The influence of burnout on cardiovascular disease: a systematic review and meta-analysis.

Background: Burnout is a public health problem with various health consequences, among which cardiovascular disease is the most investigated but still under debate. Our objective was to conduct a systematic review and meta-analysis on the influence of burnout on cardiovascular disease. Methods: Studies reporting risk (odds ratio, relative risk, and hazard ratio) of cardiovascular disease following burnout were searched in PubMed, PsycINFO, Cochrane, Embase, and ScienceDirect. We performed a random-effect meta-analysis stratified by type of cardiovascular disease and searched for putative influencing variables. We performed sensitivity analyses using the most adjusted models and crude risks. Results: We included 25 studies in the systematic review and 9 studies in the meta-analysis (4 cross-sectional, 4 cohort, and 1 case-control study) for a total of 26,916 participants. Burnout increased the risk of cardiovascular disease by 21% (OR = 1.21, 95% CI 1.03 to 1.39) using the most adjusted risks and by 27% (OR = 1.27, 95% CI 1.10 to 1.43) using crude risks. Using stratification by type of cardiovascular disease and the most adjusted risks, having experienced burnout significantly increased the risk of prehypertension by 85% (OR = 1.85, 95% CI 1.00 to 2.70) and cardiovascular disease-related hospitalization by 10% (OR = 1.10, 95% CI 1.02 to 1.18), whereas the risk increase for coronary heart disease (OR = 1.79, 95% CI 0.79 to 2.79) and myocardial infarction (OR = 1.78, 95% CI 0.85 to 2.71) was not significant. Results were also similar using crude odds ratio. The risk of cardiovascular disease after a burnout was not influenced by gender. Insufficient data precluded other meta-regressions. Conclusions: Burnout seems to increase the risk of cardiovascular disease, despite the few retrieved studies and a causality weakened by cross-sectional studies. However, numerous studies focused on the pathophysiology of cardiovascular risk linked to burnout, which may help to build a preventive strategy in the workplace.

French Society for Biological Psychiatry and Neuropsychopharmacology (AFPBN) guidelines for the management of patients with partially responsive depression and treatment-resistant depression: Update 2024.

INTRODUCTION: The purpose of this update is to add newly approved nomenclatures and treatments as well as treatments yet to be approved in major depressive disorder, thus expanding the discussions on the integration of resistance factors into the clinical approach. METHODS: Unlike the first consensus guidelines based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) developed an update of these guidelines for the management of partially responsive depression (PRD) and treatment-resistant depression (TRD). The expert guidelines combine scientific evidence and expert clinicians' opinions to produce recommendations for PRD and TRD. RESULTS: The recommendations addressed three areas judged as essential for updating the previous 2019 AFPBN guidelines for the management of patients with TRD: (1) the identification of risk factors associated with TRD, (2) the therapeutic management of patients with PRD and TRD, and (3) the indications, the modalities of use and the monitoring of recent glutamate receptor modulating agents (esketamine and ketamine). CONCLUSION: These consensus-based guidelines make it possible to build bridges between the available empirical literature and clinical practice, with a highlight on the 'real world' of the clinical practice, supported by a pragmatic approach centred on the experience of specialised prescribers in TRD.

Anorexia nervosa: Enhancing motivation to change with self-determination theory.

Motivational deficits (little or no motivation to change) are often reported in patients with eating disorders, particularly anorexia nervosa. The motivational approaches frequently used by French clinicians rely solely on a dichotomous view of motivation (intrinsic vs. extrinsic). In self-determination theory, certain forms of extrinsic motivation can strengthen an individual's commitment to an activity, providing they are self-determined. This theory therefore extends and enriches the dual motivational approach by highlighting potentially useful forms of extrinsic motivation and by emphasizing the importance of behavioral regulation. Empirical work is now needed to assess how clinicians can use self-determination theory to enhance motivation to change among patients with anorexia nervosa and encourage their adherence to care management plans.

Evaluating the efficacy and safety of the currently available once-every-two months long-acting injectable formulations of aripiprazole for the treatment of schizophrenia or as a maintenance monotherapy for bipolar I disorder in adults.

INTRODUCTION: An aripiprazole long-acting injectable (LAI) antipsychotic is now available for gluteal administration every 2 months via two different formulations: aripiprazole lauroxil (AL) and aripiprazole monohydrate (Ari 2MRTU). These longer dosing regimens of aripiprazole LAI offer new potential benefits for patients. AREAS COVERED: The authors review the evidence supporting the efficacy and safety of aripiprazole LAIs given every 2 months for the treatment of schizophrenia or bipolar disorder (BD) in adults. The article culminates with the authors' expert perspectives on the subject. EXPERT OPINION: AL 1064 mg every 2 months has established efficacy for the treatment of schizophrenia based on pharmacokinetic bridging studies and prospective data for treatment of an acute exacerbation of schizophrenia. In an open-label trial, Ari 2MRTU showed efficacy for the treatment of schizophrenia and BD type I based on pharmacokinetic parameters (comparable to aripiprazole once-monthly 400 mg); it also showed efficacy regarding the secondary endpoints. Multiple doses of AL 1064 mg or Ari 2MRTU 960 mg are generally well tolerated, in line with the safety profile of oral aripiprazole, with the exception of the injection-site reactions. While AL may require a 1-day initiation regimen, Ari 2MRTU 960 covers all the recommended doses of oral aripiprazole (10-20 mg).

Variation of subclinical psychosis across 16 sites in Europe and Brazil: findings from the multi-national EU-GEI study.

BACKGROUND: Incidence of first-episode psychosis (FEP) varies substantially across geographic regions. Phenotypes of subclinical psychosis (SP), such as psychotic-like experiences (PLEs) and schizotypy, present several similarities with psychosis. We aimed to examine whether SP measures varied across different sites and whether this variation was comparable with FEP incidence within the same areas. We further examined contribution of environmental and genetic factors to SP. METHODS: We used data from 1497 controls recruited in 16 different sites across 6 countries. Factor scores for several psychopathological dimensions of schizotypy and PLEs were obtained using multidimensional item response theory models. Variation of these scores was assessed using multi-level regression analysis to estimate individual and between-sites variance adjusting for age, sex, education, migrant, employment and relational status, childhood adversity, and cannabis use. In the final model we added local FEP incidence as a second-level variable. Association with genetic liability was examined separately. RESULTS: Schizotypy showed a large between-sites variation with up to 15% of variance attributable to site-level characteristics. Adding local FEP incidence to the model considerably reduced the between-sites unexplained schizotypy variance. PLEs did not show as much variation. Overall, SP was associated with younger age, migrant, unmarried, unemployed and less educated individuals, cannabis use, and childhood adversity. Both phenotypes were associated with genetic liability to schizophrenia. CONCLUSIONS: Schizotypy showed substantial between-sites variation, being more represented in areas where FEP incidence is higher. This supports the hypothesis that shared contextual factors shape the between-sites variation of psychosis across the spectrum.

Indirect effect of impulsivity on suicide risk through self-esteem and depressive symptoms in a population with treatment-resistant depression: A FACE-DR study.

INTRODUCTION: Suicide is a major health issue. Its prevalence is particularly high in subjects presenting major depression disorder (MDD), making this a key suicide-related risk factor. Suicide attempts in severe forms of MDD were assumed to be linked to impulsivity and loss of control. Nevertheless, we failed to find data specifically investigating the link between impulsivity and suicide risk in treatment-resistant depression (TRD). This study seeks to review this relationship. METHOD: Patients were recruited for a prospective cohort. Suicide risk and impulsivity were assessed using the International Neuropsychiatric Interview and Barratt Impulsiveness Scale, Version 10, respectively, while the severity of depressive symptoms was assessed using the Montgomery-Asberg Depression Rating Scale, anxiety with the State-Trait Anxiety Inventory and childhood maltreatment using the Childhood Trauma Questionnaire. RESULTS: 220 TRD patients were enrolled in the study. The impulsivity score was correlated with self-esteem, marital status, professional status and anxiety. There was no direct link to suicide risk. However, impulsivity was associated with self-esteem (coefficient: -0.24; p value 0.043) and depressive symptom severity (coefficient: 0.; p value 0.045). The suicide risk was significantly correlated with depressive symptom severity (coefficient = 0.38, p < 0.001) and self-esteem (coefficient = -0.34, p = 0.01). Considering these correlations, we postulated that the effect of impulsivity on suicide risk could be mediated by self-esteem in terms of depressive symptom severity and we finally found a relevant mediation model within impulsivity having an indirect effect on suicide risk by impacting self-esteem and depressive symptoms with anxiety also playing a significant role as a covariable. CONCLUSION: We found that impulsivity could play an indirect role with the involvement of self-esteem and depressive symptoms and the contributing role of anxiety.

Neuropsychological assessment fails to predict relapse among cigarette smokers: A prospective study of neurocognitive abilities.

OBJECTIVES: Understanding the factors that lead to relapse is a major challenge for the clinical support of smoking cessation. Neurocognitive abilities such as attention, executive functioning and working memory, are possible predictors of relapse and can be easily assessed in everyday clinical practice. In this prospective longitudinal study, we investigated the relationship between pre-smoking cessation neurocognitive performance and relapse at six months in a sample of patients being treated for their tobacco dependence. METHODS: 130 tobacco consumers were included in the study. They completed a comprehensive neuropsychological and clinical assessment before smoking cessation. The targeted abilities were intelligence, inhibition, shifting, working memory updating, verbal fluency and decision-making. RESULTS: The rate of tobacco relapse at 6 months was 58%. Logistic regressions were used to assess which variables best explained relapse. None of the neuropsychological tests was a significant predictor of relapse at either 1, 3 or 6 months, either alone, or controlling for other covariates acting as significant predictors of relapse. CONCLUSIONS: Common neuropsychological tests, even those specifically targeting executive functioning such as inhibition, are not useful predictors of the success of a smoking cessation program in a clinical setting. Other variables, such as motivation to quit smoking or the presence of comorbid depression or anxiety disorders, appear to be more useful predictors of relapse.

Clinical and cognitive characteristics of subjects with schizophrenia and childhood attention-deficit/hyperactivity disorder: Results from the multicentric FACE-SZ cross-sectional dataset.

BACKGROUND: Childhood Attention-deficit/hyperactivity disorder (C-ADHD) is a neurodevelopmental disorder, associated with an increased risk of subsequent schizophrenia. The objective of the present study was to determine the prevalence of C-ADHD in schizophrenia and the clinical and cognitive characteristics associated with C-ADHD history in schizophrenia. METHODS: 569 subjects with schizophrenia (74 % men, mean age 30.8) were included in ten expert centers at a national level and tested with a comprehensive battery of clinician-rated, patient-reported scales and cognitive tests. C-ADHD was assessed with the WURS (Wender Utah Rating Scale) self-report questionnaire. Multivariate, correlation, and principal component analyses (PCA) were conducted. RESULTS: Thirty-nine subjects (N = 39, 6.9 %) were classified in the C-ADHD group. Compared to those without C-ADHD, subjects with C-ADHD were more frequently male, had lower education levels, more severe positive clinical symptoms, more subjective cognitive deficits complaints, and lower medication adherence with small to medium effect sizes. Two cognitive components emerged from the PCA, one component including perceptual reasoning and working memory, and another component including visuospatial search and graphomotor speed, cognitive inhibition/flexibility and central executive functioning. Both components were associated with lower performances in the C-ADHD group. CONCLUSIONS: C-ADHD is frequent in schizophrenia and associated with more severe positive symptoms and impaired cognitive performances compared to those without C-ADHD. This suggests that the pathophysiological mechanisms contributing to these disorders may lead to the worsening of the cognitive functioning in patients with both disorders. C-ADHD is a relevant clinical marker to discriminate subgroups of schizophrenia with different profiles for a precision-psychiatry approach.

Cannabis use as a potential mediator between childhood adversity and first-episode psychosis: results from the EU-GEI case-control study.

BACKGROUND: Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis. METHODS: Data were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study. Detailed history of cannabis use was collected with the Cannabis Experience Questionnaire. The Childhood Experience of Care and Abuse Questionnaire was used to assess exposure to household discord, sexual, physical or emotional abuse and bullying in two periods: early (0-11 years), and late (12-17 years). A path decomposition method was used to analyse whether the association between childhood adversity and psychosis was mediated by (1) lifetime cannabis use, (2) cannabis potency and (3) frequency of use. RESULTS: The association between household discord and psychosis was partially mediated by lifetime use of cannabis (indirect effect coef. 0.078, s.e. 0.022, 17%), its potency (indirect effect coef. 0.059, s.e. 0.018, 14%) and by frequency (indirect effect coef. 0.117, s.e. 0.038, 29%). Similar findings were obtained when analyses were restricted to early exposure to household discord. CONCLUSIONS: Harmful patterns of cannabis use mediated the association between specific childhood adversities, like household discord, with later psychosis. Children exposed to particularly challenging environments in their household could benefit from psychosocial interventions aimed at preventing cannabis misuse.

The Efficacy and Safety of Intranasal Formulations of Ketamine and Esketamine for the Treatment of Major Depressive Disorder: A Systematic Review.

Ketamine and its enantiomers represent an innovative glutamatergic agent as a treatment for individuals with treatment-resistant depression (TRD) and major depressive disorder (MDD) with suicidal ideation and behavior. Intranasal (IN) formulations could allow for quick onset of action on depressive symptoms as well as a reduction in side effects by bypassing the blood-brain barrier compared with administration via the intravenous route. The aim of this review was to provide an up-to-date analysis of the data on the efficacy and safety of IN ketamine and IN esketamine for the treatment of MDD. A systematic review following PRISMA guidelines was conducted. Databases (PubMed, Embase, MEDLINE, PsycINFO, and Google Scholar) were searched to capture articles about IN ketamine or IN esketamine for MDD. This systematic review highlighted the interest in IN routes of ketamine and esketamine for MDD patients with TRD or active suicidal ideation. They provide a rapid onset of antidepressant action within the first hours after administration. Nevertheless, the evidence of efficacy is stronger for IN esketamine than for IN ketamine in MDD patients. The safety profile appears to be acceptable for IN esketamine but requires further studies, and a more accurate IN delivery device is required for ketamine.

Could reasons for admission help to screen unhealthy alcohol use in emergency departments? A multicenter French study.

Background: Many patients admitted to general emergency departments (EDs) have a pattern of drinking that could lead to future alcohol-related complications. However, it is often difficult to screen these patients in the context of emergency. The aim of this study is to analyze whether reasons for admission could help to screen patients who have an unhealthy alcohol use. Method: Patients were recruited among six public hospital ED in France, between 2012 and 2014. During a one-month period in each hospital, anonymous questionnaires including sociodemographic questions, AUDIT-C and RAPS4-QF were administered to each patients visiting the ED. The reason for admission of each patient was noted at the end of their questionnaire by the ED practitioner. Results: Ten thousand Four hundred twenty-one patients were included in the analysis. Patients who came to the ED for injuries and mental disorders were more likely to report unhealthy alcohol use than non-harmful use or no use. Among male patients under 65 years old admitted to the ED for a mental disorder, 24.2% drank more than four drinks (40 g ethanol) in typical day at least four time a week in the last 12 months. Among these patients, 79.7% reported daily or almost daily heavy episodic drinking (HED, 60 g ethanol), and all were positive on the RAPS4-QF. Conclusion: This study highlights that unhealthy alcohol use is frequent among ED patients and particularly among those who come for injuries or mental disorders. Men under 65 years old with a mental disorder require special attention because of their increased prevalence of daily or almost daily HED.

Poverty and inequality in real-world schizophrenia: a national study.

Background: Schizophrenia has high socioeconomic impact among severe psychiatric disorders. Aims: To explore clinician-reported and patient-reported inequities between patients under the poverty threshold vs. the others. Method: 916 patients consecutively recruited in 10 national centers received a comprehensive standardized evaluation of illness severity, addictions and patient-reported outcomes. Results: 739 (80.7%) of the patients were classified in the poverty group. This group had poorer objective illness outcomes (lower positive, negative, cognitive, excitement/aggressive and self-neglect symptoms and lifetime history of planned suicide) in multivariate analyses. While they had similar access to treatments and psychotherapy, they had lower access to socially useful activities, couple's life, housing and parenthood. They had also more disturbed metabolic parameters. On the contrary, the poverty group reported better self-esteem. No significant difference for depression, risky health behavior including addictions and sedentary behavior was found. Interpretation: The equity in access to care is attributed to the French social system. However, mental and physical health remain poorer in these patients, and they still experience poor access to social roles independently of illness severity and despite healthcare interventions. These patients may have paradoxically better self-esteem due to decreased contact with society and therefore lower stigma exposure (especially at work). Schizophrenia presents itself as a distinct impoverished population concerning health-related outcomes and social integration, warranting focus in public health initiatives and improved treatment, including tailored interventions, collaborative care models, accessible mental health services, housing support, vocational training and employment support, community integration, education and awareness, research and data collection, culturally competent approaches, and long-term support.

Predictors of medication adherence in a large 1-year prospective cohort of individuals with schizophrenia: insights from the multicentric FACE-SZ dataset.

Schizophrenia is characterized by the most salient medication adherence problems among severe mental disorders, but limited prospective data are available to predict and improve adherence in this population. This investigation aims to identify predictors of medication adherence over a 1-year period in a large national cohort using clustering analysis. Outpatients were recruited from ten Schizophrenia Expert Centers and were evaluated with a day-long standardized battery including clinician and patient-rated medication adherence measures. A two-step cluster analysis and multivariate logistic regression were conducted to identify medication adherence profiles based on the Medication Adherence rating Scale (MARS) and baseline predictors. A total of 485 participants were included in the study and medication adherence was significantly improved at the 1-year follow-up. Higher depressive scores, lower insight, history of suicide attempt, younger age and alcohol use disorder were all associated with poorer adherence at 1 year. Among the 203 patients with initially poor adherence, 86 (42%) switched to good adherence at the 1-year follow-up, whereas 117 patients (58%) remained poorly adherent. Targeting younger patients with low insight, history of suicide, alcohol use disorder and depressive disorders should be prioritized through literacy and educational therapy programs. Adherence is a construct that can vary considerably from year to year in schizophrenia, and therefore may be amenable to interventions for its improvement. However, caution is also warranted as nearly one in five patients with initially good adherence experienced worsened adherence 1 year later.

Adjunctive agents to antipsychotics in schizophrenia: a systematic umbrella review and recommendations for amino acids, hormonal therapies and anti-inflammatory drugs.

QUESTION: This umbrella review and guidelines aimed to provide evidence to support the rational choice of selected adjunctive therapies for schizophrenia. STUDY SELECTION AND ANALYSIS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and World Federation of Societies of Biological Psychiatry (WFSBP)-grading recommendations, 63 randomised control trials (RCTs) (of which 4219 unique participants have completed the RCTs) and 29 meta-analyses were analysed. FINDINGS: Provisional recommendations (WFSBP-grade 1) could be made for two molecules in augmentation to antipsychotics: (1) N-acetyl-cysteine (NAC, 1200-3600 mg/day, for >12 consecutive weeks) in improving negative symptoms, general psychopathology (positive and negative syndrome scale for schizophrenia (PANSS) general psychopathology factor (G)-G subscale), with the RCTs with the longer duration showing the most robust findings; (2) polyunsaturated fatty acids (3000 mg/day of eicosapentaenoic acid, for >12 weeks) in improving general psychopathology. Weaker recommendations (ie, WFSBP-grade 2) could be drawn for sarcosine (2 g/day) and minocycline (200-300 mg/day) for improving negative symptoms in chronic schizophrenia (not early schizophrenia), and NAC for improving positive symptoms and cognition. Weak recommendations are not ready for clinical practice. There is provisional evidence that oestrogens and raloxifene are effective in some patients, but further research is needed to determine their benefit/risk ratio. CONCLUSIONS: The results of this umbrella review should be interpreted with caution as the number of RCTs included in the meta-analyses was generally small and the effect sizes were weak or medium. For NAC, two RCTs with low risk of bias have provided conflicting results and the WFSBP-grade recommendation included also the results of meta-analyses. These drugs could be provisionally prescribed for patients for whom no other treatments have been effective, but they should be discontinued if they prove ineffective.

Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression.

BACKGROUND: In treatment-resistant depression, commonly defined as a lack of response to two or more consecutive treatments during the current depressive episode, the percentage of patients with remission is low and the percentage with relapse is high. The efficacy and safety of esketamine nasal spray as compared with extended-release quetiapine augmentation therapy, both in combination with ongoing treatment with a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI), in patients with treatment-resistant depression are unknown. METHODS: In an open-label, single-blind (with raters unaware of group assignments), multicenter, phase 3b, randomized, active-controlled trial, we assigned patients, in a 1:1 ratio, to receive flexible doses (according to the summary of product characteristics) of esketamine nasal spray (esketamine group) or extended-release quetiapine (quetiapine group), both in combination with an SSRI or SNRI. The primary end point was remission, defined as a score of 10 or less on the Montgomery-Åsberg Depression Rating Scale (MADRS), at week 8 (scores range from 0 to 60, with higher scores indicating more severe depression). The key secondary end point was no relapse through week 32 after remission at week 8. All patients were included in the analysis; patients who discontinued the trial treatment were considered as having had an unfavorable outcome (i.e., they were grouped with patients who did not have remission or who had a relapse). Analyses of the primary and key secondary end points were adjusted for age and number of treatment failures. RESULTS: Overall, 336 patients were assigned to the esketamine group and 340 to the quetiapine group. More patients in the esketamine group than in the quetiapine group had remission at week 8 (91 of 336 patients [27.1%] vs. 60 of 340 patients [17.6%]; P = 0.003) and had no relapse through week 32 after remission at week 8 (73 of 336 patients [21.7%] vs. 48 of 340 patients [14.1%]). Over 32 weeks of follow-up, the percentage of patients with remission, the percentage of patients with a treatment response, and the change in the MADRS score from baseline favored esketamine nasal spray. The adverse events were consistent with the established safety profiles of the trial treatments. CONCLUSIONS: In patients with treatment-resistant depression, esketamine nasal spray plus an SSRI or SNRI was superior to extended-release quetiapine plus an SSRI or SNRI with respect to remission at week 8. (Funded by Janssen EMEA; ESCAPE-TRD ClinicalTrials.gov number, NCT04338321.).

Development of the PREMIUM computerized adaptive testing for measuring the access and care coordination for patients with severe mental illness.

Severe mental illness (SMI) patients often have complex health needs, which makes it difficult to access and coordinate their care. This study aimed to develop a computerized adaptive testing (CAT) tool, PREMIUM CAT-ACC, to measure SMI patients' experience with access and care coordination. This multicenter and cross-sectional study included 496 adult in- and out-patients with SMI (i.e., schizophrenia, bipolar disorder, or major depressive disorder). Psychometric analysis of the 13-item bank showed adequate properties, with preliminary evidence of external validity and no substantial differential item functioning for sex, age, care setting, and diagnosis, making it suitable for CAT administration. A post-hoc CAT simulation demonstrated that the tool was efficient and accurate, with an average of seven items, compared to the full item bank administration. Its use by clinicians can contribute to optimizing patient care pathways and transitioning towards more person-centered healthcare.

Real-world effectiveness of long-acting injectable antipsychotic treatments in a nationwide cohort of 12,373 patients with schizophrenia-spectrum disorders.

This mirror-image study aimed to evaluate the real-life effectiveness of long-acting injectable antipsychotics (LAI) in schizophrenia. Patients with schizophrenia initiating LAIs January 2015-December 2016 were enrolled from the French National Health Data System (SNDS). Standardized mean differences (SMD > 0.1 deemed clinically significant) were calculated for psychiatric healthcare resource utilization measures assessed one year before (during oral AP treatment) and one year after LAI initiation. LAI effectiveness was analyzed overall and by age group, gender and compliance to oral AP, defined as exposure to an AP for at least 80% of the year before LAI initiation. 12,373 patients were included. LAIs were more frequently initiated in men (58.1%), young (18-34 years, 42.0%) and non-compliant (63.7%) patients. LAI initiation was effective in reducing the number and duration of psychiatric hospitalizations and psychiatric emergency department (ED) admissions in non-compliant patients (SMD = -0.19, -0.26 and -0.12, respectively), but not in compliant patients. First-generation LAIs, paliperidone and aripiprazole LAIs reduced psychiatric hospitalizations (SMD = -0.20, -0.24, -0.21, respectively) and ED admissions (SMD = -0.15, -0.13, -0.15, respectively). No differences in effectiveness were found for age or gender. In compliant patients, only aripiprazole LAI reduced the number of psychiatric hospitalizations (SMD = -0.13). Risperidone and paliperidone LAIs increased hospitalization duration (SMD = 0.15 and 0.18, respectively). The prescription of LAIs (except risperidone) should be recommended in all non-compliant patients, even in women and patients aged 35 or older. The lower frequency of administration of LAIs than of oral APs may improve compliance and hence reduce the risk of relapse. Aripiprazole LAI may represent a treatment of choice for compliant patients that should be further investigated.

How can we improve the care of patients with schizophrenia in the real-world? A population-based cohort study of 456,003 patients.

An important step to improve outcomes for patients with schizophrenia is to understand treatment patterns in routine practice. The aim of the current study was to describe the long-term management of patients with schizophrenia treated with antipsychotics (APs) in real-world practice. This population-based study included adults with schizophrenia and who had received ≥3 deliveries of an AP from 2012-2017, identified using a National Health Data System. Primary endpoints were real-life prescription patterns, patient characteristics, healthcare utilization, comorbidities and mortality. Of the 456,003 patients included, 96% received oral APs, 17.5% first-generation long-acting injectable APs (LAIs), and 16.1% second generation LAIs. Persistence rates at 24 months after treatment initiation were 23.9% (oral APs), 11.5% (first-generation LAIs) and 20.8% (second-generation LAIs). Median persistence of oral APs, first-generation LAIs and second-generation LAIs was 5.0, 3.3, and 6.1 months, respectively. Overall, 62.1% of patients were administered anxiolytics, 45.7% antidepressants and 28.5% anticonvulsants, these treatments being more frequently prescribed in women and patients aged ≥50 years. Dyslipidemia was the most frequent metabolic comorbidity (16.2%) but lipid monitoring was insufficient (median of one occasion). Metabolic comorbidities were more frequent in women. Standardized patient mortality remained consistently high between 2013 and 2015 (3.3-3.7 times higher than the general French population) with a loss of life expectancy of 17 years for men and 8 years for women. Cancer (20.2%) and cardiovascular diseases (17.2%) were the main causes of mortality, and suicide was responsible for 25.4% of deaths among 18-34-year-olds. These results highlight future priorities for care of schizophrenia patients. The global persistence of APs used in this population was low, whereas rates of psychiatric hospitalization remain high. More focus on specific populations is needed, such as patients aged >50 years to prevent metabolic disturbances and 18-34-year-olds to reduce suicide rates.