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Can the Antidepressant Amitriptyline Mess Up Memory?

The antidepressant amitriptyline is prescribed for nerve pain, fibromyalgia, insomnia or migraines. Can amitriptyline cause memory problems?

It is estimated that nearly two million people take the antidepressant amitriptyline every day. We suspect that most are not taking this drug to improve mood. That’s because amitriptyline (Elavil) has been around for decades. It is perceived as an old-fashioned antidepressant with lots of side effects. They include constipation, dry mouth, drowsiness, dizziness, blurred vision, urinary retention, confusion and forgetfulness. Many are symptoms of powerful anticholinergic drug activity. More about that at this link. These days, the antidepressant amitriptyline is probably prescribed more for off-label purposes such as insomnia, nerve pain, fibromyalgia or migraines than for depression.

Will Antidepressant Amitriptyline Short-Circuit Memory?

This reader is concerned about long-term reliance on the antidepressant amitriptyline, even if used for an off-label purpose:

Q. I have been taking amitriptyline before bed for at least 20 years. I have fibromyalgia and it helps me sleep.

I’ve tried to get off it twice, but the insomnia was unbearable. Most doctors don’t seem to know how to help lessen the symptoms resulting from discontinuing this drug. Cutting the dosage in half did no good at all.

My short-term memory is awful. I think it’s the drug, and I’ve lost my self-confidence. What can I do to lessen symptoms of withdrawal? Is there a safe substitute for amitriptyline? I would so appreciate any help I can get.

A. Amitriptyline (Elavil) was first marketed in the United States in 1961. The FDA has approved this drug only for treating symptoms of depression. Nevertheless, many health professionals prescribe it off label to treat insomnia, nerve pain, migraines, interstitial cystitis, PTSD, anxiety and fibromyalgia. Nearly 10 million prescriptions are dispensed annually.

Amitriptyline is a strong anticholinergic medication. That means it interferes with a crucial brain chemical called acetylcholine. A study of more than 300,000 people found that those who take anticholinergic drugs like the antidepressant amitriptyline are more likely to develop dementia (BMJ, April 25, 2018).

We have listed many anticholinergic drugs that are generally inappropriate for seniors in our Guide to Drugs and Older People.

An editorial in the BMJ (April 25, 2018) notes:

“As suggested by guidelines, anticholinergics in general should be avoided in older adults.”

These experts are advising their medical colleagues to try and avoid anticholinergic drugs like the antidepressant amitriptyline unless it is absolutely essential. Here is another reader who is concerned that amitriptyline affected her memory:

Amitriptyline for Migraines?

Q. I was prescribed the antidepressant amitriptyline for migraines a few years ago and took it for several months. I experienced a number of side effects including irritability, significant weight gain, constipation, drowsiness and memory loss.

After I stopped it, my memory improved though I have some forgetfulness. I still take amitriptyline occasionally for migraines. Wearing a mask at work seems to make me more susceptible. I take it on an as-needed basis rather than daily, but I wish there were something else for migraines. The options for actual relief are limited for anyone who has to work, as I do.

A. Amitriptyline interferes with a crucial neurochemical called acetylcholine. That might explain your memory difficulties.

You might want to ask your doctor about a new class of migraine medicines used for prevention. They include erenumab (Aimovig), fremanezumab (Ajovy) and galcanezumab (Emgality). To learn more about treatments for head pain, you may wish to consult our eGuide to Headaches & Migraines. This electronic resource can be found under the Health eGuides tab of this website.

There are also a number of nondrug approaches that might be helpful. Ask your doctor about supplements such as magnesium, riboflavin, feverfew or butterbur.

Some studies report that acupuncture can be beneficial. A systematic review of this approach concludes that:

“The beneficial effects of acupuncture for migraine have been widely recognized. Acupuncture not only reduces pain intensity of acute migraine attacks, but also prevents migraine by reducing the frequency of migraine attacks, acute relief medication intake, and pain intensity” (Frontiers in Neuroscience, May 20, 2021).

Do NOT Stop Antidepressant Amitriptyline Suddenly!

Stopping amitriptyline or other antidepressants can trigger withdrawal symptoms (European Journal of Pharmacology, June 15, 2018). This has not been well researched, but we believe this is an under appreciated complication of the antidepressant amitriptyline. You may need many weeks or months of gradual dose reduction to taper off such medications.

A sleep specialist may be able to help you with nondrug sleep approaches such as progressive muscle relaxation and cognitive behavioral therapy for insomnia.

Reader Comments?

What has been your experience with amitriptyline or other anticholinergic medications.

One of our readers insists that:

“No one has found evidence that anticholinergic drugs cause dementia. I could do a study of dementia patients and show a link between aspirin, fiber cereal, denture paste or peanut butter. That doesn’t mean any of those things CAUSE dementia. Can anticholinergics cause drowsiness, short term memory loss, fuzzy brain when you take them? Absolutely. But alcohol, marijuana and sleep deprivation from chronic pain do too.”

Share your own thoughts in the comment section below.

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About the Author
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.”.
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