisted of 3.172 patients age 18 and over who were exposed to mood stabilizers (i.e. lithium, valproate) a 3 month-period in 2004 without dispensing of non-sedative antipsychotic, antidiabetic or lipid-lowering drugs. The outcome was the occurrence of a metabolic incident over the follow-up period, using the dispensing of an antidiabetic drug as a marker of diabetes and the dispensing of a lipid-lowering drug as a marker of hypercholesterolemia or hypertriglyceridemia. A Cox proportional hazard model was used to assess the metabolic impact of the antipsychotics; using mood stabilizers as a reference. Antipsychotic exposition was stratified in «current» and «recent» (discontinued for less than 6 months) at the time of the metabolic incident.
Results:
196 patients (6.2%) received a first-generation antipsychotic, 352 (11.1%) a second-generation antipsychotic, 565 (17.8%) a sedative antipsychotic and 367 patients (11.6%) presented with a metabolic incident over the study period. The recent dispensing of a second-generation antipsychotic was associated with the occurrence of a metabolic incident [HR 2.1 (95%CI 1.2-3.7) p=0.006], while current dispensing or dispensing of first-generation antipsychotics were not.
Conclusion:
Second-generation antipsychotics have a metabolic impact compared to classic mood stabilizers in patients with bipolar disorder.
To explore the links between neuropsychological performance, diagnostic category and duration of illness in subjects with psychotic and affective disorders.
Methods
Memory and executive abilities were tested in consecutively admitted patients with schizophrenia (N = 20), other non-schizophrenic psychotic disorders (N = 29), bipolar disorder (N = 33) and major depression (N = 19).
Results
Subjects with schizophrenia had poorer global memory performances than subjects with major depression, and poorer delayed verbal memory abilities than those from the other three diagnostic groups. Executive abilities explored by the Stroop test and the Wisconsin Card Sorting Test did not differ between diagnostic groups. Neuropsychological performances were not influenced by previous duration of illness.
Conclusions
Memory deficits are the most discriminatory cognitive features between subjects with schizophrenia and those with other psychotic or mood disorders. The fact that cognitive deficits are static whatever the diagnostic group indirectly suggests that they may have a neurodevelopmental origin in subjects with schizophrenia, but perhaps also in subjects with other psychotic and mood disorders.
To assess with which frequency subjects with intentional overdose of psychotropic drugs ingest their own psychotropic drug treatment, and whether prescription of a drug may be a factor influencing the choice of drugs used for the IDO.
Methods:
Demographic characteristics, psychiatric history, and currently prescribed psychotropic drug treatment were collected for all the patients (n=1654) admitted to an emergency department (ED) for IDO with psychotropic drugs (anxiolytics, hypnotics, antidepressants, antipsychotics and mood stabilizers) over a period of 18 months.
Results:
Two-thirds of the patients ingested during the IDO at least one of their own prescribed psychotropic drugs. Compared with the subjects who had ingested psychotropic drugs not prescribed for them, they were more likely to have a history of psychiatric hospitalization (OR 4.2; 95%CI 3.1-5.5), of parasuicide (OR 2.5; 95%CI 1.9-3.3), to be a psychiatric outpatient (OR 3.9; 95%CI 3.0-5.1), and to present with a serious IDO (OR 2; 95%CI 1.4-2.9). Independently from age and psychiatric hospitalization history (i.e. the seriousness of psychiatric disorder), they ingested during the IDO more often antidepressants (OR 4.4; 95%CI 3.0-6.4), antipsychotics (OR 2.9; 95%CI 1.7-4.8) and mood stabilizers (OR 4.1; 95%CI 1.6-10.7). No association was found with prescription for overdose of benzodiazepine or paracetamol.
Conclusion:
Prescription of the psychotropic drugs plays an important role in the choice of the drugs ingested for the IDO. It might make potentially “dangerous” drugs available for the patient. Physicians have always to balance the benefit of the treatment against the risk of drug overdose.
– Studies have suggested that women with pregnancy anxiety may be at greater risk of postnatal depression (PND). However, due to the high comorbidity between anxiety and depressive disorders, this finding may be confounded by the association between prenatal depression and postnatal depression. The aim of the present prospective study was to assess whether anxiety disorder (AD) during pregnancy is an independent predictor of intensity of postnatal depressive symptoms.
Method.
– The MATQUID cohort survey was conducted on pregnant women (n = 497) attending a state maternity hospital. Psychiatric status during pregnancy was assessed during the third trimester using a structured diagnostic interview. Intense postnatal depressive symptoms at 6 weeks post-partum were defined by a score >12 on the Edinburgh Postnatal Depression Scale (EPDS).
Results.
– Nearly one out of four women (24.1%) presented with at least one pregnancyAD, and 29 (5.8%) presented with a score >12 on the EPDS. After adjustment for presence of major depression during pregnancy and other confounding factors, women with pregnancy AD were nearly three times more likely to present with intense postnatal depressive symptoms (OR = 2.7, 95%CI 1.1-6.3, P = 0.03).
Conclusion.
– Promoting the recognition and management of AD in pregnant women may be of interest for the prevention of postnatal depression.
As practice guidelines recommend to maintain antidepressant treatments for a long duration after improvement of symptoms in order to prevent relapse or recurrence, our objectives were to explore the duration of the antidepressant drug treatment in France and to characterise the antidepressant users with a short duration of treatment.
Methods:
An observational retrospective cohort study was conducted in the community-dwelling population 18 year-old and over through claims databases of the public health insurance. A random sample of 34.663 outpatients who initiated an antidepressant treatment between the 1st January 2005 and the 31st December 2006 were selected. The dependent variable was the duration of the first episode of antidepressant treatment, categorised a priori in short duration [1-6 months[ versus long duration [6 months and more] according to guidelines. Characteristics independently associated with the treatment duration were investigated using logistic regressions.
Results:
Nearly two thirds of the individuals were females. Most patients were not on welfare. Three quarters of them did not present with chronic conditions. The duration of the antidepressant treatment complied with the international recommendations for only one patient of six. Adequate treatment duration was associated with being a female, being older, not being on welfare, presenting with a chronic condition and a treatment introduction by a psychiatrist or a hospital practitioner.
Conclusion:
The recommendations concerning the duration of an antidepressant treatment are rarely respected in a real-life setting in France. Further analyses should be conducted to characterise the patterns of prescription according to antidepressant classes and associated treatments.
To describe the types of psychotropic drugs ingested during intentional drug overdose (IDO) in subjects consecutively admitted to an emergency department and to assess which ones were a prognostic factor associated with increased morbidity during hospitalization.
Methods:
Demographic characteristics, psychiatric history, current drug treatment, characteristics of the IDO were collected for 1654 patients admitted for IDO with psychotropic drugs (anxiolytics, hypnotics, antidepressants, antipsychotics and mood stabilizers). IDOs were a priori categorized as serious if associated with at least one of the following outcomes or technical events: death, hospitalization in the ED longer than 48 hours, respiratory support, use of vasopressive drugs, cardiac massage or dialysis. All types of psychotropic drugs were entered into a logistic regression model adjusted for age and gender. A stepwise selection was used to assess the types independently associated with serious IDO. Then, numerous confounding variables were entered one at a time in the final model.
Results:
Nearly all the patients ingested psychotropic medications during the IDO (88.4%), most often benzodiazepines (71.6%), and half used at least two various psychotropic products. 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 (OR 1.6; 95%CI 1.1-2.3).
Conclusion:
Some drugs may be dangerous because of low toxic doses; prescriptions of short duration may be recommended. Moreover, for safety reasons, prescribers may prefer SSRIs to tricyclics and benzodiazepines to carbamates or phenothiazines.
Few studies of the effects of postnatal depression on child development have considered the chronicity of depressive symptoms. We investigated whether early postnatal depressive symptoms (PNDS) predicted child developmental outcome independently of later maternal depressive symptoms.
Methods
In a prospective, longitudinal study, mothers and children were followed-up from birth to 2 years; repeated measures of PNDS were made using the Edinburgh Postnatal Depression Scale (EPDS); child development was assessed using the Bayley Scales II. Multilevel modelling techniques were used to examine the association between 6 week PNDS, and child development, taking subsequent depressive symptoms into account.
Results
Children of mothers with 6 week PNDS were significantly more likely than children of non-symptomatic mothers to have poor cognitive outcome; however, this association was reduced to trend level when adjusted for later maternal depressive symptoms.
Conclusion
Effects of early PNDS on infant development may be partly explained by subsequent depressive symptoms.
Very little is known about the impact of manic post-partum episods (MPPE) and mother-baby interactions.
Aim
The objective of this preliminary work was to compare mother-baby interactions of mothers hospitalized for MPPE with the baby, and mother-baby interactions of mothers recruited in the community.
Methods
Interactions between 20 MPPE mothers and their babies aged between 2-6 months, and 13 community mothers and their babies (2-6 months), were evaluated with the «Global Rating Scales of Mother-Infant Interaction».
Results
MPPE mothers were more intrusive than community mothers. The MPPE babies were more withdrawn than community babies.
Discussion
More research is needed to evaluate the long term impact of such pattern of early interactions.
To assess the factors predicting the delay between onset of psychotic symptoms and first admission in a populationbased sample.
Method:
The duration of psychosis before admission was ascertained in a standardised way for 59 consecutively first-admitted patients presenting with psychotic symptoms.
Results:
The median of the duration of psychosis before admission was 3 months (interquartile range 0.5-14). A delay ≥ 3 months was independently predicted by family history of psychiatric hospitalisation (odds ratio [OR] = 12.1, 95% confidence interval [CI] 1.15-97.0, P = 0.02). low educational level (OR = 7.7, 95% CI 1.0-50.0, P = 0.05), poor global adjustment in the preceding year (OR = 0.93, 95% CI 0.860.99, P = 0.04). and by greater global severity of illness at admission (OR = 4.0, 95% CI 0.87-18.3, P = 0.07).
Conclusion:
As these factors are also known to predict poor outcome, our results suggest that the association between duration of untreated psychosis and poor prognosis may be mediated, at least in part, by such demographic and clinical variables.
Previous studies have shown that schizophrenic patients are more likely to be born in winter or early spring months than the general population. Data on 4,207 patients with a hospital diagnosis of schizophrenia were obtained from a mailed survey to public departments of adult psychiatry in metropolitan France. For each year from 1900 to 1965, the expected monthly number of schizophrenic births was calculated and any seasonal variation of live births in the general population was taken into account. Cumulative distributions of the observed and expected number of schizophrenic births were compared using a Kolmogorov-Smirnov type statistic. The seasonal distribution of schizophrenic births was significantly different from that of the general population (P < 0.01). An excess of schizophrenic births was found in the first half of the year, with a peak in April (+ 13%).