Anything that interferes with the crucial neurotransmitter acetylcholine can be bad for the brain. A great many medications have what has been called “anticholinergic” activity. Research has verified that anticholinergic drugs may have a serious impact on the brain.
A study published in JAMA Internal Medicine (June 24, 2019) detected a higher risk of dementia among people taking several anticholinergic drugs. The British investigators found that medications for depression, Parkinson disease, schizophrenia and similar disorders, overactive bladder and epilepsy were especially likely to cause people trouble. Taking more than one of these drugs, or taking a high dose for an extended period, increased the likelihood of cognitive difficulties among these individuals who were 55 years old or older.
Anticholinergic (AC) Drug Complications:
Older people in particular may be taking a number of anticholinergic (AC) drugs that together have a negative effect on cognitive function.
“The use of anticholinergic drugs has been strongly associated with adverse health outcomes, including cognitive impairment, dementia, falls, functional decline, hospitalization and mortality, especially in older adults.”
The authors studied older veterans in Taiwan. Their conclusions:
“The results of the present study showed that approximately half of the residents living in veterans’ homes had exposure to anticholinergic drugs, and these AC(+) residents had a significantly higher risk for short-term cognitive decline.”
Although older people are more vulnerable to the complications of anticholinergic drugs, younger people are not necessarily immune. Much depends upon the number of such medications people take. We call this the anticholinergic burden or load.
What Are Anticholinergic Drugs Prescribed For?
This is a key question. That’s because many physicians were taught in medical school that this class of drugs was primarily used for problems of digestive distress like irritable bowel syndrome, diverticulitis and diarrhea. In this case such drugs are often called antispasmodics.
They are also prescribed for overactive bladder and incontinence, motion sickness, dizziness, symptoms of Parkinson’s disease and breathing problems like asthma and COPD (chronic obstructive pulmonary disease).
Many medications prescribed for anxiety, depression, allergies, pain, high blood pressure, mental illness, heart failure and heartburn can also have anticholinergic activity. This comes as a shock to patients and physicians alike. The real problem occurs when people take a handful of pills for a diverse range of health problems and end up with a substantial anticholinergic burden.
What Drugs Have Anticholinergic Action?
It can be challenging to tell whether a medicine has anticholinergic activity. Health professionals may not realize that the medicine they are prescribing could affect the brain. In our opinion medical students are not given enough information on this crucial topic. And prescribers do not have easy access to a list of drugs that affect the action of acetylcholine in the brain. Here is one reader’s question about an interview we did on the radio with a key investigator.
Q. I listened to your interview on the radio with Dr. Shelly Gray about drugs that might increase your risk of developing Alzheimer’s disease. I am not sure of the spelling, but I believe you called them anti-colonergic, or something like that.
I have been taking sleeping pills for several years and worry about forgetfulness. I have a terrible time remembering people’s names and faces.
Please share the list of drugs that could affect memory. I do not want to hasten dementia. I have seen what this condition can do and it is a terrible thing for family and friends to deal with.
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Uncovering the Impact of Anticholinergic Drugs:
A. The actual category of medications you are referring to is spelled anticholinergic. Anticholinergic drugs interfere with the action of the neurochemical acetylcholine. This article explains how anticholinergic drugs could affect your brain. Some people may be more susceptible to anticholinergic effects than others. Some medications have stronger anticholinergic activity than others. What we worry about more than anything is the total anticholinergic burden that may be created by a combination of different drugs.
A study in the journal JAMA Neurology (June 1, 2016) noted that when patients use medications with medium or high anticholinergic activity there was an association with:
“poorer cognition (particularly in immediate memory recall and executive function), reduced glucose metabolism [in the brain], whole-brain and temporal lobe atrophy, and clinical decline. The effect appeared additive because an increased burden of AC [anticholinergic] medications was associated with poorer executive function and increased brain atrophy…These results suggest that medications with AC properties may be detrimental to brain structure and function, as well as cognition.”
No one should ever stop such a medication without consulting with the prescriber. If you are taking one or more of these drugs, however, be sure to discuss with your physician whether there may be alternative treatments that do not put you at increased risk for dementia.
Here is a link to our interview with Dr. Gray. To stream the audio for free, click on the green arrow inside the black circle above the photo. You can purchase a CD to give to your physician or download the MP3 version.
Medications Included in Dr. Gray’s Study
We have identified drugs with high, moderate and low anticholinergic (AC) action in brackets. The greater the AC activity the more worrisome the cognitive impact. The rankings are somewhat arbitrary and controversial since some research categorizes these drugs differently. This is our best assessment at this time. It may change as better research is conducted.
Doxepin (Adapin, Silenor, Sinequan) [high AC activity]
Fesoterodine (Toviaz) [moderate to high AC activity]
Hydroxyzine (Atarax, Vistaril) [high AC activity]
Hyoscyamine (Anaspaz, Levbid, Levsin, Levsinex, NuLev) [high AC activity]
Imipramine (Tofranil) [high AC activity]
Meclizine (Antivert, Bonine) [high AC activity]
Mepenzolate (Cantil) [high AC activity]
Nortriptyline (Pamelor) [high AC activity]
Olanzapine (Zyprexa) [high AC activity]
Orphenadrine (Norflex) [high AC activity]
Oxybutynin (Ditropan, Oxytrol) [high AC activity]
Paroxetine (Brisdelle, Paxil) [low AC activity]
Perphenazine (Trilafon) [high AC activity]
Prochlorperazine (Compazine) [moderate AC activity]
Promethazine (Phenergan) [high AC activity]
Protriptyline (Vivactil) [high AC activity]
Pseudoephedrine HCl/Triprolidine HCl (Aprodine) [moderate to high AC activity]
Scopolamine (Transderm Scop) [high AC activity]
Thioridazine (Mellaril) [high AC activity]
Tolterodine (Detrol) [high AC activity]
Trifluoperazine (Stelazine) [high AC activity]
Trimipramine (Surmontil) [high AC activity]
Dr. Shelly Gray’s article, “Cumulative Use of Strong Anticholinergics and Incident Dementia,” was published Jan. 26, 2015, in JAMA Internal Medicine. Here’s a link to the abstract.
Other Drugs that May Have Some Anticholinergic Activity
Alprazolam (Xanax) [low AC activity]
Amantadine (Symmetrel) [low AC activity]
Baclofen [moderate AC activity]
Brompheniramine [high AC activity]
Carbamazepine (Tegretol) [moderate AC activity]
Carbinoxamine (Arbinoxa) [moderate to high AC activity]
Carisoprodol (Soma) [moderate AC activity]
Cetirizine (Zyrtec) [moderate AC activity]
Cimetidine (Tagamet) [moderate AC activity]
Clemastine (Tavist) [moderate to high AC activity]
Clidinium & chlordiazepoxide (Librax) [low to moderate AC activity]
Clorazepate (Tranxene) [low AC activity]
Codeine [low AC activity]
Colchicine [low AC activity]
Darifenacin (Enablex) [moderate to high AC activity]
Digoxin (Lanoxicaps, Lanoxin) [low AC activity]
Dimenhydrinate (Dramamine, Gravol, etc) [high AC activity]
Diphenoxylate plus atropine (Lomotil) [moderate to high AC activity]
Disopyramide (Norpace) [low to moderate AC activity]
Flavoxate (Urispas) [moderate AC activity]
Fluphenazine (Prolixin) [moderate AC activity]
Furosemide (Lasix) [low AC activity]
Hydrochlorothiazide (Esidrix, Dyazide, HydroDIURIL, Maxzide & literally scores of other medications for high blood pressure) [low AC activity]
Loperamide (Imodium) [moderate AC activity]
Loratadine (Alavert, Claritin) [moderate AC activity]
Loxapine (Loxitane) [moderate AC activity]
Maprotiline [low to moderate AC activity]
Meperidine (Demerol) [moderate AC activity]
Methadone [moderate AC activity]
Methocarbamol (Robaxin) [moderate AC activity]
Methotrimeprazine (Nozinan) [moderate AC activity]
Nifedipine (Adalat, Procardia) [low AC activity]
Olanzapine (Zyprexa) [moderate AC activity]
Orphenadrine (Norflex) [moderate AC activity]
Oxcarbazepine (Trileptal) [moderate AC activity]
Quetiapine (Seroquel) [moderate AC activity]
Pimozide (Orap) [moderate AC activity]
Procyclidine (Kemadrin) [moderate AC activity]
Propantheline (Pro-Banthine) [moderate to high AC activity]
Ranitidine (Zantac) [low AC activity]
Solifenacin (VESIcare) [low to moderate AC activity; more research necessary]
Thiothixene (Navane) [high AC activity]
Tizanidine (Zanaflex) [high AC activity]
Tramadol (Ultram) [low AC activity]
Trihexyphenidyl (Artane) [high AC activity]
Trospium (Sanctura) [high AC activity]
The drugs listed above were not included in the study by Dr. Gray and her colleagues. Older people who take several of these medications might accumulate a substantial anticholinergic burden.
In compiling this list we relied on a number of resources. There is not unanimity among investigators. Sadly, there is no perfect list. We did our best to locate likely drug candidates and provide a qualitative assessment of the potency of the effect. Resources we consulted included:
List based in part on information found in part in the publication, “Association Between Anticholinergic Medication Use and Cognition, Brain Metabolism, and Brain Atrophy in Cognitively Normal Older Adults,” (JAMA Neurology, online, April 18, 2016). Also “An anticholinergic burden score for German prescriber: Score development,” (BMC Geriatrics, Oct. 11, 2018)
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Injuries Due to Falls:
Another worrisome side effect of multiple anticholinergic drugs is a greater chance of a dangerous fall (Drugs & Aging, March 2019). A study of more than 10,000 older Americans found that those taking two or more medicines with moderate or high anticholinergic activity were twice as likely to injure themselves in a fall.
Remember, never stop taking any medication without medical supervision. Some of the drugs on this list can trigger serious withdrawal symptoms if stopped suddenly. We offer this list to enhance communication between patients and healthcare providers.
Stories from Readers:
We have heard from hundreds of visitors to this website regarding anticholinergic complications. It’s one thing to read a list of side effects and quite another to see personal stories. Here are just a handful:
Lucia in Louisiana shares her experience:
“I believe it and have personally witnessed it. I have taken more than one of the medications from the list of anticholinergic drugs at various time. Some were prescribed.
“I have had to get off these drugs due to difficulty processing and recalling information. I have had trouble finding the right words. A long time ago I decided for myself that anticholinergic meds create stupidity in me. I can’t afford to swallow stupidity.”
B. in Gloucester, Virginia states:
“My wife used scopolamine patches for three weeks on a vacation to prevent motion sickness which it did. Unfortunately it also caused memory loss.
“That was over four years ago and memory loss continues to this day. We have met with three neurologists and they have done brain scans but offered no remedies. Prior to the day the scopolamine patch was attached my wife had absolutely no memory problems or symptoms of dementia or Alzheimer’s. Her life style and family history indicated no danger signs. We are still searching in vain for a remedy.”
Eileen in Alberta, Canada, is caught between a rock and a very hard place:
“I have been on amitriptyline for my fibromyalgia. I have tried other meds but Elavil is the only one that worked.
“I am suffering memory loss. I used to have a photographic memory. Now I can’t remember from second to second. I have also been experiencing dizziness. I have been on this medication for twenty years. I have tried getting off the amitriptyline, but after two weeks I could hardly move. I had severe pain every where.”
Are the Anticholinergic Effects Reversible?
We received this excellent question from a reader of our newspaper column. We think you will find it of interest:
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.” Read Joe's Full Bio.
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Coupland CAC et al, "Anticholinergic drug exposure and the risk of dementia: A nested case-control study." JAMA Internal Medicine, June 24, 2019. doi:10.1001/jamainternmed.2019.0677
Wu YH et al, "Association between using medications with anticholinergic properties and short-term cognitive decline among older men: A retrospective cohort study in Taiwan." Geriatrics & Gerontology International, April 2017. DOI: 10.1111/ggi.13032
Risacher SL et al, "Association between anticholinergic medication use and cognition, brain metabolism, and brain atrophy in cognitively normal older adults." JAMA Neurology, June 2016. DOI: 10.1001/jamaneurol.2016.0580
Kiesel EK et al, "An anticholinergic burden score for German prescribers: Score development." BMC Geriatrics, Oct. 11, 2018. DOI: 10.1186/s12877-018-0929-6
Green AR et al, "Drugs contributing to anticholinergic burden and risk of fall or fall-related injury among older adults with mild cognitive impairment, dementia and multiple chronic conditions: A retrospective cohort study." Drugs & Aging, March 2019. DOI: 10.1007/s40266-018-00630-z
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