doctor in a lab coat with a handful of pills

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.

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. A study in Geriatrics and Gerontology International (April 17, Suppl. 1, 2017) noted that:

“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.

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.

Show 979: Health News Update on Defending the Brain

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.

  • Amitriptyline (Elavil) [high AC activity]
  • Atropine [high AC activity]
  • Benztropine (Cogentin) [high AC activity]
  • Chlorpheniramine (Actifed, Allergy & Congestion Relief, Chlor-Trimeton, Codeprex, Efidac-24 Chlorpheniramine, etc.) [high AC activity]
  • Chlorpromazine (Thorazine) [high AC activity]
  • Clomipramine (Anafranil) [high AC activity]
  • Clozapine (Clozaril) [high AC activity]
  • Cyclobenzaprine (Amrix, Fexmid, Flexeril) [moderate AC activity]
  • Cyproheptadine (Periactin) [moderate AC activity]
  • Desipramine (Norpramin) [high AC activity]
  • Dexchlorpheniramine (Polaramine) [high AC activity]
  • Dicyclomine (Bentyl) [high AC activity]
  • Diphenhydramine (Advil PM, Aleve PM, Bayer PM, Benadryl, Excedrin PM, Nytol, Simply Sleep, Sominex, Tylenol PM, Unisom, etc.) [high AC activity]
  • 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 (BrisdellePaxil) [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]
  • 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]
  • Quetiapine (Seroquel) [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, Spasmex) [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:

European Journal of Clinical Pharmacology (July, 2013)

BMC Geriatrics (March, 25, 2015)

Journal of Clinical Pharmacology (Dec. 2006)

Magellan Anticholinergic Risk Scale

Pharmacist’s Letter

Side Effects of Anticholinergic Drugs:

Drugs in this category can produce a variety of symptoms including:

  • Dry mouth & nose, difficulty swallowing
  • Decreased sweating
  • Constipation
  • Dizziness, drowsiness, unsteady gait
  • Headache
  • Difficult urination, urinary retention
  • Confusion, disorientation, memory problems
  • Difficulty paying attention, cognitive decline
  • Fatigue, muscle weakness, clumsiness, unsteadiness
  • Dry skin
  • Visual difficulties

List revised 5/4/17 based 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).

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 the Elavil is the only one that worked in shutting my brain.

“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:

Can You Reverse Memory Problems from Anticholinergic Drugs?

Can You reverse Memory Problems from Anticholinergic Drugs?

If you found this article helpful, please vote at the top of this page. Share your own experience below in the comment section.

Revised by Joe Graedon 5/4/17

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  1. judy
    south carolina
    Reply

    Every medication behind the pharmacy counter has its dangers; the limiting factor is how much can the body tolerate, or more precisely, how much is the patient willing to gamble on his health? What is most disturbing is how many over-the-counter drugs are also included.

  2. jody
    IN
    Reply

    My 80 yr old sister used xanax for napping and sleeping at night. Neither I nor my nurse niece could talk her out of it. Robbed her of her memory and finally took her life. Xanax is a short-term med and commonly abused by seniors and others.

  3. Carol
    Youngstown, OH
    Reply

    Where is Ambien (Zolpidem) on the list? I take 5mg to sleep only when traveling. My dr. said to quit, and I know it means I will not sleep while away from home.

    I take no meds, but need a safe one for sleeping to enjoy a vacation. I truly need to know, What is safe? I read that naltrexone is , but it takes weeks before being effective, therefore of no help to me.

  4. Gerry
    Fla
    Reply

    I take low dose benedryl and zyrtec nightly for angiodema, a severe allergic condition; in addition to melatonin for sleep help. The only sleepless time of the month is the full moon. Guess I’m a “lunatic” for sure. I’ve taken these since year 2000 and still have no memory problems of which I’m aware.

  5. Joan
    Pa.
    Reply

    I have restless legs. What can I do other than take the Miapex that I am taking now ?

  6. Lily
    Reply

    My Mother was on several of the high-risk drugs listed here for over thirty years, and when she passed on aged 86 her memory was as sharp as ever. So I wonder about this report. I do know that certain drugs do impair the thinking process but is it only down to drugs? I find if I take something that interferes with my thinking ability it kicks in after about three days, yet a lot of the commentators admit to being on these medicines over 20 years. I personally take the lowest dose of any drug for the shortest time possible and look for a more natural remedy for whatever ails me. I also research everything I have to take thoroughly and even try to look up drugs I currently do not need just in case I do so I can ask for the one that has the least side effects.

    I find Drs are all too quick to prescribe medicine for ailments rather than looking at the root cause. I once had severe pain radiating from my spine into my arms and legs. My GP took a look and handed over a script for Tramadol. I took two and soon realised these drugs were mind-altering so I went instead to a chiropractor. Four months later I was totally pain-free and my spine realigned. She actually eased my pain the first day, and over the following months straightened my spine and taught me exercises to maintain it.

  7. Carol
    OH
    Reply

    I’d like to know why Google Chrome no longer shows full lists of all these medications & who the list originates from. I used to be able to find the full lists & what group they were in as to a high chance or medum chance of loss of cognitive function, memory loss, etc. & there were also listed, drugs that were thought to possibly have anticholinergic effects. I can no longer find these lists. I’d like to know why. I printed 2 of the lists when they were in Google Chrome’s vast lot of information & I found that I had taken many of them for extensive periods of time. There were many antidepressants included in these lists. I’d like to be able to print all of these lists as some did not agree with others. This AARP list is not a full list.

    • olson
      TN
      Reply

      I agree with you. There used to be a huge spreadsheet listing all suspected anticholinergic meds and it has been taken down and it angers me.

  8. BarbX
    Phillips WI
    Reply

    I, too have been taking Amitripyline 50 mg for at least 20 years before bed to help me sleep. I have Fibromyalgia. I tried to get off of it twice, but ended up with insomnia and felt I was having a nervous breakdown. I do not believe most doctors know how to help lessen the symtoms that result from discontinuing this drug. Doctors tried to lessen dosage to half, which did no good at all. My short term memory is awful and has caused me to lose self-confidence, feeling so different from everyone else. Has anyone been successful getting off this drug? What is the process? What can I do to lessen symptoms of withdrawal, and what drug is safe to take in place of the Amitriptylene? Should I see a neurologist? I would so appreciate any help I can get. Thanks.

  9. Bryon
    The Woodlands, Texas
    Reply

    Where is Benadryl on your list of anticholinergics?

    • Judy M
      Edmonton Alberta, Canada
      Reply

      I am going through the same thing, I’ve been on amitriptyline for ten years or more. My cognition is not that great, and has a negative affect on my life. I am 64 years old. I am wanting to stop taking it, and I am on day two, my nerves are really jangly. I also have fibromyalgia, and have been taking it for pain management. I am going to go see my doctor today. I have been diagnosed with sojgrens, which causes drying, it is systematic in the way that lupus is.

      It can affect any part of the body including the brain, joints, eyes, nose, glands. The amitriptyline is probably contributing to it. I am at a loss to know what else to do. I read that it takes at least 4 days for the drug to clear out of your system. They say that you should come of it gradually, but I am only taking the 50 mgs, so I’m trying it cold.

      So far, it is only affecting my central nervous system. I am experiencing a bit of anxiety, I am going to try and tolerate it, because it scares me. My mom had Alzheimer’s real bad, she passed away last year. I am afraid that I may end up like her. I am quitting this drug, no matter what.

      • Lori
        VIRGINIA
        Reply

        Low-dose naltrexone, and I emphasize, LOW DOSE NALTREXONE or LDN, is a very safe and effective treatment for controlling pain associated with Fibromayalgia and Rheumatoid Diseases. The initial dose is usually 1.5mg and then is very slowly increased over 4-6 weeks until you reach a maximum dose of 4mg. Also, the supplement, Alpha Lipoic Acid, seems to help quite a few people with their Fibro or RA pain and is a much safer alternative to many prescription medications especially those with high anticholinergic properties. Even taking medications, including OTC medications, with low anticholinergic properties, when used in combination with other medications with low anticholinergic properties, can result in a high overall anticholinergic burden. Regarding insomnia, some people have an imbalance in the autonomic nervous system, due to an overactive sympathetic nervous system, the “fight or flight” system, and/or an underractive or impaired parasympathetic nervous system, the “rest and digest”, system and may benefit from taking a vagus nerve supplement since the vagus nerve controls the parasympathetic nervous system. Vagus nerve supplements are intended to: (1) stimulate the parasympathetic nervous system, and (2) usually include either a form of acetylcholine and/or an acetylcholinerastase inhibitor, that affects the protein that breaks down acetylcholine, the result is both an increase in the level and duration of acetylcholine in the body. I began taking a vagus nerve supplement called Parasym Plus for treatment of autonomic dysfunction (POTS), suspected of being caused by an autoimmune disease called Myasthenia Gravis (MG), which ironically involves a deficiency of acetylcholine caused by impaired acetylcholine receptors. The improvement in my symptoms has been significant. The acetylcholine in this supplement is only available in Europe as a prescription medication and has been used for many years there to treat people suffering from Alzheimer’s and age-related dementia. Also, it contains a high level of Thiamin (I haven’t researched the significance of this yet), and an herb that’s been used in ancient Chinese medicine the active ingredient of which is Huperzine A, an acetylcholinerastase inhibitor very similar to the prescription medication, Mestinon. Mestinon has been safely used for decades in people suffering from MG. Research on Hurpezine A has shown it to be more effective than Mestinon since it produces a longer lasting effect than Mestinon, a major complaint from people taking this drug. However, this and any other vagus nerve supplement, that contains acetylcholine and/or an acetylcholinesterase inhibitor, should NOT be taken without first consulting your physician. Combining one acetylcholine supplement or acetylcholinerastase inhibitor with another or with Mestinon or another similar prescription medication, could produce a dangerous, and potentially life threatening cholinergic crisis.

  10. Evelyn
    Ashburn, VA
    Reply

    Have been taking amitriptyline for severe insomnia (and depression) for the past 20 yrs. It was the only thing that worked, and it changed my life. I am 57 now, and my short term memory is declining rapidly. I can’t remember what someone just said to me seconds ago. I heard it and even replied to it when it was first said, but seconds later I have no clue what it was. So like everyone here, I’m stuck trying to decide if I should suffer the severe withdrawal, insomnia and depression that will most likely destroy my life, or choose to stay on them and have my brain become mush.

  11. Susan M
    Indiana
    Reply

    My Mom is on like 3 of these drugs and I can tell when she has taken them. She cannot process any information or remember what we talked about 5 minutes ago. I highly recommend moving to safer options if you can.

    Re the question about aluminum. The last time I researched this, my impression was that the blood-brain barrier gets damaged and dangerous stuff (like aluminum) gets in when it shouldn’t, and then the brain’s “cleansing” system can get overloaded or damaged too, and then the harmful substances don’t get cleared out and cause tangles and do damage, etc. So, even though aluminum may not be the actual CAUSE, it is a known neurotoxin, and there is no reason you should be putting it in your body. Use tums. Or plain old baking soda in water.

  12. Jan
    Atlanta
    Reply

    For those of you on anticholinergic sleep meds, a possible low-tech, cheap solution is a sleep mask. Once peri-menopause hit I just stopped sleeping! With a small dose of melatonin and my mask, I sleep like a rock now.

    • lynn
      Campbell, CA
      Reply

      What is a sleep mask? You mean one of those sinus or headache type gel masks for sleep.

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