A treadmill exercise reduced cardiac fibrosis, inflammation and vulnerability to ischemia-reperfusion in rat pristane-induced arthritis.

AIMS: To explore cardiac structural and functional parameters and myocardial sensitivity to ischemia in a rat model of chronic arthritis, pristane-induced arthritis (PIA), and to investigate the effects of a running exercise protocol on cardiac disorders related to rheumatoid arthritis (RA). MAIN METHODS: 3 groups of male Dark Agouti rats were formed: Controls, PIA and PIA-Exercise. The PIA-Exercise group was subjected to an individualized treadmill running protocol during the remission phase. At acute and chronic phases of PIA, cardiac structure was analyzed by histology. Cardiac function was explored in isolated hearts to measure left ventricular developed pressure (LVDP), cardiac compliance and infarct size before and after ischemia/reperfusion. Cardiac inflammation was evaluated through VCAM-1 mRNA expression by RT-qPCR. Plasma irisin levels were measured by ELISA. KEY FINDINGS: PIA rats exhibited myocardial hypertrophy fibrosis and inflammation at the 2 inflammatory phases of the model. At chronic phase only, LVDP and cardiac compliance were lower in PIA compared to controls. As compared to sedentary PIA, exercise did not change cardiac function but reduced fibrosis, inflammation, infarct size, and arthritis severity and increased irisin levels. Cardiac inflammation positively correlated with fibrosis, while irisin levels negatively correlated with cardiac inflammation and fibrosis. SIGNIFICANCE: In the PIA model that recapitulated most cardiac disorders of RA, a daily program of treadmill running alleviated cardiac fibrosis and inflammation and improved resistance to ischemia. These data provide arguments to promote the practice of exercise in RA patients for cardiac diseases prevention.

General hospital admissions in young and middle-aged people who use psychoactive substances: Impact of Covid-19 lockdowns.

BACKGROUNDS: The Covid-19 pandemic offered a unique opportunity to investigate trends in hospitalizations related to psychoactive substance intoxication, since the usual health burden of social use at parties and gatherings was likely to be decreased during lockdowns and curfew periods. Since young adults are the main users of psychoactive substances for experimental and recreational purposes, this study identified and compared hospitalization trends in young adults and adults over 30 years old. METHODS: This national cohort study was conducted using the French hospital discharge database. An interrupted time-series analysis for the period between 2014 and 2020 was performed in two groups: young (age 18-29) and other adults (30+) to ascertain the trends in the monthly incidence of hospitalization related to psychoactive substance intoxication (opiates, cocaine, benzodiazepines, psychostimulants, alcohol and cannabis). Hospitalization characteristics during the first and second lockdown and the period between them were compared to the reference period (from 01/01/2014 to 29/02/2020). RESULTS: Among 1,358,007 stays associated with psychoactive substance intoxication, 215,430 concerned young adults. Compared with adults 30+, hospitalization trends in young adults showed a greater decrease in the number of stays during lockdown, with a maximum decrease of -39% during the first lockdown (1,566 vs. 2,576; CI95%: 2,285-2,868) versus -20% (10,212 vs. 12,894; CI95%: 12,001-13,787) in the second lockdown. Presentations for alcohol intoxication decreased throughout the pandemic, particularly during the second lockdown, while admissions for benzodiazepine intoxication increased during both lockdowns. Admissions for cannabis intoxication increased throughout the entire period. CONCLUSIONS: Lockdowns were associated with fewer hospitalizations related to psychoactive substance intoxication in both age groups, especially among young adults, which might reflect a decrease in social use. Recreational use might therefore be an important target for prevention and risk minimization.

[Euthanasia and assisted suicide for psychiatric disorder]. / La pratique de l'euthanasie et du suicide assisté pour motif psychiatrique.

OBJECTIVES: Assisted death has been discussed for years in medicine. Ten countries have adopted legislation that authorises some form of euthanasia or assisted suicide, and the incidence and practices vary from country to country. Consideration of psychological pain linked to psychiatric disorders as a sufficient legal condition for enabling assisted death has added a new layer of complexity to the debate. Thus, Switzerland, Netherlands, Belgium and Luxembourg legalised assisted suicide or euthanasia for psychiatric reasons. In these cases, it is not a question of choosing death conditions but the occurrence of death. This manuscript is a narrative review of the literature about characteristics of patients with psychiatric disorders who requested assisted death in these countries. METHODS: Scientific manuscripts, reports and legal documents were reviewed. RESULTS: The incidence of assisted death for psychiatric reasons was low but has increased over the years. They represented 1.1 % of assisted deaths in Belgium (n=23) and 1.3 % in Netherlands (n=83) in 2017, and 4.5 % in Switzerland in 2014 when also considering dementia. The most frequent diagnoses were depressive and personality disorders. Patients were more often women than men, unlike suicide and middle aged. CONCLUSIONS: Authors who support these practices emphasise the right to die with dignity and the inequality of ruling out patients with psychiatric reasons, whereas they meet the legal requirements, and psychological pain is as severe as somatic pain. Some major issues are highlighted: the close relationship between mood symptoms and death wish, thinking biases and cognitive disturbances that limit the ability to decide, access and consent to medical care, the difficulty of assessing psychological pain, and the definitions of incurability or treatment refractoriness in psychiatry. To date, medical knowledge and assessment tools are not sufficient to define possible indications and offer the best support possible to these patients.

Multi-trajectories of antidepressant and antipsychotic use: a 11-year naturalistic study in a community-based sample.

OBJECTIVE: To explore the temporal dynamic of antidepressant and antipsychotic co-prescribing in real-life conditions. METHODS: The study was performed using reimbursement data from the French Insurance Healthcare system in a cohort of 118 454 persons with at least one dispensing of antidepressants and/or antipsychotics over the period 2006-2016. Latent class analyses were used to identify homogeneous groups of persons following similar multi-trajectories of antidepressant and/or antipsychotic dispensing. Multivariate polynomial logistic regression models were used to explore the characteristics independently associated with distinct trajectories. RESULTS: Five multi-trajectories of antidepressant and/or antipsychotic dispensing were identified: more than half of the sample (58%) had very low antidepressant and antipsychotic use; two groups had chronic (12%) or decreasing (11%) antidepressant use with very low antipsychotic use; two groups used both antidepressants and antipsychotics simultaneously either in an increasing (12%) or chronic (7%) way. Persons with chronic antidepressant-antipsychotic use presented with markers of poor social and mental health conditions. CONCLUSIONS: Most persons using antipsychotics over the follow-up also used antidepressants over the same period. The benefit/risk ratio of these prescribing practices should be further explored as the long-term efficacy of antidepressant-antipsychotic polypharmacy is poorly documented, while this combination increases the risk of adverse effects.

Interest of pharmacoepidemiology for the study of psychotropic drugs.

In psychiatry, drug evaluation using pharmacoepidemiological methods has been of growing interest in recent decades. Studies based on observational databases are particularly useful for psychotropic drugs due to their important prevalence in populations, and their use over long period. The authors discussed the specific interest of pharmacoepidemiological studies in the field of psychiatry through two examples: first, the use of antidepressants, and, second, the risks associated with antipsychotics.

[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.

Trajectory analysis of anxiolytic dispensing over 10 years among new users aged 50 and older.

OBJECTIVE: To identify temporal trajectories of anxiolytic benzodiazepine (A-BZD) use over 10 years among new A-BZD users aged 50 and older and describe treatment patterns and demographic and clinical characteristics associated with each trajectory. METHOD: A representative cohort of the French national health insurance fund users was tracked from 2006 through 2015. We used latent class mixed models to identify the trajectories. RESULTS: We observed four trajectories among new users (no A-BZD dispensing in 2005) plus one non-use trajectory. The proportion of occasional use among users was 60%; early increasing use, 10%; late increasing use, 17%; and increasing/decreasing use, 13%. Prevalence of occasional use decreased with age in women, but not men. Duration of treatment episodes and doses differed between trajectories. Multiple regression analyses with occasional use as the reference showed that the other three trajectories shared characteristics (age, coprescriptions of other psychotropic drugs, and more general practitioner consultations) but differed by the presence at inclusion or occurrence during follow-up of psychiatric, neurodegenerative, and somatic conditions. CONCLUSION: We found four different long-term temporal trajectories in new A-BZD users (occasional, early increasing, late increasing, and increasing/decreasing use). Difficulties quitting or reducing consumption may be very different for each trajectory, requiring tailored care approaches.

Risk of discontinuation of antipsychotic long-acting injections vs. oral antipsychotics in real-life prescribing practice: a community-based study.

OBJECTIVE: To compare the risk of discontinuation of ambulatory antipsychotic treatment in persons treated with antipsychotic long-acting injections (LAIs) or by oral antipsychotics (OAPs). METHODS: The study was performed in a representative sample of persons newly treated with OAPs (n = 6904) affiliated to the French Insurance Healthcare system. The risk of all-cause discontinuation was compared in patients prescribed OAPs (n = 246) vs. matched patients prescribed LAIs (n = 246) using multivariate survival analyses. Confounding by indication was minimized by matching on type of antipsychotic drug and by the high-dimensional propensity score method. RESULTS: Discontinuation was more frequent with OAPs (69%) compared to LAIs (57%) [adjusted relative risk (aRR) = 1.6, 95% CI 1.23-2.07]. Risk of discontinuation was higher for first-generation (FGA) OAPs vs. FGA LAIs (aRR = 1.94, 95% CI 1.22-3.08) as well as for second-generation (SGA) OAPs vs. SGA LAIs (aRR = 1.58, 95% CI 1.15-2.17). Over the 6-month period after discontinuation of LAIs, a new antipsychotic drug was dispensed in 58% of patients, the most frequent pattern being dispensing of the same LAI as that prescribed before discontinuation. CONCLUSIONS: Although less frequent than with OAPs, the rate of ambulatory treatment discontinuation was high with LAIs. Prescription of LAIs should be associated with intervention strategies aimed at promoting medication adherence.

Geographical disparities in prescription practices of lithium and clozapine: a community-based study.

OBJECTIVE: To explore the socioeconomic and health resource characteristics associated with geographical variations of lithium and clozapine dispensing rates in France. METHOD: The study was performed using reimbursement data from the French Insurance Healthcare system over the period 2006-2013 in a community-based sample of persons aged 16 years and over. An ecological design was used to assess whether lithium and clozapine prescribing rates were associated with socioeconomic and health resource characteristics of the zone of residence (n = 95 French administrative subdivisions). RESULTS: Large geographical disparities were observed in dispensing rates: lithium dispensing rates by zone of residence ranged from 0 to 6.6 per 1000 (mean 2.4 per 1000) and clozapine dispensing rates ranged from 0 to 4.9 per 1000 (mean 0.8 per 1000). Higher density of GPs and regular communication between mental health services and primary care were independently associated with higher rates of lithium and clozapine dispensing and with a higher proportion of lithium users among mood-stabilizer users. CONCLUSION: A sufficient density of GPs and an effective communication and collaboration between mental healthcare services and primary care seems to favor greater access to psychotropic drugs with demonstrated efficacy but often viewed as 'risky' to prescribe.

Determination of endocrine disruptors and endogenic androgens and estrogens in rat serum by high-performance liquid chromatography-tandem mass spectrometry.

To simultaneously measure some targeted endocrine disruptors and several forms of sex hormones in rat serum, an accurate analytical procedure was developed. First, a comparison between a polymeric-based solid-phase extraction (SPE) and a micro-extraction by packed sorbent was performed to choose the optimal method to extract and concentrate the analytes: bisphenol A, atrazine, vinclozolin metabolite, testosterone, androstenedione, estrone, estradiol, estrone-sulfate and glucuronide and estradiol-sulfate and glucuronide. The analyses were then performed by high-performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) with electrospray ionisation in positive and negative modes. The protocol based on SPE was validated using the ICH/2005 guidelines. The validation demonstrated good performance in terms of linearity (R(2)>0.99), recovery (71-90%) and repeatability (relative standard deviation: 1-18%). The method was sensitive with LOQ comprised between 0.1 and 0.4 ng/ml for androgens and between 0.098 and 10.2 ng/ml for estrogens. The results obtained on the serum of rats exposed to the targeted endocrine disruptors showed the suitability of this analytical strategy.

Caged mudsnail Potamopyrgus antipodarum (Gray) as an integrated field biomonitoring tool: exposure assessment and reprotoxic effects of water column contamination.

This study highlights the usefulness of gastropods for water quality monitoring. Gastropods were caged upstream and downstream of an effluent discharge. Exposure was assessed by measurement of organic contaminants in water. Contamination of the Potamopyrgus antipodarum mudsnail was also measured using innovative techniques at the end of the 42 days of exposure. Biological effects were measured at the individual level (growth, reproduction) and subindividual level (energy reserves, vitellin-like proteins, steroid levels, expression of genes involved in estrogen signaling pathways), thus providing a better understanding of reprotoxic effects. The effluent was mainly contaminated by pharmaceutical compounds, as was the mudsnail. The highest concentrations were measured for oxazepam and were higher than 2 mg/kg downstream of the effluent discharge. Alkylphenols, bisphenol A, and vertebrate-like sex-steroid hormones were also bioaccumulated by the mudsnail downstream of the effluent. The combined use of water and snail contamination provided a complete exposure assessment. Exposure was further linked to biological effects. The mudsnail was shown to be a better adapted species for in situ exposures than Valvata piscinalis. Reproduction was sharply decreased after 6 weeks of exposure in the mudsnail. Feeding issues were excluded, confirming the toxic origin. These effects were related to estrogen signaling pathways using genomic analysis. Genes coding for proteins involved in nongenomic signaling pathways were inhibited, and those of genomic pathway repressors were induced. These results suggest that the chemical contamination due to the effluent discharge altered steroid control of reproduction and blocked the transition between oocyte and unshelled embryo, resulting in a drastic decrease of embryo production, while survival was not affected.

[First-episodes psychosis: clinical and epidemiological news]. / Premiers épisodes psychotiques: actualités cliniques et épidémiologiques.

In the context of the development of early intervention for first-episode psychosis, this manuscript reviews new data with respect to its incidence, risk factors and evolution. Annual incidence of non-affective psychosis appeared to be between 14 and 30/100,000 in people aged 18-64. Incidence decreases with age and is twice higher in men than in women. There is an interaction between age and gender; the risk of psychosis decreases with age faster in men than in women. Thus, for schizophrenia, incidence rate is twice higher in men under 45 year-old and similar in both genders after. There is evidence that genetic and environmental factors may cause enduring liability to psychotic disorder, and, in addition, that genes and environment may interact synergistically. Some environmental factors have been identified; they concern foetal life, childhood or adolescence and may be conceptualized at the individual or the contextual level. The definition of recent onset psychosis may be based on duration of psychosis, between two and five years. Its development is identified through the occurrence of major psychotic symptoms, such as positive, negative symptomatology or disorganization, and impairment of social functioning. The types and patterns of occurrence and of evolution of psychotic symptoms have a prognostic impact. A long duration of untreated psychosis impacts symptomatology. It is associated with less severe positive symptoms at baseline and more severe after three years, insidious onset, male gender, early onset, and diagnosis of schizophrenia. Recent onset psychosis is often associated with comorbidities, such as depression, anxiety disorders, suicidal behaviours, and addiction. Symptomatic remission rates are found between 25 and 60%. Symptomatic and functional remissions favour each other. A third to half of patients is active, employed or students. Symptoms and evolution are various in studies, probably corresponding to various patho-physiological mechanisms.

Economic impact of antidepressant treatment duration in naturalistic conditions.

OBJECTIVE: To assess the economic impact of the duration of antidepressant drug treatment in a real-life setting. METHOD: A historical fixed cohort study included 27 917 patients aged 18 and over with a new antidepressant treatment registered in the national insurance database. The economic impact concerned healthcare expenditure in the first 3 months after treatment discontinuation. Generalized linear models were used to compare two groups of treatment duration: <6 months and 6 months and over. RESULTS: After adjustment for care costs before and during treatment episode, gender, age, chronic diseases, welfare and prescriber specialty, total healthcare costs (in log) [-0.06 (-0.14;0.01) P = 0.11] and psychiatric care costs (in square root) [-0.08 (-0.41;0.25) P = 0.6] were similar in both groups. Non-psychiatric care costs were significantly lower in the 'long treatment duration' group compared with the 'short treatment duration' group [-11.4 (-15.8; -7.0) P < 0.0001]. The decreases in total and non-psychiatric care costs over the antidepressant treatment episode were larger in the 'long treatment duration' group compared with the 'short treatment duration' group. CONCLUSION: With regard to healthcare costs and global health, antidepressant drug treatments of short duration appear less effective than treatment of recommended duration.

[Metabolic testing rates after initiation of antipsychotic treatment in persons initially treated by conventional mood-stabilizers]. / Surveillance métabolique biologique après initiation d'un traitement antipsychotique chez des personnes traitées par lithium ou anticonvulsivants.

OBJECTIVES: To assess the rate of metabolic testing after initiation of second-generation antipsychotics (SGA) prescription in persons initially treated by conventional mood-stabilizers (lithium or anticonvulsants, as a proxy of bipolar disorder diagnosis) and to compare the rates of metabolic testing in these persons with those in persons with initiation of first-generation antipsychotics (FGA) prescription or with no antipsychotic prescription. METHOD: Data were anonymously extracted from the 2004 to 2006 French national health database of the Régime Social des Travailleurs Indépendants (RSI). Patients aged 18 years and over were included in the cohort if they fulfilled the following criteria over a three-month inclusion period: refunding of lithium or anticonvulsant over the 3 months without discontinuation (as a proxy of bipolar disorder diagnosis), no concomitant refunding over the 3months of antipsychotic, and no concomitant refunding over the 3 months of an anti-diabetic drug (as a marker of diabetes) or a lipid-lowering drug (as a marker of hyperlipidemia). Metabolic testing was assessed using information collected in the RSI database on the reimbursement of glucose-specific serum tests (glycaemia) and lipid-specific serum tests (total cholesterol). Serum glucose and lipid testings were assessed at baseline and at 12-week follow-up for the first episode of antipsychotic dispensing. Multivariate analyses were performed to compare the rate of metabolic testing in users of SGA to those of users of FGA and to those of non-users of antipsychotics. RESULTS: Three thousand one hundred and seventy patients were included. Of the 490 (15.4%) persons with a first episode of antipsychotic dispensing after the index date, 138 (4.3%) were dispensed only FGA over the first episode and 352 (11.1%) SGA (including 37 patients with both SGA and FGA dispensing). Metabolic testing at baseline and at 12-week follow-up was performed for 14% of persons with initiation of FGA and 12% with initiation of SGA. Almost no patient had both baseline and follow-up testing. Testing rates were lower for lipid testing than for glucose testing. Compared to persons with no antipsychotic, persons with SGA were significantly more likely to have metabolic testing at baseline and at follow-up, independently from other characteristics (adjusted OR=0.24, 95% CI 0.16 to 0.36). No difference was found between persons with SGA and those with FGA (adjusted OR=1.12, 95%CI 0.62 to 2.0). Regarding the other characteristics associated with likelihood of metabolic testing (irrespective of the treatment group), women were more likely than men to have metabolic testing at baseline but not at follow-up. Elderly persons and persons with low occupational status were more likely to have metabolic testing at follow-up. CONCLUSION: From a public health point of view, such findings indicate that the metabolic risks associated with SGA use in real-life conditions are widely underestimated. Regarding the temporal trends of antipsychotic prescription, with the dramatic rise of SGA use observed in most countries, it is a public health priority to improve metabolic monitoring in SGA users, irrespective of the underlying diagnosis. Since it is more complex to modify pre-existing inadequate practices than to initiate correct ones in new prescribers, great attention should be paid to the need for delivering strong messages regarding the metabolic risks associated with SGA prescription during the initial training of physicians.

[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.

Natural character posing from a large motion database.

An interactive inverse kinematics approach robustly generates natural poses in a large human-reachable space. It employs adaptive kd clustering to select a representative frame set from a large motion database and employs sparse approximation to accelerate training and posing. Model training is required only once.

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.

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.