Characteristics of medication-induced xerostomia and effect of treatment.

OBJECTIVE: Side-effects of medications cause xerostomia. There have been cases where a medication has been discontinued owing to its severe side-effects. Therefore, the xerostomia must be treated to ensure that the primary disease is managed effectively. This study analyzed the actual status of patients with medication-induced xerostomia and investigates factors associated with its improvement. METHODS: This study assessed 490 patients diagnosed with medication-induced xerostomia who had an unstimulated salivary flow of ≤0.1 mL/min and received treatment for xerostomia at a xerostomia clinic. Patient age, sex, medical history, medications used, disease duration of xerostomia, and psychological disorders were recorded. The anticholinergic burden was assessed using the Anticholinergic Cognitive Burden scale. The unstimulated salivary flow was measured by the spitting method. According to their symptoms and diagnoses, the patients were introduced to oral lubricants, instructed on how to perform massage, and prescribed Japanese herbal medicines, and sialogogues. Factors associated with the subjective improvement of xerostomia and objective changes in the salivary flow rate were recorded at six months. RESULTS: Xerostomia improved in 338 patients (75.3%). The improvement rate was significantly lower in patients with psychiatric disorders (63.6%) (P = 0.009). The improvement rate decreased as more anticholinergics were used (P = 0.018). However, xerostomia improved in approximately 60% of patients receiving three or more anticholinergics. The unstimulated salivary flow increased significantly more in patients who reported an improvement of xerostomia (0.033±0.053 mL/min) than in those who reported no improvement (0.013±0.02 mL/min) (P = 0.025). CONCLUSION: Xerostomia treatment improved oral dryness in 75.3% of patients receiving xerogenic medications in this study. If xerostomia due to side-effects of medications can be improved by treatment, it will greatly contribute to the quality of life of patients with xerogenic medications and may reduce the number of patients who discontinue medications.

Third-line therapy for overactive bladder in the elderly: Nuances and considerations.

INTRODUCTION: Overactive bladder (OAB) disproportionally affects older adults in both incidence and severity. OAB pharmacotherapy is often problematic in the elderly due to polypharmacy, adverse side effect profiles and contraindications in the setting of multiple comorbidities, and concerns regarding the risk of incident dementia with anticholinergic use. The burden of OAB in older patients coupled with concerns surrounding pharmacotherapy options should motivate optimization of nonpharmacologic therapies in this population. At the same time, several aspects of aging may impact treatment efficacy and decision-making. This narrative review critically summarizes current evidence regarding third-line OAB therapy use in the elderly and discusses nuances and treatment considerations specific to the population. METHODS: We performed an extensive, nonsystematic evidence assessment of available literature via PubMed on onabotulinumtoxinA (BTX-A), sacral neuromodulation, and percutaneous tibial nerve stimulation (PTNS) for OAB, with a focus on study in elderly and frail populations. RESULTS: While limited, available studies show all three third-line therapies are efficacious in older populations and there is no data to support one option over another. BTX-A likely has a higher risk of urinary tract infection and retention in older compared to younger populations, especially in the frail elderly. PTNS incurs the lowest risk, although adherence is poor, largely due to logistical burdens. CONCLUSION: Advanced age and frailty should not preclude third-line therapy for refractory OAB, as available data support their efficacy and safety in these populations. Ultimately, treatment choices should be individualized and involve shared decision-making.

Comparative associations between anticholinergic burden and emergency department visits for anticholinergic adverse events in older Korean adults: a nested case-control study using national claims data for validation of a novel country-specific scale.

BACKGROUND: Considering the limited generalizability of previous anticholinergic burden scales, the Korean Anticholinergic Burden Scale (KABS) as a scale specific to the Korean population was developed. We aimed to validate the KABS by detecting the associations between high anticholinergic burden, measured with the KABS, and emergency department (ED) visits compared to the pre-existing validated scales in older Korean adults. METHODS: A nested case-control study was conducted using national claims data. The cases included the first anticholinergic ED visits between July 1 and December 31, 2016. Anticholinergic ED visits were defined as ED visits with a primary diagnosis of constipation, delirium, dizziness, fall, fracture, or urinary retention. Propensity score-matched controls were identified. Average daily AB scores during 30 days before the index date were measured. Multivariate logistic regression analyses were performed. RESULTS: In total, 461,034 were included. The highest proportion of those with high AB was identified with KABS (5.0%). Compared with those who had a KABS score of 0, older adults with a score ≥ 3 were at higher risk for overall anticholinergic ED visits (aOR, 1.62, 95% CI, 1.53-1.72), as well as visits for falls/fractures (aOR: 1.54, 95% CI: 1.40-1.69), dizziness (aOR: 1.44, 95% CI: 1.30-1.59), delirium (aOR: 2.96, 95% CI: 2.28-3.83), constipation (aOR: 1.84, 95% CI: 1.68-2.02), and urinary retention (aOR: 2.13, 95% CI: 1.79-2.55). High AB by KABS showed a stronger association with overall anticholinergic ED visits and visits due to delirium and urinary retention than those by other scales. CONCLUSIONS: In conclusion, KABS is superior to pre-existing scales in identifying patients with high AB and predicting high AB-related ED visits in older Korean adults.

Features of anticholinergic prescriptions and predictors of high use in the elderly: Population-based study.

PURPOSE: Older people are especially vulnerable to negative anticholinergic effects. Although anticholinergic drugs are commonly used among older people, drugs with potent antimuscarinic properties are considered as potentially inappropriate medications for older people. Here, we examined features of anticholinergic use and investigated predictors for the high use of strong anticholinergic agents (ACs) in the elderly. METHODS: A total of 388,629 Korean elderly aged ≥70 years were recruited from the 2012 National Health Insurance Service Elderly cohort database. The use of ACs in 2012 was quantitatively assessed by calculating standardized prescribed doses. Multivariate logistic regression was conducted to identify predictors of the high use of strong ACs (≥90 doses). RESULTS: Almost half of the subjects (47.2%) used more than 15 doses of strong ACs during 2012. 17.0% of the subjects had an annual cumulative use of strong ACs over 90 doses. Morbidities such as depression (odds ratio [OR], 95% confidence interval [CI] = 2.56, 2.48-2.63), Parkinson's disease (2.41, 2.26-2.56), genitourinary diseases (2.12, 2.07-2.16), polypharmacy (3.28, 3.21-3.36), and low income (1.29, 1.25-1.33) were strong predictors of their high use. Antihistamines (chlorpheniramine) and antidepressants (amitriptyline) greatly contributed to the total prescription of strong ACs. CONCLUSIONS: Despite the vulnerability of older people to the adverse reactions of strong ACs, their use seems to be at a high level in terms of cumulative usage among some elderly. More attention should be paid to older people with predictive factors of high use of strong ACs. Key points Despite the susceptibility of older people to negative anticholinergic effects, high use of strong anticholinergic agents was is quite frequent; 17.0% of the elderly had an annual cumulative use of these drugs ≥90 doses. Parkinson's disease, depression, genitourinary diseases, low income, and polypharmacy strongly predicted the high use of strong anticholinergic agents. A few strong anticholinergic agents, including antihistamines (chlorpheniramine) and antidepressants (amitriptyline), accounted for the majority of medications prescribed. Understanding the predictors of their high use by medical practitioners may result as more appropriate anticholinergic medications.

Cumulative Antidepressant Use and Risk of Dementia in a Prospective Cohort Study.

OBJECTIVES: To determine whether antidepressant use is associated with dementia risk. DESIGN: Prospective cohort study. SETTING: Kaiser Permanente Washington (KPWA), an integrated healthcare delivery system. PARTICIPANTS: Community-dwelling individuals aged 65 and older without dementia and with 10 years or more of KPWA enrollment at baseline (N=3,059). MEASUREMENTS: Primary exposures were selective serotonin reuptake inhibitors (paroxetine vs other), tricyclic antidepressants, and serotonin antagonist and reuptake inhibitors. Using health plan pharmacy data, we calculated cumulative medication exposure, defined as total standardized daily doses (TSDDs), over rolling 10-year windows. Exposure in the most recent year was excluded to avoid use related to prodromal symptoms. The Cognitive Abilities Screening Instrument was administered every 2 years; low scores triggered clinical evaluation and consensus diagnosis procedures. Dementia risk was estimated according to medication use using Cox proportional hazards models. RESULTS: During a mean follow-up of 7.7 years, 775 participants (25%) developed dementia; 659 (22%) developed possible or probable Alzheimer's disease. Individual antidepressant classes were not associated with differences in dementia risk, although paroxetine use was associated with higher risk of dementia for all TSDD categories than no use (0-90 TSDDs: hazard ratio (HR)=1.69, 95% confidence interval (CI)=1.18-2.42; 91-365 TSDDs: HR=1.40, 95% CI=0.88-2.23; 366-1095 TSDDs: HR=2.13, 95% CI=1.32-3.43; ≥1095 TSDDs: HR=1.42, 95% CI=0.82-2.46). CONCLUSION: Most commonly prescribed nonanticholinergic depression medications used in late life do not appear to be associated with dementia risk. Paroxetine and other anticholinergic antidepressants may be exceptions in older individuals. Future studies are warranted to improve scientific understanding of potential associations in other settings and populations.

Interventional management of hyperhidrosis in secondary care: a systematic review.

BACKGROUND: Hyperhidrosis is uncontrollable excessive sweating, which occurs at rest, regardless of temperature. The symptoms of hyperhidrosis can significantly affect quality of life. OBJECTIVES: To undertake a systematic review of the clinical effectiveness and safety of treatments available in secondary care for the management of primary hyperhidrosis. METHODS: Fifteen databases (including trial registers) were searched to July 2016 to identify studies of secondary-care treatments for primary hyperhidrosis. For each intervention randomized controlled trials (RCTs) were included where available; where RCT evidence was lacking, nonrandomized trials or large prospective case series were included. Outcomes of interest included disease severity, sweat rate, quality of life, patient satisfaction and adverse events. Trial quality was assessed using a modified version of the Cochrane Risk of Bias tool. Results were pooled in pairwise meta-analyses where appropriate, otherwise a narrative synthesis was presented. RESULTS: Fifty studies were included in the review: 32 RCTs, 17 nonrandomized trials and one case series. The studies varied in terms of population, intervention and methods of outcome assessment. Most studies were small, at high risk of bias and poorly reported. The interventions assessed were iontophoresis, botulinum toxin (BTX) injections, anticholinergic medications, curettage and newer energy-based technologies that damage the sweat gland. CONCLUSIONS: The evidence for the effectiveness and safety of treatments for primary hyperhidrosis is limited overall, and few firm conclusions can be drawn. However, there is moderate-quality evidence to support the use of BTX for axillary hyperhidrosis. A trial comparing BTX with iontophoresis for palmar hyperhidrosis is warranted.

[The Overrated Impact of Inhaled Substances (LABA, LAMA, ICS) on Exacerbation Rates in COPD]. / Die überschätzte Beeinflussung der Exazerbationsrate bei COPD durch Inhalativa (LABA, LAMA, ICS).

Numerous studies have shown that exacerbation rates in COPD can be significantly reduced by long acting beta-2-agonists (LABA), long acting anticholinergic agents (LAMA) and inhaled steroids (ICS). Elaborate and extensive investigations however failed to prove that the reduction in exacerbation rates leads to life prolongation. As opposed to this, numerous studies have shown a reduction in life expectancy with increasing number and severity of exacerbations.This review aimed at comparing these studies and to elaborate the relevance and reduction of exacerbations rates by LABA, LAMA and ICS application through effect size calculation by means of Cohens' d. These studies display a common pattern. The reduction of exacerbation rates is only being achieved for less severe exacerbations (Cohens' d max. 0.21). For more severe exacerbations and for the comparison of different substances Cohens' d remains below 0.1, indicating that the effect of the medications is practically irrelevant. The impact of LABA's, LAMA's and ICS on exacerbation rates in COPD patients is obviously overrated.

Anisocoria Secondary to Anticholinergic Mydriasis from Homeopathic Pink Eye Relief Drops.

A woman, aged 70 years, developed anisocoria after applying homeopathic eye drops (Similasan Pink Eye Relief) to her left eye. Her pupil was dilated for two weeks and did not respond to light or near stimuli for one week. Both 0.1% and 1% pilocarpine failed to constrict her left pupil, and magnetic resonance imaging of her brain did not reveal any abnormality. The eye drops she had used contain belladonna extracts which have a natural atropine component. This case demonstrates the importance, when evaluating a patient presenting with anisocoria, of knowing the chemical ingredients of the homeopathic eye drops, which often are not listed.

[Anticholinergic syndrome caused by contaminated herbal tea; acting swiftly to identify the source]. / Anticholinerg syndroom door verontreinigde kruidenthee.

BACKGROUND: Despite good manufacturing practice and quality control, consumer products can become contaminated. In some cases, this can result in severe and life-threatening intoxication with potentially fatal consequences. CASE DESCRIPTION: A 27-year-old man and a 28-year-old pregnant woman presented to the Emergency Department with severe anticholinergic syndrome after using a marshmallow root (Althaea officinalis) herbal remedy, mixed into hot chocolate drink, to reduce symptoms of common cold. After a short stay in Intensive Care, the symptoms diminished and the patients could be released from hospital. The herbs were found to be contaminated with atropine, most probably derived from deadly nightshade (Atropa belladonna). Analyses of the contaminated product indicated that the patients were exposed to 20-200 mg atropine, while a dose of 2 mg is already considered mildly toxic. CONCLUSION: Consultation of the Dutch National Poisons Information Center resulted in rapid detection of the contamination; close collaboration with the Netherlands Food and Consumer Product Safety Authority and the manufacturer of the product allowed rapid identification of the source of contamination and facilitated the prevention of an epidemic.

A short review of drug-food interactions of medicines treating overactive bladder syndrome.

Background Overactive bladder syndrome is a condition where one or more of the symptoms such as pollakiuria, urgent need to urinate, nocturia and urinary incontinence is observed. Its prevalence ranges between 7 and 27 % in men and 9-43 % in women. The role of a pharmacist is to educate the patient on medications administration scheme, and drug interactions with particular food or food components. Aim of the review To assess a potential impact of food and fruit juice on the pharmacokinetic and therapeutic effects of medications used in treating overactive bladder syndrome. This information will enhance pharmaceutical care and is vital and helpful for pharmacists counseling their patients. Method In order to gather information on interactions of medications employed in bladder dysfunctions, the English language reports published in the PubMed, Embase, Cochrane and CINAHL database over the years 1996-2015 were studied. Additionally, other resources, namely drugs.com, Medscape, UpToDate, Micromedex, Medical Letter, as well as Stockley Drugs Interaction electronic publication were included in the study. The analysis also covered product data sheets for particular medicinal products. Results Meals and the consumption of grapefruit juice were found to exert a diversified effect on the pharmacokinetics of drugs employed in overactive bladder syndrome therapy. Neither tolterodine, nor mirabegron interact with food and citrus fruit juice, whereas darifenacin, fesoterodine, oxybutynin and solifenacin do interact with grapefruit and others citrus fruit juice. The effects of such interactions may potentially be negative to patients. Trospium absorption is significantly decreased by food. Conclusion For selected medicines used in treating bladder dysfunctions food and grapefruit juice consumption may significantly affect efficacy and safety of the therapy. All information on the topic is likely to enhance the quality of pharmaceutical care.

Association Between Anticholinergic Medication Use and Cognition, Brain Metabolism, and Brain Atrophy in Cognitively Normal Older Adults.

IMPORTANCE: The use of anticholinergic (AC) medication is linked to cognitive impairment and an increased risk of dementia. To our knowledge, this is the first study to investigate the association between AC medication use and neuroimaging biomarkers of brain metabolism and atrophy as a proxy for understanding the underlying biology of the clinical effects of AC medications. OBJECTIVE: To assess the association between AC medication use and cognition, glucose metabolism, and brain atrophy in cognitively normal older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Indiana Memory and Aging Study (IMAS). DESIGN, SETTING, AND PARTICIPANTS: The ADNI and IMAS are longitudinal studies with cognitive, neuroimaging, and other data collected at regular intervals in clinical and academic research settings. For the participants in the ADNI, visits are repeated 3, 6, and 12 months after the baseline visit and then annually. For the participants in the IMAS, visits are repeated every 18 months after the baseline visit (402 cognitively normal older adults in the ADNI and 49 cognitively normal older adults in the IMAS were included in the present analysis). Participants were either taking (hereafter referred to as the AC+ participants [52 from the ADNI and 8 from the IMAS]) or not taking (hereafter referred to as the AC- participants [350 from the ADNI and 41 from the IMAS]) at least 1 medication with medium or high AC activity. Data analysis for this study was performed in November 2015. MAIN OUTCOMES AND MEASURES: Cognitive scores, mean fludeoxyglucose F 18 standardized uptake value ratio (participants from the ADNI only), and brain atrophy measures from structural magnetic resonance imaging were compared between AC+ participants and AC- participants after adjusting for potential confounders. The total AC burden score was calculated and was related to target measures. The association of AC use and longitudinal clinical decline (mean [SD] follow-up period, 32.1 [24.7] months [range, 6-108 months]) was examined using Cox regression. RESULTS: The 52 AC+ participants (mean [SD] age, 73.3 [6.6] years) from the ADNI showed lower mean scores on Weschler Memory Scale-Revised Logical Memory Immediate Recall (raw mean scores: 13.27 for AC+ participants and 14.16 for AC- participants; P = .04) and the Trail Making Test Part B (raw mean scores: 97.85 seconds for AC+ participants and 82.61 seconds for AC- participants; P = .04) and a lower executive function composite score (raw mean scores: 0.58 for AC+ participants and 0.78 for AC- participants; P = .04) than the 350 AC- participants (mean [SD] age, 73.3 [5.8] years) from the ADNI. Reduced total cortical volume and temporal lobe cortical thickness and greater lateral ventricle and inferior lateral ventricle volumes were seen in the AC+ participants relative to the AC- participants. CONCLUSIONS AND RELEVANCE: The use of AC medication was associated with increased brain atrophy and dysfunction and clinical decline. Thus, use of AC medication among older adults should likely be discouraged if alternative therapies are available.

Evaluation of a pharmacist-led pilot service based on the anticholinergic risk scale.

OBJECTIVES: To determine primary care physician (PCP) acceptance rates of electronic medication therapy recommendations based on anticholinergic burden for high-risk elderly patients, and to evaluate potential associations between recommendation acceptance and patient-provider characteristics. SETTING: Two medical clinics within Dean Health System, an integrated health care organization comprising ambulatory surgery centers, medical clinics, community pharmacies, specialty pharmacies, a health plan, and a pharmacy benefits management company. PRACTICE INNOVATION: In this pilot service, the medical records of patients at least 60 years old who met the following criteria were evaluated bimonthly: 1) PCP visit within 2 weeks; (2) three or more inpatient hospitalizations or emergency department visits in the past year; and (3) ten or more active medications. Anticholinergic Risk Scale (ARS) scores of eligible patients were calculated, and medication therapy recommendations were sent electronically to PCPs for patients with an ARS score greater than 3. Post-visit recommendation outcomes were recorded. EVALUATION: Descriptive statistics were utilized to characterize patients, physicians, and recommendations. A generalized linear mixed effects model with physician specific random effects was employed to evaluate recommendation acceptance rates, and odds ratios were calculated to quantify associations between baseline patient/provider characteristics and the likelihood of recommendation acceptance. Changes in aggregate ARS scores were evaluated with the use of a paired t test. RESULTS: Fifty-nine patients were included in this pilot, with 89 medication therapy recommendations made to 21 PCPs. An overall recommendation acceptance rate of 50% (95% confidence interval [CI] 37%-63%) was observed. There were no significant associations identified between baseline patient/provider characteristics and medication recommendation acceptance. CONCLUSION: High recommendation acceptance rates were achieved with the combination of objective anticholinergic risk assessment and algorithm-driven medication therapy recommendations. The lack of identified associations between patient/provider characteristics and recommendation acceptance supports the future scalability of this novel service.

[Influence of drugs on urological diseases]. / Einfluss von Medikamenten auf urologische Krankheiten.

A number of drugs prescribed for the treatment of various diseases can induce urological symptoms as side effects. Antihypertensive drugs (particularly alpha blockers) can result in stress incontinence, whereas selective serotonin reuptake inhibitors (SSRI) can cause urge incontinence and estrogen promotes both forms. A wide range of drugs with anticholinergic activity, among them neuroleptics, tricyclic antidepressants and certain drugs used in airway disorders are associated with urinary retention. Only very few drugs bear a relevant risk for urolithiasis, i. e. the diuretic triamterene and protease inhibitors, such as indinavir; however, the widely used combination of calcium and vitamin D supplementation for prevention of osteoporosis may be an underdiagnosed cause of renal calculi. Drug-induced sexual dysfunction is a frequent side effect of antihypertensive treatment, particularly with beta adrenoceptor blockers and diuretics. The SSRI and some neuroleptics can also impair sexual function.

[Pharmacological treatment of benign prostatic hyperplasia]. / Medikamentöse Therapie des benignen Prostatasyndroms.

The pharmacological treatment of benign prostatic hyperplasia (BPH) is indicated when men suffer from lower urinary tract symptoms (LUTS) but there are no absolute indications for prostate surgery or severe bladder outlet obstruction. Phytotherapy can be used in men with mild to moderate LUTS and alpha-blockers can quickly and effectively decrease the LUTS and symptomatic disease progression. Phosphodiesterase type 5 inhibitors (PDE5-I) are an alternative to alpha-blockers when men experience bothersome side effects from alpha-blockers or erectile dysfunction. If patients predominantly have bladder storage symptoms and a small prostate, muscarinic receptor antagonists are a viable treatment option. The combination of alpha-blocker plus muscarinic receptor antagonist is more efficacious in reducing LUTS than the single drugs alone. The 5 alpha-reductase inhibitors (5ARI) can significantly decrease LUTS and disease progression (e.g. acute urinary retention and need for prostate surgery) in men with larger prostates (> 30-40 ml). The combination of 5ARI plus alpha-blocker can reduce LUTS and disease progression more effectively than drug monotherapy. Combination therapy with PDE5-I (tadalafil) plus 5ARI (finasteride) reduces LUTS more substantially than 5ARI alone and, additionally, PDE5-Is reduce the sexual side effects during 5ARI treatment.

Percutaneous tibial nerve stimulation versus tolterodine for overactive bladder in women: a randomised controlled trial.

OBJECTIVE: We performed a randomised controlled trial of percutaneous tibial nerve stimulation (PTNS) versus tolterodine for treating treatment naïve women with overactive bladder (OAB). STUDY DESIGN: 36 patients with symptoms of OAB were randomised to 3 months of treatment with weekly PTNS or tolterodine (2mg bid p.o.). The primary outcome measure was the difference of micturitions per 24h. The secondary outcome measure was the impact on quality of life (QoL) measured with a visual analogue scale (VAS) between baseline and after 3 months of therapy. RESULTS: Micturition frequencies did not decline significantly (p=0.13) over time and there were no significant treatment differences (p=0.96). QoL was significantly dependent from its level at baseline (p=0.002) and showed improvement over time compared to baseline measurements but no significant differences between both treatment groups (p=0.07). Incontinence episodes per 24h depended significantly on the level at baseline (p=0.0001) and declined significantly (p=0.03) during 3 months of therapy in both therapy groups. However no significant treatment differences on the reduction of incontinence episodes in 24h could be shown between both therapy groups (p=0.89). PTNS had fewer side effects than tolterodine (p=0.04). CONCLUSION: PTNS and tolterodine were both effective in reducing incontinence episodes and improving QoL in patients with OAB but not micturition frequencies. PTNS had fewer side effects.

Risk of Injury in Older Adults Using Gastrointestinal Antispasmodic and Anticholinergic Medications.

OBJECTIVES: To determine the risk of injury associated with gastrointestinal (GI) antispasmodic and anticholinergic use in elderly adults. DESIGN: Retrospective case-control study. SETTING: Integrated healthcare system. PARTICIPANTS: Healthcare system members aged 65 and older (N = 260,010; 54,152 cases, 205,858 controls). MEASUREMENTS: Cases were identified as individuals with an injury resulting in a hospitalization, emergency department, or urgent care visit (index date) from January 2009 through December 2010. Cases and controls were matched in a 1:4 ratio based on age and sex. GI antispasmodic and anticholinergic current and past exposure for cases and controls was evaluated. Individuals were classified as current users if the days' supply of the GI prescription overlapped the index date and past users if the days' supply ended more than 60 days before the index date. Duration of use for current users was analyzed for short- and long-term use. Conditional logistic regression produced adjusted odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Of the total population, 1,068 (0.4%) had current exposure to a GI antispasmodic or anticholinergic (302 (0.6%) cases, 766 (0.4%) controls). Current users had a small but significantly greater risk of injury than nonusers (OR = 1.16, 95% CI = 1.01-1.34, P = .03). Past use was not significantly different from no use. Short-term users had a significantly greater risk of injury (OR = 1.31, 95% CI = 1.01-1.70, P = .04) than nonusers. Long-term use was associated with greater risk, but the difference was not statistically significant. CONCLUSION: Older adults using GI antispasmodic and anticholinergic drugs have greater risk of injury. These findings support recommendations to limit the prescribing of GI antispasmodics and anticholinergics in elderly adults.

Anticholinergic medications and risk of community-acquired pneumonia in elderly adults: a population-based case-control study.

OBJECTIVES: To determine whether use of anticholinergics is associated with risk of community-acquired pneumonia in older adults. DESIGN: Population-based case-control study. SETTING: An integrated healthcare delivery system in Washington State. PARTICIPANTS: Data from a nested case-control study of community-dwelling immunocompetent adults aged 65 to 94 were analyzed. Pneumonia cases (n=1,039) were ascertained according to International Classification of Diseases, Ninth Revision, codes from 2000 to 2003 and validated using chart review. Controls (n=2,022) were matched 2:1 to cases according to age, sex, and year. MEASUREMENTS: Anticholinergic medication exposure was ascertained using prescription data; acute use was defined as one or more prescription fills 90 days or less before the index date (date of pneumonia diagnosis), past use was defined as one or more prescription fills within the prior year but none within 90 days, and chronic use was defined as three or more prescription fills within the prior year. The reference group was those with no fills in the prior year. Conditional logistic regression was used to analyze the association between anticholinergic use and pneumonia, adjusted for comorbidities. RESULTS: Acute use of anticholinergics was observed in 59% of cases and 35% of controls (adjusted odds ratio (aOR)=2.55, 95% confidence interval (CI)=2.08-3.13) and past use in 17% of cases and 23% of controls (aOR=1.19, 95% CI=0.92-1.53). Chronic use of anticholinergics was observed in 53% of cases and 36% of controls (aOR 2.07, 95% CI=1.68-2.54). Results were not different for high- and low-potency anticholinergic medications. CONCLUSION: In older adults, anticholinergic medication use is associated with pneumonia risk, adding to substantial evidence suggesting that these medications are high risk.

Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study.

IMPORTANCE: Many medications have anticholinergic effects. In general, anticholinergic-induced cognitive impairment is considered reversible on discontinuation of anticholinergic therapy. However, a few studies suggest that anticholinergics may be associated with an increased risk for dementia. OBJECTIVE: To examine whether cumulative anticholinergic use is associated with a higher risk for incident dementia. DESIGN, SETTING, AND PARTICIPANTS: Prospective population-based cohort study using data from the Adult Changes in Thought study in Group Health, an integrated health care delivery system in Seattle, Washington. We included 3434 participants 65 years or older with no dementia at study entry. Initial recruitment occurred from 1994 through 1996 and from 2000 through 2003. Beginning in 2004, continuous replacement for deaths occurred. All participants were followed up every 2 years. Data through September 30, 2012, were included in these analyses. EXPOSURES: Computerized pharmacy dispensing data were used to ascertain cumulative anticholinergic exposure, which was defined as the total standardized daily doses (TSDDs) dispensed in the past 10 years. The most recent 12 months of use was excluded to avoid use related to prodromal symptoms. Cumulative exposure was updated as participants were followed up over time. MAIN OUTCOMES AND MEASURES: Incident dementia and Alzheimer disease using standard diagnostic criteria. Statistical analysis used Cox proportional hazards regression models adjusted for demographic characteristics, health behaviors, and health status, including comorbidities. RESULTS: The most common anticholinergic classes used were tricyclic antidepressants, first-generation antihistamines, and bladder antimuscarinics. During a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia (637 of these [79.9%] developed Alzheimer disease). A 10-year cumulative dose-response relationship was observed for dementia and Alzheimer disease (test for trend, P < .001). For dementia, adjusted hazard ratios for cumulative anticholinergic use compared with nonuse were 0.92 (95% CI, 0.74-1.16) for TSDDs of 1 to 90; 1.19 (95% CI, 0.94-1.51) for TSDDs of 91 to 365; 1.23 (95% CI, 0.94-1.62) for TSDDs of 366 to 1095; and 1.54 (95% CI, 1.21-1.96) for TSDDs greater than 1095. A similar pattern of results was noted for Alzheimer disease. Results were robust in secondary, sensitivity, and post hoc analyses. CONCLUSIONS AND RELEVANCE: Higher cumulative anticholinergic use is associated with an increased risk for dementia. Efforts to increase awareness among health care professionals and older adults about this potential medication-related risk are important to minimize anticholinergic use over time.