Problem gambling in psychotic disorders: A systematic review and meta-analysis of prevalence.

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.

Speech markers to predict and prevent recurrent episodes of psychosis: A narrative overview and emerging opportunities.

Preventing relapse in schizophrenia improves long-term health outcomes. Repeated episodes of psychotic symptoms shape the trajectory of this illness and can be a detriment to functional recovery. Despite early intervention programs, high relapse rates persist, calling for alternative approaches in relapse prevention. Predicting imminent relapse at an individual level is critical for effective intervention. While clinical profiles are often used to foresee relapse, they lack the specificity and sensitivity needed for timely prediction. Here, we review the use of speech through Natural Language Processing (NLP) to predict a recurrent psychotic episode. Recent advancements in NLP of speech have shown the ability to detect linguistic markers related to thought disorder and other language disruptions within 2-4 weeks preceding a relapse. This approach has shown to be able to capture individual speech patterns, showing promise in its use as a prediction tool. We outline current developments in remote monitoring for psychotic relapses, discuss the challenges and limitations and present the speech-NLP based approach as an alternative to detect relapses with sufficient accuracy, construct validity and lead time to generate clinical actions towards prevention.

The effects of antipsychotic discontinuation or maintenance on the process of recovery in remitted first-episode psychosis patients - A systematic review and meta-analysis of randomized controlled trials.

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.

Treatment with psychostimulants and atomoxetine in people with psychotic disorders: reassessing the risk of clinical deterioration in a real-world setting.

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.

Impact of gaming disorder on first episode psychosis patients' evolution: Protocol for a multicentered prospective study.

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.

Performance Kinetics During Repeated Sprints is Influenced by Knowledge of Task Endpoint and Associated Peripheral Fatigue.

The regulation of exercise intensity allows an athlete to perform an exercise in the fastest possible time while avoiding debilitating neuromuscular fatigue development. This phenomenon is less studied during intermittent activities. To investigate anticipatory and real-time regulation of motor output and neuromuscular fatigue during repeated-sprint exercise, twelve males randomly performed one (S1), two (S2), four (S4) and six (S6) sets of five 5-s cycling sprints. Mechanical work and electromyographic activity were assessed during sprints. Potentiated quadriceps twitch force (ΔQtw,pot) and central activation ratio (QCAR) were quantified from response to supra-maximal magnetic femoral nerve stimulation pre-vs post-exercise. Compared with S1, mechanical work developed in the first sprint and in the entire first set was reduced in S6 (-7.8% and -5.1%, respectively, P < 0.05). Work developed in the last set was similar in S4 and S6 (P = 0.82). Similar results were observed for EMG activity. The QCAR was also more reduced in S4 (-5.8%, P < 0.05) and S6 (-8.3%, P < 0.05) than in S1. However, ΔQtw,pot was not significantly different across all trials (-33.1% to -41.9%, P = 0.46). Perceived exhaustion increased across sprints to reach a maximal and similar level in S2, S4 and S6 (all 19.2, P < 0.01 vs S1). These results suggest that the regulation of performance, exerted at the beginning and continuously during repeated sprints, is based on the task endpoint, presumably to avoid excessive peripheral muscle and associated conscious overwhelming sensations.

Differences Between East Asians and Westerners in the Mental Representations and Visual Information Extraction Involved in the Decoding of Pain Facial Expression Intensity.

Effectively communicating pain is crucial for human beings. Facial expressions are one of the most specific forms of behavior associated with pain, but the way culture shapes expectations about the intensity with which pain is typically facially conveyed, and the visual strategies deployed to decode pain intensity in facial expressions, is poorly understood. The present study used a data-driven approach to compare two cultures, namely East Asians and Westerners, with respect to their mental representations of pain facial expressions (experiment 1, N=60; experiment 2, N=74) and their visual information utilization during the discrimination of facial expressions of pain of different intensities (experiment 3; N=60). Results reveal that compared to Westerners, East Asians expect more intense pain expressions (experiments 1 and 2), need more signal, and do not rely as much as Westerners on core facial features of pain expressions to discriminate between pain intensities (experiment 3). Together, those findings suggest that cultural norms regarding socially accepted pain behaviors shape the expectations about pain facial expressions and decoding visual strategies. Furthermore, they highlight the complexity of emotional facial expressions and the importance of studying pain communication in multicultural settings. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-023-00186-1.

Problem gambling among people with first-episode psychosis: protocol for a prospective multicenter cohort study.

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.

Pain in the eye of the beholder: Variations in pain visual representations as a function of face ethnicity and culture.

Pain experienced by Black individuals is systematically underestimated, and recent studies have shown that part of this bias is rooted in perceptual factors. We used Reverse Correlation to estimate visual representations of the pain expression in Black and White faces, in participants originating from both Western and African countries. Groups of raters were then asked to evaluate the presence of pain and other emotions in these representations. A second group of White raters then evaluated those same representations placed over a neutral background face (50% White; 50% Black). Image-based analyses show significant effects of culture and face ethnicity, but no interaction between the two factors. Western representations were more likely to be judged as expressing pain than African representations. For both cultural groups, raters also perceived more pain in White face representations than in Black face representations. However, when changing the background stimulus to the neutral background face, this effect of face ethnic profile disappeared. Overall, these results suggest that individuals have different expectations of how pain is expressed by Black and White individuals, and that cultural factors may explain a part of this phenomenon.

Clozapine rechallenge or continuation despite neutropenia or agranulocytosis using colony-stimulating factor: A systematic review.

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.

Sex-specific immune mechanisms in PTSD symptomatology and risk: A translational overview and perspectives.

Altered immune function in patients with posttraumatic stress disorder (PTSD) may play a role in the disorder pathophysiology and onset. Women are more likely to develop PTSD, suggesting potential sex-specific inflammatory mechanisms underlying the dichotomous prevalence and risk of PTSD in men and women. In this review we examine the available literature to better assess the state of knowledge in the field. In humans, increased systemic inflammation is found in both men and women with PTSD, but seems to be at a greater extend in women. Despite the existence of few clinical studies taking account of sex as a factor in the observed immune changes in PTSD, challenges in the study of sex-specific immune function in humans include: controlling for confounding variates such as the type of trauma and the ethnicity; and limited methodologies available to study central nervous system (CNS)-relevant changes. Thus, preclinical studies are a valuable tool to provide us with key insights on sex-specific peripheral and CNS immune mechanisms underlying PTSD. Available preclinical studies reported increased systemic and CNS inflammation, as well as elevated trafficking of monocytes from the periphery to the brain in both male and female rodents. To date, psychological trauma-induced inflammation is more robust in female vs male rodents. Limitations of preclinical studies include animal models hardly applicable to female rodents, and hormonal changes across estrus phases that may affect immune function. The present review: (1) highlights the key findings from both human and animal studies, (2) provides guidance to address limitations; and (3) discusses the gap of knowledge on the complex intertwined interaction between the brain, neurovascular, and systemic units.

Gaming Disorder and Psychotic Disorders: A Scoping Review.

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.

Facial expression of pain: Sex differences in the discrimination of varying intensities.

It has been proposed that women are better than men at recognizing emotions and pain experienced by others. They have also been shown to be more sensitive to variations in pain expressions. The objective of the present study was to explore the perceptual basis of these sexual differences by comparing the visual information used by men and women to discriminate between different intensities of pain facial expressions. Using the data-driven Bubbles method, we were able to corroborate the woman advantage in the discrimination of pain intensities that did not appear to be explained by variations in empathic tendencies. In terms of visual strategies, our results do not indicate any qualitative differences in the facial regions used by men and women. However, they suggest that women rely on larger regions of the face that seems to completely mediate their advantage. This utilization of larger clusters could indicate either that women integrate simultaneously and more efficiently information coming from different areas of the face or that they are more flexible in the utilization of the information present in these clusters. Women would then opt for a more holistic or flexible processing of the facial information, while men would rely on a specific yet rigid integration strategy. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Real-life effectiveness of transitioning from paliperidone palmitate 1-monthly to paliperidone palmitate 3-monthly long-acting injectable formulation.

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] = 0.725-0.856). Comorbid diagnoses of personality disorders and substance use disorders were associated with hazard rates (HRs) of 3.6 (95% CI = 1.8-7.3, p < 0.001) and 3.1 (95% CI = 1.6-6.2), 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.

Clozapine Rechallenge or Continuation Despite Neutropenia, an Extended Follow-up of a Consecutive Quebec Case Series.

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.

A practical guide for translating in-person simulation curriculum to telesimulation.

This article provides a road map, along with recommendations, for the adoption and implementation of telesimulation at a large scale. We provide tools for translating an in-presence simulation curriculum into a telesimulation curriculum using a combination off-the-shelf telecommunication platform. We also describe the roles and tasks that emerged within the simulation team when planning and delivering a telesimulation curriculum.

Response of sediment phosphorus partitioning to lanthanum-modified clay amendment and porewater chemistry in a small eutrophic lake.

Sustained eutrophication of the aquatic environment by the remobilization of legacy phosphorus (P) stored in soils and sediments is a prevailing issue worldwide. Fluxes of P from the sediments to the water column, referred to as internal P loading, often delays the recovery of water quality following a reduction in external P loads. Here, we report on the vertical distribution and geochemistry of P, lanthanum (La), iron (Fe) and carbon (C) in the culturally eutrophied Lake Bromont. This lake underwent remediation treatment using La modified bentonite (LMB) commercially available as Phoslock™. We investigated the effectiveness of LMB in decreasing soluble reactive phosphorus (SRP) availability in sediments and in reducing dissolved fluxes of P across the sediment-water interface. Sediment cores were retrieved before and after LMB treatment at three sites representing bottom sediment, sediment influenced by lakeside housing and finally littoral sediment influenced by the lake inflow. Sequential extractions were used to assess changes in P speciation. Depth profiles of dissolved porewater concentrations were obtained after LMB treatment at each site. Results indicate that SRP extracted from the sediments decreased at all sites, while total extracted P (PTOT) bound to redox-sensitive metal oxides increased. 31P NMR data on P extract reveals that 20-43% of total solid-phase P is in the form of organic P (Porg) susceptible to be released via microbial degradation. Geochemical modelling of porewater data provides evidence that LaPO4(s) mineral phases, such as rhabdophane and/or monazite, are likely forming. However, results also suggest that La3+ binding by dissolved organic carbon (DOC) hinders La-phosphate precipitation. We rely on thermodynamic modelling to suggest that high Fe2+ would bind to DOC instead of La3+, therefore promoting P sequestrations by LMB under anoxic conditions.

Antipsychotic utilization trajectories three years after initiating or reinitiating treatment of schizophrenia: A state sequence analysis approach.

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.

Association between previous and future antipsychotic adherence in patients initiating clozapine: real-world observational study.

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.