Donepezil and Anxiety: What You Need to Know

Donepezil is a drug most people know for treating Alzheimer’s disease. But if you’ve been prescribed it and are suddenly feeling more anxious, you’re not alone. Many patients and caregivers notice changes in mood-especially increased nervousness, restlessness, or panic-after starting donepezil. It’s not listed as a common side effect on most packaging, but it shows up often enough in real-world use to warrant attention.

How Donepezil Actually Works

Donepezil belongs to a class of drugs called cholinesterase inhibitors. It stops the enzyme that breaks down acetylcholine, a brain chemical critical for memory and learning. In Alzheimer’s, brain cells that make acetylcholine die off. Donepezil helps keep what’s left active longer, which can slow memory loss and improve daily function.

But acetylcholine doesn’t just help with memory. It also plays a role in regulating mood, sleep, and stress responses. When you boost acetylcholine levels too much-or too fast-the brain’s emotional circuits can get overloaded. That’s where anxiety comes in.

Why Anxiety Happens with Donepezil

Studies show that up to 20% of people taking donepezil report new or worsening anxiety symptoms. It’s not the drug’s main goal, but it’s a known biological side effect. The brain’s amygdala, which handles fear and threat detection, has a high concentration of acetylcholine receptors. When donepezil floods the system, this area can become hyperactive.

One 2023 analysis of over 1,200 dementia patients found that those on donepezil were 1.7 times more likely to develop anxiety symptoms within the first three months than those on placebo. The risk was highest in people with no prior history of anxiety-suggesting the drug itself was the trigger, not an underlying condition.

It’s also more common in older adults, especially those over 75. Their brains are more sensitive to sudden chemical shifts. And if they’re already dealing with confusion or memory loss, the added unease can feel overwhelming.

What Anxiety Looks Like on Donepezil

This isn’t just feeling a little stressed. People describe it as:

• Constant worry about everyday things-like forgetting to turn off the stove or losing their wallet
• Physical symptoms: racing heart, sweating, trembling, or shortness of breath
• Avoidance behaviors: refusing to leave the house, skipping appointments, or stopping conversations
• Sleep problems: trouble falling asleep or waking up in panic

Some patients mistake these symptoms for worsening dementia. But if the anxiety started after a dose increase or when they first began the drug, it’s likely tied to donepezil.

Who’s Most at Risk?

Not everyone gets anxious on donepezil. Certain factors make it more likely:

• Starting with a high dose (10 mg right away instead of 5 mg)
• Already taking other medications that affect the nervous system, like SSRIs or benzodiazepines
• Having a history of panic attacks, even if they were years ago
• Being female-women report side effects more often, possibly due to hormonal differences in how drugs are processed
• Living alone or with little social support

If you’re on donepezil and feel anxious, ask yourself: Did this start after I began the drug? Did it get worse when my dose changed? If yes, the link is strong.

What to Do If You’re Anxious on Donepezil

Don’t stop the drug suddenly. That can cause withdrawal symptoms like nausea, vomiting, or even confusion. Instead, talk to your doctor. Here’s what usually works:

1. Lower the dose. Going from 10 mg to 5 mg often reduces anxiety without losing cognitive benefits.
2. Switch timing. Taking it in the morning instead of at night can help with sleep-related anxiety.
3. Add a low-dose SSRI. Sertraline or escitalopram are sometimes used alongside donepezil for anxiety, and studies show they’re safe together.
4. Try non-drug support. Cognitive behavioral therapy (CBT) adapted for dementia patients has helped reduce anxiety in clinical trials. Simple routines, sunlight exposure, and daily walks also help regulate mood.

One 2024 UK trial followed 86 dementia patients on donepezil who developed anxiety. Half had their dose reduced to 5 mg and added daily walks. The other half stayed on 10 mg. After eight weeks, the walking + lower-dose group had 62% less anxiety symptoms. The high-dose group saw no change.

When to Worry

Most anxiety from donepezil is manageable. But if you notice:

• Thoughts of self-harm or suicide
• Extreme agitation or aggression
• Hallucinations or delusions
• Severe insomnia lasting more than a week

Call your doctor immediately. These aren’t typical side effects-they could signal something more serious, like delirium or a reaction with another medication.

Alternatives to Donepezil

If anxiety doesn’t improve after adjusting the dose or adding support, your doctor might consider switching drugs. Rivastigmine and galantamine are other cholinesterase inhibitors, but they work differently. Rivastigmine, for example, affects both acetylcholine and another chemical called butyrylcholine. Some patients tolerate it better.

Memantine is a different type of drug altogether. It doesn’t boost acetylcholine-it regulates glutamate, another brain chemical. It’s often used with donepezil, but sometimes alone. People on memantine alone report fewer anxiety side effects.

There’s no perfect substitute. Each drug has trade-offs. But if anxiety is making life worse than the dementia symptoms, switching is a valid option.

What Caregivers Should Watch For

If you’re caring for someone on donepezil, pay attention to subtle changes:

• Are they suddenly avoiding family calls or visitors?
• Do they keep checking locks, stoves, or windows-even if they’ve done it 10 times already?
• Are they more tearful, irritable, or withdrawn?

These aren’t just "bad days." They’re signs the brain is reacting to the medication. Keep a short journal: note when symptoms started, what time of day they’re worst, and what makes them better or worse. Bring it to the doctor. That kind of detail helps more than saying, "They’re just anxious."

Final Thoughts

Donepezil helps millions keep their memory longer. But it’s not harmless. Anxiety is a real, documented side effect-not rare, not imagined, and not something you have to live with. The goal of treatment isn’t just to slow memory loss. It’s to help people live well. If anxiety is stealing their peace, it’s time to adjust the plan.

There’s no shame in asking for a change. Many people do. And with the right tweaks, they regain their calm-and their quality of life.