Optimising antipsychotic prescribing in schizophrenia : understanding the factors contributing to antipsychotic polypharmacy and personalising treatment to improve pharmacotherapy

Schizophrenia is one of the most severe psychiatric illnesses, and affects about 1% of the world's population. Antipsychotics are the only drugs currently registered for its treatment. Antipsychotic polypharmacy, the simultaneous use of two or more antipsychotics by a patient, is common worldwide for the treatment of schizophrenia, although its superior efficacy over antipsychotic monotherapy is not supported by high-quality evidence. Worse, patients on antipsychotic polypharmacy experience poorer outcomes than those on antipsychotic monotherapy. With the help of translational research and a multidisciplinary team, the aim of the present thesis is to provide insight about the ways of improving individual pharmacotherapy with antipsychotics in patients suffering from schizophrenia. This project paves the way for future implementation studies aimed at deprescribing antipsychotics to reach antipsychotic monotherapy.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 202

Measuring the professional social capital of psychiatrists: adaptation and validation of the Resource Generator for Psychiatrists (RG-Psy)

Introduction Psychiatrists need access to professional resources to care for their patients. In mental health settings, clinical innovations such as a new therapeutic approach, clinical guidelines or new drugs can diffuse more or less, depending on the social capital of these clinicians. The Resource Generator developed by Snijders & Van Der Gaag (2004) measures access to resources within a social network for the general population. It may therefore not capture access to social capital in the professional field of psychiatry. Objectives We aimed to develop and validate the Resource Generator for Psychiatrists and to detect factors influencing the social capital of clinicians. Methods The development of the final 11-item questionnaire followed multiple steps. First, the items were selected and adapted by an expert in the sociology of mental health to match the sector of psychiatry. Content validity and detection of important issues or misunderstandings were ensured by cognitive interviews with a panel of 6 clinicians. Each item has a 6-point response scale, rated from 0 to 6. Answers were coded “0” when the respondent did not need a certain resource or it was not applicable to their situation, while answering the closest resource was coded “6”. The online self-completion questionnaire was administered through a link sent by email to all adult psychiatrists and psychiatric residents licensed to work in Belgium. Additional warm contacts were performed for psychiatrists working in ambulatory care. An exploratory factor analysis was conducted. Internal consistency was ensured with Pearson’s correlation, item-total correlation and Cronbach’s alpha. Test-retest reliability was also measured. Multivariable linear regression analysis assessed the association between psychiatrist demographics and the RG-Psy total score. Results The Resource Generator for Psychiatrists questionnaire completed by 152 psychiatrists showed a normal distribution with a mean of 32.5 (SD=12), good test-retest reliability (ICC=0.81), and good total Cronbach’s alpha (0.74). Exploratory factor analysis revealed two main subtypes in psychiatrists’ social capital: “attention and access to advice” and “practical assistance, knowledge and expertise”, with Cronbach’s alpha of 0.62 and 0.7 respectively. Clinicians attending institutional seminars (β=5.5221, p=0.013) and working in multidisciplinary settings such as hospitals (β=4.7448, p=0.023) or a mobile team (β=8.7475, p=0.014) were more likely to have higher social capital. Conclusion Psychiatrists’ access to professional resources can be reliably measured by a 11-item questionnaire and can be used to test the influence of their professional social capital on different outcomes

Antipsychotic polypharmacy- Evolution of prescribing patterns between admission and discharge of 5 Belgian hospitals

Objectives: Antipsychotic polypharmacy (APP) is common worldwide in the treatment of schizophrenia. We aimed at describing APP during psychiatric hospitalization in Belgium and comparing it to the European practice. Methods: We collected retrospective data from 5 hospitals in 2020-2021. The inclusion criteria were adult inpatients, hospitalized in a psychiatric unit, presenting with a diagnosis of schizophrenia or schizoaffective disorder, and taking an antipsychotic at admission. The proportion of patients on APP, antipsychotics’ exposition (i.e. prescribed daily dose (PDD)/defined daily dose (DDD) ratio) and excessive dosing (i.e. PDD/DDD>1,5), type, route, and cotreatment were compared between admission and discharge of hospitalization. Results: Of the 420 patients analyzed, 197 (46,9%) were on APP at admission and 244 (58,1%) at discharge (p<0,001). These figures largely exceed the European mean (23,0%; Gallego et al. (2012)). The antipsychotics’ exposition increased significantly from 1,70 at admission to 1,96 at discharge (p<0,001), so as the proportion of patients receiving excessive dosing (from 49,2% to 57,0% respectively; p<0,001). Compared to admission, more patients had a combination of a long-acting injectable with an oral antipsychotic at discharge (18,6% and 27,4%; p<0,001), and more were treated with a combination of a first-generation and an atypical antipsychotic (28,3% and 36,2%; p<0,001). Finally, more patients were on mood stabilizers (17,4% and 21,4%; p=0,019), benzodiazepines (45,2% and 56,7%; p<0,001), antiparkinsonian drugs (9,3% and 11,7%; p=0,06), or received an antipsychotic for insomnia (22,1% and 30,2%; p<0,001) at discharge compared to admission. Conclusions: APP is highly prescribed in Belgium and increases after a psychiatric hospitalization

Antipsychotics deprescribing in schizophrenia: trends and associated characteristics in Belgium and Québec

Background : Antipsychotic polypharmacy (APP) is common worldwide in schizophrenia, while switch to antipsychotic monotherapy reduces adverse effects. Canada has been the leader in deprescribing policies in the last decades. Aims : To detect factors, including countries, associated with successful antipsychotic deprescribing after a psychiatric hospitalisation. Methods : Retrospective data were collected in a tertiary care hospital in Montreal (QC, Canada) and compared to data collected in 6 Belgian hospitals, in 2020-2021. Adult inpatients with a diagnosis of schizophrenia or schizoaffective disorder and discharged from a psychiatric unit after an acute hospitalisation were included. Results : At discharge, the daily number of antipsychotics had decreased in 22.2% of the 63 Canadian and 9.9% of the 516 Belgian patients, and increased in 17.5% of the Canadian and 24.3% of the Belgian patients. Living in a residential facility (OR=2.51, 95% CI 1.05-4.39), ≥2 previous antipsychotic trials (OR=15.38, 95% CI 3.62-65.36), having an antipsychotic side effect (OR=1.86, 95% CI 1.01-3.44), being in a general hospital (OR=2.28, 95% CI 1.09-4.75) and in Canada (OR=4.13, 95% CI 1.48-11.5) increased the odds of successful antipsychotic deprescribing at hospital discharge. Patients with a LAI (OR=0.51, 95% CI 0.26-0.98), prior clozapine use (OR=0.36, 95% CI 0.13-0.95), a greater antipsychotic exposure (OR=0.35, 95% CI 0.2-0.61) and a higher number of hypno-sedatives (OR=0.65, 95% CI 0.43-0.98) were less likely to have a deprescription. Conclusion : Antipsychotic deprescribing is feasible and already performed in identifiable patients, settings or situations. Patients hospitalised in Canada are more likely to have a deprescription than in Belgium

Antipsychotic polypharmacy and clozapine prescribing patterns: evolution and correlates before and after a psychiatric hospitalisation

Aim: To explore the evolution of antipsychotic polypharmacy (APP) and other psychotropic prescribing patterns during psychiatric hospitalisations, to detect characteristics associated with APP on admission and at discharge, and to examine clozapine prescribing patterns. Methods: Data on adult inpatients diagnosed with schizophrenia spectrum disorders were collected retrospectively from 6 Belgian hospitals. Results: Of the 516 patients included, APP prescribing increased significantly from 47.9% on hospital admission to 59.1% at discharge. On admission and at discharge, APP was associated with prior clozapine use (ORadmission=2.53, CI=1.1-5.84, ORdischarge=11.01, CI=4.45-27.28), treatment with a first-generation antipsychotic (ORadmission=26.79, CI=13.08-54.86, ORdischarge=25.2, CI=12.2-52.04), increased antipsychotic exposure (ORadmission=8.93, CI=5.13-15.56, ORdischarge=19.89, CI=10-39.54), and a greater number of hypno-sedatives (ORadmission=1.88, CI=1.23-2.88, ORdischarge=4.18, CI=2.53-6.91), and negatively associated with involuntary admission (ORadmission=0.31, CI=0.14-0.7, ORdischarge=0.3, CI=0.13-0.68). When using an alternative definition of monotherapy (i.e., including patients with an add-on low-dose antipsychotic for sleep disorders), alcohol use disorder (ORadmission=0.26, CI=0.13-0.54) and higher age (ORdischarge=0.53, CI=0.29-0.95) were negatively associated with APP, and living in a residential facility (ORdischarge=2.39, CI=1.21-4.71) and a higher daily dosage of benzodiazepines during the stay (ORdischarge=1.32, CI=1.03-1.69) increased the odds of being discharged on APP. Although 28.1% of patients were eligible for clozapine treatment, only 9.3% were being treated with clozapine on admission, and 11% at discharge. Seven of the ten patients with a new clozapine prescription were directly being prescribed a combination of antipsychotics, without a prior trial of clozapine monotherapy. Conclusion: Suboptimal prescriptions of antipsychotics in patients with schizophrenia persist after psychiatric hospitalisations and are associated with identifiable characteristics

Characterising the evolution of antipsychotic polypharmacy and clozapine prescribing patterns in schizophrenia patients during psychiatric hospitalisations

Introduction: A high prevalence of antipsychotic polypharmacy (APP) and low utilisation of clozapine is considered as inappropriate prescribing that can lead to suboptimal treatment, increased risk of poor response or adverse effects. Objectives: To explore the evolution of prevalence of APP and associated factors as well as clozapine prescribing patterns between hospital admission and discharge. Methods: We collected retrospective data on adult inpatients diagnosed with schizophrenia spectrum disorders in 2020-2021 in 6 Belgian hospitals. Results: Of the 516 patients analysed, APP prescribing significantly increased from 47.9% on hospital admission to 59.1% at discharge. Both on admission and at discharge, APP was associated with treatment with a first-generation antipsychotic, not being treated with an antidepressant nor a mood stabilizer, high antipsychotic dosage, increased number of psychoactive cotreatments and total medicines. A lower number of comorbidities (OR=0.68, CI=0.50- 0.91), no treatment with benzodiazepines (OR=0.02, CI=0.01- 0.09) nor with trazodone or sedative antihistamines (OR=0.06, CI=0.01-0.03) and two or more previous antipsychotic trials (OR= 4.91, CI=1.30-18.57) was associated with APP on admission only. APP at discharge was more frequent in patients with antipsychotic adverse effects (OR=2.57, CI=1.10-6.00), prior clozapine use (OR =16.30, CI=3.27-81.22) and not involuntary admitted (OR=0.26 CI=0.08-0.88). Contrary to admission, treatment with benzodiazepines was associated with APP at discharge (OR=10.9, CI= 3.38-5.38). Only 9.3% of admitted patients were treated with clozapine. Although 28.1% were eligible, clozapine was introduced to 10 patients leading to 11% being discharged on it. Conclusions: Inappropriate prescribing of antipsychotics to schizophrenia patients persist after psychiatric hospitalisations and are associated with identifiable characteristics

Optimizing pharmacists' detection of prescribing errors: Comparison of on‐ward and central pharmacy services

WHAT IS KNOWN AND OBJECTIVE: Prescribing errors are the leading cause of adverse drug events in hospitalized patients. Pharmaceutical validation, defined as the review of drug orders by a pharmacist, associated with clinical decision support (CDS) systems, significantly reduces these errors and adverse drug events. In Belgium, because clinical pharmacy services have limited public financial support, most pharmaceutical validations are performed at the central pharmacy instead of on-ward, by hospital pharmacists doing dispensing activities. In that context, we aimed at evaluating whether the strategy of CDS-guided central validation was the most appropriate method to improve the quality and safety of medicines' use compared to an on-ward pharmaceutical validation. METHODS: Our retrospective observational study was conducted in a Belgian tertiary care hospital, in 2018-2019. Data were extracted from our validation software and pharmacists' charts. The outcomes of the study were the number of pharmaceutical interventions due to the detection of prescribing errors, reasons for interventions, their acceptance rate and their potential clinical impact (according to two blinded experts) in the central pharmacy and on-ward validation groups. RESULTS AND DISCUSSION: Despite the use of the same CDS, a pharmaceutical intervention following the detection of a prescribing error was made for 2.9% (20/698) of central group patients and 13.3% (93/701) of on-ward patients (χ2 = 49.97, p < 0.001). Interventions made at the central pharmacy (n = 20) mostly relied on CDS-alerts (i.e. drug-drug interaction [25%] or overdosing [20%]) while interventions made on-ward (n = 93) were also for pharmacotherapy optimization (i.e. no valid indication [25%] or inappropriate drug's choice [11%]). The on-ward validation group showed a higher acceptance rate compared to the central group (84% and 65%, respectively [Fisher's test, p = 0.053]). Proportions of interventions with significant or very significant clinical impact were similar between the two groups but as fewer interventions were made centrally, a significant proportion of errors were probably not detected by the central validation. WHAT IS NEW AND CONCLUSION: On-ward pharmaceutical validation leads to a higher rate of prescribing error detection. Pharmaceutical interventions made by on-ward pharmacists are also better accepted and more relevant, going further than CDS-alerts

Pharmaceutical validation : centralized or on-ward ?

Background: Prescription errors are the leading cause of adverse drug events in hospitalised patients. Clinical decision support systems (CDSS), integrated in clinical prescription order entry (CPOE), significantly reduce these errors and adverse drug events. Pharmaceutical validation, defined as the review of drug orders by a pharmacist, combined with CDSS, can further decrease medication errors. Whether onward validation lead to a higher rate of medication errors detection than central validation, acceptance of pharmaceutical interventions, type of errors detected and clinical impact for patients have not been studied yet by direct comparison. Objective: The aim of this study is to compare onward and central validation of medical prescriptions. Methods : Our retrospective observational study was conducted at the Cliniques universitaires Saint-Luc (Brussels, Belgium), a tertiary care hospital, in April and May 2019. Data were extracted from the local validation software and pharmacist’s charts. The “central validation” and “onward validation” groups referred to pharmaceutical validation made at the central hospital pharmacy in September and November 2018, and within the cardiology unit in February and March 2019, respectively. Each group validated all medical prescriptions of the cardiology unit on an everyday basis during the study period of data sources. They are compared in term of rate of pharmaceutical interventions due to medication errors, reasons for interventions (e.g. contra-indication, drug-drug interaction, overdosing, underdosing), their potential clinical impact according to two experts (a senior cardiologist and a senior clinical pharmacist) and their acceptance rate. Results: 2,9% (20/698) and 13,2% (93/701) of patients had interventions for medication errors in the group “central validation” and “onward validation” respectively (χ2 = 49,97, p <0,001). Interventions made at the central pharmacy were most of the time because of drug-drug interaction (25%), computerized-created error (20%) and overdosing (20%) while interventions made onward were for no valid indication (25%), overdosing (18%) and inadequate or non-optimal molecule choice regarding guidelines (11%). The group “onward validation” showed a higher acceptance rate than the group “central validation” (84% and 65% respectively (Fisher’s test, p = 0,053)). Finally, according to the experts, there were similar proportions of interventions with significant or very significant clinical impact between the two groups (but the absolute number of interventions was higher onward), more interventions with potentially deleterious impact in the group “central validation” and interventions with vital impact were only made in the group “onward validation”. Conclusion: The benefit of onward validation of medical prescriptions is a higher rate of prescription errors detection, a better acceptance rate, and interventions about optimization of pharmacotherapy and not only about prescription errors such as drug-drug interactions or overdosing. Onward pharmaceutical validation must be considered as a complementary approach in targeted units to improve medication safety

Prescribing and deprescribing trends in schizophrenia : An overview of inpatients in Belgium and in the Canadian province of Québec

Although switching to antipsychotic monotherapy improves patient outcomes in schizophrenia, antipsychotic deprescribing is rarely performed, and its use varies between countries, as do psychotropic prescribing patterns. This study aimed to determine factors associated with antipsychotic deprescribing at discharge after a psychiatric hospitalization and to compare psychotropic prescribing patterns between Belgium and Québec, Canada. Data on adult inpatients with schizophrenia were collected retrospectively in seven hospitals. At discharge, the number of antipsychotics had decreased in 22.2% of the 63 Canadian patients and 9.9% of the 516 Belgian patients. A number of factors increased the likelihood of antipsychotic deprescribing: a hospitalization in the Canadian hospital (aOR = 4.13, 95% CI 1.48–11.5), living in a residential facility (aOR = 2.51, 95% CI 1.05–4.39), ≥2 previous antipsychotic trials (aOR = 15.38, 95% CI 3.62–65.36), having an antipsychotic side effect (aOR = 1.86, 95% CI 1.01–3.44) and being in a general hospital (aOR = 2.28, 95% CI 1.09–4.75). Patients on a long-acting injectable antipsychotic (aOR = 0.51, 95% CI 0.26– 0.98), with prior clozapine use (aOR = 0.36, 95% CI 0.13–0.95), greater antipsychotic exposure (aOR = 0.35, 95% CI 0.2–0.61) and more hypno-sedatives (aOR = 0.65, 95% CI 0.43–0.98), were less likely to be prescribed. Specific deprescribing interventions could target patients who are less likely to be deprescribed

Impact of a Caffeine Restriction Policy on Inpatients With Schizophrenia- A Pre-Post Comparison Using Electronic Health Records

Background/Purpose: Caffeine is the most commonly used psychostimulant worldwide. Although its large intake is suspected toworsen psychotic symptoms because of increasing dopamine neurotransmission, schizophrenic patients are heavier caffeine consumers than the general population. This study aims to assess the impact of a caffeine restriction policy in a psychiatric hospital on patient psychopathology, hospitalization characteristics, and psychotropic prescribing patterns. Methods: It is a retrospective cross-sectional study based on electronic health records of a psychiatric hospital in the French-speaking area of Belgium. Two different periodswere compared, the first (n = 142), in 2017,when caffeinewas available in the institution and the second (n = 119), between November 2018 andNovember 2019 after the restriction of access to caffeinewas implemented. Adult inpatients with schizophrenia or schizoaffective disorder admitted for an acute hospitalization were included. Antipsychotic exposure, benzodiazepine daily dose, Global Assessment of Functioning scores, length of hospital stay, and some other factors were tested for their potential association with the decaffeinated period. Results: After adjusting for potential confounders, reduced caffeine availability inside the hospital was significantly associated with higher Global Assessment of Functioning scores at discharge (adjusted odds ratio [aOR] = 2.86, 95% confidence interval [CI] = 1.77–4.62) and shorter hospital stays (aOR = 0.68, 95% CI = 0.47–0.99) but was not associated with change in antipsychotic exposure at discharge (aOR= 1.04,95%CI = 0.64–1.7) or benzodiazepine daily dose (aOR = 0.89, 95% CI = 0.61–1.29). Conclusions: Limiting access to caffeine in psychiatric hospitals is a simple and inexpensive intervention tha