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Background: Potentially inappropriate prescribing (PIP) is frequent in geriatrics and results in an increased risk for adverse effects, morbidity, mortality and reduced quality of life. Research on PIP in psychiatry has mainly focused on elderly patients and inpatients. Objectives: To determine the prevalence and the predictors of PIP of psychotropic medication in outpatients with severe mental illness. Design: This study is part of the Muva study, a pragmatic open Stepped Wedge Cluster Randomized Trial of a physical activity intervention for patients (age ⩾ 16 years) with severe mental illness. Methods: A structured medication interview, questionnaires on social functioning, quality of life and psychiatric symptoms, and BMI and waist circumference measurements were performed followed by a structured medication review. Patients were divided into groups: PIP versus no PIP. Between-group differences were calculated and a multivariate binary logistic regression was performed to examine predictors for PIP. A receiver operating characteristics analysis was performed to determine the area under the curve (AUC). Results: In 75 patients, an average of 5.2 medications of which 2.5 psychotropic medication was used. 35 (46.7%) patients were identified with PIP. Unindicated long-term benzodiazepine use was the most frequently occurring PIP (34.1%). Predictors of PIP were female gender [odds ratio (OR) = 4.88, confidence interval (CI) = 1.16–20.58, p = 0.03], number of medications (OR = 1.41, CI = 1.07–1.86, p = 0.02) and lower social functioning (OR = 1.42, CI = 1.01–2.00, p = 0.05). The AUC was 0.88 for the combined prediction model. Conclusion: The prevalence of PIP of psychotropic medication in outpatients with severe mental illness is high. It is therefore important to identify, and where possible, resolve PIP by frequently performing a medication review with specific attention to females, patients with a higher number of medications and patients with lower social functioning. Trial registration: This trial was registered in The Netherlands Trial Register (NTR) as NTR NL9163 on 20 December 2020 ( https://trialsearch.who.int/Trial2.aspx?TrialID=NL9163 ).

Introduction: Preventing side effects is important to ensure optimal psychopharmacotherapy and therapeutic adherence among psychiatric patients. Obtaining the pharmacogenetic profile of CYP2C19 and CYP2D6 can play an important role in this. When the genotype-predicted phenotype shifts because of the use of co-medication, this is called phenoconversion. The aim was to study the influence of the pharmacogenetic (PGx) profile and phenoconversion on side effects experienced by psychiatric patients.Methods: A retrospective cohort study was performed using data from 117 patients from a psychiatric outpatient clinic. Patients were genotyped with a psychiatric PGx panel and side effects were evaluated using the Udvalg for Kliniske Undersølgelser side effects rating scale (UKU).Results: Of all patients, 10.3% and 9.4% underwent phenoconversion (any shift in predicted phenotype) for CYP2C19 and CYP2D6 respectively. No significant associations were found between the phenotype and UKU-score. 75% of the patients with an Intermediate metabolizer (IM) or Poor metabolizer (PM) phenoconverted phenotype of CYP2C19 experienced nausea and vomiting compared to 9.1% of the Normal metabolizer (NM) and Ultrarapid metabolizer (UM) patients (p = 0.033). 64% of the patients with an IM or PM phenoconverted phenotype of CYP2D6 experienced the side effect depression compared to 30.4% NMs and UMs (p = 0.020). CYP2D6 IM and PM patients had a higher concentration-dose ratio than NM patients (p < 0.05).Discussion: This study underlines the importance to consider phenoconversion when looking at a patient’s genotype. This is important for a better prediction of the phenotype and preventing possible side effects under a specific psychopharmacotherapy.

Abstract (N = 351) Background Drug-drug interactions (DDIs) are highly prevalent in older patients but little is known about prevalence of DDIs over time. Our main objective was to assess changes in the prevalence and characteristics of drug-drug interactions (DDIs) during a one-year period after hospital admission in older people, and associated risk factors. Methods We conducted a sub-study of the European OPERAM trial (OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people), which assessed the effects of a structured medication review (experimental arm) compared to usual care (control arm) on reducing drug-related hospital readmissions. All OPERAM patients (≥70 years, with multimorbidity and polypharmacy, hospitalized in four centers in Bern, Brussels, Cork and Utrecht between December 2016 and October 2018, followed over 1 year) who were alive at hospital discharge and had full medication data during the index hospitalization (at baseline i.e., enrolment at admission, and at discharge) were included. DDIs were assessed using an international consensus list of potentially clinically significant DDIs in older people. The point-prevalence of DDIs was evaluated at baseline, discharge, and at 2, 6 and 12 months after hospitalization. Logistic regression models were performed to assess independent variables associated with changes in DDIs 2 months after baseline. Results Of the 1950 patients (median age 79 years) included, 1045 (54%) had at least one potentially clinically significant DDI at baseline; point-prevalence rates were 58, 57, 56 and 57% at discharge, and 2, 6 and 12 months, respectively. The prevalence increased significantly from baseline to discharge (P

Abstract Background Antipsychotic-induced Weight Gain (AiWG) is a debilitating and common adverse effect of antipsychotics. AiWG negatively impacts life expectancy, quality of life, treatment adherence, likelihood of developing type-2 diabetes and readmission. Treatment of AiWG is currently challenging, and there is no consensus on the optimal management strategy. In this study, we aim to evaluate the use of metformin for the treatment of AiWG by comparing metformin with placebo in those receiving treatment as usual, which includes a lifestyle intervention. Methods In this randomized, double-blind, multicenter, placebo-controlled, pragmatic trial with a follow-up of 52 weeks, we aim to include 256 overweight participants (Body Mass Index (BMI) > 25 kg/m2) of at least 16 years of age. Patients are eligible if they have been diagnosed with schizophrenia spectrum disorder and if they have been using an antipsychotic for at least three months. Participants will be randomized with a 1:1 allocation to placebo or metformin, and will be treated for a total of 26 weeks. Metformin will be started at 500 mg b.i.d. and escalated to 1000 mg b.i.d. 2 weeks thereafter (up to a maximum of 2000 mg daily). In addition, all participants will undergo a lifestyle intervention as part of the usual treatment consisting of a combination of an exercise program and dietary consultations. The primary outcome measure is difference in body weight as a continuous trait between the two arms from treatment inception until 26 weeks of treatment, compared to baseline. Secondary outcome measures include: 1) Any element of metabolic syndrome (MetS); 2) Response, defined as ≥5% body weight loss at 26 weeks relative to treatment inception; 3) Quality of life; 4) General mental and physical health; and 5) Cost-effectiveness. Finally, we aim to assess whether genetic liability to BMI and MetS may help estimate the amount of weight reduction following initiation of metformin treatment. Discussion The pragmatic design of the current trial allows for a comparison of the efficacy and safety of metformin in combination with a lifestyle intervention in the treatment of AiWG, facilitating the development of guidelines on the interventions for this major health problem. Trial registration This trial was registered in the Netherlands Trial Register (NTR) at https://www.trialregister.nl/trial/8440 as NTR NL8840 on March 8, 2020.

Abstract Background Several approaches to medication optimisation by identifying drug-related problems in older people have been described. Although some interventions have shown reductions in drug-related problems (DRPs), evidence supporting the effectiveness of medication reviews on clinical and economic outcomes is lacking. Application of the STOPP/START (version 2) explicit screening tool for inappropriate prescribing has decreased inappropriate prescribing and significantly reduced adverse drug reactions (ADRs) and associated healthcare costs in older patients with multi-morbidity and polypharmacy. Therefore, application of STOPP/START criteria during a medication review is likely to be beneficial. Incorporation of explicit screening tools into clinical decision support systems (CDSS) has gained traction as a means to improve both quality and efficiency in the rather time-consuming medication review process. Although CDSS can generate more potential inappropriate medication recommendations, some of these have been shown to be less clinically relevant, resulting in alert fatigue. Moreover, explicit tools such as STOPP/START do not cover all relevant DRPs on an individual patient level. The OPERAM study aims to assess the impact of a structured drug review on the quality of pharmacotherapy in older people with multi-morbidity and polypharmacy. The aim of this paper is to describe the structured, multi-component intervention of the OPERAM trial and compare it with the approach in the comparator arm. Method This paper describes a multi-component intervention, integrating interventions that have demonstrated effectiveness in defining DRPs. The intervention involves a structured history-taking of medication (SHiM), a medication review according to the systemic tool to reduce inappropriate prescribing (STRIP) method, assisted by a clinical decision support system (STRIP Assistant, STRIPA) with integrated STOPP/START criteria (version 2), followed by shared decision-making with both patient and attending physician. The developed method integrates patient input, patient data, involvement from other healthcare professionals and CDSS-assistance into one structured intervention. Discussion The clinical and economical effectiveness of this experimental intervention will be evaluated in a cohort of hospitalised, older patients with multi-morbidity and polypharmacy in the multicentre, randomized controlled OPERAM trial (OPtimising thERapy to prevent Avoidable hospital admissions in the Multi-morbid elderly), which will be completed in the last quarter of 2019. Trial registration Universal Trial Number: U1111-1181-9400 Clinicaltrials.gov: NCT02986425 , Registered 08 December 2016. FOPH (Swiss national portal): SNCTP000002183 . Netherlands Trial Register: NTR6012 (07-10-2016).

In this article the design of three master programs (MSc in Pharmacy) and two postgraduate specialization programs for community or hospital pharmacist is described. After a preceding BSc in Pharmacy, these programs cover the full pharmacy education capacity for pharmacists in primary and secondary health care in the Netherlands. All programs use the CanMEDS framework, adapted to pharmacy education and specialization, which facilitates the horizontal integration of pharmacists’ professional development with other health care professions in the country. Moreover, it is illustrated that crossing the boundary from formal (university) education to experiential (workplace) education is eased by a gradual change in time spent in these two educational environments and by the use of comparable monitoring, feedback, and authentic assessment instruments. A reflection on the curricula, based on the principles of the Integrative Pedagogy Model and the Self-determination Theory, suggests that the alignment of these educational programs facilitates the development of professional expertise and professional identity of Dutch pharmacists.