Seizure disorders can have many causes. In some cases, a drug or substance may trigger unusual bursts of electrical activity in the brain, leading to a seizure as a side effect or complication. Up to 9 percent of cases of status epilepticus (a seizure that lasts more than five minutes) are linked to a drug or toxic substance.

Drug-induced seizures are not the same as epilepsy — without the drug, the person wouldn’t have had a seizure. Some medications and substances can also lower the seizure threshold. This makes it more likely that someone who already has a seizure disorder, such as epilepsy, will experience a seizure. These drugs include certain prescription medications, over-the-counter (OTC) products, and illicit substances used for nonmedical or recreational purposes.

Read on to learn which medications and substances can increase the risk of seizures — and what to watch out for.

Prescription Drugs and Seizures

Many prescription medications have the potential to cause seizures. In fact, they are one of the leading causes of drug-induced seizures. These seizures can happen even in people with no history of epilepsy or prior seizures.

Most drug-induced seizures don’t cause long-term harm, but repeated or severe seizures may lead to more serious complications.

The U.S. Food and Drug Administration (FDA) tracks serious side effects through its Adverse Event Reporting System (FAERS), which helps identify medications that may be linked to seizures. One study of calls to a poison control center in California found that the prescription drugs most commonly associated with seizures were antidepressants, pain medications, and antibiotics.

In one study, the prescription drugs most commonly associated with seizures were antidepressants, pain medications, and antibiotics.

Below, we’ll look at some of the prescription drug categories most often linked to seizures.

Antidepressants

Antidepressants are medications commonly prescribed to treat mental health conditions such as depression and anxiety. Between 20 percent and 55 percent of people living with epilepsy also experience depression, so it’s important to understand how antidepressants may affect seizure risk.

The risk of seizures can vary depending on the type of antidepressant and the dose. Some antidepressants are linked to a higher risk of seizures, especially at higher doses.

Antidepressants with the highest risk of seizures include:

• Bupropion
• Tricyclic antidepressants, such as amitriptyline, clomipramine, and doxepin
• Venlafaxine

Selective serotonin reuptake inhibitors (SSRIs) — like sertraline and fluoxetine — are considered the safest type of antidepressants for people with epilepsy.

Antipsychotic Drugs

Antipsychotics are prescribed to help manage mental health conditions such as schizophrenia, bipolar disorder, and depression. While many newer antipsychotics have a low or moderate risk of triggering seizures, some are more strongly linked to an increased risk.

Clozapine is the antipsychotic most associated with seizures and carries a boxed warning from the FDA for this side effect. The risk increases at higher doses. Other risk factors include:

• Being younger
• Starting at a higher dose or increasing the dose quickly
• Taking clozapine with certain other medications — such as lithium

Research has found that several antipsychotics aren’t associated with a higher risk of seizures, including:

• Aripiprazole
• Risperidone
• Ziprasidone

ADHD Medications

Stimulant medications commonly used to treat attention-deficit/hyperactivity disorder (ADHD) — such as amphetamine and methylphenidate — have been associated with seizure risk in the past. However, more recent research suggests the risk may be lower than once believed.

One study found that people with epilepsy who started a stimulant medication had a lower risk of seizures. Research also shows that children with ADHD may be more likely to have seizures than those without ADHD, regardless of whether they’re taking medication. This means the underlying condition, not the treatment, may play a bigger role in seizure risk.

Pain Medications

Tramadol, a prescription opioid used to treat pain, is linked to a higher risk of seizures in people of all ages. In the study of calls to the California poison control center, tramadol was involved in 7.5 percent of drug-related seizure cases. Additionally, between 1997 and 2017, the FDA received 30,730 reports of adverse reactions to tramadol, and 7 percent of those reports involved seizures.

Seizures can occur even when tramadol is taken at the prescribed dose, but the risk increases with higher doses. Research shows that seizures are reported in more than half of all tramadol overdose cases.

Antibiotics

Although rare, seizures can sometimes occur as a side effect of certain antibiotics. These include:

• Cephalosporin
• Ciprofloxacin
• Imipenem
• Isoniazid
• Levofloxacin
• Penicillin

These medications can interfere with neurotransmitters (brain chemicals) that normally help control nerve signals. People with a history of seizures, liver or kidney disease, or other brain conditions may have a higher risk of seizures when taking these antibiotics.

Most seizures related to antibiotics resolve on their own and don’t require long-term treatment.

Prescription Withdrawal and Seizures

In some cases, withdrawing from a prescription medication — especially suddenly — can trigger seizures. In the California poison control study, 2.1 percent of drug-related seizures were linked to sedative withdrawal.

Benzodiazepines, which are used to treat conditions like anxiety disorders, are a type of sedative medication known to be associated with withdrawal-induced seizures.

Benzodiazepines are also commonly used as the first-line treatment for drug‐induced seizures. Neurology research shows they boost the effectiveness of a brain chemical called gamma-aminobutyric acid (GABA), which helps calm excessive electrical activity in the brain and stop seizures.

When someone suddenly stops taking benzodiazepines, GABA’s calming effects are reduced, leading to more brain activity, which can increase the risk of seizures.

Over-the-Counter Drugs and Seizures

Some over-the-counter medications have been linked to seizures. According to the Epilepsy Foundation, the most commonly associated OTC drug is diphenhydramine, an antihistamine found in many allergy, sleep, and cough-and-cold products.

In the California poison control study, diphenhydramine was involved in 8.3 percent of the drug-induced seizure cases. Other common ingredients in cold medicines, including pseudoephedrine and dextromethorphan, may also lower the seizure threshold, making seizures more likely in some people.

Certain over-the-counter drugs, including some found in products for cough, cold, allergies, and heartburn, can raise the risk of seizures.

Some OTC medications used for heartburn or gastroesophageal reflux disease (GERD) may affect how anti-seizure drugs work in the body by changing their levels in the bloodstream. Always check with your healthcare provider or pharmacist to make sure the OTC products you choose don’t have a drug interaction with your current medications.

Read about what to do if you vomit your seizure medication.

Illicit Drugs and Seizures

Many illegal or recreational drugs are associated with seizures. In the California poison control study:

• Amphetamines (such as methamphetamine, or meth) made up 6.9 percent of drug-induced seizure cases.
• MDMA (also known as ecstasy or molly) made up 3.4 percent.
• Cocaine made up 4.9 percent.

The use of synthetic cannabinoids known as “spice” has also been linked to seizures.

Many illicit and recreational drugs are associated with seizures.

Alcohol Use and Seizures

Although alcohol isn’t a drug, alcohol use — especially heavy or long-term use — can affect brain activity and increase the risk of seizures. Seizures may occur during alcohol withdrawal or, in some cases, while someone is intoxicated. According to the Epilepsy Foundation, alcohol-related seizures can include serious complications such as status epilepticus, a medical emergency involving prolonged or repeated seizures.

Staying Safe With Epilepsy

Knowing which drugs, medications, and other substances could make your seizures more likely to occur can help you stay safe when you have epilepsy. Ask your neurologist or pharmacist about the potential side effects and risks before taking any new medication or OTC drug.

Find out ways to participate in Epilepsy Awareness Month in November.

Join the Conversation

On MyEpilepsyTeam, people share their experiences with epilepsy, get advice, and find support from others who understand.

Have you or a loved one had a drug-induced seizure? Let others know in the comments below.