A tool for safer prescribing in vulnerable adults: the continuing development of the Medichec app and website.

AIMS AND METHOD: Adverse effects are a common concern when prescribing and reviewing medication, particularly in vulnerable adults such as older people and those with intellectual disability. This paper describes the development of an app giving information on side-effects, called Medichec, and provides a description of the processes involved in its development and how drugs were rated for each side-effect. Medications with central anticholinergic action, dizziness, drowsiness, hyponatraemia, QTc prolongation, bleeding and constipation were identified using the British National Formulary (BNF) and frequency of occurrence of these effects was determined using the BNF, product information and electronic searches, including PubMed. RESULTS: Medications were rated using a traffic light system according to how commonly the adverse effect was known to occur or the severity of the effect. CLINICAL IMPLICATIONS: Medichec can facilitate access to side-effects information for multiple medications, aid clinical decision-making, optimise treatment and improve patient safety in vulnerable adults.

Anticholinergic action is rarely a good thing.

The evidence for the risks associated with anticholinergic agents has grown considerably in the last two decades. Not only are they associated with causing peripheral side effects such as dry mouth, blurred vision and constipation, but they can also cause central effects such as cognitive impairment; and more recently, they have consistently been linked with an increased risk of dementia and death in older people. This paper reviews the evidence for the associations of anticholinergic agents and the risk of dementia and increased mortality in dementia.

Managing drugs with anticholinergic activity.

Over the past two decades, considerable data have emerged on an association between drugs with anticholinergic activity and serious adverse effects in older people. Well-recognised anticholinergic adverse effects include dry mouth, blurred vision, constipation and urinary retention. Of particular concern is the potential impact on cognitive function with several studies showing that long-term use of medicines with anticholinergic activity is associated with worsening of cognitive function, increased incidence of dementia and increased mortality. This article gives an overview of the evidence, discusses some of the tools used to identify high-risk drugs and highlights issues to consider when prescribing drugs with anticholinergic activity with a view to reducing potential risks in older people and those at highest risk of cognitive impairment.

Antipsychotic monitoring in dementia: quality of completion of antipsychotic monitoring forms in an older adult mental health service.

AIMS AND METHOD: To support safe prescribing of antipsychotics in dementia, antipsychotic monitoring forms were embedded into our electronic health records. We present a review of the data collected on these forms to assess prescribing and identify areas for improvement in our practice and processes. Data were extracted from the structured fields of antipsychotic initiation and review forms completed between 1 January 2018 and 31 January 2020. RESULTS: We identified gaps in practice where improvements could be made, mainly with regard to physical health monitoring (and particularly electrocardiograms, performed in only 50% of patients) and the low (less than 50%) recorded use of non-pharmacological interventions for behavioural and psychological symptoms of dementia. In addition, antipsychotic treatment was continued despite lack of benefit in almost 10% of reviews. CLINICAL IMPLICATIONS: We advocate for recommendations on physical health monitoring of people with dementia taking antipsychotics to be added to the National Institute for Health and Care Excellence guidance on dementia and the Prescribing Observatory for Mental Health (POMH-UK) national audit.

Improving quantification of anticholinergic burden using the Anticholinergic Effect on Cognition Scale - a healthcare improvement study in a geriatric ward setting.

OBJECTIVE: Anticholinergic burden refers to the cumulative effects of taking multiple medications with anticholinergic effects. This study was carried out in a public hospital in Singapore, aimed to improve and achieve a 100% comprehensive identification and review of measured, anticholinergic burden in a geriatric psychiatry liaison service to geriatric wards. We evaluated changes in pre-to post-assessment anticholinergic burden scores and trainee feedback. METHOD: Plan Do Study Act methodology was employed, and Anticholinergic Effect on Cognition scale (AEC) was implemented as the study intervention. A survey instrument evaluated trainee feedback. RESULTS: There was no measured anticholinergic burden in a baseline of 170 assessments. 75 liaison psychiatry assessments were conducted between June and November 2021 in two cycles. 94.7% of pre-assessments (at the time of assessment) and 71.1% of post-assessments (following assessment) had a record of AEC scores in clinical documentation in cycle one, improving in the second cycle to 100%, 94.6%, respectively. A high post-assessment AEC score of 3 and over reduced from 15.8% in cycle one to 5.4% in cycle two. The trainee feedback suggested an enriching educational experience. CONCLUSIONS: Using the AEC scale, the findings support the feasibility of comprehensive identification and review of measured anticholinergic burden in older people with neurocognitive disorders.

Sedation-Associated Medications at Dementia Diagnosis, Their Receptor Activity, and Associations With Adverse Outcomes in a Large Clinical Cohort.

OBJECTIVES: We aimed to investigate whether sedative medications are associated with adverse outcomes in people with dementia, and whether specific characteristics of these medications predict a higher risk of harm. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: 15,210 patients diagnosed with dementia between 2008 and 2017 in South London. METHODS: From recorded medications at dementia diagnosis, we ascertained those with drowsiness listed as a side effect (termed "sedative" hereafter) and subdivided them by frequency and strength of sedation, receptor profile, half-life, and whether they were psychotropics. Multivariable Cox regression models were applied to determine risk of mortality and emergency hospitalization, and generalized estimating equations to investigate cognitive decline. Final models were adjusted for 19 potential confounders, including measures of physical and mental health, functioning, and central anticholinergic burden. RESULTS: At diagnosis, 70.4% of patients with dementia were receiving at least 1 sedative medication. Median survival time was 4.0 years and median time to first hospitalization 1.4 years. After controlling for potential confounders, receipt of any sedative medication at dementia diagnosis was associated with accelerated cognitive decline and a higher hospitalization risk, but only medications with a cautionary warning yielded an increased mortality hazard. Medications acting through γ-aminobutyric acid agonism, psychotropic sedatives, and those with a short half-life were associated with a higher risk of mortality. γ-aminobutyric acid agonists, N-methyl-d-aspartate receptor antagonists, and nonpsychotropic sedatives were associated with an increased hospitalization risk. α1 antagonist, antihistamines, N-methyl-d-aspartate receptor antagonists, psychotropic sedatives, and those with the shortest or longest half-life were associated with accelerated cognitive decline. CONCLUSIONS AND IMPLICATIONS: Receipt of any sedative agent was associated with hospitalization and accelerated cognitive decline. Differences in hazard appear to exist between frequency and strength of sedation, receptor profiles, half-life, and prescribing indication. These differences should be taken into consideration in medication reviews at the time of dementia diagnosis.

Centrally-acting anticholinergic drugs- associations with mortality, hospitalisation and cognitive decline following dementia diagnosis in people receiving antidepressant and antipsychotic drugs.

OBJECTIVES: Long-term use of anticholinergic medication in older people is associated with increased risk of cognitive decline and mortality, but this relationship could be confounded by the underlying illness the drugs are treating. To investigate associations between central anticholinergic antidepressants or antipsychotics and mortality, hospitalisation and cognitive decline in people with dementia. METHOD: In cohorts of patients with a dementia diagnosis receiving antidepressant and/or antipsychotic medication (N = 4,380 and N = 2,335 respectively), assembled from a large healthcare database, central anticholinergic burden scores were estimated using the Anticholinergic Effect on Cognition (AEC) scale. Data were linked to national mortality and hospitalisation data sources, and Mini-Mental State Examination (MMSE) scores were used to investigate cognitive decline. RESULTS: There was a reduced mortality risk in people receiving agents with high central anticholinergic burden compared to those with no or low burden which was statistically significant in the antidepressant cohort (Hazard ratio (HR): 0.88; 95% confidence interval (CI): 0.79-0.98; p = 0.023) but not the antipsychotic one (HR: 0.91; 95% CI: 0.82-1.02; p = 0.105). Patients on antidepressants with no central anticholinergic burden had accelerated cognitive decline compared with other groups, whereas no differences were found in the antipsychotic cohort. No significant associations were detected between antidepressant or antipsychotic-related central anticholinergic burden and hospitalisation. CONCLUSION: These counter-intuitive findings may reflect factors underlying the choice of psychotropics rather than the agents themselves, although do not support a strong role for central anticholinergic drug actions on dementia outcomes. Further studies, including randomized switching of agents are needed to clarify this relationship.

Centrally Acting Anticholinergic Drugs Used for Urinary Conditions Associated with Worse Outcomes in Dementia.

OBJECTIVES: To investigate the associations between central anticholinergic burden and mortality, hospitalization, and cognitive impairment in people with dementia prescribed anticholinergic drugs for urinary symptoms. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Patients diagnosed with dementia receiving anticholinergic medication for bladder conditions (N = 540), assembled from a large healthcare database. METHODS: Central anticholinergic burden related to bladder drugs was estimated using the anticholinergic effect on cognition scale. Data were linked to national mortality and hospitalization data sources, and serially recorded Mini-Mental State Examination scores were used to investigate cognitive decline. RESULTS: Patients had a median survival of 4.1 years. Urinary drugs with a high anticholinergic effect on cognition score (tolterodine, oxybutynin) were associated with a 55% increased mortality risk (hazard ratio 1.55; 95% confidence interval 1.19‒2.01; P = .001) compared with drugs with low or no central anticholinergic burden (darifenacin, fesoterodine, trospium, mirabegron, solifenacin). Cognitive decline over a 24-month period around diagnosis was only detectable in the high central anticholinergic group, but there was no significant difference in cognitive trajectories between the high and low/no anticholinergic bladder drug groups. No increase of emergency hospitalization risk was seen in relation to central anticholinergic burden. CONCLUSIONS AND IMPLICATIONS: Urinary drugs with high central anticholinergic burden cause more harm than those acting peripherally and should be avoided in people with dementia. Further research is needed to test whether centrally acting anticholinergic agents in general cause worse outcomes in dementia.

Anticholinergic drugs and risk of dementia: Time for action?

Evidence suggests that the prescription of bladder anticholinergics is increasing. Recent studies have accentuated concerns about whether certain prescribed medications could increase risk of dementia, including anticholinergic drugs, and specifically anticholinergics used for bladder symptoms. Nevertheless, it can be difficult to draw together the evidence to review the case for possible causation. Recognising this issue in 1965, Bradford-Hill set out nine criteria to help assess whether evidence of a causal relationship could be inferred between a presumed cause and an observed effect. In this commentary, we explore the extent to which associations between anticholinergics and dementia satisfy the Bradford-Hill criteria and examine the potential implications. First, we look at studies that have examined the relationship between anticholinergic drugs with urological properties (bladder drugs) and the onset of dementia, and then present those studies which specifically focus on the cognitive effects of bladder drugs that affect muscarinic receptors in the brain versus the bladder on older people along with suggestions for future research. We also discuss the risks and benefits of these drugs for treating overactive bladder. If it can be shown that certain medications carry a specific risk of dementia, it is possible that initiatives to change prescribing could become a key tool in reducing the risk of dementia and may be easier to implement than some lifestyle changes.

Aspirin in people with dementia, long-term benefits, and harms: a systematic review.

PURPOSE: People with dementia may have indications for aspirin prescription and clinicians are asked to balance the potential risks against benefits. This review examines the evidence for the risk and benefit of long-term aspirin use in people with dementia aged over 65 years, including randomised controlled trials and observational studies. METHODS: We searched three databases for research published between 2007 and 2020. Each eligible article was assessed for risk of bias, and confidence in findings was rated using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Four papers met inclusion criteria: one randomised controlled trial, two cohort studies, and one with pooled data. All looked only at dementia of Alzheimer's type, and none addressed myocardial or cerebral infarction as outcomes. Dementia progression was reported by two studies, with conflicting results. The trial found no significant effect of aspirin on mortality (odds ratio aspirin vs. no aspirin 1.07, 95% confidence interval 0.58-1.97) but found more events of severe bleeding with aspirin (OR aspirin vs. no aspirin 6.9, 1.5-31.2). An excess in intracranial haemorrhage in the aspirin group was judged plausible based on two non-randomised studies. CONCLUSIONS: The review findings are limited because studies include only people with Alzheimer's-type dementia and lack confirmatory studies, although an increased risk of bleeding events is recognised. Further research that addresses the benefits and risks of aspirin in more representative groups of people with dementia is needed to guide prescribing decisions.

Emerging and experimental treatments for COVID-19 and drug interactions with psychotropic agents.

As yet, no agents have been approved for the treatment of COVID-19, although several experimental drugs are being used off licence. These may have serious adverse effects and potential drug interactions with psychotropic agents. We reviewed the common agents being used across the world for the treatment of COVID-19 and investigated their drug interaction potential with psychotropic agents using several drug interaction databases and resources. A preliminary search identified the following drugs as being used to treat COVID-19 symptoms: atazanavir (ATV), azithromycin (AZI), chloroquine (CLQ)/hydroxychloroquine (HCLQ), dipyridamole, famotidine (FAM), favipiravir, lopinavir/ritonavir (LPV/r), nitazoxanide, remdesivir, ribavirin and tocilizumab. Many serious adverse effects and potential drug interactions with psychotropic agents were identified. The most problematic agents were found to be ATV, AZI, CLQ, HCLQ, FAM and LPV/r in terms of both pharmacokinetic as well as serious pharmacodynamic drug interactions, including QTc prolongation and neutropenia. Significant caution should be exercised if using any of the medications being trialled for the treatment of COVID-19 until robust clinical trial data are available. An even higher threshold of vigilance should be maintained for patients with pre-existing conditions and older adults due to added toxicity and drug interactions, especially with psychotropic agents.

The anticholinergic effect on cognition (AEC) scale-Associations with mortality, hospitalisation and cognitive decline following dementia diagnosis.

OBJECTIVES: To investigate associations between central anticholinergic burden (determined through the anticholinergic effect on cognition [AEC] scale) and mortality, hospitalisation and cognitive decline in patients with dementia. METHODS: The South London and Maudsley NHS Foundation Trust (SLaM) Clinical Records Interactive Search (CRIS) application was used to identify patients with a first diagnosis of dementia. Medication exposure was extracted through a natural language processing algorithm, allowing for calculations and comparisons of AEC scores. Data were linked to national mortality and hospitalisation data sources, and serially recorded Mini-Mental State Examination (MMSE) scores were used to investigate cognitive decline. RESULTS: We identified 14 093 patients with dementia, 60.7% were female and the mean age at diagnosis was 79.8 years. Patients for whom a review of their medication was indicated (AEC score ≥ 2 for any individual drug or total AEC score ≥ 3) had an increased risk of mortality (hazard ratio 1.07; 95% confidence interval [CI]: 1.01-1.15) and emergency hospitalisation (1.10; 95% CI: 1.04-1.17), but there were no associations with duration of hospitalisation. Cognitive trajectory analyses showed that this exposure group had lower MMSE scores at diagnosis and a sharper increase in MMSE scores over the subsequent 6 months, but similar slopes for the 6 to 36 months period compared to the remainder of the sample. CONCLUSIONS: Patients with dementia receiving medication with high central anticholinergic activity appear to have worse prognosis in terms of mortality and hospitalisation risk, but have, primarily, acutely impaired cognitive function, rather than longer-term differences in cognitive decline. J Am Geriatr Soc 68:-, 2020.

'Real time' monitoring of antipsychotic prescribing in patients with dementia: a study using the Clinical Record Interactive Search (CRIS) platform to enhance safer prescribing.

BACKGROUND: The use of antipsychotic drugs in dementia has been reported to be associated with increased risk of cerebrovascular events and mortality. There is an international drive to reduce the use of these agents in patients with dementia and to improve the safety of prescribing and monitoring in this area. OBJECTIVES: The aim of this project was to use enhanced automated regular feedback of information from electronic health records to improve the quality of antipsychotic prescribing and monitoring in people with dementia. METHODS: The South London and Maudsley NHS Foundation Trust (SLaM) incorporated antipsychotic monitoring forms into its electronic health records. The SLaM Clinical Record Interactive Search (CRIS) platform provides researcher access to de-identified health records, and natural language processing is used in CRIS to derive structured data from unstructured free text, including recorded diagnoses and medication. Algorithms were thus developed to ascertain patients with dementia receiving antipsychotic treatment and to determine whether monitoring forms had been completed. We used two improvement plan-do-study-act cycles to improve the accuracy of the algorithm for automated evaluation and provided monthly feedback on team performance. RESULTS: A steady increase in antipsychotic monitoring form completion was observed across the study period. The percentage of our sample with a completed antipsychotic monitoring form more than doubled from October 2017 (22%) to January 2019 (58%). CONCLUSION: 'Real time' monitoring and regular feedback to teams offer a time-effective approach, complementary to standard audit methods, to enhance the safer prescribing of high risk drugs.

Benefits and Harms of Statins in People with Dementia: A Systematic Review and Meta-Analysis.

OBJECTIVES: More people with dementia also fall into the category of high vascular risk, for which a statin is usually prescribed. However, these recommendations are based on studies in people without dementia. We aimed to evaluate the evidence for the long-term effectiveness and harm of statin therapy in patients with dementia. DESIGN: Systematic review of randomized controlled trials and observational research. SETTING: Publications from developed countries indexed in the PubMed, Web of Science, and Cochrane trial database between 2007 and 2019. PARTICIPANTS: Trials including people with all types of dementia with a mean age older than 65 years. INTERVENTION: Treatment with a statin for 6 months or longer. MEASUREMENTS: Major adverse cardiovascular events, dementia progression, and general health at 2 years, or medication adverse events (AEs) at any time. Each article was assessed for bias using the Newcastle-Ottawa or Cochrane Collaboration tools. A narrative synthesis and pooled analyses are reported. RESULTS: Five articles met the inclusion criteria. They reported only on dementia of the Alzheimer's type. There was no evidence regarding cardiovascular events or general health. We made a very low confidence finding that statins reduce dementia progression based on three cohort studies of heterogeneous design. We made a very low confidence finding of no significant difference in AEs based on two randomized controlled trials of 18 months: odds ratios of any AE = 1.21 (95% confidence interval [CI] = .83-1.77), serious AE = 1.03 (95% CI = .76-1.87), and death = 1.69 (95% CI = .79-3.62). CONCLUSION: Evidence was insufficient to fully evaluate the efficacy of statins in people with dementia. We found that statins may have a small benefit delaying progression in Alzheimer's dementia, although this conflicted with previous findings from shorter randomized trials. For safety, the trial data lacked power to show clinically important differences between the groups. We recommend that clinical data be leveraged for further observational studies to inform prescribing decisions. J Am Geriatr Soc 68:650-658, 2020.

Safe prescribing in cognitively vulnerable patients: the use of the anticholinergic effect on cognition (AEC) tool in older adult mental health services.

Aims and methodMedication with anticholinergic action is associated with potentially serious adverse effects in older people. We present an evaluation of a novel anticholinergic burden scale introduced into routine practice in older adult services in the South London and Maudsley (SLaM) NHS Foundation Trust. Our aim was to assess whether this tool improved the accurate identification of anticholinergic medication and guided safer prescribing in cognitively vulnerable older people. RESULTS: The introduction of the anticholinergic effect on cognition (AEC) tool into clinical practice led to an increase in the identification and reporting to general practitioners of anticholinergic medication from 11 to 85% of cases (P = 0.0015).Clinical implicationsApplication of the AEC tool led to improved detection of anticholinergic medication and advice to primary care on when a medication review is necessary. This is an important step towards improving the safety of prescribing in this patient group.Declaration of interestSLaM NHS Foundation Trust owns both the app and IP for Medichec.

Anticholinergic effect on cognition (AEC) of drugs commonly used in older people.

OBJECTIVE: Use of anticholinergic drugs in older people is associated with increased risk of cognitive decline and of dementia and death. METHOD: We identified drugs widely used in older people and attempted to classify their anticholinergic effect on cognition (AEC) according to our three-point scale which scored AEC according to in vitro anticholinergic potency, capacity to cross the blood-brain barrier and statements made in standard texts. RESULTS: In total, 165 drugs were examined. We identified 21 drugs with an AEC score of 3, 18 with a score of 2, 21 with a score of 1 and 62 with a score of 0. Owing to insufficient information, we were unable to classify 43 drugs. CONCLUSIONS: A large number of drugs commonly used in older people are likely to be associated with cognitive impairment. Copyright © 2016 John Wiley & Sons, Ltd.

Safe prescribing of physical health medication in patients with dementia.

OBJECTIVE: The prescription of multiple medications for older people is common, despite concerns over the dangers associated with this. Older adults are particularly vulnerable to adverse effects of medication, and this is an even greater risk in patients with dementia. Many drugs used for physical health conditions can negatively affect cognition. Our aim was to identify areas of concern and which drugs to avoid in patients with dementia. DESIGN: A review of the literature was carried out using Pubmed, Medline and Embase. RESULTS: Many drugs used for physical health conditions may worsen the symptoms of dementia. They do this either by negating the effects of cognitive enhancers or through direct adverse effects on cognition CONCLUSIONS: Where evidence exists, we provide guidance as to the safest drugs to prescribe in particular clinical situations. Anticholinergic drugs should be avoided in dementia wherever possible. Effective pain management is important in older patients, but caution should be used when selecting an opioid analgesic because of their adverse central effects. Cardiac drugs have overall negligible effects on cognition, although some have been reported to cause delirium.

Quality of prescribing for schizophrenia: evidence from a national audit in England and Wales.

The National Audit of Schizophrenia (NAS) examined the quality of care received in England and Wales. Part of the audit set out to determine whether six prescribing standards, set by the national clinical guidelines for schizophrenia, were being implemented and to prompt improvements in care. Mental Health Trusts and Health Boards provided data obtained from case-notes for adult patients living in the community with schizophrenia or schizoaffective disorder. An audit of practice tool was developed for data collection. Most of the 5055 patients reviewed were receiving pharmacological treatment according to national guidelines. However, 15.9% of the total sample (95%CI: 14.9-16.9) were prescribed two or more antipsychotics concurrently and 10.1% of patients (95%CI: 9.3-10.9) were prescribed medication in excess of recommended limits. Overall 23.7% (95%CI: 22.5-24.8) of patients were receiving clozapine. However, there were many with treatment resistance who had no clear reason documented as to why they had not had a trial of clozapine (430/1073, 40.1%). In conclusion, whilst most people were prescribed medication in accordance with nationally agreed standards, there was considerable variation between service providers. Antipsychotic polypharmacy, high dose prescribing and clozapine underutilisation in treatment resistance were all key concerns which need to be further addressed.

Adverse effects of clozapine in older patients: epidemiology, prevention and management.

Research into the use of clozapine in older people is somewhat scarce. Clozapine is associated with serious adverse effects such as agranulocytosis, seizures, myocarditis and metabolic syndrome. Other common undesirable effects such as sedation, constipation (which can be fatal), urinary incontinence and hypersalivation further limit its use. These adverse effects are particularly important for the use of clozapine in older people, who are generally more susceptible to medication-related adverse effects. Whilst clozapine should be used with caution in elderly people, strict monitoring procedures can help to prevent harmful effects through early detection, and certain management techniques exist to minimise them. This review outlines the epidemiology of clozapine-related adverse effects in older people and discusses potential prevention and management strategies.

Olanzapine: a systematic review and meta-regression of the relationships between dose, plasma concentration, receptor occupancy, and response.

OBJECTIVE: To conduct a systematic review examining the relationships between olanzapine dose, clinical outcome, dopamine occupancy, and plasma concentration; and to evaluate the potential for therapeutic drug monitoring. METHODS: A search using Embase, Medline, and Pubmed was conducted; and the literature was systematically reviewed. Studies meeting inclusion criteria were examined. The relationships between olanzapine dose, response, dopamine occupancy, and concentration were analyzed using statistical regression. RESULTS: Ten studies were included in the analysis for dose-response. The effect size-dose relationship showed a typical dose-response curve with minimal rise in slope for doses higher than 10 mg/d. For the dose-occupancy relationship, 6 studies were included. Doses more than approximately 12 mg/d were sufficient to block 65% of striatal D2 receptors. Doses higher than 20 mg led to minimally higher receptor occupancies. Fifteen studies were included in the meta-regression of olanzapine mean concentrations. A linear relationship between mean plasma concentration and mean dose was observed. CONCLUSIONS: Our review suggests that the likelihood of a favorable response with olanzapine is maximized at doses of 10 to 15 mg/d (perhaps lower in nonsmoking females). Higher doses may be considered if 15 mg is ineffective and if plasma level is less than 20 ng/mL on that dose. There is a direct linear relationship between olanzapine dose and plasma concentration. Therapeutic drug monitoring may be useful in patients who are suspected of nonadherence, where there is potential for a drug interaction, and in patients taking 15 mg/d or more and who have not reached clinical response.