Tailoring a complex intervention to reduce antidepressants in institutionalized older persons with dementia

INTRODUCTION: First-line treatment for behavioral and psychiatric symptoms of dementia is non-pharmacological. Still, psychotropic medication is widely used, despite its limited effect and harmful side-effects. More than half of all nursing home residents with dementia receive antidepressants, even though deprescribing is safe and feasible. Interventions to promote deprescribing of antidepressants in nursing homes are few and complex. To optimize the deprescribing process through an intervention, transparency for the development of the intervention is needed. We aim to describe the steps in the development and tailoring of an intervention targeting GPs, nursing home staff, and relatives to enhance collaboration on reducing the use of antidepressants in institutionalized older persons with dementia in Denmark. METHOD: A step-wise process guided by the core elements in the Medical Research Council constituted the tailoring process. Five steps were included; 1) a literature search, 2) interviews with stakeholders, 3) drafting the intervention prototype, 4) professionals’ assessment of the intervention, and 5) refinement of the intervention. The steps were conducted from June 2020 to June 2022. RESULTS: Based on the literature search, interviews with stakeholders, and professionals’ assessment of the intervention, four main themes were identified; 1) focusing on antidepressants, 2) importance of professional qualifications, 3) collaboration and communication, and 4) patient and relative involvement. They guided intervention development and refinement of the final intervention, which included 1) a case-based training course and 2) a dialog tool including a symptom assessment scale to be used in a structured consultation at the nursing home. CONCLUSION: This study presents a detailed account of the tailoring process for a complex intervention to optimize deprescribing of antidepressants for older persons with dementia at nursing homes. By presenting a thorough development process, we expect to achieve increased adherence to the intervention which is currently being tested in an ongoing cluster randomized controlled trial. The transparency of the process will also increase the future development of other similar complex interventions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12913-022-08961-9

Drug Use among Nursing Home Residents in Denmark for Drugs Having Pharmacogenomics Based (PGx) Dosing Guidelines: Potential for Preemptive PGx Testing

Background: Polypharmacy is most prevalent among the elderly population and in particular among nursing home residents. The frequency of the use of drugs with pharmacogenomics (PGx)-based dosing guidelines for CYP2D6, CYP2C9, CYP2C19 and SLCO1B1 were measured among nursing home residents in the Capital Region of Denmark as well as drug–drug interactions. The aim was to evaluate the potential of applying PGx-test as a supportive tool in medication reviews. Methods: Drug use among nursing home residents during 2017–2018 in the Capital Region of Copenhagen, for drugs with PGx-based dosing guidelines available through the PharmGKB website, were measured. Drug–drug interactions were scored in severity by using drug interaction checkers. Results: The number of residents using drugs with PGx-based actionable dosing guidelines (AG) were 119 out of 141 residents (84.3%). Of these 119 residents, 87 residents used drugs with AG for CYP2C19, 47 residents for CYP2D6, and 42 residents for SLCO1B1. In addition, 30 residents used two drugs with an AG for CYP2C19, and for CYP2D6, it was only seven residents. The most used drugs with AG were clopidogrel (42), pantoprazole (32), simvastatin (30), metoprolol (25), and citalopram (24). The most frequent drug interactions found with warnings were combinations of proton pump inhibitors and clopidogrel underscoring the potential for phenoconversion. Conclusion: this study clearly showed that the majority of the nursing home residents were exposed to drugs or drug combinations for which there exist PGx-based AG. This indeed supports the notion of accessing and accounting for not only drug–gene but also drug–drug–gene interactions as a supplement to medication review

Use of Clopidogrel and Proton Pump Inhibitors Alone or in Combinations in Persons with Diabetes in Denmark; Potential for CYP2C19 Genotype-Guided Drug Therapy

Background: Clopidogrel and proton pump inhibitors (PPIs) are among the most used drugs in Denmark for which there exists pharmacogenomics (PGx)-based dosing guidelines and FDA annotations. In this study, we further scrutinized the use of clopidogrel and PPIs when prescriptions were redeemed from Danish Pharmacies alone or in combination in the Danish population and among persons with diabetes in Denmark. The focus deals with the potential of applying PGx-guided antiplatelet therapy taking both drug–drug interactions (DDI) and drug–gene interactions (DGI) into account. Methods: The Danish Register of Medicinal Product Statistics was the source to retrieve consumption data. Results: The consumption of PPIs and clopidogrel in terms of prevalence (users/1000 inhabitants) increased over a five-year period by 6.3% to 103.1 (PPIs) and by 41.7% to 22.1 (clopidogrel), respectively. The prevalence of the use of clopidogrel and PPIs in persons with diabetes are 3.8 and 2.1–2.8 times higher compared to the general population. When redeemed in combination, the prevalence increased to 4.7. The most used combination was clopidogrel and pantoprazole. Conclusions: The use of clopidogrel and PPIs either alone or in combination is quite widespread, in particular among the elderly and persons with diabetes. This further supports the emerging need of accessing and accounting for not only DDI but also for applying PGx-guided drug therapy in clinical decision making for antiplatelet therapy with clopidogrel having a particular focus on persons with diabetes and the elderly

Comparison of Multidrug Use in the General Population and among Persons with Diabetes in Denmark for Drugs Having Pharmacogenomics (PGx) Based Dosing Guidelines

Background: This study measures the use of drugs within the therapeutic areas of antithrombotic agents (B01), the cardiovascular system (C), analgesics (N02), psycholeptics (N05), and psychoanaleptics (N06) among the general population (GP) in comparison to persons with diabetes in Denmark. The study focuses on drugs having pharmacogenomics (PGx) based dosing guidelines for CYP2D6, CYP2C19, and SLCO1B1 to explore the potential of applying PGx-based decision-making into clinical practice taking drug–drug interactions (DDI) and drug–gene interactions (DGI) into account. Methods: This study is cross-sectional, using The Danish Register of Medicinal Product Statistics as the source to retrieve drug consumption data. Results: The prevalence of use in particular for antithrombotic agents (B01) and cardiovascular drugs (C) increases significantly by 4 to 6 times for diabetic users compared to the GP, whereas the increase for analgesics (N02), psycoleptics, and psychoanaleptics (N06) was somewhat less (2–3 times). The five most used PGx drugs, both in the GP and among persons with diabetes, were pantoprazole, simvastatin, atorvastatin, metoprolol, and tramadol. The prevalence of use for persons with diabetes compared to the GP (prevalence ratio) increased by an average factor of 2.9 for all PGx drugs measured. In addition, the prevalence of use of combinations of PGx drugs was 4.6 times higher for persons with diabetes compared to GP. In conclusion, the findings of this study clearly show that a large fraction of persons with diabetes are exposed to drugs or drug combinations for which there exist PGx-based dosing guidelines related to CYP2D6, CYP2C19, and SLCO1B1. This further supports the notion of accessing and accounting for not only DDI but also DGI and phenoconversion in clinical decision-making, with a particular focus on persons with diabetes