Top 10 Seizure Treatment Tips with Cases

by Roy Strowd, MD

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    00:01 So let's talk about some common tips.

    00:03 So the top 10 seizure treatment tips when we're selecting and using medications.

    00:10 So let's talk about some seizure tips or clinical pearls to think about when selecting a seizure treatment.

    00:17 And we'll go through some cases.

    00:19 The first is a 13-year-old boy, who's referred from his PCP.

    00:23 The 13-year-old boy presents to the ED on referral from his PCP.

    00:27 He initially presented with problems in school, staring about eight months ago.

    00:31 Initially was diagnosed with ADD but recently there's been some concern for seizures.

    00:37 He's also has depressed mood and at times is reported to have episodes of pressured speech and grandiose behavior.

    00:43 He was placed on Tegretol three weeks ago, as he was not able to get and see a neurologist for another two months.

    00:49 Unfortunately, he has developed seizures that have worsened and have now had five spells a day, where he was only having up to 1 to 2 weeks before.

    00:59 So what's going on in this case? Well, this is someone, who initially had episodes of behavioral arrest that were thought to be from ADD, but were likely underlying seizures.

    01:10 He was placed on carbamazepine, and then those episodes worsened in frequency.

    01:15 This is a key clinical pearl about what medications worsen primary generalized seizures.

    01:20 The clinical description is consistent with a generalized onset epilepsy.

    01:25 And here we see one of the common offenders.

    01:28 These medications include carbamazepine, as in this case.

    01:31 Vigabatrin, gabapentin, Trileptal or oxcarbazepine, and Tiagabine.

    01:37 These are medications that we don't tend to use for primary generalized epilepsy.

    01:42 We can in selected cases, but we don't tend to because they can worsen those patients seizures.

    01:46 A good clinical pearl.

    01:50 Let's consider a 34-year-old woman with a long history of temporal lobe epilepsy who presents to the ED in status epilepticus.

    01:57 She developed progressively worsening complex partial seizures over the past six months.

    02:02 She's been on phenytoin and for many years.

    02:04 Given an increase in seizure frequency, her phenytoin has gradually been increased and increased to a serum level around 25.

    02:11 With continued seizures, valproic acid is added three days prior to her presentation.

    02:17 You recommend that the ED checker levels to determine compliance.

    02:20 Her total phenytoin level is high.

    02:23 Her valproic acid level is normal.

    02:26 So what antiepileptic medications have strong protein-protein interaction? And that's what's going on with this patient.

    02:33 Phenytoin and valproic acid have protein-protein binding and both interact.

    02:38 When we add the valproic acid to the phenytoin the valproic acid binds to protein more than phenytoin and we see an increase in the free phenytoin level.

    02:49 Protein binding is important for medications like phenytoin and valproic acid.

    02:53 Valproic acid has a greater affinity to protein than phenytoin.

    02:58 And adding valproic acid to phenytoin displaces the phenytoin in from its bound state on the protein, resulting in a lower serum concentration, but higher free drug levels.

    03:08 And so patients can become phenytoin toxic.

    03:12 Let's consider a 28-year-old woman who presents for management of a known seizure disorder.

    03:17 She has been on Topamax for three years and was tolerating it well.

    03:21 But his reporting increased issues with difficulty with her thinking.

    03:24 She's interested in changing medications and is wondering about carbamazepine or Tegretol.

    03:29 Given associated mood complaints that she has.

    03:32 You agree starter on 200 milligrams twice a day, and titrate up to 400 milligrams twice a day after one week.

    03:40 You see the patient back after three months, and she says, that at first, she felt horrible.

    03:44 Had intense vomiting sodium channel side effects after each dose of the medication.

    03:49 But over time, this resolved.

    03:51 Now, she's concerned that the medication is not working, because she's back to having one to two light seizures per week.

    03:57 So what's going on with this patient? Well, this is a great example of what anti-seizure medicines are associated with hepatic auto-induction? And the one to remember is carbamazepine.

    04:10 Carbamazepine causes auto-induction.

    04:12 It induces the expression of the CYP3A4 enzyme in the liver.

    04:17 This enzyme is involved in metabolism of carbamazepine.

    04:20 So as the medication is initiated, the liver at the first doses doesn't have the CYP3A4 enzyme around.

    04:27 So it's not rapidly metabolized.

    04:30 Over time as the liver becomes used to the carbamazepine, there's increased expression of the CYP3A4 enzyme.

    04:37 Increased metabolism of the carbamazepine and lower drug levels.

    04:42 So carbamazepine is typically a drug that we start over the first couple of weeks and check a level after several weeks, and would plan to further titrate the medication based on the degree of hepatic auto-induction.

    04:53 And this is a great clinical example of what's going on for this patient.

    04:58 And then, let's consider an 18-year-old woman who presents to your clinic six months after a new patient appointment for a treatment evaluation of seizures.

    05:06 She's very furious.

    05:08 She says that she is not married and has become pregnant since you saw her last.

    05:13 She has been on birth control pills, consistently over this period of time and is not sure how this happened.

    05:19 And she blames you.

    05:21 This is a good example of counseling needed for patients when we're starting selected seizure medications.

    05:26 We must warn our patients about the potential of oral contraceptive failure on selected agents.

    05:32 So what are those anti-seizure medications that can interfere with activity of oral contraceptive pills? Well, here's a list.

    05:40 Levetiracetam, gabapentin, tiagabine, vigabatrin, zonisamide, topiramate, all of those medications have no effect on endogenous steroid hormone concentrations.

    05:50 They're okay to use without seeing problems with oral contraceptive pills.

    05:55 The medications that can cause contraceptive failure are lamotrigine, phenytoin, phenobarbital, and carbamazepine.

    06:03 And important to counsel patients when starting these medications.

    06:08 And then let's consider a 13-year-old boy with mild mental retardation who presents for a return appointment for management of medically refractory generalized epilepsy.

    06:17 He was on Lamictal monotherapy and things were stable on this medication for many years, until recently.

    06:23 His mother called with increased seizure frequency and breakthrough seizures about one month ago.

    06:29 He's six inches taller and skinnier at this visit then last.

    06:32 His mother was concerned about increased seizure frequency and asked and to start him on an additional medication.

    06:38 You recommend valproic acid.

    06:40 She says, that since that, since starting valproic acid over the past week, he's been sleepy or and sleeper, and seemed somewhat confused.

    06:49 So what anti-seizure medication is associated with hyperammonemia? That's what's going on in this case.

    06:55 Hyperammonemia is associated with valproic acid.

    06:58 This is a medication that can be associated with idiosyncratic pancreatitis and hepatitis as well as, as spontaneous increases in circulating ammonia levels.

    07:09 Hyperammonemia can occur in the absence of transaminitis or other LFT abnormalities.

    07:14 And we note that this can be particularly the case when valproic acid is combined with lamotrigine where there is drug-drug interaction.

    07:21 So this is a good example of a patient who's suffering from hyperammonemic-induced encephalopathy that was precipitated by the combination of valproic acid and lamotrigine.

    About the Lecture

    The lecture Top 10 Seizure Treatment Tips with Cases by Roy Strowd, MD is from the course Seizures and Epilepsy.

    Included Quiz Questions

    1. Lamotrigine
    2. Topiramate
    3. Gabapentin
    4. Levetiracetam
    5. Zonisamide
    1. Carbamazepine
    2. Topiramate
    3. Lamotrigine
    4. Levetiracetam
    5. Phenytoin
    1. Carbamazepine
    2. Topiramate
    3. Lamotrigine
    4. Levetiracetam
    5. Phenytoin

    Author of lecture Top 10 Seizure Treatment Tips with Cases

     Roy Strowd, MD

    Roy Strowd, MD

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    Great work; thank you so much.
    By Saif A. on 31. December 2022 for Top 10 Seizure Treatment Tips with Cases

    Very well explained and clinically oriented. Great work; thank you so much.