Polypharmacy In Treatment Research Articles

Validation of a novel Artificial Pharmacology Intelligence (API) system for the management of patients with polypharmacy

ObjectiveMedication management of patients with polypharmacy is highly complex. We aimed to validate a novel Artificial Pharmacology Intelligence (API) algorithm to optimize the medication review process in a comprehensive, personalized, and scalable way. Materials and methodsThe study was conducted on anonymized retrospective electronic health records (EHR) of 49 patients. Each patient's file was reviewed by the API system, a clinical pharmacist, and a judging committee. Validation was assessed by comparing the overall agreement of the judging committee (as the gold standard, blinded to the identity of the analyzer) to both the API system and clinical pharmacists' conclusions. Five medication-related problem (MRP) categories were assessed: duplication of therapy, age-related issues, incorrect dose, current side effects and future side effects' risk. For each category the overall validity parameters, agreement, positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity were analyzed. ResultsThe agreement between the API system and the judging committee was 93.5 % (95 % CI 92.7–94.4), while the agreement between the clinical pharmacists and the judging committee was 73.9 % (95 % CI 72.5–75.3). The PPV was 92.2 % (90.9–93.5) and NPV was 94.2 % (93.1–95.2) for the API system and 76.3 % (69.8–82.8) and 73.5 % (72.3–74.8) respectively for the clinical pharmacists. DiscussionAI systems can equip clinicians with sophisticated tools and scale manual processes such as comprehensive medication reviews, thus reducing MRPs and drug-related hospitalizations related to multidrug treatments. The API system validated in this study provided comprehensive, multidrug, multilayered analysis intended to bridge the innate complexity of personalized polypharmacy treatment. ConclusionsThe API system was validated as a tool for providing actionable clinical insights non-inferior to a manual clinical review of a clinical pharmacist. The API system showed promising results in reducing MRPs.

Effects of stigma on the quality of life in patients with epilepsy

BackgroundThis study was aimed to evaluate the stigma and quality of life (QoL) in adult patients with epilepsy (PWEs) and explore the relationship between stigma and QoL.MethodsTwo hundred and ninety-eight PWEs admitted to the Epilepsy Center of the First Affiliated Hospital of Chongqing Medical University during September 2020 and March 2021 were enrolled in this study. All participants completed self-reported questionnaires including the Stigma Scale for Epilepsy and the Quality of Life in Epilepsy Inventory-31 (QOLIE-31).ResultsA total of 146 (49%) PWEs reported an experience of stigma. The total score of QOLIE-31 and the individual scores of seven subscales (worry about new seizures, emotion, well-being, energy and fatigue, cognitive impairment, medication effect, and social function) were significantly decreased in these patients (P < 0.001). Multivariate stepwise linear regression analysis showed that the annual household income per capita, the number of antiseizure medications and stigma had statistically significant effects on QoL (P < 0.05). Among them, stigma had the most significant negative effect.ConclusionsNearly half of PWEs have experienced stigma. Stigma, lower household income per capita, and polypharmacy treatment are associated with poorer QoL. Stigma has the most obvious negative impact.

The effect of polypharmacy on rheumatoid and psoriatic arthritis treatment: retrospective study.

Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic, progressive inflammatory diseases that can be accompanied by other diseases. In recent years, with the increase in the lifespan of individuals, the concept of polypharmacy has become more prominent. We aimed to show the prevalence of polypharmacy and the effects of polypharmacy on disease activity in RA and PsA. This study included PsA patients who had peripheral joint involvement and, RA patients. Since PsA has a heterogeneous clinical picture, only patients with peripheral joint involvement were included in the study and patients with inflammatory low back pain or radiological sacroiliitis or spondylitis, dactylitis or enthesitis were not included in the study due to homogeneity concerns. The numbers of medications used by the patients at the onset of their treatment and at sixth months into their treatment were recorded. Polypharmacy was accepted as the simultaneous use of at least five medications by the person. The Disease Activity Score 28 joints C-Reactive Protein (DAS-28 CRP) was used to assess disease activity for both disease. The modified Charlson Comorbidity Index (CCI) scores of the patients were calculated based on their chronic diseases. The sample of the study included 232 RA and 73 PsA patients. Polypharmacy was present at the treatment onset in 115 (49.6%) of the RA patients and 28 (38.4%) of the PsA patients. At the sixth month of treatment, polypharmacy was present in the sixth month of the treatment in 217 (93.5%) RA and 61 (83.6%) PsA patients. The mean ages of the RA and PsA patients who were receiving polypharmacy treatment at the beginning were significantly older than the mean ages of those who were not receiving polypharmacy treatment. In both the RA and PSA groups, the patients with polypharmacy at the beginning had statistically significantly higher DAS-28 CRP scores at six months of treatment than those without polypharmacy at the beginning (p<0.001). Polypharmacy was present both at the time of diagnosis and in the treatment process in the RA and PsA patients, and the presence of polypharmacy at the beginning of the treatment was among the factors that affected the treatment of these patients by significantly affecting their 6th-month DAS-28 CRP values.

Indirect adjusted comparison of 6-month clinical outcomes between esketamine nasal spray and other real-world polypharmacy treatment strategies for treatment resistant depression: results from the ICEBERG study.

The efficacy of esketamine nasal spray (NS) as a rapid-acting agent for treatment resistant depression (TRD) was demonstrated in comparisons with placebo, when both were given in addition to a newly initiated selective serotonin reuptake inhibitor (SSRI)/serotonin norepinephrine reuptake inhibitor (SNRI). How esketamine NS compares with commonly used real-world (RW) polypharmacy treatment strategies is not known. ICEBERG was an adjusted indirect treatment comparison that analysed data from SUSTAIN-2 (NCT02497287; clinicaltrials.gov), a long-term, open-label study of esketamine NS plus SSRI/SNRI, and the European Observational TRD Cohort (EOTC; NCT03373253; clinicaltrials.gov), an observational study of routine clinical practice. Data were compared between patients receiving esketamine NS (SUSTAIN-2) and those from the EOTC treated with polypharmacy treatment strategies, either combination or augmentation. Analyses were adjusted for potential confounders, using rescaled average treatment effect among treated estimates. Threshold analyses were conducted to assess potential impact of unmeasured confounders on the robustness of analyses where esketamine NS was found to be significantly superior. Sensitivity analyses were used to understand the impact of analysis method selection and data handling. Esketamine NS treatment resulted in a higher probability of 6-month response (49.7% [95% confidence interval (CI) 45.6-53.9]) and remission (33.6% [95% CI 29.7-37.6]) versus RW polypharmacy (26.8% [95% CI 21.0-32.5] and 19.4%, [95% CI 14.2-24.6], respectively). Relative risk calculations showed esketamine NS was 1.859 (95% CI 1.474-2.345; p < 0.0001) times as likely to result in response and 1.735 (1.297-2.322; p = 0.0002) times as likely to result in remission versus RW polypharmacy at 6 months. Threshold and extensive sensitivity analyses supported that analyses of esketamine NS superiority were robust. ICEBERG supports esketamine NS being superior to current RW individualized polypharmacy strategies, including augmentation, with benefits extending beyond acute use, to improved chance of 6-month response and remission. While unobserved confounding factors may certainly impact results of an indirect comparison, threshold analysis supported a low likelihood of this affecting the conclusions.To view an animated summary of this publication, please click on the Supplementary video.

The Risk of Adverse Drug-Drug Interactions for Stable Angina Pectoris Patients with Heart Failure Complication Prescribed Polypharmacy

Stable angina pectoris (SAP) is an imbalance that occurs when myocardial oxygen need increases disproportionally, causing complaints of chest pain. Uncontrolled SAP can lead to a complication of heart failure (HF). Polypharmacy treatment frequently given to SAP patients with HF complications can be potentially detrimental for them. This study aims to determine the risk of adverse drug-drug interactions in SAP patients with HF complications prescribed polypharmacy. This was an analytic observational study with a cross-sectional approach using retrospective data from medical record data from 2020-2021 among hospitalized patients in cardiology ward Ulin General Hospital, Banjarmasin. Potential drug-drug interactions were determined using the Lexicomp tool from the UpToDate® site. Prevalence Odds Ratio (POR) and 95% Confidence Interval (95%CI) were determined using the Logistic Regression test at the 95% level of confidence. Twenty-four SAP patients with HF were recruited. According to its potential interactions, the most interactions were under category C (82.6%), followed by category B (11.3%) and category D (6.0%). Based on its level of severity, the most common was moderate (77.4%), followed by minor (13.0%) and major (9.5%). SAP patients with HF who were not prescribed polypharmacy had a lower risk of adverse drug-drug interactions by 64.7% compared to polypharmacy users, although it was not statistically difference (crude POR 0.353, 95% CI; 0.360-3.421; p-value = 0.369). This study shows that there is a tendency of lower risk of adverse drug-drug interactions in SAP patients with HF complication prescribed polypharmacy compared to those without polypharmacy, but the association is not statistically significant.

Polypharmacy in Outpatients with Bipolar Disorder: Associated Factors and Treatment Characteristics in Türkiye

Objective: Polypharmacy is frequently used in the treatment of the bipolar disorder. We aimed to investigate polypharmacy rates, associated factors, and the types of drugs preferred in treatment among outpatients with bipolar disorder. &#x0D; Method: A total of 209 bipolar disorder patients attending an outpatient psychiatry clinic were included in this study. Drug types, active substances, and combination forms were examined. &#x0D; Results: The rate of polypharmacy among bipolar outpatients was 79.40%. Antipsychotics were the most frequently preferred drug for the treatment. The most commonly used antipsychotic was quetiapine, whereas the mood stabilizer was sodium valproate and the antidepressant was paroxetine. The most common form of treatment for bipolar disorder was the combined use of a mood stabilizer and an antipsychotic. &#x0D; Conclusion: In contrast to treatment guidelines, polypharmacy has virtually become a standard in the treatment of bipolar disorder. It appears that the adoption of polypharmacy in treatment will persist for various reasons. As such, there is a need to develop new guidelines to guide psychiatrists in determining the patient groups and combinations in which combination therapy will be preferred. Moreover, interventions are needed to minimize the possible side effects, and risk of drug-drug interactions related to the use of multiple drugs, determine the benefit/harm ratio and reduce unnecessary psychotropic drug use.

Modified Atkins diet in children with epilepsy with eyelid myoclonia (Jeavons syndrome)

BackgroundEpilepsy with eyelid myoclonia(EEM) or Jeavons syndrome is considered a genetic generalized epilepsy with a typical age of onset in childhood. Many types of seizures can be observed, including eyelid myoclonia, absence, generalized tonic-clonic, and myoclonic seizures. Seizures tend to be difficult to control requiring polypharmacy treatment or become drug-resistant. Dietary therapy, particularly with Modified Atkins Diet (MAD), as a treatment of seizures in this syndrome has rarely been studied. We report efficacy and tolerability of MAD in children with epilepsy with eyelid myoclonia. MethodsWe reviewed medical records of children with EEM treated at the University of Chicago Ketogenic Diet program from 2017 to 2022. Patient’s demography, seizure characteristics, EEG findings, response to treatment, and adverse effects were reviewed. ResultSix patients with EEM were identified. Average age of seizure onset was 6 (2–11) years and an average age when the MAD started was 10.7 (6–15) years. All patients were started on MAD and completed at least 6 months on the diet at the time of report. An average of 4 (0–9) anti-seizure medications (ASM) had been tried prior to the MAD. All patients achieved ketosis with an average level of serum beta-hydroxybutyrate of 1.9 (1.03–3.61) mmol/L. At the 6-month follow-up visit, all patients (100%) experienced a greater than 50% seizure reduction, 3/6 patients (50%) had more than 90% seizure reduction, 1/6 patients (17%) became seizure-free. All seizure types demonstrated a greater than 80% reduction in frequency.Absence and myoclonic seizures showed the greatest reduction with 100% seizure reduction. Eyelid myoclonia and generalized tonic-clonic seizures showed more than 80% seizure reduction.Moreover, all patients reported improvement in alertness, mood, and concentration. Initial weight loss and mild gastrointestinal disturbances were reported in 2/6 patients (33%) and corrected with dietary adjustment. ConclusionThe Modified Atkins Diet has shown to be effective and welltolerated for children with EEM in our study. Cognitive improvement has also been subjectively reported in all patients. Adverse effects are tolerable and correctable. The MAD, therefore, may be considered as a treatment option for patients with epilepsy with eyelid myoclonia.

Minimization of drug interactions in polypharmacy treatments of diabetes mellitus type 2 with cardiovascular comorbidities by using the decision support tool PM-TOM

BackgroundCombined polypharmacy treatments of multi-diseases like diabetes mellitus type 2 (DMT2) with its comorbidities could lead to serious adverse reactions (ADR) due to drug-drug interactions (DDIs). This study aimed to demonstrate that these DDI ADRs can be significantly reduced by carefully examining DDIs of recommended drugs and using advanced clinical decision support (CDS) tools, like PM-TOM (Personal Medicine: Therapy Optimization Method). MethodDMT2 with heart failure (HF) and atherosclerotic cardiovascular disease (ASCVD) were taken for analysis. First, 20 drug classes were selected, recommended in relevant medical guidelines (US, European and Canadian); for example, biguanides, sodium-glucose transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, insulins, angiotensin 2 receptor blockers, angiotensin-converting enzyme inhibitors, beta-adrenergic blockers, diuretics, and statins. Next, these classes were combined into polypharmacy treatment cases, which were organized into three groups: Basic (combinations of three drug classes), Medial (five), and Advanced (eight). Then, the tool PM-TOM was used to find treatments with minimal and maximal drug interactions (MIN-DDI and MAX-DDI) for each case. Finally, these two treatments' minimal, average and maximal DDIs were calculated and statistically analyzed to examine the scope and effects of optimizing polypharmacy treatments in each case group. ResultsIn the Basic group, 16 polypharmacy treatment cases were created; in the Medial 210 and the Advanced 736. The MIN-DDI and MAX-DDI treatments in each case group showed significant DDI differences; for example, in the Basic group, the average DDI count in the MIN-DDI treatments was 0.19 and in the MAX-DDI ones 1.75, while in the Medial and Advanced groups, these indicators were 1.66 and 7.66, and 5.76 and 20.52, respectively. Also, 87% of optimized treatments (MIN-DDI) in the Basic group showed no DDIs, 37% in the Medial, and 9% in the Advanced. In addition, 70% of cases in the Medial group had at most two DDIs, and 49% in the Advanced group at most five. ConclusionsThese findings suggest that DDI ADRs in randomly selected (unoptimized) DMT2 polypharmacy treatments can be substantially reduced using specialized decision support tools, increasing patients' chances for successful treatment and decreasing health care costs. Similar findings can be expected for other multi-diseases as well.

Polypharmacy in Treatment of Behavioral Issues in Dementia-Use of Atypical Antipsychotics.

Behavioral and psychological symptoms of dementia (BPSD) may occur in most patients with dementia. Symptoms such as agitation, aggression, and psychosis often lead to higher rates of hospitalization, morbidity, and mortality. Despite the prevalence of BPSD, safe and effective treatment options are limited. This often leads to off-label prescribing and trends toward polypharmacy. Notwithstanding modest efficacy in BPSD, antipsychotics seem to be one of the most commonly prescribed medications in its treatment. Polypharmacy with antipsychotics is particularly troublesome due to the increased risk of potentially lethal adverse effects. As such, their use should be judiciously monitored with the goal of gradual dose reduction.

A one-year follow-up study of treatment-compliant suicide attempt survivors: relationship of CYP2D6-CYP2C19 and polypharmacy with suicide reattempts

This study of a cohort of 1-year treatment-compliant survivors of a suicide attempt examined for the first time whether a high CYP2D6-CYP2C19 metabolic capacity (pharmacogenes related to psychopathology, suicide, and attempt severity) and/or polypharmacy treatments predicted repeat suicide attempts, adjusting for sociodemographic and clinical factors as confounders. Of the 461 (63% women) consecutively hospitalized patients who attempted suicide and were evaluated and treated after an index attempt, 191 (67.5% women) attended their 6- and 12-month follow-up sessions. Clinicians were blinded to the activity scores (AS) of their genotypes, which were calculated as the sum of the values assigned to each allele (CYP2C19 *2, *17; CYP2D6 *3, *4, *4xN, *5, *6, *10, wtxN). No differences were found in polypharmacy prescription patterns and the variability of CYP2D6 and CYP2C19 genotypes between adherents and dropouts, but the formers were older, with a higher frequency of anxiety and bipolar disorders and fewer alcohol and substance use disorders. The risk of reattempts was higher for CYP2D6 ultrarapid (AS > 2) metabolizers (β = 0.561, p = 0.005) and violent suicide survivors (β = −0.219, p = 0.042) if the attempt occurred during the first 6-month period, individuals with an increased number of MINI DSM-IV Axis I mental disorders (β = 0.092, p = 0.032) during the second 6-month period and individuals with a combined high CYP2D6-CYP2C19 metabolic capacity (AS > 4) (β = 0.345, p = 0.024) and an increased use of drugs other than antidepressants, anxiolytics-depressants and antipsychotics-lithium (β = 0.088, p = 0.005) in multiple repeaters during both periods. CYP2D6 and CYP2C19 rapid metabolism and polypharmacy treatment for somatic comorbidities must be considered to prevent the severe side effects of short-term multiple suicide reattempts after a previous attempt.

Association of polypharmacy and potential drug-drug interactions with adverse outcomes in older adults with advanced cancer receiving systemic treatment.

12053 Background: Polypharmacy (PP) is common in older adults starting cancer treatment and associated with increased risk of potential drug-drug interactions (PDI). PP and PDI may affect treatment-related outcomes in older patients. This study evaluates the association of PP and PDI with systemic treatment adverse outcomes in older adults with advanced cancer. Methods: This secondary analysis of prospectively collected data from the GAP 70+ Trial (NCT02054741; PI: Mohile) enrolled patients aged 70+ with advanced (i.e. incurable) cancer; had ≥1 geriatric assessment domain impairment; and planned to start a new chemotherapy regimen or another regimen with high risk of toxicity. PP was assessed prior to initiation of treatment and defined as concurrent use of ≥8 medications (meds). PDI among all drugs were reviewed prior to initiation of treatment using Lexi-Interact® Online with category D and X considered “major PDI”. Study outcomes were assessed within 3 months of treatment initiation and included: 1) total number of Grade ≥2 toxicities according to National Cancer Institute Common Toxicity Criteria; 2) total number of Grade ≥3 toxicities; and 3) early treatment discontinuation due to toxicity. Multivariable linear and logistic regression models were used to examine the association of PP and PDI with treatment adverse-outcomes adjusted for age, gender, cancer type, comorbidity, physical function, social support, and study arm. Results: Among 718 participants, the mean age was 77 (range 70-96); 43% were females; and 57% had lung or gastrointestinal cancers. The median number of meds was 5 (range 0-24); 28% received ≥8 concurrent meds; and 25% had ≥1 major PDI. The mean number of Grade ≥2 toxicities for patients with PP was 9.8 versus 7.7 in patients without PP (adjusted β=1.87, standard error [SE]=0.71, P&lt;0.01). The mean number of Grade ≥3 toxicities for patients with PP was 2.9 versus 2.2 in patients without PP (adjusted β=0.59, SE=0.29, P=0.04). Patients with ≥1 major PDI had 59% higher odds of early treatment discontinuation versus those without major PDI (adjusted odds ratio 1.59, 95% confidence interval=1.03-2.46, P=0.03). There was no significant association between PP and early treatment discontinuation. Major PDI were not significantly associated with toxicity (Ps&gt;0.05). Conclusions: In a cohort of vulnerable older adults with advanced cancer, PP and PDI are associated with increased risk of systemic treatment adverse outcomes. Providing meaningful screening and interventional tools to optimize medication use may improve treatment outcomes in these patients. Funding:UG1CA18996, U01CA233167.

Older Adults with Hypertension: Prevalence of Falls and Their Associated Factors.

Falls are prominent health issues among older adults. Among hypertensive older adults, falls may have a detrimental effect on their health and wellbeing. The purpose of this study is to determine the prevalence of falls among hypertensive older adults and to identify the associated factors that contribute to their falls. This was a cross-sectional study conducted among two hundred and sixty-nine hypertensive older adults who were selected via systematic random sampling in two primary health clinics in Kuala Terengganu, Malaysia. Data on their socio-demographic details, their history of falls, medication history and clinical characteristics were collected. Balance and gait were assessed using the Performance Oriented Mobility Assessment (POMA). It was found that 32.2% of participants reported falls within a year. Polypharmacy (adjusted OR 2.513, 95% CI 1.339, 4.718) and diuretics (adjusted OR 2.803, 95% CI 1.418, 5.544) were associated with an increased risk of falls. Meanwhile, a higher POMA score (adjusted OR 0.940, 95% CI 0.886, 0.996) and the number of antihypertensives (adjusted OR 0.473, 95% CI 0.319, 0.700) were associated with a low incidence of falling among hypertensive older adults. Falls are common among hypertensive older adults. Older adults who are taking diuretics and have a polypharmacy treatment plan have a higher incidence of falls. However, older adults taking a higher number of anti-hypertensive medications specifically were not associated with an increased prevalence of falls.

Polypharmacy Results in Functional Impairment in Mice: Novel Insights Into Age and Sex Interactions.

Males and females may respond differently to medications, yet knowledge about sexual dimorphisms in the effects of polypharmacy remains limited, particularly in aging. This study aimed to assess the effect of high Drug Burden Index (DBI) polypharmacy treatment compared to control on physical function and behavior in young and old, male and female mice. We studied whether age and sex play a role in physical function and behavior following polypharmacy treatment and whether they are paralleled by differences in serum drug levels. Young (2.5 months) and old (21.5 months), C57BL/6 mice were randomized to control or high DBI polypharmacy treatment (simvastatin, metoprolol, oxybutynin, oxycodone, and citalopram; n = 6-8/group) for 4-6 weeks. Compared to control, polypharmacy reduced physical function (grip strength, rotarod latency, gait speed, and total distance), middle zone distance (increased anxiety), and nesting score (reduced activities of daily living) in mice of both ages and sexes (p < .001). Old animals had a greater decline in nesting score (p < .05) and midzone distance (p < .001) than young animals. Grip strength declined more in males than females (p < .05). Drug levels at steady state were not significantly different between polypharmacy-treated animals of both ages and sexes. We observed polypharmacy-induced functional impairment in both age and sex groups, with age and sex interactions in the degree of impairment, which were not explained by serum drug levels. Studies of the pathogenesis of functional impairment from polypharmacy may improve management strategies in both sexes.

Investigation of DRD2 and HTR2A mRNA Expression in Two Therapeutic States of Antipsychotic Polypharmacy and Aripiprazole Monotherapy in the Peripheral Blood of Patients With Schizophrenia

Objectives: Schizophrenia is a severe psychiatric disorder that has profound effects on both individuals and the community. Notwithstanding the suggestion for treating schizophrenia with a minimum dose of drugs, antipsychotic polypharmacy increases the patient’s care costs and drug interactions. Aripiprazole reduces the metabolic side effects of antipsychotic polypharmacy treatment. DRD2 and HTR2A can serve as predictors for response to treatment in schizophrenic patients. The purpose of this survey was to measure the DRD2 and HTR2A genes expression in the peripheral blood samples using Real-Time Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). Methods: A total of 19 patients with a long history of schizophrenia who received at least two types of antipsychotics with daily doses of more than 500 mg of chlorpromazine were entered into the study. The response rates to the treatment based on scores in the Brief Psychiatric Rating Scale (BPRS) questionnaire and DRD2 and HTR2A expression were compared between antipsychotic polypharmacy status and 6 months after monotherapy with aripiprazole. Results: The levels of DRD2 expression decreased significantly after the intervention. The mean changes in HTR2A expression and the BPRS questionnaire and also the relationship between changes in DRD2 and HTR2A expression and changes in BPRS score after the intervention were not significant. Discussion: The conversion of the antipsychotic polypharmacy state to monotherapy with aripiprazole has been accompanied by a significant decrease in DRD2A expression. These genes can be used for evaluating the response rate of schizophrenia treatments in the future.

Polypharmacy, socioeconomic indicators and number of diseases: results from ELSA-Brasil.

To estimate the prevalence of polypharmacy, describe the pharmacotherapeutic classes used, and investigate whether polypharmacy is associated with demographic and socioeconomic indicators, regardless of the number of diseases, among participants in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline (2008-2010). In this analysis, 14,523 adults and elderly (35-74 years) participated. Polypharmacy was characterized as regular use of five or more medicines. The demographic and socioeconomic indicators analyzed were: gender, age, education level, per capita family income, and access to private health insurance. The independent association between demographic and economic indicators and polypharmacy was estimated by binary logistic regression. The prevalence of polypharmacy was 11.7%. The most used drugs were those with action on the cardiovascular system. After adjustments, including by number of diseases, the chances of being on polypharmacy treatment were significantly higher among women, older participants and those with greatest number of diseases. Individuals without health insurance had lower chance to be under polypharmacy, as well as those with lower income. The occurrence of polypharmacy among ELSA-Brasil baseline participants was mainly due to drugs for the treatment of chronic diseases. The relation between polypharmacy and the female gender, as well as its association with old age, are in consonance with the results obtained in other studies. Despite the absence of an association between polypharmacy and education level, the income and health insurance results reinforce the existence of social inequalities regarding drug use.

Polypharmacy and Pharmacological Treatment of Diabetes in Older Individuals: A Population-Based Study in Quebec, Canada.

Our objectives were to describe the use of pharmacological treatments in older adults with diabetes and to identify the factors associated with the use of a combination of hypoglycemic, antihypertensive and lipid-lowering agents. Using the Quebec Integrated Chronic Disease Surveillance System, we conducted a population-based cohort study among individuals aged 66–75 years with diabetes in 2014–2015. We described the number of medications and the classes of medications used and calculated the proportion of individuals using at least one medication from each of these classes: hypoglycemics, antihypertensives and lipid-lowering agents. We identified the factors associated with the use of this combination of treatments by performing robust Poisson regressions. The 146,710 individuals used an average of 12 (SD 7) different medications, mostly cardiovascular (91.3% of users), hormones, including hypoglycemic agents (84.5%), and central nervous system medications (79.8%). The majority of individuals (59%) were exposed to the combination of treatments and the factor most strongly associated was the presence of cardiovascular comorbidities (RR: 1.29; 99% CI: 1.28–1.31). Older individuals with diabetes are exposed to a large number of medications. While the use of the combination of treatments is significant and could translate into cardiovascular benefits at the population level, the potential risk associated with polypharmacy needs to be documented.

Evaluation of polypharmacy in Japan using the national health insurance claims database in 2015-2017

Abstract Background There is growing awareness of polypharmacy as a global issue. Several countries have introduced policies to optimize multidrug prescriptions. In Japan, hospital prescription fee “F100” and outpatient prescription fee “F400” have been instituted to promote the correct use of drugs, the medical treatment fee is restricted when seven or more types of drugs are prescribed. However, non-polypharmacy patients who need multiple drugs are also comprehensively evaluated within the purview of the same drug insurance claim criteria. Thus, the current state of such policies is still unclear. This study identified the age group in which drug claims have changed based on drug insurance claim criteria and elucidated the relationship between policy interventions and multidrug prescriptions. Methods We analyzed F100 and F400 cases using open data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan from April 2015 to March 2017. These sources include a population of about 69 million patients. Moreover, the growth rate of the number of patients who were prescribed seven or more types of drugs was evaluated. Results F100 prescription claims decreased by − 12.7% (n = 3,239,070) in 2016 as compared to 2015 (n = 3,700,396), and the number of F400 prescription claims decreased by − 7.7% (n = 28,745,468) in 2016 as compared to 2015 (n = 31,142,484), for seven or more types of drugs. The drug insurance claim rate among people over the age of 65 was 74.2% to F100 and 77.9% to F400, and this age group represented the highest proportion among all age groups. Conclusions The rate of health insurance claims for multidrug prescriptions clearly decreased after the institution of policy interventions to optimize the use of seven or more types of drugs. The present study suggests that the prescription fee restriction could reduce the rate of multidrug prescriptions and consequent decreases the risk of adverse drug-related events in polypharmacy patients. Key messages Policy interventions related to the optimization of drug prescriptions encourage behavioral factors of healthcare providers. Polypharmacy treatment must be established through prescriptions information linkage between clinical practices and community.

Role of valproate in hyperammonemic encephalopathy in women in a tertiary psychiatric clini

Objective: In patients with acute mental status change with elevated serum ammonia levels, when there is conco-mitant use of valproate, carbamazepine or any other susceptible agent, hyperammonemic encephalopathy is a possible phenomenon. Our aim was to describe this underreported phenomenon in detail and find possible risk factors associated with valproate induced hyperammonemic encephalopathy. Methods: We analyzed retrospective records of two years for female inpatients in the psychiatric ward for women in our hospital. Spearman’s rho correlation analysis was used for assessing the relation between serum ammonia and valproate levels. During the two years’ period, 961 patients were treated in the inpatient clinic. Because of a suspicion of hyperammonemic encephalopathy, serum ammonia levels of 37 patients were analyzed, revealing a total of 34 patients with high ammonia levels, warranting a diagnosis of hyperammonemic encephalopathy. Results: In 28 of these patients hyperammonemic encephalopathy was associated with valproate use. The time interval between initiation of valproate treatment and hyperammonemia was 11±7 days. For these patients, initiation dose of valproate was 883.93±249.83 mg/day (median: 1000 mg/day), daily valproate dose was 914.90±202.87 (median: 928.25) mg and during encephalopathy; valproate blood level was 82.36±25.80 ng/mL (median: 87.50 ng/mL). Serum ammonia level was positively correlated with the initiation dose of valproate ((28)=0.472, p=0.011) and valproate blood levels during hyperammonemia ((28)=0.522, p=0.004). Polypharmacy and long-term intramuscular treatment were also prevalent in patients with hyperammonemic encephalopathy. Discussion: Early suspicion of hyperammonemic encephalopathy in patients taking valproate may improve the outcome of this under recognized problem.

Antipsychotic polypharmacy in the treatment of schizophrenia in China and Japan.

Although antipsychotic monotherapy is recommended as the main treatment for schizophrenia, antipsychotic polypharmacy is not rare in practice. However, longitudinal data on antipsychotic polypharmacy in schizophrenia treatment are limited. This longitudinal database study described antipsychotic polypharmacy in the treatment of schizophrenia in real-world settings in China and Japan. We retrieved information about antipsychotic treatment for schizophrenia from January 2010 to December 2014 from two hospital Electronic Medical Records databases in China and one claims database, Japan Medical Data Centre in Japan. Eligible patients had a diagnosis of schizophrenia (International Classification of Diseases, Tenth Revision F20.x) and at least one prescription for first or second generation antipsychotics. Antipsychotic polypharmacy was defined as having more than one antipsychotic medication overlapping for ⩾60 days. The Japan Medical Data Centre study cohort was further stratified by employees (insurance beneficiaries) and their dependents. The study cohorts comprised 11,961 patients from China and 25,034 (10,661 employee sub-cohort and 14,373 dependent sub-cohort) from 14 days Japan Medical Data Centre in Japan. Most patients were prescribed monotherapy (87.3% in China and 80.1% in Japan), of which oral second-generation antipsychotics were the majority (78.9% in China and 65.8% in Japan). The prevalence rate of antipsychotic polypharmacy was 12.7% in China and 19.9% in Japan (13.7% in employees vs 24.5% in dependents). The most common combinations were two oral antipsychotics. Combinations of more than two drugs were uncommon in China (0.3%) but were prescribed for 5.3% of patients in Japan. Among patients treated with monotherapy, 12.6/100 person-years (11.8%) in China and 9.6/100 person-years (11.0%) in Japan switched to antipsychotic polypharmacy during follow-up. Younger patients were more likely to switch to antipsychotic polypharmacy than older patents in all study cohorts. The observed rates of antipsychotic polypharmacy ranged from 12.7% in China to 19.9% in Japan. Switching from monotherapy to antipsychotic polypharmacy was most likely to occur in younger patients with schizophrenia.

Differential Risk of Increasing Psychotropic Polypharmacy Use in Children Diagnosed With ADHD as Preschoolers.

To characterize treatment trajectories in children newly diagnosed with attention-deficit/hyperactivity disorder (ADHD). We utilized billing records of children aged 3 to 18 years in 28 US states' Medicaid programs between 1999 and 2006. Children entered the cohort at the first ADHD diagnosis (ICD-9-CM: 314.00) preceded by ≥ 6 months with no psychotropic medication use and no psychiatric diagnoses. We followed children for 5 years to assess use of (1) psychotropic polypharmacy (the use of ≥ 3 psychotropic medication classes), (2) antipsychotics, and (3) anticonvulsants. We used mixed-effects logistic regression to model the probability of each utilization outcome as a function of age at ADHD diagnosis and follow-up year, adjusted for sociodemographic factors. Our cohort included 16,626 children of whom 79.2% received stimulants, 33.2% antidepressants, and 23.1% α-agonists, and 25.3% received psychotropic polypharmacy treatment at least once in a subsequent year. Antipsychotics (7.1%-14.7%), anticonvulsants (4.0%-7.9%), and psychotropic polypharmacy (8.5%-13.4%) use increased from year 1 to 5, but this increase was confined to children between ages 3 and 9 at ADHD diagnosis. Children diagnosed at age 3 had the most substantial increase in each outcome (OR = 1.80 [95% CI, 1.36-2.38]; 1.85 [1.38-2.47]; 2.14 [1.45-3.16]), respectively. Also, 39.1% of 9,680 children-years with psychotropic polypharmacy therapy had no psychiatric diagnoses other than ADHD. Psychotropic polypharmacy, antipsychotic, and anticonvulsant use increased with each year of follow-up. This effect was strongly mediated by the age of ADHD diagnosis with substantial increases in preschoolers but no corresponding effect in older children. It was only partially explained by physician diagnoses of concomitant mental disorders.