12 Medications That Can Lower the Seizure Threshold

We often associate seizures with epilepsy — a brain disorder that causes seizures. People with epilepsy experience repeated, unprovoked seizures. But you may be surprised to learn that not everyone that experiences a seizure has epilepsy. In fact, seizures can have other causes, like fever, trauma, and certain medications.

Your “seizure threshold” refers to how likely you are to have a seizure. A lower seizure threshold means a higher risk for experiencing a seizure. Taking certain medications can lower your seizure threshold. 

Below, we discuss medications known to lower the seizure threshold. We’ll also cover seizure symptoms you should watch for if you’re taking these medications. 

Which medications can lower your seizure threshold?

Numerous medications are thought to lower your seizure threshold. Below are a few common examples. 

1. Bupropion

Bupropion is an antidepressant used to treat major depressive disorder (MDD) and seasonal affective disorder (SAD). It’s also available as Zyban, a medication used for smoking cessation. Bupropion is available as immediate-release (IR), sustained-release (SR), and extended-release (XL) forms.

Seizure risk is thought to go up with higher doses of bupropion. And this risk may be more likely with the IR form. Because of this, the dosage is raised slowly over time, not to exceed the maximum daily amount. The maximum daily dose is 450 mg (IR), 400 mg (SR), or 300 mg (XL).

Bupropion shouldn’t be prescribed to people at higher risk for seizures. This includes people with epilepsy, a current or prior eating disorder, or those abruptly stopping alcohol or certain medications.

2. Tricyclic antidepressants

Tricyclic antidepressants (TCAs) are antidepressants used to treat conditions like MDD. Examples include amitriptyline and imipramine (Tofranil). 

It’s believed that TCAs can cause seizures due to how they affect certain brain chemicals. TCAs can lower the seizure threshold when used at higher doses. So, the dosage is started low and raised slowly over time.

3. Antipsychotic medications

Antipsychotics medications are used to treat mental health and psychological conditions, like schizophrenia. They’re broken up into two categories: typical and atypical antipsychotics. Both groups can lower the seizure threshold. It’s believed that this is due to how they affect certain chemicals in the brain. 

Seizures are more likely to happen with atypical antipsychotics. Clozapine (Clozaril) is an atypical antipsychotic most closely linked to lowering the seizure threshold. Because of this, clozapine is used cautiously in people with a history of seizures. 

Seizure risk appears to go up with higher doses of clozapine. Like the above medications, the dosage is raised slowly over time to manage this risk. 

4. Stimulants

Stimulants are medications used to treat attention deficit-hyperactivity disorder (ADHD). Examples include amphetamine salt combo (Adderall) and methylphenidate (Ritalin). 

Stimulants have been thought to worsen seizures in people with epilepsy. But recent data suggests this may not actually be the case. Even so, tell your healthcare provider if you’ve had seizures in the past before starting a stimulant. 

5. Cyclobenzaprine

Cyclobenzaprine is a muscle relaxant that’s very similar to TCAs. Because of this, it can also lower the seizure threshold. This is especially the case with higher doses. Cyclobenzaprine is also known to cause seizures in cases of overdose, specifically with doses above 1,000 mg. This is far above the maximum total daily dose of 30 mg.

6. Cyclosporine

Cyclosporine (Sandimmune) is used to help prevent solid organ transplant rejection. Drug-resistant epilepsy (DRE) has been reported with use, usually in children. DRE is when you can’t become or stay seizure-free after trying two seizure medications.

7. Carbamazepine

Carbamazepine (Tegretol) is a medication used to treat seizures. But it has been found to worsen seizures in some people with certain seizure disorders. 

Carbamazepine can also cause seizures if you suddenly stop taking the medication. Take it exactly as directed by your healthcare provider. Don’t stop taking it unless they tell you to. They can help slowly lower your dose over time to help prevent withdrawal seizures.

8. Diphenhydramine

Diphenhydramine (Benadryl) is an over-the-counter (OTC) antihistamine. It’s used to treat allergies, cold symptoms, and sleeping problems. It can potentially worsen seizures in people with epilepsy or cause a first-time seizure.

9. Methotrexate

Methotrexate (Trexall) is used to treat rheumatoid arthritis, psoriatic arthritis, and some cancers. Although rare, it can cause nerve cell damage, resulting in seizures. This risk can depend on your dose.

10. Opioids

Opioids are medications used to treat pain. They can lower the seizure threshold to varying degrees. Tramadol (Ultram), in particular, has been linked to a risk of seizures.

11. Tacrolimus

Tacrolimus (Prograf) is used to help prevent solid organ transplant rejection. It can cause neurological effects, including seizures. This can depend on the amount of tacrolimus in your body. That’s why it’s important to get all of the recommended blood tests while taking tacrolimus. 

12. Theophylline

Theophylline is used to treat asthma and chronic obstructive pulmonary disease (COPD). It can worsen seizures in people with seizure disorders.

Can these medications trigger seizures even if you’ve never experienced one before?

It depends. Some of these medications may trigger seizures, even if you’ve never experienced one before. But for others, this risk is extremely low.

Seizure risk from medications can also depend on other medical conditions you have. Examples of medical conditions that can raise the risk of seizures include:

• Eating disorders like anorexia

• Brain tumor

• Head trauma

• History of stroke

What symptoms should you watch for if you’re taking these medications?

If you’re taking these medications, it’s important to know about seizure symptoms. Some people experience what’s known as aura before a seizure. An aura can cause symptoms like nausea and a change in sensations. Although it’s considered a seizure, an aura can serve as a warning.

Other symptoms of a seizure can include:

• Difficulty speaking or breathing

• Fast, jerky body movements

• Feeling confused

• Hallucinations (seeing or hearing things that aren’t actually there)

• Losing consciousness

• Numbness, tingling, or an “electric shock”-like sensation in your body

• Repetitive eye blinking

• Stiff, rigid muscles

• Vision changes, such as blurry vision or seeing spots

Contact your healthcare provider right away if you experience any of the above symptoms while taking these medications. 

If you’re taking these medications, what can you do to lower your seizure risk?

If you’re taking a medication that lowers seizure threshold, it’s best to avoid alcohol or drink in moderation. Alcohol usually doesn’t trigger seizures when consumed in small amounts on its own. But having three or more drinks can significantly raise this risk. Your healthcare provider can tell you how much alcohol is safe for you to drink.

It’s also important to tell your healthcare provider and pharmacist about all medications you take. This includes OTC medications and dietary supplements. They can check for potential interactions that can raise your seizure risk. In some cases, your dose may need to be adjusted or you may be switched to a safer option.

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Written by:

Alex Brewer, PharmD, MBA

Alex Brewer, PharmD, MBA, is a licensed pharmacist specializing in chronic disease and health and wellness. Upon completing his residency, he worked in the managed care field, conducting medication therapy management and adherence counseling sessions with Medicaid, Medicare, and private insurance patients, before transitioning to a career in medical writing.

Edited by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

Reviewed by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

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