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Browsing by Subject "Cholinergic antagonists"
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Item A 12-Year Retrospective Study of the Prevalence of Anticholinergic Polypharmacy and Associated Outcomes Among Medicare Patients with Overactive Bladder in the USA(Springer, 2021) Campbell, Noll L.; Hines, Lisa; Epstein, Andrew J.; Walker, David; Lockefeer, Amy; Shiozawa, Aki; Medicine, School of MedicineBackground and objective: Antimuscarinics, drugs with anticholinergic properties, are frequently prescribed for overactive bladder, and anticholinergic burden is associated with adverse events. The "Polypharmacy: Use of Multiple Anticholinergic Medications in Older Adults" (Poly-ACH) measure was developed by the Pharmacy Quality Alliance and is used by the Centers for Medicare and Medicaid Services. Using the Poly-ACH measure, we assessed the prevalence of anticholinergic polypharmacy among Medicare patients in the USA with overactive bladder and determined associations between polypharmacy and medical conditions, care, and spending. Methods: This was a retrospective cohort study of Medicare beneficiaries with overactive bladder (coverage period: 2006-2017). Anticholinergic polypharmacy, measured by the Poly-ACH, was defined as concurrent use of two or more anticholinergics, each with two or more prescription claims on different dates of service for ≥ 30 cumulative days. Change in annual frequency of anticholinergic polypharmacy was assessed using logistic regression. Associations between anticholinergic polypharmacy over 3 years and falls, fractures, mental status, and medical care spending were assessed with longitudinal regression models. Results: In total, 226,712 patients contributed 940,201 person-years of follow-up after overactive bladder diagnosis. The share of patients meeting the Poly-ACH definition was 3.3% in 2006 and 1.7% in 2017. Women and nursing home residents had higher risks of anticholinergic polypharmacy. Having 1 year or more of positive Poly-ACH status in the 3 years prior was associated with higher rates of all outcomes. Conclusions: Anticholinergic polypharmacy was uncommon among older adults with overactive bladder. Prevalence was higher among women and nursing home residents, and it was associated with negative outcomes, highlighting potential longitudinal implications of anticholinergic burden.Item Muscarinic Cholinergic Receptor Agonist and Peripheral Antagonist for Schizophrenia(Massachusetts Medical Society, 2021-02-25) Brannan, Stephen K.; Sawchak, Sharon; Miller, Andrew C.; Lieberman, Jeffrey A.; Paul, Steven M.; Breier, Alan; Psychiatry, School of MedicineBackground: The muscarinic receptor agonist xanomeline has antipsychotic properties and is devoid of dopamine receptor-blocking activity but causes cholinergic adverse events. Trospium is a peripherally restricted muscarinic receptor antagonist that reduces peripheral cholinergic effects of xanomeline. The efficacy and safety of combined xanomeline and trospium in patients with schizophrenia are unknown. Methods: In this double-blind, phase 2 trial, we randomly assigned patients with schizophrenia in a 1:1 ratio to receive twice-daily xanomeline-trospium (increased to a maximum of 125 mg of xanomeline and 30 mg of trospium per dose) or placebo for 5 weeks. The primary end point was the change from baseline to week 5 in the total score on the Positive and Negative Syndrome Scale (PANSS; range, 30 to 210, with higher scores indicating more severe symptoms of schizophrenia). Secondary end points were the change in the PANSS positive symptom subscore, the score on the Clinical Global Impression-Severity (CGI-S) scale (range, 1 to 7, with higher scores indicating greater severity of illness), the change in the PANSS negative symptom subscore, the change in the PANSS Marder negative symptom subscore, and the percentage of patients with a response according to a CGI-S score of 1 or 2. Results: A total of 182 patients were enrolled, with 90 assigned to receive xanomeline-trospium and 92 to receive placebo. The PANSS total score at baseline was 97.7 in the xanomeline-trospium group and 96.6 in the placebo group. The change from baseline to week 5 was -17.4 points with xanomeline-trospium and -5.9 points with placebo (least-squares mean difference, -11.6 points; 95% confidence interval, -16.1 to -7.1; P<0.001). The results for the secondary end points were significantly better in the xanomeline-trospium group than in the placebo group, with the exception of the percentage of patients with a CGI-S response. The most common adverse events in the xanomeline-trospium group were constipation, nausea, dry mouth, dyspepsia, and vomiting. The incidences of somnolence, weight gain, restlessness, and extrapyramidal symptoms were similar in the two groups. Conclusions: In a 5-week trial, xanomeline-trospium resulted in a greater decrease in the PANSS total score than placebo but was associated with cholinergic and anticholinergic adverse events. Larger and longer trials are required to determine the efficacy and safety of xanomeline-trospium in patients with schizophrenia.