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Anticholinergics May Increase Dementia Risk in Elderly

Worst Pills, Best Pills Newsletter article August, 2015

A recent study[1] provides the best evidence to date linking strong anticholinergics — certain medications indicated for seasonal allergies, depression, insomnia, overactive bladder and other illnesses — to an increased risk for dementia in older adults. The study also shows that higher doses and longer use of these drugs are associated with higher risk for dementia.

Common anticholinergic drugs include the over-the-counter drug diphenhydramine (ADVIL PM, ALEVE PM, BENADRYL ALLERGY,...

A recent study[1] provides the best evidence to date linking strong anticholinergics — certain medications indicated for seasonal allergies, depression, insomnia, overactive bladder and other illnesses — to an increased risk for dementia in older adults. The study also shows that higher doses and longer use of these drugs are associated with higher risk for dementia.

Common anticholinergic drugs include the over-the-counter drug diphenhydramine (ADVIL PM, ALEVE PM, BENADRYL ALLERGY, SOMINEX) and antidepressant prescription drugs such as doxepin (SILENOR, ZONALON).

Anticholinergics are frequently used by patients of almost all ages. But their use is particularly prevalent among people 65 or older.

The new study[2]

The study, published online on Jan. 26 in JAMA Internal Medicine, was led by researchers at the University of Washington, with funding from the National Institutes of Health. The study was unique in that it examined only drugs with strong anticholinergic activity (see table, this page, for examples), as determined by an expert group of health care professionals.

The researchers tracked approximately 3,400 men and women age 65 or older living in the Seattle, Wash., area. The study found that 23 percent of the patients (both users and non-users of strong anticholinergics) developed dementia. Of that subgroup, nearly 80 percent developed Alzheimer’s disease during follow-up.

Patients who used strong anticholinergics were significantly more likely to have developed any type of dementia or Alzheimer’s disease compared with non-users. The higher a patient’s cumulative use of anticholinergics over the previous 10 years, the greater his or her risk for developing dementia or Alzheimer’s disease.

Specifically, taking a strong anticholinergic for three months to three years increased dementia risk by about 20 percent, while taking such medications for more than three years increased the risk by 54 percent, compared with non-users.

The increased risk for Alzheimer’s disease itself with longer anticholinergic use was similar: Cumulative use for three months to three years increased the risk by up to 30 percent, while use for longer than three years increased the risk by 63 percent, compared with non-users.

Notably, most of the anticholinergic drugs that were included in the new study have previously been classified as Do Not Use or Limited Use by Public Citizen’s Health Research Group.

It is not very clear whether anticholinergic-induced dementia is reversible after a patient stops taking such drugs.

What You Can Do

You should talk with your health care provider to find out if your current prescription or over-the-counter medications have anticholinergic effects.

Nondrug therapy — such as sleep hygiene for insomnia and bladder training for urinary incontinence — should be tried first. However, if nondrug therapy is ineffective, talk with your health care provider about using a non-anticholinergic drug.

If you or a loved one — especially an older adult — is currently using a strong anticholinergic drug and has been taking it for longer than three months, you should talk to a health care provider about gradually discontinuing this drug and switching to a safer alternative treatment.

If you or your loved one must use an anticholinergic drug, ask the health care provider for the lowest effective dose for the shortest time possible and consult with him or her about stopping the drug if it is ineffective.

Watch for changes in memory or thinking abilities, as these could possibly be early signs of dementia, in which case these medications need to be discontinued. Do not stop taking a drug without talking with your health care provider. Some drugs can cause serious side effects when stopped suddenly.

Examples of Strong Anticholinergics

Anticholinergic class* Drug examples
Antidepressants
  • amitriptyline (only available in generic)**
  • clomipramine (ANAFRANIL)
  • desipramine (NORPRAMIN)***
  • doxepin (SILENOR, ZONALON)**
  • imipramine (TOFRANIL, TOFRANIL PM)**
  • nortriptyline (PAMELOR)***
  • paroxetine (BRISDELLE, PAXIL, PAXIL CR, PEXEVA)***
  • protriptyline (VIVACTIL)***
  • trimipramine (SURMONTIL)***
Antihistamines (used for allergy relief, sleep aids and other uses)
  • chlorpheniramine (ADVIL ALLERGY AND CONGESTION RELIEF, ADVIL ALLERGY SINUS, CHLOR-TRIMETON, TUSSICAPS, TUSSIONEX PENNKINETIC, TUZISTRA XR, VITUZ, ZUTRIPRO)
  • cyproheptadine (only available in generic)
  • diphenhydramine (ADVIL PM, ALEVE PM, BENADRYL ALLERGY, SOMINEX)
  • hydroxyzine (VISTARIL)
Antipsychotics
  • chlorpromazine (only available in generic)***
  • clozapine (CLOZARIL, FAZACLO ODT, VERSACLOZ)***
  • olanzapine (SYMBYAX, ZYPREXA)***
  • thioridazine (only available in generic)**
  • trifluoperazine (only available in generic)***
Gastrointestinal antispasmodics
  • atropine (LOMOTIL, LONOX, METOFEN)**
  • dicyclomine (BENTYL)**
  • homatropine (TUSSIGON)**
  • hyoscyamine (LEVSIN)**
  • propantheline (only available in generic)
  • scopolamine (TRANSDERM SCOP)
Muscle relaxants
  • cyclobenzaprine (AMRIX)**
  • orphenadrine (only available in generic)**
Overactive bladder control medications
  • fesoterodine (TOVIAZ)**
  • oxybutynin (DITROPAN XL, GELNIQUE, OXYTROL, OXYTROL FOR WOMEN)***
  • tolterodine (DETROL, DETROL LA)***
Parkinson’s disease medications
  • benztropine (COGENTIN)**
  • biperiden (AKINETON)
  • trihexyphenidyl (only available in generic)**

*The listed drug classes and drugs include many, but not all, of the drugs mentioned in the new study.
**Public Citizen’s Health Research Group lists these drugs as Do Not Use.
***Public Citizen’s Health Research Group lists these drugs as Limited Use.

References
[1] Gray SL, Anderson ML, Dublin S, et al. Cumulative use of strong anticholinergics and incident dementia: A prospective cohort study. JAMA Intern Med. 2015;175(3):401-407.

[2] Gray SL, Anderson ML, Dublin S, et al. Cumulative use of strong anticholinergics and incident dementia: A prospective cohort study. JAMA Intern Med. 2015;175(3):401-407.