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BMC Geriatrics Mar 2023As people age, they accumulate several health conditions, requiring the use of multiple medications (polypharmacy) to treat them. One of the challenges with polypharmacy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
As people age, they accumulate several health conditions, requiring the use of multiple medications (polypharmacy) to treat them. One of the challenges with polypharmacy is the associated increase in anticholinergic exposure to older adults. In addition, several studies suggest an association between anticholinergic burden and declining physical function in older adults.
OBJECTIVE/PURPOSE
This systematic review aimed to synthesise data from published studies regarding the association between anticholinergic burden and mobility. The studies were critically appraised for the strength of their evidence.
METHODS
A systematic literature search was conducted across five electronic databases, EMBASE, CINAHL, PSYCHINFO, Cochrane CENTRAL and MEDLINE, from inception to December 2021, to identify studies on the association of anticholinergic burden with mobility. The search was performed following a strategy that converted concepts in the PECO elements into search terms, focusing on terms most likely to be found in the title and abstracts of the studies. For observational studies, the risk of bias was assessed using the Newcastle Ottawa Scale, and the Cochrane risk of bias tool was used for randomised trials. The GRADE criteria was used to rate confidence in evidence and conclusions. For the meta-analyses, we explored the heterogeneity using the Q test and I test and the publication bias using the funnel plot and Egger's regression test. The meta-analyses were performed using Jeffreys's Amazing Statistics Program (JASP).
RESULTS
Sixteen studies satisfied the inclusion criteria from an initial 496 studies. Fifteen studies identified a significant negative association of anticholinergic burden with mobility measures. One study did not find an association between anticholinergic intervention and mobility measures. Five studies included in the meta-analyses showed that anticholinergic burden significantly decreased walking speed (0.079 m/s ± 0.035 MD ± SE,95% CI: 0.010 to 0.149, p = 0.026), whilst a meta-analysis of four studies showed that anticholinergic burden significantly decreased physical function as measured by three variations of the Instrumental Activities of Daily Living (IADL) instrument 0.27 ± 0.12 (SMD ± SE,95% CI: 0.03 to 0.52), p = 0.027. The results of both meta-analyses had an I statistic of 99% for study heterogeneity. Egger's test did not reveal publication bias.
CONCLUSION
There is consensus in published literature suggesting a clear association between anticholinergic burden and mobility. Consideration of cognitive anticholinergic effects may be important in interpreting results regarding the association of anticholinergic burden and mobility as anticholinergic drugs may affect mobility through cognitive effects.
Topics: Humans; Aged; Activities of Daily Living; Cholinergic Antagonists; Walking Speed; Polypharmacy; Quality of Life
PubMed: 36949391
DOI: 10.1186/s12877-023-03820-6 -
The Cochrane Database of Systematic... Aug 2022Medications with anticholinergic properties are commonly prescribed to older adults with a pre-existing diagnosis of dementia or cognitive impairment. The cumulative... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Medications with anticholinergic properties are commonly prescribed to older adults with a pre-existing diagnosis of dementia or cognitive impairment. The cumulative anticholinergic effect of all the medications a person takes is referred to as the anticholinergic burden because of its potential to cause adverse effects. It is possible that a high anticholinergic burden may be a risk factor for further cognitive decline or neuropsychiatric disturbances in people with dementia. Neuropsychiatric disturbances are the most frequent complication of dementia that require hospitalisation, accounting for almost half of admissions; hence, identification of modifiable prognostic factors for these outcomes is crucial. There are various scales available to measure anticholinergic burden but agreement between them is often poor.
OBJECTIVES
Our primary objective was to assess whether anticholinergic burden, as defined at the level of each individual scale, was a prognostic factor for further cognitive decline or neuropsychiatric disturbances in older adults with pre-existing diagnoses of dementia or cognitive impairment. Our secondary objective was to investigate whether anticholinergic burden was a prognostic factor for other adverse clinical outcomes, including mortality, impaired physical function, and institutionalisation.
SEARCH METHODS
We searched these databases from inception to 29 November 2021: MEDLINE OvidSP, Embase OvidSP, PsycINFO OvidSP, CINAHL EBSCOhost, and ISI Web of Science Core Collection on ISI Web of Science.
SELECTION CRITERIA
We included prospective and retrospective longitudinal cohort and case-control observational studies, with a minimum of one-month follow-up, which examined the association between an anticholinergic burden measurement scale and the above stated adverse clinical outcomes, in older adults with pre-existing diagnoses of dementia or cognitive impairment. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, and undertook data extraction, risk of bias assessment, and GRADE assessment. We summarised risk associations between anticholinergic burden and all clinical outcomes in a narrative fashion. We also evaluated the risk association between anticholinergic burden and mortality using a random-effects meta-analysis. We established adjusted pooled rates for the anticholinergic cognitive burden (ACB) scale; then, as an exploratory analysis, established pooled rates on the prespecified association across scales. MAIN RESULTS: We identified 18 studies that met our inclusion criteria (102,684 older adults). Anticholinergic burden was measured using five distinct measurement scales: 12 studies used the ACB scale; 3 studies used the Anticholinergic Risk Scale (ARS); 1 study used the Anticholinergic Drug Scale (ADS); 1 study used the Anticholinergic Effect on Cognition (AEC) Scale; and 2 studies used a list developed by Tune and Egeli. Risk associations between anticholinergic burden and adverse clinical outcomes were highly heterogenous. Four out of 10 (40%) studies reported a significantly increased risk of greater long-term cognitive decline for participants with an anticholinergic burden compared to participants with no or minimal anticholinergic burden. No studies investigated neuropsychiatric disturbance outcomes. One out of four studies (25%) reported a significant association with reduced physical function for participants with an anticholinergic burden versus participants with no or minimal anticholinergic burden. No study (out of one investigating study) reported a significant association between anticholinergic burden and risk of institutionalisation. Six out of 10 studies (60%) found a significantly increased risk of mortality for those with an anticholinergic burden compared to those with no or minimal anticholinergic burden. Pooled analysis of adjusted mortality hazard ratios (HR) measured anticholinergic burden with the ACB scale, and suggested a significantly increased risk of death for those with a high ACB score relative to those with no or minimal ACB scores (HR 1.153, 95% confidence interval (CI) 1.030 to 1.292; 4 studies, 48,663 participants). An exploratory pooled analysis of adjusted mortality HRs across anticholinergic burden scales also suggested a significantly increased risk of death for those with a high anticholinergic burden (HR 1.102, 95% CI 1.044 to 1.163; 6 studies, 68,381 participants). Overall GRADE evaluation of results found low- or very low-certainty evidence for all outcomes. AUTHORS' CONCLUSIONS: There is low-certainty evidence that older adults with dementia or cognitive impairment who have a significant anticholinergic burden may be at increased risk of death. No firm conclusions can be drawn for risk of accelerated cognitive decline, neuropsychiatric disturbances, decline in physical function, or institutionalisation.
Topics: Aged; Cholinergic Antagonists; Cognitive Dysfunction; Dementia; Humans; Prospective Studies; Retrospective Studies
PubMed: 35994403
DOI: 10.1002/14651858.CD015196.pub2 -
Urologia Internationalis 2023The aim of the study was to assess the effectiveness of the main classes of drugs used at reducing morbidity related to ureteric stents.
BACKGROUND
The aim of the study was to assess the effectiveness of the main classes of drugs used at reducing morbidity related to ureteric stents.
SUMMARY
After establishing a priori protocol, a systematic electronic literature search was conducted in July 2019. The randomized clinical trials (RCTs) selection proceeded in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and was registered (PROSPERO ID 178130). The risk of bias and the quality assessment of the included RCTs were performed. Ureteral Stent Symptom Questionnaire (USSQ), International Prostate Symptom Score (IPSS), and quality of life (QoL) were pooled for meta-analysis. Mean difference and risk difference were calculated as appropriate for each outcome to determine the cumulative effect size. Fourteen RCTs were included in the analysis accounting for 2,842 patients. Alpha antagonist, antimuscarinic, and phosphodiesterase (PDE) inhibitors significatively reduced all indexes of the USSQ, the IPSS and QoL scores relative to placebo. Conversely, combination therapy (alpha antagonist plus antimuscarinic) showed in all indexes of the USSQ, IPSS, and QoL over alpha antagonist or antimuscarinic alone. On comparison with alpha blockers, PDE inhibitors were found to be equally effective for urinary symptoms, general health, and body pain parameters, but sexual health parameters improved significantly with PDE inhibitors. Finally, antimuscarinic resulted in higher decrease in all indexes of the USSQ, the IPSS, and QoL relative to alpha antagonist.
KEY MESSAGE
Relative to placebo, alpha antagonist alone, antimuscarinics alone, and PDE inhibitors alone have beneficial effect in reducing stent-related symptoms. Furthermore, there are significant advantages of combination therapy compared with monotherapy. Finally, PDE inhibitors are comparable to alpha antagonist, and antimuscarinic seems to be more effective than alpha antagonist alone.
Topics: Humans; Male; Adrenergic alpha-Antagonists; Muscarinic Antagonists; Pain; Quality of Life; Stents; Ureter
PubMed: 34818261
DOI: 10.1159/000518387 -
Age and Ageing Sep 2023Anticholinergic medications block the neurotransmitter acetylcholine in the brain and peripheral nervous system. Many medications have anticholinergic properties, and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Anticholinergic medications block the neurotransmitter acetylcholine in the brain and peripheral nervous system. Many medications have anticholinergic properties, and the cumulative effect of these medications is termed anticholinergic burden. Increased anticholinergic burden can have short-term side effects such as dry mouth, blurred vision and urinary retention as well as long-term effects including dementia, worsening physical function and falls.
METHODS
We carried out a systematic review (SR) with meta-analysis (MA) looking at randomised controlled trials addressing interventions to reduce anticholinergic burden in older adults.
RESULTS
We identified seven papers suitable for inclusion in our SR and MA. Interventions included multi-disciplinary involvement in medication reviews and deprescribing of AC medications. Pooled data revealed no significant difference in outcomes between control and intervention group for falls (OR = 0.76, 95% CI: 0.52-1.11, n = 647), cognition (mean difference = 1.54, 95% CI: -0.04 to 3.13, n = 405), anticholinergic burden (mean difference = 0.04, 95% CI: -0.11 to 0.18, n = 710) or quality of life (mean difference = 0.04, 95% CI: -0.04 to 0.12, n = 461).
DISCUSSION
Overall, there was no significant difference with interventions to reduce anticholinergic burden. As we did not see a significant change in anticholinergic burden scores following interventions, it is likely other outcomes would not change. Short follow-up time and lack of training and support surrounding successful deprescribing may have contributed.
Topics: Humans; Aged; Quality of Life; Cholinergic Antagonists; Acetylcholine; Brain; Cognition
PubMed: 37740900
DOI: 10.1093/ageing/afad176 -
BMC Pharmacology & Toxicology Dec 2022The aim of this work was to investigate the association between anticholinergic burden or anticholinergic drug use and xerostomia and/or xerophtalmia in elderly through...
PURPOSE
The aim of this work was to investigate the association between anticholinergic burden or anticholinergic drug use and xerostomia and/or xerophtalmia in elderly through a systematic review of the published literature.
METHODS
A search was carried out in 3 databases (CINAHL, Embase and Pubmed). Studies conducted in people ≥65 years of age, who took anticholinergic medications, and measured the association between the anticholinergic burden or the use of these medications with the prevalence of xerostomia and / or xerophthalmia, published up to August 2022, were selected. Studies published in languages other than Spanish and/or English were excluded.
RESULTS
One thousand two hundred eleven articles were identified, 10 were selected for this review: six cross-sectional studies, two cohorts, one case-control and one randomized controlled clinical trial. A total of 3535 patients included in the different studies were studied. The most used scales were the Anticholinergic Drug Scale (ADS) and the Anticholinergic Risk Scale (ARS). Four articles studied the relationship between the use of anticholinergic medication and the prevalence of xerostomia and / or xerophthalmia, finding a positive relationship with xerostomia in all of them. Another 6 measured the relationship between anticholinergic burden and xerostomia and / or xerophthalmia. Four found a positive relationship between anticholinergic burden and xerostomia and/or xerophthalmia.
CONCLUSIONS
Our findings suggest a clear relationship between the use of anticholinergic drugs or anticholinergic burden and the presence of xerostomia. This relationship was less conclusive in the case of xerophthalmia.
Topics: Humans; Aged; Cholinergic Antagonists; Xerophthalmia; Cross-Sectional Studies; Xerostomia; Prevalence; Randomized Controlled Trials as Topic
PubMed: 36539885
DOI: 10.1186/s40360-022-00637-8 -
Journal of the American Medical... Sep 2022To summarize current evidence regarding facility and prescriber characteristics associated with potentially harmful medication (PHM) use by residents in nursing homes... (Review)
Review
OBJECTIVES
To summarize current evidence regarding facility and prescriber characteristics associated with potentially harmful medication (PHM) use by residents in nursing homes (NHs), which could inform the development of interventions to reduce this potentially harmful practice.
DESIGN
Scoping review.
SETTING AND PARTICIPANTS
Studies conducted in the United States that described facility and prescriber factors associated with PHM use in NHs.
METHODS
Electronic searches of PubMed/MEDLINE were conducted for articles published in English between April 2011 and November 2021. PHMs were defined based on the Beers List criteria. Studies testing focused interventions targeting PHM prescribing or deprescribing were excluded. Studies were characterized by the strengths and weaknesses of the analytic approach and generalizability.
RESULTS
Systematic search yielded 1253 articles. Of these, 29 were assessed in full text and 20 met inclusion criteria. Sixteen examined antipsychotic medication (APM) use, 2 anticholinergic medications, 1 sedative-hypnotics, and 2 overall PHM use. APM use was most commonly associated with facilities with a higher proportion of male patients, younger patients, and patients with severe cognitive impairment, anxiety, depression, and aggressive behavior. The use of APM and anticholinergic medications was associated with low registered nurse staffing ratios and for-profit facility status. No studies evaluated prescriber characteristics.
CONCLUSIONS AND IMPLICATIONS
Included studies primarily examined APM use. The most commonly reported facility characteristics were consistent with previously reported indicators of poor NH quality and NHs with patient case mix more likely to use PHMs.
Topics: Antipsychotic Agents; Cholinergic Antagonists; Drug Prescriptions; Female; Humans; Inappropriate Prescribing; Male; Nursing Homes; United States
PubMed: 35868350
DOI: 10.1016/j.jamda.2022.06.008 -
PloS One 2023Half the US population uses drugs with anticholinergic properties. Their potential harms may outweigh their benefits. Amitriptyline is among the most frequently... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Half the US population uses drugs with anticholinergic properties. Their potential harms may outweigh their benefits. Amitriptyline is among the most frequently prescribed anticholinergic medicinal products, is used for multiple indications, and rated as strongly anticholinergic. Our objective was to explore and quantify (anticholinergic) adverse drug reactions (ADRs) in patients taking amitriptyline vs. placebo in randomized controlled trials (RCTs) involving adults and healthy individuals.
METHODS
We searched electronic databases from their inception until 09/2022, and clinical trial registries from their inception until 09/2022. We also performed manual reference searches. Two independent reviewers selected RCTs with ≥100 participants of ≥18 years, that compared amitriptyline (taken orally) versus placebo for all indications. No language restrictions were applied. One reviewer extracted study data, ADRs, and assessed study quality, which two others verified. The primary outcome was frequency of anticholinergic ADRs as a binary outcome (absolute number of patients with/without anticholinergic ADRs) in amitriptyline vs. placebo groups.
RESULTS
Twenty-three RCTs (mean dosage 5mg to 300mg amitriptyline/day) and 4217 patients (mean age 40.3 years) were included. The most frequently reported anticholinergic ADRs were dry mouth, drowsiness, somnolence, sedation, fatigue, constitutional, and unspecific anticholinergic ADRs. Random-effects meta-analyses showed anticholinergic ADRs had a higher odd's ratio for amitriptyline versus placebo (OR = 7.41; [95% CI, 4.54 to 12.12]). Non-anticholinergic ADRs were as frequent for amitriptyline as placebo. Meta-regression analysis showed anticholinergic ADRs were not dose-dependent.
DISCUSSION
The large OR in our analysis shows that ADRs indicative of anticholinergic activities can be attributed to amitriptyline. The low average age of participants in our study may limit the generalizability of the frequency of anticholinergic ADRs in older patients. A lack of dose-dependency may reflect limited reporting of the daily dosage when the ADRs occurred. The exclusion of small studies (<100 participants) decreased heterogeneity between studies, but may also have reduced our ability to detect rare events. Future studies should focus on older people, as they are more susceptible to anticholinergic ADRs.
REGISTRATION
PROSPERO: CRD42020111970.
Topics: Adult; Aged; Humans; Amitriptyline; Cholinergic Antagonists
PubMed: 37018325
DOI: 10.1371/journal.pone.0284168 -
Journal of Comparative Effectiveness... Dec 2022To determine the economic burden associated with anticholinergic medication use in adults with overactive bladder (OAB) in the USA. A systematic literature review was... (Review)
Review
To determine the economic burden associated with anticholinergic medication use in adults with overactive bladder (OAB) in the USA. A systematic literature review was conducted to identify articles assessing healthcare resource utilization (HCRU) and costs associated with anticholinergic use in adults with OAB. From the 34 articles identified, increased anticholinergic burden, switching anticholinergic treatments and potentially inappropriate anticholinergic use were associated with increased HCRU and/or costs. However, studies comparing patients with OAB receiving anticholinergics to individuals with untreated OAB or without OAB reported a mix of increases and decreases in HCRU and costs. Additional controlled studies assessing the economic impact of anticholinergics in OAB are needed and may enable optimization of economic and potentially patient outcomes.
Topics: Humans; Adult; Urinary Bladder, Overactive; Cholinergic Antagonists; Financial Stress; Costs and Cost Analysis; Patient Acceptance of Health Care
PubMed: 36354285
DOI: 10.2217/cer-2022-0160 -
Drugs & Aging Dec 2020Medications with anticholinergic activity (MACs) are used to treat diseases common in older adults. Evidence on the association between anticholinergic burden (AB) and...
INTRODUCTION
Medications with anticholinergic activity (MACs) are used to treat diseases common in older adults. Evidence on the association between anticholinergic burden (AB) and increased risk of fractures and osteoporosis or reduced bone mineral density (BMD) is inconsistent. Our aim was to conduct a systematic review of observational studies on AB with fractures and osteoporosis or reduced BMD and provide methodological appraisal of included studies.
METHODS
We searched MEDLINE, EMBASE, Science Citation Index and CENTRAL as well as grey literature from database inception up to August 2020. Eligibility criteria were: observational design, AB-exposure measured through a scale, fracture of any type or osteoporosis or reduced BMD as outcome, and reported measure of association between exposure and outcome. No restrictions related to time, language or type of data were applied. Eligibility and risk of bias assessment as well as data extraction were performed independently by two reviewers. Risk of bias of the included studies was assessed using the Newcastle-Ottawa Scale and the RTI Item Bank.
RESULTS
The majority of the nine included studies had low risk of bias but heterogeneous methodology. No study used a new user design. Seven studies reported an increased risk of fractures associated with AB. In four studies using the Anticholinergic Risk Scale (ARS), adjusted risk of fractures was increased by 2-61% for ARS = 1, by 0-97% for ARS = 2, by 19-84% for ARS = 3, and by 56-96% for ARS ≥ 4; in three studies the ARS was aggregated, risk increased by 39% for ARS = 1-2 and 17% for ARS = 2-3. Two studies reported increased risk of fractures of 14 and 52% in the highest AB-category and one study reported that change in ARS of ≥ 3 during hospitalization was associated with a 321% increased risk in fractures. Two studies did not find an association between AB and fractures. The association between AB and osteoporosis or reduced BMD could only be assessed in two studies, one reporting increased risk of lower BMD at Ward's triangle, the other reporting no association between AB and BMD T-score change at the femoral neck.
DISCUSSION
Our study suggests an association between AB and increased risk of fractures with possible dose-exposure gradient in studies using the ARS. The low number of studies and heterogeneity of methods calls for the conduct of more studies. We conducted a study investigating the risk of fractures associated with anticholinergic burden, which is the result of taking one or more medication with anticholinergic activity. The results of our study suggest that persons who experience anticholinergic burden might have a higher risk of fractures. However, since we were only able to include nine studies, more studies conducted in a similar way are needed.
Topics: Aged; Aged, 80 and over; Bias; Bone Density; Cholinergic Antagonists; Dose-Response Relationship, Drug; Female; Fractures, Bone; Humans; Male; Observational Studies as Topic; Osteoporosis; Prevalence; Risk Assessment
PubMed: 33094444
DOI: 10.1007/s40266-020-00806-6 -
Annals of Medicine Dec 2023To conduct a meta-analysis and systematic review on the association between anticholinergic medication uses and the risk of pneumonia in elderly adults. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To conduct a meta-analysis and systematic review on the association between anticholinergic medication uses and the risk of pneumonia in elderly adults.
MATERIALS AND METHODS
Medical databases were searched included PubMed, Web of Science, EBSCO and Google Scholar (up to December 7, 2022). Studies evaluating association between anticholinergic medication uses and the risk of pneumonia in elderly adults were included. Studies without available data were excluded. We made meta-analysis by using adjusted odds ratio (aOR) with 95% confidence intervals (CIs) from random-effects model. The risk of bias was assessed using ROBINS-I tool and statistical heterogeneity using the statistic. Registration: INPLASY202330070.
RESULTS
A total of six studies with 107,012 participants were included. Meta-analysis results showed that anticholinergic medication uses was related with an increased risk of pneumonia (aOR = 1.59; 95%CI, 1.32-1.92) and stroke-associated pneumonia (aOR = 2.02; 95%CI, 1.76-2.33). Moreover, risk estimates of pneumonia for high-potency anticholinergics (aOR = 1.96; 95%CI, 1.22-3.14) were higher than those for low-potency anticholinergics (aOR = 1.58; 95%CI, 1.27-1.97). And increased risk of pneumonia was associated with the anticholinergic medication uses within 30 days (aOR = 2.13; 95%CI, 1.33-3.43), within 90 days (aOR = 2.03; 95%CI, 1.26-3.26) and chronic use (aOR = 1.65; 95%CI, 1.09-2.51).
CONCLUSIONS
The risk of pneumonia is increased in elderly adults with anticholinergic medication, especially with higher-potency anticholinergic drugs and in the initiation phase of anticholinergic medication. Clinicians should monitor their use in older patients carefully, especially when the pneumonia-related signs and symptoms are identified.
Topics: Adult; Aged; Humans; Bias; Cholinergic Antagonists; Pneumonia
PubMed: 37190776
DOI: 10.1080/07853890.2023.2209736