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Due to its reliance on heterogeneous symptomatology, the accurate diagnosis of psychotic disorders remains a challenging task in clinical practice. Precise and early diagnosis of psychotic disorders facilitates early intervention, which has been shown to have substantial benefits for long-term outcomes. Still, the lack of specific biomarkers is an important limitation in early diagnosis and intervention. Exosomes, which act as messengers between cells, including brain cells, contain a vast array of molecules that hold promise for unveiling disorder-specific abnormalities. In this review, we discuss recent evidence highlighting the potential of circulating exosomes and brain-derived exosomes as valuable tools for the identification of accessible, non-invasive, and blood-based biomarkers of psychotic symptomatology and risk. We discuss current limitations in biomarker discovery studies focusing on exosomes. To enhance diagnosis specificity and treatment response, we also provide guidance for future investigations that need to target biomarkers of risk and relapse, as well as consider duration of untreated psychosis, biological sex, and other factors in the multifactorial biosignature of psychosis.
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Biomarcadores , Exossomos , Transtornos Psicóticos , Humanos , Exossomos/metabolismo , Transtornos Psicóticos/diagnóstico , Biomarcadores/sangue , Biomarcadores/metabolismo , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Diagnóstico PrecoceRESUMO
AIM: To develop a typology of care trajectories (CTs) 1 year before and after a first dementia diagnosis in individuals aged ≥65 years, with prevalent schizophrenia or bipolar disorder. METHODS: This was a longitudinal, retrospective cohort study using health administrative data (1996-2016) from Quebec (Canada). We selected patients aged ≥65 years with an incident diagnosis of dementia between 1 January 2014 and 31 December 2016, and a diagnosis of schizophrenia and/or or bipolar disorder. A CT typology was generated by a multidimensional state sequence analysis based on the "6 W" model of CTs. Three dimensions were considered: the care setting ("where"), the reason for consultation ("why") and the specialty of care providers ("which"). RESULTS: In total, 3868 patients were categorized into seven distinct types of CTs, with varying patterns of healthcare use and comorbidities. Healthcare use differed in terms of intensity, but also in its distribution around the diagnosis. For instance, whereas one group showed low healthcare use, healthcare use abruptly increased or decreased after the diagnosis in other groups, or was equally distributed. Other significant differences between CTs included mortality rates and use of long-term care after the diagnosis. Most patients (67%) received their first dementia diagnosis during hospitalization. CONCLUSIONS: Our innovative approach provides a unique insight into the complex healthcare patterns of people living with serious mental illness and dementia, and provides an avenue to support data-driven decision-making by highlighting fragility areas in allocating care resources. Geriatr Gerontol Int 2024; 24: 577-586.
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Demência , Humanos , Demência/diagnóstico , Demência/epidemiologia , Masculino , Feminino , Idoso , Estudos Retrospectivos , Quebeque/epidemiologia , Idoso de 80 Anos ou mais , Estudos Longitudinais , Esquizofrenia/diagnóstico , Esquizofrenia/epidemiologia , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/epidemiologia , Hospitalização/estatística & dados numéricos , Estudos de CoortesRESUMO
INTRODUCTION: Problem gambling (PBG) is more common in people with mental health disorders, including substance use, bipolar, and personality disorders, than in the general population. Although individuals with psychotic disorders might be expected to be more vulnerable to PBG, fewer studies have focused on this comorbidity. The aim of this review was to estimate the prevalence of PBG in people with psychotic disorders. METHODS: Medline (Ovid), EMBASE, PsycINFO (Ovid), CINAHL, CENTRAL, Web of science, and ProQuest were searched on November 1, 2023, without language restrictions. Observational and experimental studies including individuals with psychotic disorders and reporting the prevalence of PBG were included. Risk of bias was assessed using the Joanna Briggs Institute critical appraisal for systematic reviews of prevalence data. The pooled prevalence of PBG was calculated using a fixed effects generalized linear mixed model and presented through forest plots. RESULTS: Of 1271 records screened, 12 studies (n = 3443) were included. The overall prevalence of PBG was 8.7% (95% CI = 7.8%-9.7%, I2 = 69%). A lower prevalence was found in studies with a low risk of bias (5.6%; 95% CI = 4.4%-7.0%) compared with studies with a moderate risk of bias (10.4%; 95% CI = 9.2%-11.7%). Different methods used to assess PBG also contributed to the heterogeneity found. CONCLUSION: This meta-analysis found substantial heterogeneity, partly due to the risk of bias of the included studies and a lack of uniformity in PBG assessment. Although more research is needed to identify those at increased risk for PBG, its relatively high prevalence warrants routine screening for gambling in clinical practice.
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Comorbidade , Jogo de Azar , Transtornos Psicóticos , Humanos , Jogo de Azar/epidemiologia , Transtornos Psicóticos/epidemiologia , PrevalênciaRESUMO
The effectiveness of universal preventive approaches in reducing the incidence of affective/psychotic disorders is unclear. We therefore aimed to synthesise the available evidence from randomised controlled trials. For studies reporting change in prevalence, we simulated all possible scenarios for the proportion of individuals with the disorder at baseline and at follow-up to exclude them. We then combined these data with studies directly measuring incidence and conducted random effects meta-analysis with relative risk (RR) to estimate the incidence in the intervention group compared to the control group. Eighteen studies (k=21 samples) were included investigating the universal prevention of depression in 66,625 individuals. No studies were available investigating universal prevention on the incidence of bipolar/psychotic disorders. 63â¯% of simulated scenarios showed a significant preventive effect on reducing the incidence of depression (k=9â¯-â¯19, RR=0.75-0.94, 95â¯%CIs=0.55-0.87,0.93-1.15, p=0.007-0.246) but did not survive sensitivity analyses. There is some limited evidence for the effectiveness of universal interventions for reducing the incidence of depression but not for bipolar/psychotic disorders.
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Transtornos Psicóticos , Humanos , Transtornos Psicóticos/prevenção & controle , Transtornos Psicóticos/epidemiologia , Incidência , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/prevenção & controle , Transtornos do Humor/epidemiologia , Transtornos do Humor/prevenção & controleRESUMO
BACKGROUND: The optimal duration of antipsychotic treatment following remission of first-episode psychosis (FEP) is uncertain, considering potential adverse effects and individual variability in relapse rates. This study aimed to investigate the effect of antipsychotic discontinuation compared to continuation on recovery in remitted FEP patients. METHODS: CENTRAL, MEDLINE (Ovid), Embase, and PsycINFO databases were searched on November 2, 2023, with no language restrictions. RCTs evaluating antipsychotic discontinuation in remitted FEP patients were selected. The primary outcome was personal recovery, and secondary outcomes included functional recovery, global functioning, hospital admission, symptom severity, quality of life, side effects, and employment. Risk of bias was assessed using the Cochrane risk-of-bias tool 2, and the certainty of evidence was evaluated with GRADE. Meta-analysis used a random-effect model with an inverse-variance approach. RESULTS: Among 2185 screened studies, 8 RCTs (560 participants) were included. No RCTs reported personal recovery as an outcome. Two studies measured functional recovery, and discontinuation group patients were more likely to achieve functional recovery (RR 2.19; 95% CIs: 1.13, 4.22; I2 = 0%; n = 128), although evidence certainty was very low. No significant differences were found in hospital admission, symptom severity, quality of life, global functioning, or employment between the discontinuation and continuation groups. CONCLUSIONS: Personal recovery was not reported in any antipsychotic discontinuation trial in remitted FEP. The observed positive effect of discontinuation on functional recovery came from an early terminated trial and an RCT followed by an uncontrolled period. These findings should be interpreted cautiously due to very low certainty of evidence.
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Antipsicóticos , Transtornos Psicóticos , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Antipsicóticos/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Suspensão de TratamentoRESUMO
BACKGROUND: Although attention-deficit hyperactivity disorder (ADHD) is often comorbid with schizophrenia spectrum and other psychotic disorders (SZSPD), concerns about an increased risk of psychotic events have limited its treatment with either psychostimulants or atomoxetine. AIMS: To examine whether the risk of hospital admission for psychosis in people with SZSPD was increased during the year following the introduction of such medications compared with the year before. METHOD: This was a retrospective cohort study using Quebec (Canada) administrative health registries, including all Quebec residents with a public prescription drug insurance plan and a diagnosis of psychotic disorder, defined by relevant ICD-9 or ICD-10 codes, who initiated either methylphenidate, amphetamines or atomoxetine, between January 2010 and December 2016, in combination with antipsychotic medication. The primary outcome was time to hospital admission for psychosis within 1 year of initiation. State sequence analysis was also used to visualise admission trajectories for psychosis in the year following initiation of these medications, compared with the previous year. RESULTS: Out of 2219 individuals, 1589 (71.6%) initiated methylphenidate, 339 (15.3%) amphetamines and 291 (13.1%) atomoxetine during the study period. After adjustment, the risk of hospital admission for psychosis was decreased during the 12 months following the introduction of these medications when used in combination with antipsychotics (adjusted HR = 0.36, 95% CI 0.24-0.54; P < 0.0001). CONCLUSIONS: These findings suggest that, in a real-world setting, when used concurrently with antipsychotic medication, methylphenidate, amphetamines and atomoxetine may be safer than generally believed in individuals with psychotic disorders.
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Antipsicóticos , Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Deterioração Clínica , Metilfenidato , Transtornos Psicóticos , Humanos , Cloridrato de Atomoxetina/efeitos adversos , Antipsicóticos/uso terapêutico , Estudos Retrospectivos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Metilfenidato/efeitos adversos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/epidemiologia , Anfetaminas/efeitos adversosRESUMO
AIMS: The objective of this study is to underline the impact of Gaming Disorder on the clinical evolution of patients with First Episode Psychosis. The specific aims of the study are to determine the prevalence of gaming disorder among those patients and assess the consequences of gaming on their clinical trajectory. METHODS: This is a prospective multicenter cohort study that will enrol 800 patients diagnosed with a first episode psychosis, with a follow-up period of up to 3 years. Using a systematic screening procedure for gaming disorder, the clinical staff will assess patients gaming habits at admission and every 6 months thereafter. Information from patients' medical records will also be extracted using the same timeframe. RESULTS: The patients' characteristics at admission and during follow-up will be presented in the form of descriptive statistics and compared between different subgroups of patients using uni- and multivariate logistic regression models. Repeated measures ANCOVA will also be performed to analyse the impact of gaming disorders on patients' clinical path as assessed by the Positive and Negative Syndrome Scale and the Clinical Global Impression scale, considering covariates such as psychiatric diagnosis, pharmacological treatment, age, sex/gender, and duration of untreated psychosis. CONCLUSION: These findings will guide the development of prevention, detection, and treatment strategies for the comorbidity between gaming disorder and first episode psychosis, ultimately improving the patients' recovery.
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BACKGROUND: The limited available data suggest that the prevalence of problem gambling is increased among young adults with first-episode psychosis, possibly due in part to several risk factors for problem gambling that are common in this population. Aripiprazole, a widely used antipsychotic drug, has also been linked to cases of problem gambling, but causality remains uncertain. Although the consequences of problem gambling further hinder the recovery of people with first-episode psychosis, there is a paucity of research about this comorbidity and its risk factors. Additionally, to our knowledge, no screening instrument for problem gambling tailored to these individuals exists, contributing to its under-recognition. Further, treatment approaches for problem gambling adapted to this population are at an embryonic stage, while existing treatments effectiveness remains to be documented. Using an innovative screening and assessment procedure for problem gambling, this study aims to identify risk factors for problem gambling among people with first-episode psychosis and to document the effectiveness of standard treatment approaches. METHODS: This is a multicenter prospective cohort study conducted in two first-episode psychosis clinics, including all patients admitted between November 1st, 2019, and November 1st, 2023, followed for up to 3 years until May 1st, 2024. These 2 clinics admit approximately 200 patients annually, for an expected sample size of 800 individuals. The primary outcome is the occurrence of a DSM-5 diagnosis of gambling disorder. All patients are screened and evaluated for problem gambling using a systematic procedure at admission, and every 6 months thereafter. Socio-demographic and clinical variables are prospectively extracted from the patients' medical records. The nature and effectiveness of treatments for problem gambling offered to affected individuals are also documented from medical records. Survival analyses with Cox regression models will be used to identify potential risk factors for problem gambling. Descriptive statistics will document the effectiveness of treatments for problem gambling in this population. DISCUSSION: A better understanding of potential risk factors for problem gambling among people with first-episode psychosis will allow for better prevention and detection of this neglected comorbidity. Results of this study will also hopefully raise clinicians' and researchers' awareness and serve as the basis to adapted treatments that will better support recovery. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05686772. Retrospectively registered, 9 January 2023.
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Antipsicóticos , Jogo de Azar , Transtornos Psicóticos , Adulto Jovem , Humanos , Estudos Prospectivos , Jogo de Azar/complicações , Jogo de Azar/epidemiologia , Transtornos Psicóticos/complicações , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/tratamento farmacológico , Antipsicóticos/uso terapêutico , Aripiprazol/uso terapêutico , Estudos Multicêntricos como AssuntoRESUMO
OBJECTIVES: Rechallenge/continuation of clozapine in association with colony-stimulating factors (CSFs) following neutropenia/agranulocytosis has been reported, but many questions remain unanswered about efficacy and safety. This systematic review aims to assess the efficacy and safety of rechallenging/continuing clozapine in patients following neutropenia/agranulocytosis using CSFs. METHODS: MEDLINE, Embase, PsycInfo, and Web of Science databases were searched from inception date to July 31, 2022. Articles screening and data extraction were realized independently by two reviewers, according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 systematic review guidance. Included articles had to report on at least one case where clozapine was rechallenged/continued using CSFs despite previous neutropenia/agranulocytosis. RESULTS: Eight hundred forty articles were retrieved; 34 articles met the inclusion criteria, totaling 59 individual cases. Clozapine was successfully rechallenged/continued in 76% of patients for an average follow-up period of 1.9 years. There was a trend toward better efficacy reported in case reports/series, compared with consecutive case series (overall success rates of 84% and 60%, respectively, p-value = 0.065). Two administration strategies were identified, "as-needed" and prophylactic, both yielding similar success rates (81% and 80%, respectively). Only mild and transient adverse events were documented. CONCLUSIONS: Although limited by the relatively small number of published cases, factors such as time of onset to first neutropenia and severity of the episode did not seem to impact the outcome of a subsequent clozapine rechallenge using CSFs. While the efficacy of this strategy remains to be further adequately evaluated in more rigorous study designs, its long-term innocuity warrants considering its use more proactively in the management of clozapine hematological adverse events as to maintain this treatment for as many individuals as possible.
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Antipsicóticos , Clozapina , Neutropenia , Humanos , Clozapina/efeitos adversos , Antipsicóticos/efeitos adversos , Neutropenia/induzido quimicamente , Fator Estimulador de Colônias de GranulócitosRESUMO
BACKGROUND: There is a growing interest in understanding the impact of video games in the clinical field, given that their excessive use could be associated with health issues. Particularly, gaming disorder (GD) is considered as an addictive behavioral disorder. Clinicians widely recognize the comorbidity of gaming and psychotic disorders (PDs). Furthermore, association between addictive (i.e., substance use disorders) and PDs are well recognized by clinicians. It seems of high interest to explore GD among people with PDs. To this day, little is known about the consequences of GD in vulnerable populations. OBJECTIVES: The aim of this scoping review was to summarize the available research on the comorbidity between GD and PD and to identify the knowledge gaps in this field. METHODS: We used Levac's six-stage methodology for scoping review. Two-hundred and forty-two articles from seven databases were identified. Eight articles respected our inclusion and exclusion criteria. RESULTS: No available study has assessed the prevalence or incidence of GD among patients with PDs. The cases reported highlight the possibility that excessive video gameplay or abrupt gaming disruption could trigger psychosis in some patients. CONCLUSION: The results highlight a significant lack of knowledge concerning PDs associated with GD as only a few reported cases and one empirical study exposed the potential association between those conditions.
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Comportamento Aditivo , Transtornos Psicóticos , Jogos de Vídeo , Humanos , Comportamento Aditivo/diagnóstico , Comportamento Aditivo/epidemiologia , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/epidemiologia , Comorbidade , Prevalência , InternetRESUMO
Background: Non-adherence to antipsychotics in schizophrenia is associated with an increased risk of psychotic relapse and hospitalization, a risk that is reduced with the use of long-acting injectable (LAI) antipsychotics. Randomized clinical trials (RCTs) have demonstrated the efficacy of paliperidone palmitate 3-monthly (PP3M) for psychotic relapse prevention in schizophrenia, but it remains poorly documented among individuals treated in real-life settings who can benefit the most out of LAIs. Objectives: The objective of this study was to evaluate the effectiveness of PP3M in relapse prevention among patients with schizophrenia. Methods: This is a multicentre retrospective study conducted in four outpatients' clinics across Canada. All consecutive patients with a main diagnosis of schizophrenia who initiated PP3M between June 2016 and March 2020 were included. The primary outcome was psychotic relapse, defined using broad and clinically relevant criteria. Results: Among 178 consecutive patients who were switched to PP3M, the 12-month relapse rate was 18.5% and the relapse-free survival probability was 0.788 (95% confidence interval [CI]â=â0.725-0.856). Comorbid diagnoses of personality disorders and substance use disorders were associated with hazard rates (HRs) of 3.6 (95% CIâ=â1.8-7.3, p < 0.001) and 3.1 (95% CIâ=â1.6-6.2), respectively. Increased psychopathology severity was associated with an increased likelihood of relapse, while having a job or being in school was protective. Conclusion: These findings reinforce the necessity of conducting research in patients with comorbid psychiatric disorders who are typically underrepresented in RCTs, yet overrepresented in real-life settings, in order to better inform and guide clinical practice.
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For patients at high-risk for developing schizophrenia, a delayed diagnosis could be affected, among many reasons, by their patterns of healthcare use. This study aims to describe and generate a typology of patients' care trajectories (CTs) in the 2 years preceding a first diagnosis of schizophrenia, over a medico-administrative database of 3712 adults with a first diagnosis between April 2014 and March 2015 in Quebec, Canada. This study applied a multidimensional approach of State Sequence Analysis, considering together sequences of patients' diagnoses, care settings and care providers. Five types of distinct CTs have emerged from this data-driven analysis: The type 1, shared by 77.6% of patients, predominantly younger men, shows that this group sought little healthcare, among which 17.5% had no healthcare contact for mental disorders. These individuals might benefit from improved promotion and prevention of mental healthcare at the community level. The types 2, 3 and 4, with higher occurrence of mental disorder diagnoses, represent together 19.5% of the study cohort, mostly middle-aged and women. These CTs, although displaying roughly similar profiles of mental disorders, revealed very dissimilar sequences and levels of care providers encounters, primary and specialized care use, and hospitalizations. Surprisingly, patients of these CTs had few consultations with general practitioners. An increased attentiveness for middle-aged patients and women with high healthcare use for mental disorders could help to reduce delayed diagnosis of schizophrenia. This calls for further consideration of healthcare services for severe mental illness beyond those offered to young adults.
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BACKGROUND: Clozapine is the most efficacious antipsychotic for treatment-resistant schizophrenia. However, clozapine-induced neutropenia may warrant treatment discontinuation, hindering recovery. Several case reports describe clozapine rechallenge or continuation despite neutropenia, although many are subject to selective reporting, with incomplete information and short follow-up periods. Thus, consecutive case series, devoid of such bias, with long-term comprehensive follow-up are needed to better assess this practice. This study aimed to describe consecutively the evolution of every patient in the Québec City catchment area for whom clozapine was either reintroduced after neutropenia during a previous clozapine trial or was maintained despite a first neutropenia. METHODS: Patients were identified through clozapine's national hematological monitoring database and their medical records between January 1, 2000, and October 22, 2017. RESULTS: Twenty-three patients were identified, 8 continued clozapine despite neutropenia, while 15 discontinued clozapine and attempted rechallenge; among the latter, 4 patients were successfully rechallenged after agranulocytosis without the use of granulocyte colony-stimulating factors, which is the largest published consecutively. A total of 6 patients experienced further neutropenia episodes. Every patient who had a neutropenia recurrence also had a possible explanation for neutropenia other than exposure to clozapine. After a median follow-up of 4.8 years, 16 patients were still on clozapine and 3 cases discontinued because of a hematological event. CONCLUSIONS: This study adds further data on the subject of clozapine rechallenge or continuation despite neutropenia. Clozapine rechallenge after agranulocytosis may be less perilous than first thought, but a systematic review on this specific subject is needed.
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Agranulocitose , Antipsicóticos , Clozapina , Neutropenia , Esquizofrenia , Agranulocitose/induzido quimicamente , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Seguimentos , Humanos , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Quebeque , Esquizofrenia/tratamento farmacológicoRESUMO
OBJECTIVE: To compare the effectiveness and safety of various second-generation antipsychotics (SGAs), newer oral and long-acting injectable (LAI) SGAs, and first-generation antipsychotics (FGAs) treatments in patients with schizophrenia or schizoaffective disorder (SCZ). METHODS: This retrospective cohort study included medical administrative information for patients with a diagnosis of SCZ living in Quebec (Canada), initiating or reinitiating at least one antipsychotic (AP) drug (with a clearance baseline period of 12 months without any APs). Effectiveness was defined by a reduced risk of hospitalization for mental disorder and discontinuation, and safety by a reduced risk of all-cause death and hospitalization for non-mental disorder, 2 years after AP initiation or reinitiation. Cox proportional hazard models were used to estimate the events associated with different antipsychotics compared with oral olanzapine. RESULTS: The study cohort included 19,615 patients initiating or reinitiating an antipsychotic drug between January 2006 and December 2015. Results showed better effectiveness of clozapine (adjusted HR 0.36, 95% CI 0.30-0.42, p < 0.0001) and LAI SGAs (adjusted HR 0.56, 95% CI 0.51-0.61, p < 0.0001) compared with oral olanzapine when adding discontinuation to hospitalizations for mental disorder as a composite measure of effectiveness, as opposed to oral FGAs (adjusted HR 1.36, 95% CI 1.27-1.46, p < 0.0001) and LAI FGAs (adjusted HR 1.22, 95% CI 1.12-1.32, p < 0.0001). Most APs were as safe as oral olanzapine. CONCLUSION: The effectiveness of LAI SGAs and clozapine appears to justify their use and are as safe as a recognized treatment (oral olanzapine) in Quebec (Canada).
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Antipsicóticos , Clozapina , Esquizofrenia , Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Preparações de Ação Retardada/uso terapêutico , Humanos , Olanzapina/uso terapêutico , Estudos Retrospectivos , Esquizofrenia/diagnósticoRESUMO
OBJECTIVE: This study aims to describe the utilization patterns of antipsychotic (AP) medication in patients with schizophrenia (SCZ), three years after initiating or reinitiating a given AP. METHODS: Based on medico-administrative information on patients living in Quebec (Canada), this retrospective cohort study included 6444 patients with a previous diagnosis of SCZ initiating or reinitiating AP medication between January 1, 2012, and December 31, 2014, with continuous coverage by public drug insurance. For each day of follow-up (1092 days), patient was either exposed to one of the chosen categories of APs, or to none. This patient's sequence of AP exposure overtime has been referred to as the "antipsychotic utilization trajectory". These trajectories were analyzed using a State Sequence Analysis, an innovative approach which provides useful visual information on the continuation and discontinuation patterns of use over time. RESULTS: Clozapine and long-acting injectable second-generation APs had the best continuation and discontinuation patterns over 3 years among all other groups, including less switching of APs, while oral first-generation APs had the poorest patterns. These findings were comparable among incident and non-incident cohorts. Oral second-generation antipsychotics, excluding clozapine, had a poorer continuation and discontinuation pattern than long-acting injectable antipsychotics. CONCLUSION: State Sequence Analysis provides a clear representation of treatment adherence in comparison with dichotomous indicators of adherence or discontinuation. Consequently, this innovative method has shed light on the impact of the AP chosen to initiate or reinitiate treatment in SCZ, which has been identified as a key factor for long-term treatment continuation and discontinuation.
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Antipsicóticos , Clozapina , Esquizofrenia , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Humanos , Estudos Retrospectivos , Esquizofrenia/tratamento farmacológico , Análise de SequênciaRESUMO
BACKGROUND: Although recognised as the most effective antipsychotic for treatment-resistant schizophrenia, clozapine remains underused. One reason is the widespread concern about non-adherence to clozapine because of poor adherence before initiating clozapine. AIMS: To determine if prior poor out-patient adherence to treatmentbefore initiating clozapine predisposes to poor out-patient adherence to clozapine or to any antipsychotics (including clozapine) after its initiation. METHOD: This cohort study included 3228 patients with schizophrenia living in Quebec (Canada) initiating (with a 2-year clearance period) oral clozapine (index date) between 2009 and 2016. Using pharmacy data, out-patient adherence to treatment was measured by the medication possession ratio (MPR), over a 1-year period preceding and following the index date. Five groups of patients were formed based on their prior MPR level (independent variable). Two dependent variables were defined after clozapine initiation (good out-patient adherence to any antipsychotics and to clozapine only). Along with multiple logistic regressions, state sequence analysis was used as a visual representation of antipsychotic-use trajectories over time, before and after clozapine initiation. RESULTS: Although prior poor adherence to antipsychotics was associated with poor adherence after clozapine initiation, the absolute risk of subsequent poor adherence remained low, regardless of previous adherence level. Most patients adhered to their treatment after initiating clozapine (>68% to clozapine and >84% to any antipsychotics). CONCLUSIONS: Despite the fact that poor adherence prior to initiating clozapine is widely recognised by clinicians as a barrier for the prescription of clozapine, the current study supports the initiation of clozapine in all eligible patients.
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In the current study, we provide the list of pharmacological interventions applied during the one-year follow-up period of the Pharmacological treatment profiles in the FACE-BD cohort study. These data show the treatments used in the new clusters formed in this previous study and also in usual bipolarity subtypes. The proportion of each treatment used during the follow-up was calculated. Days on each treatment were also included in this dataset. The complete clinical and paraclinical data analyzed for clusters and bipolar subtypes were included in this dataset. Socio-demographic self-administered and clinician-administered scales, clinical evaluation during the follow-up, psychiatric and somatic comorbidities, and blood tests are shown in this material.
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BACKGROUND: Despite thorough and validated clinical guidelines based on bipolar disorders subtypes, large pharmacological treatment heterogeneity remains in these patients. There is limited knowledge about the different treatment combinations used and their influence on patient outcomes. We attempted to determine profiles of patients based on their treatments and to understand the clinical characteristics associated with these treatment profiles. METHODS: This multicentre longitudinal study was performed on a French nationwide bipolar cohort database. We performed hierarchical agglomerative clustering to search for clusters of individuals based on their treatments during the first year following inclusion. We then compared patient clinical characteristics according to these clusters. RESULTS: Four groups were identified among the 1795 included patients: group 1 ("heterogeneous" n = 1099), group 2 ("lithium" n = 265), group 3 ("valproate" n = 268), and group 4 ("lamotrigine" n = 163). Proportion of bipolar 1 disorder, in groups 1 to 4 were: 48.2%, 57.0%, 48.9% and 32.5%. Groups 1 and 4 had greater functional impact at baseline and a less favorable clinical and functioning evolution at one-year follow-up, especially on GAF and FAST scales. LIMITATIONS: The one-year period used for the analysis of mood stabilizing treatments remains short in the evolution of bipolar disorder. CONCLUSIONS: Treatment profiles are associated with functional evolution of patients and were not clearly determined by bipolar subtypes. These profiles seem to group together common patient phenotypes. These findings do not seem to be influenced by the duration of disease prior to inclusion and neither by the number of treatments used during the follow-up period.