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Am Fam Physician. 2009;79(5):online-only-

Background: Medications with anticholinergic properties are often associated with adverse events, including falls, cognitive dysfunction, delirium, and loss of independence. An estimated 12 to 21 percent of older patients in the United States use at least one medication with the potential for anticholinergic adverse effects. Given that patients older than 65 years are typically prescribed an average of six medications, and given that this age group is expected to double to 70 million by 2030, the risks of polypharmacy will also rise among the aging population. Rudolph and colleagues developed the Anticholinergic Risk Scale (ARS) to estimate the risk of developing adverse effects from medications with anticholinergic potential.

The Study: The authors reviewed 500 commonly prescribed oral medications for anticholinergic effects via an evidence-based review of Medline medical literature searches and the National Institute of Mental Health psychoactive drug screening KiBank database. Each medication received a ranking from zero to three points based on its likelihood of causing an anticholinergic adverse effect, including dry mouth, dry eyes, dizziness, confusion, constipation, and falls.

To investigate whether the ARS could identify the risk of anticholinergic effects from medications, the authors recruited participants from the primarily male population 65 years and older who were followed by the Veteran Affairs Boston Healthcare System. Two cohorts were evaluated separately: a retrospective cohort of patients from the geriatric evaluation and management (GEM) clinics and a prospective cohort who attended the primary care clinics.

Both cohorts were interviewed for recent problems that were consistent with anticholinergic adverse effects, including central effects (i.e., falls, dizziness, or confusion) and peripheral effects (i.e., dry mouth, dry eyes, or constipation). Each adverse effect was assigned one point, and the primary outcome was the total of anticholinergic adverse effects.

Results: The retrospective cohort followed 132 GEM patients, and the prospective cohort followed 117 primary care patients. The GEM patients were significantly older than the primary care patients, with a mean age of 78.7 and 71.5 years, respectively. In both cohorts, the number of anticholinergic adverse effects increased with higher ARS scores: at least 70 percent of patients reported two or more anticholinergic effects when the ARS score was three or greater.

Although the GEM patients were taking significantly fewer medications than the primary care cohort (7.9 versus 9.0 medications), their average ARS score was higher (1.4 versus 0.7), and was correlated with significantly more central adverse effects. Forty percent of the GEM cohort had experienced falls and 38.6 percent reported confusion, compared with 12 percent each among the primary care patients. The incidence of dry eyes was greater in the GEM cohort (13.6 versus 5.1 percent), whereas the primary care cohort reported a higher rate of dry mouth (44.4 versus 10.6 percent). No significant differences were noted in the likelihood of dizziness or constipation between the two cohorts, but both increased equally with higher ARS scores.

Conclusion: Risk of anticholinergic adverse events can be quickly estimated in older patients by determining the relative ARS scores of their medications (see accompanying table). This may be useful in preventing unnecessary adverse reactions associated with these medications.

3 points2 points1 point
Antidepressants/antipsychotics
Amitriptyline (Elavil*)
Benztropine (Cogentin)
Fluphenazine (Prolixin*)
Imipramine (Tofranil)
Perphenazine (Trilafon*)
Thioridazine (Mellaril*)
Thiothixene (Navane)
Trifluoperazine (Stelazine*)
Clozapine (Clozaril)
Desipramine (Norpramin)
Nortriptyline (Pamelor)
Olanzapine (Zyprexa)
Haloperidol (Haldol)
Paroxetine (Paxil)
Quetiapine (Seroquel)
Risperidone (Risperdal)
Trazodone (Desyrel*)
Ziprasidone (Geodon)
Antihistamines
Chlorpheniramine (Chlor-Trimeton)
Cyproheptadine (Periactin*)
Diphenhydramine (Benadryl)
Hydroxyzine (Vistaril)
Meclizine (Antivert)
Cetirizine (Zyrtec)
Cimetidine (Tagamet)
Loratadine (Claritin)
Ranitidine (Zantac)
Anti-Parkinsonism agents/antispasmodics
Carisoprodol (Soma)
Dicyclomine (Bentyl)
Hyoscyamine products
Oxybutynin (Ditropan)
Tizanidine (Zanaflex)
Baclofen (Lioresal)
Tolterodine (Detrol)
Carbidopa/levodopa (Sinemet)
Methocarbamol (Robaxin)
Pramipexole (Mirapex)
Selegiline (Eldepryl)
Antinausea/antidiarrheal agents
Promethazine (Phenergan) Loperamide (Imodium)
Prochlorperazine (Compazine*)
Metoclopramide (Reglan)

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