Common Seizure Medications – Seizure Treatment

00:01 So let's talk through some of the more common seizure medications that we use clinically, and that you'll see on a clinical vignette.

00:08 And we'll discuss the key points, the dosing considerations, some of the side effects, and clinical pearls for using that agent.

00:15 We'll start with phenytoin.

00:17 This is one of our older seizure medicines.

00:19 It's been around for a long time. It's used commonly in the clinic.

00:22 And we know a lot about it.

00:24 It's an old agent. It's an enzyme inducer, it's a hepatic inducer as with our other older anti-epileptics.

00:31 Carbamazepine and phenobarbital it induces the metabolism of other medications.

00:36 And so we can see the lower drug levels of medicines that are metabolized hepatically.

00:41 And it is highly protein bound, which means it'll have drug-drug interactions with other selected agents.

00:48 When we're loading this medicine, and specifically when we're treating status epilepticus the loading formulation is fosphenytoin.

00:55 And that's the IV formulation is has faster onset, less irritation to the veins, and likely less cardiotoxicity.

01:02 Some of the side effects to think about with phenytoin it's a sodium channel active agent, so it can cause nausea, vomiting, ataxia, tremor, rarely an allergic hepatitis can be seen.

01:13 And the long term side effects and toxicities that we think about are gingival hyperplasia, osteoporosis, cerebellar atrophy, and sometimes neuropathy.

01:22 Those are commonly tested long-term complications or side effects of this medication.

01:28 It's also a medicine that has zero-order pharmacokinetics.

01:31 And this means that small dose adjustments lead to large changes in the serum concentration.

01:37 We typically use doses between 100 milligrams, three times a day, or 300 milligrams at night, to 400-500, or rarely 600 milligrams.

01:45 And again, small adjustments leads to large changes in concentration.

01:50 It is highly protein bound.

01:52 And so this can cause drug-drug interactions, as well as in patients with malnutrition.

01:58 We can see adjustment in the dose.

02:00 We must correct Dilantin levels for albumin concentration and given that protein-protein binding, or nowadays, we frequently check free phenytoin in levels to get at the actual serum concentration for patients.

02:16 What about Depakote or valproic acid? Again, this is one of our older anti-epileptics.

02:21 It's effective, very effective for both focal onset and generalized onset epilepsies.

02:26 It is not an enzyme inducing agent.

02:28 It is an enzyme inhibiting agents. So it's a hepatic inhibitor.

02:32 It inhibits hepatic metabolism of various agents and can increase their drug levels.

02:38 So we always check for drug-drug interactions, when starting this medication.

02:43 There are a number of side effects that we need to think about with this medicine.

02:46 It can result in fatal liver toxicity which is extremely rare.

02:50 It can be seen in children less than two years of age, who have errors of inborn metabolism.

02:56 And so those are important to screen for on a history or consider when using in young children.

03:01 It can result in pancreatitis, which is an idiosyncratic reaction, meaning it can happen at any point of time, not just when you start the drug or those who have been on it in a long time, at any point in time during their treatment.

03:14 It can produce hair loss, and we treat that typically with zinc and selenium, as well as thrombocytopenia and weight gain.

03:20 It's also a teratogen.

03:22 And that's something that we need to consider when prescribing this to patients who could be of childbearing age.

03:26 It is another protein-bound medication.

03:29 So when we use Dilantin, and Depakote, or valproic acid together, we need to consider that one drug may increase the levels of the other.

03:36 And important notes, it's the least risk of causing skin hypersensitivity reaction.

03:42 There are a number of seizure medications that can cause severe rash and this is the least likely to do that.

03:47 And it also works as a very good mood stabilizer and a migraine prophylactic medicine.

03:53 And so we typically consider it in patients who also have migraines, or may benefit from mood stabilization.

04:00 Tegretol or carbamazepine is also one of our older seizure medicines, and it's frequently used.

04:06 It's the most widely used anti-epileptic drug in the world.

04:10 It is an auto-inducer of its own metabolism.

04:12 And it's also an enzyme inducer, hepatic enzyme inducer.

04:16 So it induces the metabolism of other medications that are statically cleared and can lower their drug levels.

04:24 Side effects that we think about with Tegretol or carbamazepine, are hyponatremia, which we monitor with a blood chemistry.

04:31 Agranularcytosis, which is uncommon, but very important to recognize, and it causes other sodium channel side effects.

04:38 Nausea, vomiting, problems with imbalance or discoordination.

04:44 I think it's also good to mention that Tegretol can be used for trigeminal neuralgia.

04:48 It can have some mood stabilization properties in patients.

04:52 And it is also used in some pain syndromes where it can help control effective transmission.

05:00 Levetiracetam is one of the most commonly used first line agents for treating epilepsy.

05:04 It's metabolized in the kidneys and not the liver.

05:08 And so that's an important difference with this medication.

05:10 It does have some anti-epileptic properties.

05:13 Many of our seizure drugs help to reduce seizures, but don't prevent long-term continuation of the epilepsy.

05:20 Patients who are on levetiracetam are more likely to become seizure free and be able to come off their medication.

05:27 Side effects are similar to all anti-epileptic drugs include sedation.

05:31 And about 5% of adults, and somewhere between 5 to 25% of kids may have increase in irritability, or agitation, or mood changes on this medication.

05:41 This can be loaded IV.

05:42 And there's a one-to-one ratio of IV to PO dosing.

05:46 And typically, the maintenance doses are around 3,000 to 4000 milligrams a day.

05:50 There's not really a ceiling.

05:51 Patients don't develop dose dependent side effects, but we tend to see reduced efficacy in doses higher than these that you see here.

05:59 How about Topamax or topiramate? This is a great medication.

06:03 It's used both for seizures and it's a medication effective for migraine.

06:07 So in seizure patients who have severe migraines or headaches, we commonly think about this medication.

06:13 It can slow cognition.

06:14 We can see cognitive slowing or bradyphrenia.

06:16 And the main side effect that we see it as a dose dependent side effect.

06:21 Some of the other side effects, we see reduced body weight.

06:23 So patients can lose weight on this medication.

06:26 Sometimes that's a beneficial side effect, other times, it's something we need to avoid.

06:30 Other side effects include dizziness, confusion, drowsiness, paraesthesias, impaired memory, and slowed responsiveness, or speed of thought is really what patients describe.

06:40 And importantly, it can cause painful, closed-angle glaucoma.

06:45 And that's important to screen for in patients who have head pain and a red eye.

06:49 Patients need to be evaluated by an ophthalmologist emergently.

06:54 Interestingly, topiramate as well as zonisamide have carbonic anhydrase inhibitor properties.

07:01 And this is active in the liver resulting in metabolic acidosis, hypercalciuria, and an increased risk of kidney stones.

07:08 So we need to screen for kidney stones in these patients.

07:11 And patients who have recurrent kidney stones should be counseled on aggressive hydration are really considered for another anti-epileptic besides topiramate and zonisamide.

07:23 And then lastly, we'll talk about lamotrigine.

07:25 This is a very safe and highly effective agent.

07:27 It is category C in pregnancy.

07:29 So that's one of the safest anti-epileptic drugs that we have for use in pregnancy or the postpartum period.

07:35 It has a broad spectrum of activity.

07:37 We use it for focal onset epilepsy and generalized onset epilepsy.

07:41 The main thing to consider with this agent is rash.

07:44 It's very safe. We see very few side effects.

07:47 It's also used as a mood stabilizer and can help with pain.

07:51 But patients can develop Stevens-Johnson syndrome, a very severe rash, that develops when patients begin on this medicine at too fast or rapid of a dose.

08:01 So typically, we begin in a very low dose and the titration period is often between 8 to 10 weeks, when patients are slowly brought on to a therapeutic dose.

08:11 So this medication is not one that we use when we need to treat seizures now.

08:15 But can be begun or add as an adjunctive agent for patients where we're looking for long-term seizure control.