A Rare Case of Status Epilepticus in a Patient Prescribed CBD

This transcript has been edited for clarity.

Andrew N. Wilner, MD: Welcome to Medscape. I'm Dr Andrew Wilner reporting on the recent, virtually held American Epilepsy Society meeting.

With me today is Dr Charles Szabo, professor and chief of epilepsy at the University of Texas Health Science Center at San Antonio. Dr Szabo presented a very interesting case at this year's meeting about a patient on cannabidiol (CBD) adjunctive therapy. Welcome, Dr Szabo.

Charles A. Szabo, MD: Thank you very much for inviting me.

Wilner: Tell us about your case report.

Szabo: It's about a patient with a history of epilepsy since he was 7 years old. When we reported on him, he was 63 years old. His seizures had been very well controlled for a long time. He had mainly tonic and myoclonic seizures, often in his sleep or just upon awakening, and at times during the day too.

Suddenly, when he was 57 or 58, without any clear reason or cause, his seizures started to recur more frequently. He started having more serious seizures, such as convulsive seizures.

This prompted us to try different medications. We went through a number of different options before ending up with a very unusual regimen, even for epileptologists, consisting of tiagabine, perampanel, levetiracetam, lacosamide, and clonazepam.

He did quite well with that regimen, with maybe two to three seizures a month. He was happy but wished to get back to driving. He has a son, was a real estate agent at one point, and really wanted to become a little bit more independent and not mainly stuck in his house.

He was very interested in trying CBD. At first, we weren't able to prescribe him Epidiolex owing to the limited indications from the insurance companies. Instead, we started him on a CBD preparation that was permitted by the Texas Compassionate Use Act. At that time, this was allowed to be prescribed for people only with medically refractory epilepsy.

We got him on this regimen initially, and he was pleased because his seizures went down to maybe one per month, although he was a little bit tired and lethargic. We started looking into some of the interactions and decided to lower one of his medicines, perampanel, and that helped.

However, there was an unusual development at one point. During a dinner party, he became confused and had myoclonic twitches for about 20-30 minutes. His wife had never seen him experience something like this.

We didn't have an explanation for why this was happening. But because he had such a good response to the CBD, we decided to continue with that treatment. He was then able to qualify for the Epidiolex, so we started him on that, titrating him over a course of 1-2 months to a dose of 20 mg/kg.

Initially, he felt there was an improvement of his seizures. But then every week or 2 weeks, he started having these unusual episodes that were similar to what he experienced at the dinner party, however always during the daytime, usually late in the morning. These episodes lasted not only 30 minutes but sometimes a few hours. He was very confused. Sometimes he was responsive, sometimes he wasn't. He occasionally exhibited some unusual motor behaviors. He was really amnesic for the entire episode and usually very tired afterward and required sleep.

When we heard about this, we weren't sure what was happening or whether this was a side effect. But he wasn't hurting or injuring himself. He was in a safe situation. We discussed with his wife that if he has any more of these episodes, she should bring him to the hospital so we could find out what these were.

When we admitted him, that's when we found via EEG that he had nonconvulsive status epilepticus. Of course, we treated that at that point, but we also withdrew the Epidiolex. Since then, he hasn't had another of these episodes.

The big question in our abstract was whether this was due to the Epidiolex or potentially to interactions with other medications.

A Side Effect or an Interaction?

Wilner: And what's the answer?

Szabo: We don't have the answer yet. We haven't seen any other similar reports of de novo nonconvulsive status epilepticus in a patient taking CBD.

The clinical studies of this medication were mainly looking at people with Lennox-Gastaut syndrome and Dravet syndrome. There were a number of patients who had to be withdrawn from the study because they developed status epilepticus. But of course, these are very severe neurologic diseases where people tend to have status epilepticus. It wasn't necessarily a de novo episode. But CBD has been seen to potentially aggravate seizures in some cases.

However, this case was a patient with a focal epilepsy and no known genetic disorder. He responded with a totally new type of seizure, which is what we think is interesting about it.

The larger point is that many patients seek to start CBD because they feel it's a natural product and therefore must be good for you. I think this abstract points out that one has to be aware not only of CBD side effects but also the interactions with other medications, of which there are quite a few.

Wilner: Your paper attracted my attention because I participated years ago in the development of tiagabine and had a patient who developed nonconvulsive status epilepticus. I was totally perplexed at the time. I still remember having him in the examining room, and him just being kind of spacey. We see that a lot, usually from drug toxicity, and at the time, tiagabine was a brand-new drug. This led us to assume that the patient was maybe taking too much, but we didn't know.

So, we brought him into the hospital for epilepsy monitoring. Sure enough, this showed nonconvulsive status epilepticus. That was a new thing at the time, but now it's well known that tiagabine can have that effect.

I noticed that your patient was also on tiagabine and thought perhaps that's what pointed you in that direction to take a closer look at this patient.

Considerations When Prescribing CBD

Wilner: Before we wrap up, can you clarify when we should we be considering CBD? In which indications is it approved by the US Food and Drug Administration?

Szabo: The specific FDA-approved product is Epidiolex, which has an indication in Lennox-Gastaut syndrome and also for Dravet syndrome for patients 2 years of age or older. It's basically used as an adjunctive therapy.

But it's interesting the way the indication is phrased, which is for seizures related to these syndromes, and these seizures could also include focal seizures. Of course, insurance companies read this perhaps a little bit more narrowly. That's been a little bit of a challenge to get people on this medication.

It was really very efficacious in the studies as an adjunctive therapy for people with Lennox-Gastaut syndrome and Dravet syndrome, producing, I believe, seizure reduction of approximately 40% in both of those indications.

But there are side effects. I think one of the biggest issues is that there are a number of medication-medication interactions. CBD actually blocks or inhibits a number of the CYP450 enzymes, some of which are important, for example, in metabolizing tiagabine, topiramate, or other medications. It's crucial to know those type of interactions when you're starting this medication.

Just because CBD is natural doesn't mean that it's always safe. There are a number of other side effects to pay attention to, such as hepatotoxicity, especially when you're combining it with medications like valproic acid or clobazam.

These are all the things that one has to sort of pay attention to when you start a patient on this medicine.

Wilner: I'm sure you're going to continue to follow this patient, so maybe we'll have an update at some point. He may tell you that he wants to try it again. We'll see what happens.

I'd like to thank you for sharing this paper with Medscape.

Szabo: Thank you very much.

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