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BackgroundPrescribing cascades are important contributors to polypharmacy. Little is known about which older adults are at highest risk of experiencing prescribing cascades. We explored which older veterans are at highest risk of the gabapentinoid (including gabapentin and pregabalin)-loop diuretic (LD) cascade, given the dramatic increase in gabapentinoid prescribing in recent years.MethodsUsing Veterans Affairs and Medicare claims data (2010-2019), we performed a prescription sequence symmetry analysis (PSSA) to assess loop diuretic initiation before and after gabapentinoid initiation among older veterans (≥66 years). To identify the cascade, we calculated the adjusted sequence ratio (aSR), which assesses the temporality of LD relative to gabapentinoid initiation. To explore high-risk groups, we used multivariable logistic regression with prescribing order modeled as a binary dependent variable. We calculated adjusted odds ratios (aORs), measuring the extent to which factors are associated with one prescribing order versus another.ResultsOf 151,442 veterans who initiated a gabapentinoid, there were 1,981 patients who initiated a LD within 6 months after initiating a gabapentinoid compared to 1,599 patients who initiated a LD within 6 months before initiating a gabapentinoid. In the gabapentinoid-LD group, the mean age was 73 years, 98% were male, 13% were Black, 5% were Hispanic, and 80% were White. Patients in each group were similar across patient and health utilization factors (standardized mean difference

Ageing is associated with an increased risk of adverse drug reactions. This calls for great care and diligent follow up when prescribing medication to older patients. Yet, this is seldom the case and the proportion of older people taking five or more medications has quadrupled from 12% to 49% in the last 20 years. Certain medications are riskier than others. Those with anticholinergic effects are of particular concern. Adverse effects of anticholinergics include dry mouth, nausea, dizziness, fatigue, vomiting, constipation, abdominal pain, urinary retention, blurred vision, tachycardia and neurologic impairment, such as confusion and agitation. Anticholinergic medication can cause daytime drowsiness and cognitive decline, while increasing the risk of fall and can lead to increased mortality. Although anticholinergic medication should be avoided in older people whenever possible, their use has almost doubled in the last 20 years, and those who are most vulnerable to its adverse effects had the greatest increase in use. This article examines why older people are at increased risk of adverse drug reactions and how medication review can enable older persons to take medications regularly, improve quality of life and minimise medication waste. [ABSTRACT FROM AUTHOR]

Polypharmacy in the context of medicines means the prescription, dispensing, or use of multiple medications simultaneously. The correct characterization of a particular patient’s prescription or use of a medicine allows the appropriate change to be chosen. Rational pharmacotherapy aims to minimize the medication-related burden, which requires controlled and often longer-lasting intervention and gradually implemented changes in the therapy of a particular patient based on individually assessed and identified drug-related problems. For example, deprescribing options can reduce inappropriate polypharmacy by targeting medicines that occur in prescribing cascades and using comprehensive approaches and concepts. The paper presents the prescribing cascades and the possibilities of their solution within the framework of pharmacotherapy optimization, characterizing the concepts and campaigns “Less is More”, “Choose Wisely”, and “Patient pathway”. The recommendations and warnings formulated within these concepts and campaigns aim to focus the attention of healthcare professionals on the importance of evaluating and considering the necessity of their interventions. They should prioritize value-based care and avoid overloading patients with diagnostic and therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: Prescribing cascades are important contributors to polypharmacy. Little is known about which older adults are at highest risk of experiencing prescribing cascades. We explored which older veterans are at highest risk of the gabapentinoid (including gabapentin and pregabalin)–loop diuretic (LD) cascade, given the dramatic increase in gabapentinoid prescribing in recent years. Methods: Using Veterans Affairs and Medicare claims data (2010–2019), we performed a prescription sequence symmetry analysis (PSSA) to assess loop diuretic initiation before and after gabapentinoid initiation among older veterans (≥66 years). To identify the cascade, we calculated the adjusted sequence ratio (aSR), which assesses the temporality of LD relative to gabapentinoid initiation. To explore high‐risk groups, we used multivariable logistic regression with prescribing order modeled as a binary dependent variable. We calculated adjusted odds ratios (aORs), measuring the extent to which factors are associated with one prescribing order versus another. Results: Of 151,442 veterans who initiated a gabapentinoid, there were 1,981 patients who initiated a LD within 6 months after initiating a gabapentinoid compared to 1,599 patients who initiated a LD within 6 months before initiating a gabapentinoid. In the gabapentinoid–LD group, the mean age was 73 years, 98% were male, 13% were Black, 5% were Hispanic, and 80% were White. Patients in each group were similar across patient and health utilization factors (standardized mean difference <0.10 for all comparisons). The aSR was 1.23 (95% CI: 1.13, 1.34), strongly suggesting the cascade's presence. People age ≥85 years were less likely to have the cascade (compared to 66–74 years; aOR 0.74, 95% CI: 0.56–0.96), and people taking ≥10 medications were more likely to have the cascade (compared to 0–4 drugs; aOR 1.39, 95% CI: 1.07–1.82). Conclusions: Among older adults, those who are younger and taking many medications may be at higher risk of the gabapentinoid–LD cascade, contributing to worsening polypharmacy and potential drug‐related harms. We did not identify strong predictors of this cascade, suggesting that prescribing cascade prevention efforts should be widespread rather than focused on specific subgroups. [ABSTRACT FROM AUTHOR]

Prescribing cascades can lead to unnecessary medication use, healthcare costs, and patient harm. Pharmacists oversee prescriptions from multiple prescribers and are well positioned to identify such cascades, making pharmacists key stakeholders to address them. To evaluate community pharmacists' awareness, identification, and management of prescribing cascades and to assess behavioural determinants that may be targeted in future strategies to minimise inappropriate prescribing cascades. An online survey was developed using the Theoretical Domains Framework (TDF) and emailed to all registered community pharmacists in Ireland (n = 3775) in November 2021. Quantitative data were analysed using descriptive and inferential statistics. Free-text sections were given to capture reasons for non-resolution of identified prescribing cascades and suggestions to aid prescribing cascade identification and management; this text underwent content analysis. Of the 220 respondents, 51% were aware of the term ' prescribing cascade' before the survey, whilst 69% had identified a potentially inappropriate prescribing cascade in practice. Over one third were either slightly confident (26.4%) or not confident at all (10%) in their ability to identify potentially inappropriate prescribing cascades in patients' prescriptions before the survey, whilst 55.2% were concerned that patients were receiving prescribing cascades they had not identified. Most respondents wanted further information/training to help prescribing cascade identification (88.3%) and management (86.1%). Four predominant TDF domains identified were common to both i) influencing non-resolution of identified prescribing cascades and ii) in the suggestions to help identify and manage prescribing cascades: ' Environmental Context and Resources' , 'Social/Professional Role and Identity', 'Social Influences' and ' Memory, Attention and Decision Processes'. There is a clear need to provide additional resources to help community pharmacists identify and manage prescribing cascades. These findings will support the development of theory-informed behaviour change strategies to aid the minimisation of inappropriate prescribing cascades and decrease the risk of medication-related harm for patients. • First study to explore community pharmacists' views on prescribing cascades. • Pharmacists concerned they did not identify prescribing cascades in their patients. • Pharmacists want more resources to help identify and manage prescribing cascades. • To prevent prescribing cascades, most agreed that software alerts would be useful. • This study identified key behavioural targets for minimising prescribing cascades. [ABSTRACT FROM AUTHOR]

Abstract Prescribing cascade is a significant clinical problem but is often overlooked. We explore the incidence of the prescribing cascades of antigout medications related to thiazide treatment in gout-naïve hypertensive adults newly exposed to the pharmacological treatment. This population-based, retrospective cohort study used the Taiwan National Health Insurance Registry Database. Gout-naïve hypertensive adults who were newly dispensed first-line antihypertensive drugs between January 1, 2000, and December 31, 2016, were enrolled. Patients were divided into the thiazide group (n = 4192) and the non-thiazide group (n = 81,083). The non-thiazide group included patients who received an angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, calcium channel blocker, or beta-blocker. The study utilized propensity score matching and multivariable Cox regression models to investigate the prescribing cascade of antigout agents following antihypertensive treatment, adjusting for factors like age, sex, comorbidities, and concurrent medications. After propensity score matching, each group consisted of 4045 patients, with the thiazide group exhibiting a higher risk of being prescribed antigout medications across different time intervals post-treatment initiation. Specifically, adjusted hazard ratios (aHRs) for the thiazide group were 2.23, 2.07, and 2.41 for 180 days, respectively, indicating a sustained and significant risk over time. Comparative analyses revealed thiazide diuretics were associated with a higher risk of antigout medication prescriptions compared to other antihypertensive classes, particularly evident after 180 days. Subgroup analyses across various demographics and comorbidities consistently showed an increased risk in the thiazide cohort. Gout-naïve hypertensive adults newly dispensed thiazide had a higher risk of subsequently adding antigout agents than those taking other first-line antihypertensive medications. The awareness and interruption of these prescribing cascades are critical to improving patient safety.

Abstract Prescribing cascades occur when patients are prescribed medication to treat the adverse drug reaction of previously prescribed medication. Prescription sequence symmetry analysis (PSSA) can be used to assess the association between two medications in prescription or dispensing databases and thus the potential occurrence of prescribing cascades. In this article, a step-by-step guide is presented for conducting PSSA to assess prescribing cascades. We describe considerations for medication data collection and setting time periods for relevant parameters, including washout window, exposure window, continued exposure interval and blackout period. With two examples, we illustrate the impact of changes in these parameters on the strengths of associations observed. Given the impact seen, we recommend that researchers clearly specify and explain all considerations regarding medication included and time windows set when studying prescribing cascades with PSSA, and conduct subgroup and sensitivity analyses.

Background: Prescribing cascades occur when a drug adverse event is misinterpreted as a new medical condition and a second, potentially unnecessary drug, is prescribed to treat the adverse event. The population‐level consequences of prescribing cascades remain unknown. Methods: This population‐based cohort study used linked health administrative databases in Ontario, Canada. The study included community‐dwelling adults, 66 years of age or older with hypertension and no history of heart failure (HF) or diuretic use in the prior year, newly dispensed a calcium channel blocker (CCB). Individuals subsequently dispensed a diuretic within 90 days of incident CCB dispensing were classified as the prescribing cascade group, and compared to those not dispensed a diuretic, classified as the non‐prescribing cascade group. Those with and without a prescribing cascade were matched one‐to‐one on the propensity score and sex. The primary outcome was a serious adverse event (SAE), which was the composite of emergency room visits and hospitalizations in the 90‐day follow‐up period. We estimated hazard ratios (HRs) with 95% confidence intervals (CI) for SAE using an Andersen–Gill recurrent events regression model. Results: Among 39,347 older adults with hypertension and no history of HF who were newly dispensed a CCB, 1881 (4.8%) had a new diuretic dispensed within 90 days after CCB initiation. Compared to the non‐prescribing cascade group, those in the prescribing cascade group had higher rates of SAEs (HR: 1.21, 95% CI: 1.02–1.43). Conclusions: The CCB‐diuretic prescribing cascade was associated with an increased rate of SAEs, suggesting harm beyond prescribing a second drug therapy. Our study raises awareness of the downstream impact of the CCB‐diuretic prescribing cascade at a population level and provides an opportunity for clinicians who identify this prescribing cascade to review their patients' medications to determine if they can be optimized. [ABSTRACT FROM AUTHOR]

Aim: Multiple risk factors are involved in geriatric syndrome (GS) occurring in older adults. Although drug therapy often contributes to GS, the specific causes among older adults in Japan remain unclear. In this study, we examined the possible prescribing cascade rate among older outpatients eligible for Late‐stage Elderly Health Insurance and elucidated the differences between GS and GS associated with medication (GSAM) trends. Methods: This retrospective study enrolled patients from health insurance claims data in Japan between October 2018 and March 2019; hospitalized patients were excluded. Two groups were identified among the participants with GS: GS (no use of GS‐causing medications) and possible‐GSAM (p‐GSAM; use of GS‐causing medications). The collected data were analyzed using the Bell Curve for Excel, and statistical significance was set at P < 0.05. Results: In total, 137 781 outpatients were enrolled. Of the 32 259 outpatients who did not use GS‐causing medications, 7342 were classified into the GS group. Among 105 522 outpatients who used GS‐causing medications, 8347 were classified as having p‐GSAM. The mean number of prescriptions was significantly higher in the p‐GSAM group than in the GS group (P < 0.01). Furthermore, all GS symptoms showed significant differences, with impaired appetite being the most prevalent in the p‐GSAM group than in the GS group (P < 0.01). A possible prescribing cascade was suspected in 2826 (33.9%) of 8347 outpatients in the p‐GSAM group. Conclusion: Impaired appetite in patients taking GS‐causing medications might lead to prescribing cascades. Further studies are needed to prevent such prescribing cascades. Geriatr Gerontol Int 2024; 24: 61–67. [ABSTRACT FROM AUTHOR]

Prescribing cascades entail misinterpreting drug-related adverse events as new medical problems, resulting in unnecessary prescriptions and potential harm, especially in the elderly, leading to adverse outcomes like falls, cognitive defects, and increased health-care costs. For geriatric patients with complex medical histories, the intricacies of symptom differentiation and polypharmacy poses further challenges. This report focuses on managing a geriatric patient with multiple conditions, highlighting the risks and complexities of prescribing cascades.

Prescribing cascades entail misinterpreting drug-related adverse events as new medical problems, resulting in unnecessary prescriptions and potential harm, especially in the elderly, leading to adverse outcomes like falls, cognitive defects, and increased health-care costs. For geriatric patients with complex medical histories, the intricacies of symptom differentiation and polypharmacy poses further challenges. This report focuses on managing a geriatric patient with multiple conditions, highlighting the risks and complexities of prescribing cascades. [ABSTRACT FROM AUTHOR]

Purpose: Statins are among the most prevalent medications prescribed and associated with adverse events that may prompt additional treatment (i.e., a prescribing cascade). No comprehensive assessment of statin‐related prescribing cascades has been performed to our knowledge. Methods: We utilized sequence symmetry analysis to iteratively screen prescribing sequences of all therapeutic classes ("marker" classes) based on Level 4 Anatomical Therapeutic Chemical codes among adult statin initiators, using IBM Marketscan commercial and Medicare supplemental claims databases (2005–2019). Order of initiation and secular trend‐adjusted sequence ratios were calculated for each statin‐marker class dyad, among marker class initiators ±90 days of statin initiation. Among signals classified as prescribing cascades, we calculated naturalistic number needed to harm (NNTH) within 1 year as the inverse of the excess risk among exposed. Results: We identified 2 265 519 statin initiators (mean ± SD age, 56.4 ± 12.0 years; 48.7% women; 7.5% with cardiovascular disease). Simvastatin (34.4% of statin initiators) and atorvastatin (33.9%) were the most commonly initiated statins. We identified 160 significant statin‐marker class dyad signals, of which 35.6% (n = 57) were classified as potential prescribing cascades. Of the top 25 strongest signals (lowest NNTH), 12 were classified as potential prescribing cascades, including osmotically acting laxatives (NNTH, 44, 95% CI 43–46), opioids + non‐opioid combination analgesics (81, 95% CI 74–91), and first‐generation cephalosporins (204, 95% CI 175–246). Conclusions: Using high‐throughput sequence symmetry analysis screening, we identified previously known prescribing cascades as well as potentially new prescribing cascades based on known and unknown statin‐related adverse events. [ABSTRACT FROM AUTHOR]

Background: Polypharmacy may result from inappropriate prescribing of medications to treat adverse drug reactions (ADRs), i.e., "prescribing cascade." A potentially harmful prescribing cascade affecting those with severe dementia can result when anticholinergics are prescribed to manage side effects of cholinesterase inhibitors (ChEIs). We investigated 1) factors associated with co‐prescribing of anticholinergics and ChEIs and 2) whether discontinuation of ChEIs was associated with subsequent discontinuation of anticholinergics—a potentially beneficial reversal or "deprescribing cascade." Methods: We conducted a retrospective analysis of linked Medicare Part A/B/D claims, Master Beneficiary Summary File, Minimum Data Set, Area Health Resource File, and Nursing Home Compare from 2015 to 2016. Subjects were Medicare beneficiaries residing in nursing homes, ≥65 years old with severe dementia admitted for non‐skilled stays, who were prescribed ChEIs. Cross‐sectional analysis evaluated factors associated with co‐prescribing of anticholinergics with ChEIs. Longitudinal Cox proportional hazards regression examined whether discontinuation of ChEIs was associated with subsequent discontinuation of anticholinergics over a 1‐year period. Results: We found 15% of our sample experienced co‐prescribing of anticholinergics and ChEIs. Several resident and facility‐level factors were associated with co‐prescribing anticholinergics. Advancing age, minority race or ethnicity, end‐stage renal disease, heart failure, and poor appetite were associated with a decreased likelihood of co‐prescribing. Female sex, polypharmacy, and non‐geriatric prescriber‐type were associated with a higher likelihood of co‐prescribing. In longitudinal analyses, we observed that discontinuation of ChEIs was associated with a reduced likelihood (HR 0.58 [95% CI, 0.47–0.71]) of discontinuing any medications with anticholinergic properties, except for bladder antimuscarinics (HR 1.32 [95% CI, 0.83–2.09]). Conclusions: Younger, healthier older adults with dementia were more likely to experience co‐prescribing anticholinergics and ChEIs. Discontinuation of anticholinergics was infrequent. Further research is needed to understand prescribers' ability to recognize and reverse potential prescribing cascades through deprescribing. [ABSTRACT FROM AUTHOR]

Pharmacotherapy for major depressive disorder (MDD) typically consists of trial-and-error and clinician preference approaches, where patients often fail one or more antidepressants before finding an optimal regimen. Pharmacogenomics (PGx) can assist in prescribing appropriate antidepressants, thereby reducing the time to MDD remission and occurrence of adverse drug events. Since many antidepressants are metabolized by and/or inhibit cytochrome P450 enzymes (e.g., CYP2C19 or CYP2D6), drug-induced phenoconversion is common in patients on antidepressant combinations. This condition influences the interpretation of a patient's PGx results, overall risk of ineffective/adverse medication response due to multi-drug interactions, and the recommendations. This complex case describes a patient with MDD, generalized anxiety disorder, and chronic pain who experienced a fall due to excessive sedation following a prescribing cascade of fluoxetine, bupropion, and doxepin. These antidepressants delivered a significant additive sedative effect and interacted with the patient's hydrocodone, potentially contributing to uncontrolled pain, upward dose titration of hydrocodone, and a higher overall sedative burden. The PGx results and drug-induced phenoconversion described in this case report explain the patient's excessive sedation and possibly ineffective/toxic antidepressant and opioid treatment. This case report also illustrates how a more timely multi-drug interaction assessment (preferably in conjunction with preemptive PGx testing) may have informed a different prescribing pattern, reduced/avoided a prescribing cascade, and potentially prevented a drug-related fall. [ABSTRACT FROM AUTHOR]

Purpose of Review: The intent of this review is to provide an update in polypharmacy in older adults and women with a focus on common determinants and strategies to mitigate polypharmacy. Recent Findings: Polypharmacy is becoming a critical focus in the management of cardiovascular diseases. It may emerge unintentionally while managing multimorbidity in older adults or in the vulnerable subgroup of patients, such as pregnant and lactating females. Clinicians should utilize several approaches such as deprescribing, sex-specific risk assessment, and encouraging healthy lifestyle to minimize inappropriate and unnecessary use of medications. Summary: A shared decision-making model along with coordination and collaboration among healthcare providers should be utilized in the selection and management of pharmacotherapies. [ABSTRACT FROM AUTHOR]

Older adults are a vulnerable group of patients with multiple medical needs. The ageing process induces numerous physiological changes, which affect the pharmacological profile of drugs. The multiple conditions accumulated with advancing age, geriatric syndrome and frailty require that the geriatric patient use multiple medications simultaneously, which increases the risk of drug therapy problems. The comprehensive, multidimensional assessment of the geriatric patient is essential for the development of an individualised care plan that takes into account the patients’ specific health and social characteristics and goals. The pharmacist must take into account the age-specific changes that occur in the pharmacokinetics, pharmacodynamics and pharmacotoxicology of drugs in order to advise their optimal use. [ABSTRACT FROM AUTHOR]

Background: The (prescription) sequence symmetry analysis (PSSA) design has been used to identify potential prescribing cascade signals by assessing the prescribing sequence of an index drug relative to a marker drug presumed to treat an adverse drug event provoked by the index drug.Objectives: This review aimed to explore the use of the PSSA design as a pharmacovigilance tool with a particular focus on the breadth of identified signals and advances in PSSA methodology.Methods: We searched Embase, PubMed/Medline, Google Scholar, Web of Science and grey literature to identify studies that used the PSSA methodology. Two reviewers independently extracted relevant data for each included article. Study characteristics including signals identified, exposure time window, stratified analyses, and use of controls were extracted.Results: We identified 53 studies which reported original results obtained using PSSA methodology or quantified the validity of components of the PSSA design. Of those, nine studies provided validation metrics showing reasonable sensitivity and high specificity of PSSA to identify prescribing cascade signals. We identified 340 unique index drug - marker drug signals published in the PSSA literature, representing 281 unique index - marker pharmacological class dyads (i.e., unique fourth-level Anatomical Therapeutic Chemical [ATC] classification dyads). Commonly observed signals were identified for index drugs acting upon the nervous system (34%), cardiovascular system (21%), and blood and blood-forming organs (15%), and many marker drugs were related to the nervous system (25%), alimentary tract and metabolism (23%), cardiovascular system (17%), and genitourinary system and sex hormones (14%). Negative controls and positive controls were utilized in 21% and 13% of studies, respectively.Conclusions: The PSSA methodology has been used in 53 studies worldwide to detect and evaluate over 300 unique prescribing cascades signals. Researchers should consider sensitivity analyses incorporating negative and/or positive controls and additional time windows to evaluate time-varying biases when designing PSSA studies. [ABSTRACT FROM AUTHOR]

Introduction: Prescribing cascade refers to use of a medication to treat a drug-related adverse event. Prescribing cascades increase medication use, cost, and risk of adverse events. Objective: Our objective was to use administrative health data to identify whether use of medications from the anticholinergic cognitive burden scale was associated with proton pump inhibitor (PPI) prescribing consistent with a prescribing cascade in older adults with dementia. Method: The cohort was comprised of Nova Scotia Seniors' Pharmacare beneficiaries identified to have dementia and medication dispensation data recorded between 1 April 2010, or cohort entry and 31 March 2015. Anticholinergic medications from the anticholinergic cognitive burden scale (ACB) were abstracted. A look back period of 365 days identified if a PPI had been dispensed preceding anticholinergic dispensation. PPI initiation within 30, 60, 90, or 180 days of the anticholinergic medication was assessed. Demographic description of those dispensed anticholinergic medications or PPIs were reported. Risk factors for the prescribing cascade were investigated with logistic regression and Cox proportional hazards modelling including a sex-stratified analysis. Results: We identified 28,952 Nova Scotia Seniors' Pharmacare beneficiaries with dementia and prescription dispensation data. Anticholinergic medications were frequently dispensed with 63.4% of the cohort dispensed at least one prescription for an anticholinergic medication. The prescribing cascade defined as up to 180-days between anticholinergic medication inititation and PPI dispensation, occurred in 1,845 Nova Scotia Seniors' Pharmacare beneficiaries with dementia (incidence 6.4%). Multivariate regression showed those experiencing the prescribing cascade after initiating any anticholinergic were younger (OR 0.98, 95%CI [0.97–0.98]), less likely to live in an urban location (OR 0.82, 95%CI [0.74–0.91]), or to be men (OR 0.74, 95%CI [0.67–0.82]). Cox regression demonstrated an increased risk of starting a PPI within 180 days when initiating any medication from the ACB (HR 1.38, 95%CI [1.29–1.58]). Discussion: Regression modelling suggested that anticholinergic medications increased the risk of PPI dispensation consistent with a prescribing cascade in the cohort. The identification of the prescribing cascade in this population of older Nova Scotia Seniors' Pharmacare Program beneficiaries with dementia using administrative health data highlights how routinely collected health data can be used to identify prescribing cascades. [ABSTRACT FROM AUTHOR]

Key summary points: Aim: To examine the relation between drugs commonly used in NHs and diagnosis of anemia in a łarge sample of older adults resident in nursing homes (NHs). Findings: We investigated the relation between anemia and medications potentially related to anemia in nursing homes. Only the association with PPI was found. Message: Optimization of PPI prescription is needed to avoid potential adverse events and the use of drugs to treat anemia as the effect of a prescribing cascade. Purpose: Some medications can cause anemia through their effect on gastrointestinal function, such as proton pump inhibitors and H2-antagonists, and on the risk of bleeding, such as anticoagulants and antiplatelet agents. The main aim of this study is to evaluate how anemia is related with the most commonly used drugs in a large sample of NH residents. Methods: This retrospective cross-sectional multicenter study was conducted in a sample of Italian long-term care NHs distributed throughout the country. Results: In all, 2602 NH residents recruited from 27 Italian long-term NHs (mean age ± SD: 88.4 ± 8.5) and 441 (16.9%) had a diagnosis of anemia. The unadjusted model showed a significant relation with PPI (OR 1.71, 95% CI 1.39–2.11, p < 0.0001). This relation was maintained in the model adjusted for age, sex, CKD, atrophic gastritis, peptic ulcer and rheumatic disease (OR 1.61, 95% CI 1.31–1.99, p < 0.0001). PPI users were also at higher risk of being treated with antianemic drugs—iron supplements, folate, vitamin B12 and erythropoietin (OR 2.03, 95% CI 1.67–2.48, p < 0.0001)—even if they did not have anemia (OR 1.94, 95% CI 1.55–2.42, p < 0.0001). Conclusion: Proton pump inhibitors are associated with anemia in NH residents. PPIs are also related with an increased probability of receiving drugs to treat anemia, such as iron supplements, folate or cyanocobalamin and erythropoietin, as the effect of a prescribing cascade. Optimization of PPI prescription is needed to avoid adverse events and promote rational drug prescription. [ABSTRACT FROM AUTHOR]

Introduction: Prescribing cascade refers to use of a medication to treat a drug-related adverse event. Prescribing cascades increase medication use, cost, and risk of adverse events.Objective: Our objective was to use administrative health data to identify whether use of medications from the anticholinergic cognitive burden scale was associated with proton pump inhibitor (PPI) prescribing consistent with a prescribing cascade in older adults with dementia.Method: The cohort was comprised of Nova Scotia Seniors’ Pharmacare beneficiaries identified to have dementia and medication dispensation data recorded between 1 April 2010, or cohort entry and 31 March 2015. Anticholinergic medications from the anticholinergic cognitive burden scale (ACB) were abstracted. A look back period of 365 days identified if a PPI had been dispensed preceding anticholinergic dispensation. PPI initiation within 30, 60, 90, or 180 days of the anticholinergic medication was assessed. Demographic description of those dispensed anticholinergic medications or PPIs were reported. Risk factors for the prescribing cascade were investigated with logistic regression and Cox proportional hazards modelling including a sex-stratified analysis.Results: We identified 28,952 Nova Scotia Seniors’ Pharmacare beneficiaries with dementia and prescription dispensation data. Anticholinergic medications were frequently dispensed with 63.4% of the cohort dispensed at least one prescription for an anticholinergic medication. The prescribing cascade defined as up to 180-days between anticholinergic medication inititation and PPI dispensation, occurred in 1,845 Nova Scotia Seniors’ Pharmacare beneficiaries with dementia (incidence 6.4%). Multivariate regression showed those experiencing the prescribing cascade after initiating any anticholinergic were younger (OR 0.98, 95%CI [0.97–0.98]), less likely to live in an urban location (OR 0.82, 95%CI [0.74–0.91]), or to be men (OR 0.74, 95%CI [0.67–0.82]). Cox regression demonstrated an increased risk of starting a PPI within 180 days when initiating any medication from the ACB (HR 1.38, 95%CI [1.29–1.58]).Discussion: Regression modelling suggested that anticholinergic medications increased the risk of PPI dispensation consistent with a prescribing cascade in the cohort. The identification of the prescribing cascade in this population of older Nova Scotia Seniors’ Pharmacare Program beneficiaries with dementia using administrative health data highlights how routinely collected health data can be used to identify prescribing cascades.

Objectives: To evaluate the prescription sequence symmetry analysis assumption regarding balance between marker drug (i.e., medication used to treat a drug‐induced adverse event) initiation rates before and after initiation of an index drug (i.e., medication that is potentially associated with the drug‐induced adverse event) in the absence of prescribing cascades, we used a well‐described example of loop diuretic initiation to treat dihydropyridine calcium channel blockers (DH CCB)‐induced edema. Study design and setting: The University of Florida Health Integrated Data Repository from June 2011 and July 2018 was used to assess temporal prescribing of DH CCB and loop diuretics within the prescription sequence symmetry analysis framework. Validation of the prescribing cascade was performed via clinical expert chart review. Results: Among patients without heart failure who were initiated on DH CCB, 26 and 64 loop diuretics initiators started within 360 days before versus after DH CCB initiation, respectively, resulting in an adjusted sequence ratio (aSR) of 2.27 (95% CI, 1.44–3.58). Overall, 35 (54.7%) patients were determined to have a prescribing cascade. Removing patients who experienced a prescribing cascade resulted in an aSR of 1.05, 95% CI 0.62–1.78). Conclusion: Loop diuretic initiation rates before and after DH CCB initiation for reasons other a prescribing cascade were similar, thus confirming the prescription sequence symmetry analysis assumption. [ABSTRACT FROM AUTHOR]

Abstract Background Prescribing cascades occur when the side effect of a medication is treated with a second medication. The aim of the study was to understand how prescribing cascades develop and persist and to identify strategies for their identification, prevention and management. Method This qualitative study employed semi-structured interviews to explore the existence of prescribing cascades and to gather patients', caregivers' and clinicians’ perspectives about how prescribing cascades start, persist and how they might be resolved. Participants were older adults (over age 65) at an outpatient Geriatric Day Hospital (GDH) with possible prescribing cascades (identified by a GDH team member), their caregivers, and healthcare providers. Data were analyzed using an inductive content analysis approach. Results Fourteen participants were interviewed (eight patients, one family caregiver, one GDH pharmacist, three GDH physicians and one family physician) providing a total of 22 interviews about patient-specific cases. The complexity and contextually situated nature of prescribing cascades created challenges for all of those involved with their identification. Three themes impacted how prescribing cascades developed and persisted: varying awareness of medications and cascades; varying feelings of accountability for making decisions about medication-related care; and accessibility to an ideal environment and relevant information. Actions to prevent, identify or resolve cascades were suggested. Conclusion Patients and healthcare providers struggled to recognize prescribing cascades and identify when they had occurred; knowledge gaps contributed to this challenge and led to inaction. Strategies that equip patients and clinicians with resources to recognize prescribing cascades and environmental and social supports that would help with their identification are needed. Current conceptualizations of cascades warrant additional refinement by considering the nuances our work raises regarding their appropriateness and directionality.

Pharmacotherapy for major depressive disorder (MDD) typically consists of trial-and-error and clinician preference approaches, where patients often fail one or more antidepressants before finding an optimal regimen. Pharmacogenomics (PGx) can assist in prescribing appropriate antidepressants, thereby reducing the time to MDD remission and occurrence of adverse drug events. Since many antidepressants are metabolized by and/or inhibit cytochrome P450 enzymes (e.g., CYP2C19 or CYP2D6), drug-induced phenoconversion is common in patients on antidepressant combinations. This condition influences the interpretation of a patient’s PGx results, overall risk of ineffective/adverse medication response due to multi-drug interactions, and the recommendations. This complex case describes a patient with MDD, generalized anxiety disorder, and chronic pain who experienced a fall due to excessive sedation following a prescribing cascade of fluoxetine, bupropion, and doxepin. These antidepressants delivered a significant additive sedative effect and interacted with the patient’s hydrocodone, potentially contributing to uncontrolled pain, upward dose titration of hydrocodone, and a higher overall sedative burden. The PGx results and drug-induced phenoconversion described in this case report explain the patient’s excessive sedation and possibly ineffective/toxic antidepressant and opioid treatment. This case report also illustrates how a more timely multi-drug interaction assessment (preferably in conjunction with preemptive PGx testing) may have informed a different prescribing pattern, reduced/avoided a prescribing cascade, and potentially prevented a drug-related fall.

Competing Interests: Conflicts of interest: Ian and Fiona Coombes are immediate family members of Judith Coombes, who is a member of the Australian Prescriber Editorial Advisory Committee. Judith was excluded from editorial decision-making related to the acceptance and publication of this article.

Laxatives are among the most prescribed medications to nursing home (NH) patients, and we evaluated the hypothesis that laxative agents could be prescribed as a result of a prescribing cascade. The aims of the study are (1) to investigate the use of laxative drugs in a large sample of Italian NHs and (2) to assess the relationship between medications that can induce constipation and laxative use. Retrospective cross-sectional multicenter study. Individuals living in long-term care NHs. Study conducted in a sample of Italian long-term care NHs distributed throughout the country. Information on drug prescriptions, diseases and sociodemographic characteristics collected 4 times during 2018 and 2019. Among the 2602 patients recruited from 27 NHs (mean age ± standard deviation: 88.4 ± 8.5; women: 1994, 76.6%), 1248 were receiving laxatives (48%). Parkinson disease, cerebrovascular disease, and hemiplegia were associated with laxative prescription, and diabetes was associated with a decrease. Benzodiazepines, anti-Parkinson dopaminergic agents, and antidepressants (tricyclic antidepressants and mirtazapine) were associated with laxative treatment in univariate and adjusted models. Tricyclic antidepressants users were 3 times more likely to be taking laxatives than nonusers (odds ratio 2.98, 95% confidence interval 1.31-6.77, P =.0093). A larger number of drugs that can induce constipation was associated with laxative use (P =.0003). In all, 2002 individuals had at least 2 different prescription times: from the first to the last visit laxative use rose from 46.1% to 49.9%. Time of stay was also associated with laxative use (P =.016). Laxatives are among the most prescribed medications in Italian NHs. Medications that can induce constipation, such as antidepressants, anti-Parkinson dopaminergic agents, and benzodiazepines, are often used together with laxatives, and combinations of these drugs further increase the use of laxatives. Optimizing the prescription of psychotropic drugs could help reduce the "prescribing cascade" with laxatives. The length of stay in NHs is often proportional to laxative use and chronic treatment is very common. [ABSTRACT FROM AUTHOR]

Purpose: There is an increased use in the (prescription) sequence symmetry analysis (PSSA); however, limited studies have incorporated a negative control, and no study has formally quantified and controlled for within‐patient time‐varying bias using a negative control. Our aim was to develop a process to incorporate the effect of negative controls into the main analysis of a PSSA. Methods: Using a previously assessed dihydropyridine calcium channel blocker (DH‐CCB) and loop diuretic PSSA, we directly compared the adjusted sequence ratios (aSRs) of DH‐CCBs to each of the two negative control index drugs (levothyroxine and angiotensin converting enzyme [ACE] inhibitor/angiotensin‐2 receptor blocker [ARB]) using the ratio of the aSRs to estimate a relative aSR with a Z test. Further, we utilized the relative aSR in stratum‐specific analyses and varying exposure windows. Results: The relative aSR of DH‐CCBs decreased from 1.87 to 1.72 (95% CI 1.66–1.78) using levothyroxine as a negative control index drug. ACE inhibitor/ARB negative control index drug resulted in an aSR of 1.27 thus reducing the relative aSR for DH‐CBB from 1.84 to 1.45 (95% CI 1.41–1.49). When restricting the exposure window to 180 and 90 days, the relative aSR of DH‐CCBs increased to 1.68 (95% CI 1.62–1.74) and 1.86 (95% CI 1.78–1.94), respectively, relative to the ACE inhibitor/ARB negative control index drug. Conclusion: We illustrated how to incorporate negative control index drugs into a PSSA and generate relative aSRs. Stratum‐specific assessments and varying the exposure windows while using negative control index drugs can yield more informative results. [ABSTRACT FROM AUTHOR]

Purpose: Prescribing cascades occur when a physician prescribes a new drug to address the side‐effect of another drug. Persons with Alzheimer's disease and related dementias (ADRD) are at increased risk for prescribing cascades. Our objective was to develop an approach to estimating the proportion of calcium channel blocker‐diuretic (CCB‐diuretic) prescribing cascades among persons with ADRD in two U.S. health plans. Methods: We identified patients aged ≥50 on January 1, 2017, dispensed a drug to treat ADRD in the 365‐days prior to/on cohort entry date. Patients had medical/pharmacy coverage for 1 year before and through cohort entry. We excluded individuals with an institutional stay encounter in the 45 days prior to cohort entry and censored patients based on: disenrollment from coverage, death, or end of data. We identified incident and prevalent CCB use in the 183‐days following cohort entry, and identified subsequent incident diuretic use among incident and prevalent CCB‐users within 365‐days from cohort entry. Results: There were 121 538 eligible patients. Approximately 62% were female, with a mean age of 79.5 (SD ±8.6). Overall 2.1% of the cohort experienced a prevalent CCB‐diuretic prescribing cascade with 1586 incident diuretic‐users among 36 462 prevalent CCB‐users (4.3%, 95% CI 4.1–4.6%]); and there were161 incident diuretic‐users among 3304 incident CCB‐users (4.9%, 95% CI 4.2–5.7%) (incident CCB‐diuretic cascade). Conclusions: We describe an approach to identify prescribing cascades in persons with ADRD, which can be used to assess the proportion of prescribing cascades in large cohorts. We determined the proportion of CCB‐diuretic prescribing cascades was low. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aging of the population and chronic pain represents topical issues in developed countries. These often translate into polypharmacy, inappropriate medications, and adverse drug events, with the risk of misinterpreting these latter with new medical conditions, generating what is referred to prescribing cascade. Prescribing cascades may lead to the prescription of new drugs, which could cause new potential side effects and unnecessary costs for individuals and healthcare systems. Therefore, the purpose of our review was to collect a good deal of prescribing cascades examples involving pain therapy medicines, to help clinicians minimize drug-related clinical outcomes. MATERIALS AND METHODS: We search in MEDLINE database through PubMed, including 31 studies and 80 different examples of prescribing cascades. RESULTS: The medications most commonly resulting in the initial drug therapy prescribed were represented by psychoanaleptics (27/80, 33.7%). Among adverse drug events, the most common one, misinterpreted as a new medical condition, was represented by tremor and extrapyramidal symptoms (20/80, 25%). As regards the new drug therapies prescribed for adverse drug events, the therapeutic subgroups most commonly resulting in the new drug therapy prescribed were represented by psycholeptics (12/80, 15%), and by anti-Parkinson drugs (12/80, 15%). CONCLUSIONS: This study provides a list of several examples of prescribing cascades in pain medicine and is essential to raise awareness of the potential dangers they could involve in all patient populations. Collaboration between clinicians and clinical pharmacologists may lead to more appropriate polypharmacy schemes. [ABSTRACT FROM AUTHOR]

Aim: The benefits of antiplatelets to prevent cardio‐ and cerebrovascular disease are recognized and appropriate only for "secondary prevention." This multicenter retrospective study was designed to (i) examine the prevalence of residents receiving antiplatelets for primary and secondary cardio‐ and cerebrovascular prevention, and (ii) evaluate the predictors of inappropriate antiplatelet prescription. Methods: This study was conducted in a sample of Italian long‐term care nursing homes (NHs). Appropriate use of antiplatelets was defined in accordance with the strongest evidence‐based indications. Results: Among the 2579 patients recruited from 27 long‐term care NHs (age mean ± SD: 86.8 ± 7.3; women: 1995; 77.4%), 1092 were treated with antiplatelets (42.3%) and 619 (56.7%) were receiving antiplatelet agents for inappropriate primary prevention of cardio‐ or cerebrovascular atherothrombotic events. Age, dementia or cerebral atherosclerosis, congestive heart failure, peripheral vascular disease, diabetes without chronic complication and hypertension were predictors of inappropriate prescription of antiplatelets. Patients inappropriately treated with antiplatelets also had a higher risk of receiving proton pump inhibitors than those appropriately not treated in univariate (OR 95% CI = 2.79 (2.25–3.46, p < 0.0001) and multivariate models (OR 95% CI 2.71 (2.16–3.40, p < 0.0001). Conclusions: Most patients receiving antiplatelet agents in NHs are being inappropriately treated for primary prevention of cardio‐ or cerebrovascular disease. NH residents with diagnosis of dementia or cerebral atherosclerosis, congestive heart failure, peripheral vascular disease, diabetes without chronic complication and hypertension seemed more likely to receive antiplatelets inappropriately. Patients without an evidence‐based indication for antiplatelets also received proton‐pump inhibitors in an unnecessary "prescribing cascade," which should be assessed for de‐prescribing. Geriatr Gerontol Int 2020; 20: 828–832. [ABSTRACT FROM AUTHOR]

A prescribing cascade is a situation, in which an adverse drug reaction is mistaken for a new medication condition, and a new medication is prescribed. We present a case, in which risperidone led to a prescribing cascade in a geriatric patient. We share this case to improve awareness and vigilance of prescribing cascades in the geropsychiatric population.

As originally defined, the term "prescribing cascade" describes a sequence of events that begins when an adverse drug event (ADE) occurs, is misinterpreted as a new medical condition, and a subsequent drug is then inadvertently prescribed to treat the new condition. We refine the definition to encompass both recognized and unrecognized ADEs because they can both contribute to problematic prescribing practices. In addition, we discuss that although prescribing cascades are most commonly viewed as problematic, they may be appropriate and therapeutically beneficial in certain clinical situations. We differentiate between appropriate and problematic prescribing cascades by adopting a similar approach to the framework proposed in the highly acclaimed King's Fund report Polypharmacy and Medicines Optimization. Practical considerations are also presented to aid clinicians in preventing the propagation of problematic prescribing cascades within their clinical practice. Providing new perspectives on the scope and appropriateness of the prescribing cascade concept is an important step in describing clinically relevant cascades and in encouraging safe prescribing practices. J Am Geriatr Soc 67:1023–1026, 2019. [ABSTRACT FROM AUTHOR]

Older adults are given therapies to enhance the quality and longevity of life, but with the benefits of medication therapy also comes the potential for adverse drug events (ADEs). Avoiding ADEs has become a national health priority with substantial impact on health outcomes and health care costs. The presence of multimorbidity, changes in physiologic function, and polypharmacy make older adults more vulnerable to medication-related ADEs. Use of interactive support tools in the form of geriatric-friendly medication order sets and geriatric consultations along with pharmacist-led medication review and optimization are imperative to decrease the occurrence of ADEs and unnecessary prescribing cascades., (Copyright © 2023 Elsevier Inc. All rights reserved.)

OBJECTIVES: To systematically describe the resources available on preventing, detecting, and reversing prescribing cascades using a scoping review methodology. MEASUREMENTS: We searched Medline, EMBASE, PsychINFO, CINAHL, Cochrane Library, and Sociological Abstracts from inception until July 2017. Other searches (Google Scholar, hand searches) and expert consultations were performed for resources examining how to prevent, detect, or reverse prescribing cascades. We used these three categories along the prescribing continuum as an organizing framework to categorize and synthesize resources. RESULTS: Of 369 resources identified, 58 met inclusion criteria; 29 of these were categorized as preventing, 20 as detecting, and 9 as reversing prescribing cascades. Resources originated from 14 countries and mostly focused on older adults. The goal of preventing resources was to educate and increase general awareness of the concept of prescribing cascades as a way to prevent inappropriate prescribing and to illustrate application of the concept to specific drugs (e.g., anticholinergics) and conditions (e.g., inflammatory bowel disease). Detecting resources included original investigations or case reports that identified prescribing cascades using health administrative data, patient cohorts, and novel sources such as social media. Reversing prescribing cascade resources focused on the medication review process and deprescribing initiatives. CONCLUSION: Prescribing cascades are a recognized problem internationally. By learning from the range of resources to prevent, detect, and reverse prescribing cascades, this review contributes to improving drug prescribing, especially in older adults. J Am Geriatr Soc 66:2079–2085, 2018. [ABSTRACT FROM AUTHOR]

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Polypharmacy, associated with adverse health outcomes, is common in older adults owing to increasing chronic conditions. In addition to normal organ system changes that affect pharmacokinetic, and pharmacodynamics of medications, drug-drug interaction and drug-disease interactions should be reviewed. Tools to minimize polypharmacy should be considered when treating older adults., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)