Even though he was diagnosed with epilepsy at 11, John Knecht, now in his 50s, says he was in denial about his illness for years. Even so, when Knecht got the diagnosis as a child, he began taking anti-epileptic drugs to treat seizures.
His sister, Julie Lindroth, who also has epilepsy, had grand mal seizures, the type that cause violent muscle contractions throughout the body. At first, Knecht experienced only absence seizures, which are brief lapses in consciousness. These seizures don’t cause the type of dramatic physical symptoms that are common in grand mal seizures. During an absence seizure, it often may appear as though the person has just “zoned out,” or become inattentive, for a time. Those with epilepsy may not even realize when they have had an absence seizure. Knecht’s mother, friends and even college roommates could identify when he was having one, but he often could not. At 30, he experienced his first grand mal seizure.
Today, Knecht controls his seizures with a mixture of anti-epileptic medications, like many patients with epilepsy do. Over the years, with the help of several doctors, he has gone through a variety of drugs in different combinations and has had to use trial and error to find a combination that balances the goals of minimizing both the seizures and the drugs’ side effects.
When Knecht was a child, there weren’t many anti-seizure drugs. Now, there are more than 20.
At the initial epilepsy diagnosis, physicians usually start patients on just one drug. If the patient continues having seizures, the doctor will likely suggest combinations of multiple anti-epileptic drugs. “You’ve got to find a cocktail for each person to make it work, because not all the people react the same,” says Knecht.
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Side Effects of Anti-Epileptic Drugs
There are two main categories of anti-epileptic drugs: narrow-spectrum ones that treat a few specific types of seizures, like partial seizures, and broad-spectrum ones that can treat both partial seizures and grand mal or myoclonic seizures (those characterized by muscle contractions during which a patient remains conscious). Most of the drugs use similar mechanisms to decrease brain activity that leads to seizures and have similar side effects. When a doctor is choosing a drug or combination of drugs, that decision is often based on the type of seizure the patient is experiencing, the side effects that he or she needs to avoid, the doctor’s clinical experience and, lastly, the cost.
| Narrow-Spectrum AEDs: | Broad-Spectrum AEDs: |
| – phenytoin (Dilantin) | – valproic acid (Depakote) |
| – phenobarbital | – lamotrigine (Lamictal) |
| – carbamazepine (Tegretol) | – topiramate (Topamax) |
| – oxcarbazepine (Trileptal) | – zonisamide (Zonegran) |
| – gabapentin (Neurontin) | – levetiracetam (Keppra) |
| – pregabalin (Lyrica) | – clonazepam (Klonopin) |
| – lacosamide (Vimpat) | – rufinamide (Banzel |
| – vigabatrin (Sabril) |
Most side effects of anti-epileptic drugs are cognitive, agree two epilepsy specialists. The drugs reduce alertness, concentration and memory say Amanda Spinner, MD, a pediatric neurology resident physician who treats children with epilepsy at the University Hospitals of Cleveland, and Thomas Perry, MD, who has worked with epilepsy patients at the University of British Columbia and specializes in de-prescribing, which reduces the number of drugs a patient is on to possibly improve his or her quality of life. Knecht says that his side effects haven’t always been obvious, but that “when I was taking anti-epileptic drugs in high school, I slept a majority of the time.”
And more recently, Knecht has found that reading leads to exhaustion. “In reading Dr. Seuss to my son [at bedtime], I fell asleep before he did.” For Knecht, finding a doctor he trusted and could be open with was key. At one point, he took 13 different drugs simultaneously and worked with two neurologists who were not in regular contact with each other. He now has an epileptic specialist with a doctorate in pharmaceutical studies. “Ever since I’ve had him,” adds Knecht, “I have never had an issue because, essentially, we found the right cocktail.”
The new doctor has helped reduce Knecht’s medications, so he takes only three drugs now.
Lindroth, however, has gone through several treatments but has continued to struggle with side effects. “I had all sorts of bad reactions,” she says, including a severe learning disability in math that persists today. She attributes that disability to having taken phenobarbital as a child. One drug she took only briefly, she says, impaired her to the point that she appeared drunk at her son’s school performance.
Both epilepsy and the drugs used to treat it can interfere with pregnancy, and vice versa. Pregnancy can alter the frequency of seizures, and seizures can lead to birth defects such as fetal injury and preterm birth. Anti-epileptic medications, on the other hand, can also cause birth defects such as cleft palate, neural tube defects, skeletal abnormalities, and congenital heart and urinary tract defects. Sanofi, the manufacturer of valproate, marketed in France as Depakine, has been indicted for failure to inform the public about the potential harm of using the drug while pregnant. Regulators there linked the drug to over 400 birth defects or stillborn births.
Still, many women with epilepsy conceive healthy babies. It’s crucial to evaluate the risks of the illness and medications with a healthcare provider, who might wean women off of medications if their seizures are rare, or prescribe higher doses of folic acid than pregnant women typically take to help prevent neural tube defects.
Toxicity: What Causes It?
There’s a difference between day-to-day side effects and dangerous toxicities, though it’s not always easy to discern. An emergency develops when a person has been prescribed too high a dose of anti-epileptic drug; over time, the amount of the drug in their system will build up faster than it can be processed. This happened to one of Perry’s neighbors, a child who was taking Dilantin. At first, the child was doing well. After a few weeks, his mother told Perry, “He just seems to be off-balance all the time. I don’t know what’s wrong with him.” Some patients with toxicity may also appear drunk, their eyes may move uncontrollably and their body may jerk.
Once an individual reaches the point of toxicity, explains Perry, it takes time to get the drug out of their system. The body’s response is similar to when a person drinks too much alcohol, he says. The person gets to a point where she or he has had more alcohol than the liver can process and is going to be drunk until the liver catches up.
Similarly, if a patient has a kidney impairment, the body can’t process anti-epileptic drugs quickly, and he or she will need a markedly reduced dose to avoid toxicity.
If you experience toxicity, you should go to a hospital right away. Some research suggests that toxicity is more common when you’re using “first-generation anti-epileptic drugs,” such as carbamazepine, ethosuximide, phenobarbital, phenytoin, primidone and valproic acid. Newer drugs, which are less likely to cause toxicity, are felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, tiagabine, topiramate, vigabatrin and zonisamide.
How to Recognize Side Effects
Often when we experience side effects from drugs, we notice them. However, that isn’t always the case with anti-epileptic drugs. People may not associate sleepiness, irritability and other issues with these treatments, or even realize anything is different. Perry suggests taking a video of yourself talking and walking before you begin treatment. That way, you, your doctor and others can use it to help identify any behavioral changes that may be caused by the drugs.
“The most common adverse effects that people experience is that they don’t realize what the drug is doing to them. They may be impaired, but they don’t put it together,” says Perry. You can’t always count on your neurologist to pick up on mood or energy changes during regular visits. That’s why it’s so important to be vigilant, take notice of any new trends and discuss them openly with your physician.
What About Adjuvant Therapies, Lifestyle Modifications and Surgical Alternatives to Drugs?
Nausea is a common side effect of many anti-epileptic drugs. One of the first strategies that Spinner suggests is taking the drugs with food. If that doesn’t work, she may prescribe another drug.
For cognitive problems, Spinner says that she sometimes prescribes vitamin B-6. One study suggested that the vitamin helped alleviate behavioral problems in 40% of children taking anti-epileptic drugs. In another, patients who took the vitamin alleviated their cognitive side effects enough that they were able to continue using their anti-epileptic drug regimen.
Sometimes people can identify specific stimuli that trigger their seizures, like flashing lights, sounds, lack of sleep, drinking alcohol, illness or stress. These triggers vary widely between individuals, so it’s best to keep a journal of each seizure and look for similarities to help you avoid future prompts and minimize seizures. It may be as simple as avoiding parties with strobe lights or a more long-term approach, such as seeking therapeutic counseling to learn how to manage stress and avoid emotional catalysts.
The Role of Diet
When Lindroth was a teenager, her neurologist believed she had grown out of her epilepsy, and weaned her off the treatments. She had been seizure-free for over 15 years, when she became pregnant with her first child. Then her seizures returned. The neurologist tried drug after drug, but Lindroth says, “I’m allergic to almost everything.” Then, she was diagnosed with Celiac disease—a condition in which gluten, a protein found in many wheat products like bread, damages the small intestine. The main treatment is a gluten-free diet. Lindroth found that the diet also seemed to prevent her seizures. Later, her nurse practitioner suggested she follow a ketogenic diet.
Many patients find that following a strict ketogenic diet can help control seizures. A ketogenic diet is high in fat and extremely low in carbohydrates. This diet prompts the body to go into ketosis, a state in which it burns fat instead of carbohydrates for energy. “At that point, that was the best thing for me,” Lindroth says.
When Drugs Don’t Work
Anti-epileptic drugs are the first line of treatment to prevent seizures. If, after years of testing different drug combinations, your seizures remain uncontrolled, your doctor might consider discussing vagus nerve stimulation or surgery.
The vagus nerves run through the body and send messages to the brain. To treat epilepsy, a surgeon places a small stimulator in the upper chest, similar to a pacemaker. The stimulator sends electrical impulses to the vagus nerve, which helps calm brain activity. The treatment is often used in conjunction with anti-epileptic drugs rather than as a replacement for them.
Additionally, two types of brain surgery exist that may lessen epilepsy’s symptoms. However, any brain surgery is risky and has the potential to cause serious side effects.
The first involves a neurologist using imaging to locate the brain region from which the seizures are originating. After that, a surgeon removes that chunk of brain tissue. In the second, a surgeon splits the right and left sides of the brain by slicing it down the middle. There is a thin band of fibers that connects the two sides. This second type of surgery prevents seizures from spreading from one side to the other. Just as with vagus nerve stimulation, many patients may still take anti-epileptic drugs after the surgery.
Perry emphasizes that there are significant barriers to reducing reliance on anti-epileptic medications. Discontinuing anti-epileptics increases the risk of dangerous seizures. If a person is seizure-free long enough to get a driver’s license, he or she may lose it if a seizure occurs after reducing or discontinuing the drugs. Lindroth only drives short distances, and when weaning off treatments she’s had to stop driving for a month at a time.
“What if I persuaded a patient [to decrease the drugs’ dose] and then she has a seizure?” asks Perry. “You get taken to the emergency [room]. People will say, ‘What an idiot. He always thinks he knows better than other doctors. He’s always trying to cut back on drugs. And now look what’s happened.’ There’s there no possible reward for the doctor [who] would be willing to take that chance. And if you’re the patient who takes the chance, maybe you’re going to lose your driver’s license. Not only does she have seizures, but she’s noncompliant. She doesn’t listen to good advice. So there’s this huge barrier [to de-prescribing] with seizures.”
It is crucial to work through any issues with your healthcare provider, to make sure that you minimize the chances of potentially dangerous seizures caused by reducing or stopping medications. About his current doctor, Knecht says “I see him religiously and we talk openly and quite honestly. I think that’s key [when] having epilepsy.”
