Medical Therapy in Epilepsy: Treatment, Side Effects, and Drug Interactions

welcome everyone my name is Kate brokkr

director of the Wellness Institute at

the national level of C foundation we

are so thankful to dr. Manderscheid in

the National Association of County

behavioral health and development

disability directors for hosting this

educational webinar today and are so

pleased that you have joined us this

afternoon today's webinar will focus on

medical therapy and epilepsy the webinar

format for today allows for you to ask

questions by typing questions into the

panel on the right hand side if your

GoToWebinar screen we will address these

questions at the end of today's webinar

but encourage you to type your questions

in at any time during the webinar please

try to keep your questions general in

nature as we cannot provide individual

medical advice at this time I'd like to

introduce you to our speakers for today

after Barry Goodell is a professor of

pharmacy and neurology at the University

of wisconsin-madison School of Pharmacy

and Department of Neurology he received

his Bachelor of Science from the

University of Utah and his doctor of

pharmacy from the University of

Washington in Seattle

he has also completed his residency as

well as a research fellowship and

clinical Pharmakon etics at the

University of Washington dr. Gelles

research interests are in the

pharmacotherapy of evelin's give

numerous research clinical publications

and book chapters related to anti

epileptic drug drug pharmacokinetics and

pharmacodynamics and drug interactions

and adults with epilepsy after Cabella

served on the editorial boards for

several journals including the epilepsy

epilepsy research epilepsy and behavior

at Bloodseeker nets and in all's of the

pharmacotherapy he's also a member of

epilepsy foundation's editorial board

and has served on the professional

advisory board as well also with us

today is my colleague dr. Elaine Cara

kabbalists is the director of health

communications and engagement at the

National Epilepsy Foundation dr. Cara

Coppola is a graduate of McMaster

University Medical School in Hamilton

Ontario Canada she began her

postgraduate medical training as a

resident in neurosurgery at the

University of Toronto combined

her clinical training with research and

functional brain imaging she completed a

research fellowship and functional brain

imaging and transcranial magnetic brain

stimulation at Harvard University

studying cross-modal

plasticity in the adult human brain she

subsequently completed her neurology

residency in epilepsy and clinical

neurophysiology fellowship at the Beth

Israel Deaconess Medical Center in

Boston to remain in Boston serving as

the Harvard medical faculty physician

combining her clinical neurology

practice with research to improve health

outcomes for people living with epilepsy

dr. Kerry accomplished transition to the

nonprofit of the sector in 2016 and

joined the National epilepsy foundation

team in 2018 thank you both for

providing today's learning and at this

time I will turn things over to my

colleague Thank You Kate and thank you

to everyone who's joined us this

afternoon it's wonderful to be here with

you today I'd like to take a moment just

to share with everyone the mission of

the Epilepsy Foundation the Epilepsy

Foundation aims to lead the fight to

overcome the challenges of living with

epilepsy and to accelerate therapies to

stop seizures find cures and save lives

today's webinar is made possible through

a cooperative grant from the Centers for

Disease Control and Prevention now the

topic of medical therapy and epilepsy

has entire week-long conferences

dedicated to it and what we're going to

aim to do today is to provide you with a

robust overview targeting this set of

objectives which include looking at the

epidemiology which links psychiatric

disease and epilepsy together the

pharmacologic treatment of epilepsy

reviewing anti-seizure medications side

effects and common drug drug

interactions we will then talk about

adherence in epilepsy and examine risks

that accompany a diagnosis of epilepsy

and why an adherence is so important for

people living with epilepsy we will also

provide you with a look at seizure first

aid and an introduction to rescue

medications in epilepsy

we're going to start today's webinar off

with a brief review of seizures and

epilepsy for those of you who are

joining the series for the first time

the human brain is a complex and dynamic

structure and it contains about 100

billion neurons that communicate with

one another by sending and receiving

electrical impulses and neuro chemical

signals now normally the electrical

activity in the brain is carefully

balanced so a single neuron or a small

group of neurons will send a signal to

accomplish a task and then stop firing a

seizure occurs when abnormal and

excessive electrical activity

temporarily interrupts that normal brain

function the image on the right is of a

snapshot of an EEG and what you can see

when you follow the squiggly lines

reflective brain activity is that about

a quarter of the way into the EEG and

something changes the electrical

activity becomes both abnormal and

excessive indicative of a seizure

electrical disruptions like this can

cause a change in a person's movement

sensation speech behavior and awareness

and seizures can have many different

outward signs and the way it appears

depends on the type of seizure a person

is experiencing and the area of brain

involved so what does it mean for

someone to have a diagnosis of epilepsy

the diagnosis of epilepsy indicates that

a person is at increased risk for having

recurrent or more seizures it does not

indicate a cause or a prognosis and

epilepsy can be described as a spectrum

disorder it's multifactorial

multifaceted and it really varies in

severity from individual to individual

it's also important to remember there

are many different types of epilepsy

now epilepsy is sometimes referred to as

a seizure disorder and that sometimes

happens out in the general public or

even by medical providers just remember

the two terms mean the same thing

someone with a seizure disorder has

epilepsy more formally the diagnosis of

epilepsy is made when someone has two

unprovoked seizures occurring greater

than 24 hours apart or if a person has

one seizure with a high chance of having

another the definition of epilepsy also

includes that if a person has been

diagnosed with the syndrome that

includes seizures even if they only have

had one seizure a person may still be

diagnosed formally with epilepsy now

anyone can be affected by epilepsy as it

affects all ages all races and all

socio-economic groups one and twenty six

people will be diagnosed with epilepsy

during their lifetime and there are

about 3.4 million Americans that live

with active epilepsy now between 25 and

50 percent of people who live with

epilepsy will also be diagnosed with a

psychiatric comorbidity this presents

both a complex and a very common problem

it's well known that there's a

bi-directional relationship between

epilepsy and mental health and if we

look at the case of epilepsy and

depression studies have shown this

bidirectionality with patients who have

epilepsy having a 5 to 20 fold higher

risk of developing depression and

patients who have depression having a 2

to 5 hold higher risk of developing

epilepsy population-based studies have

looked at the increased prevalence of

patients with a psychiatric history that

precedes the onset of epilepsy and

compared them to a control population

and there's good evidence for this to be

the case in depression

studies have also looked at the

prevalence of other psychiatric

disorders and people with epilepsy

depression anxiety psychosis and ADHD

are reported in this chart and what

these studies tell us is that for each

listed psychiatric condition that the

prevalence is elevated than people

living with epilepsy as compared to the

general population today's webinar is

going to look at the treatment of

epilepsy why is it important than a

psychologist a social worker a nurse or

a psychiatrist have some understanding

of medical therapy and epilepsy this

scientific paper is a good example of

the questions that are still being

studied so we can have a better

understanding of how the comorbid

diseases influence one another and

affect people living with the disorders

this paper asks is depression associated

with an increased risk of treatment

resistant epilepsy questions like is

depression associated with an increased

risk of treatment resistant epilepsy is

tremendously important if we look at

anti-seizure medication considered the

first line of medical therapy for people

with epilepsy what has been established

is that for people treated with these

medications roughly two out of three

people will be able to gain seizure

control and their epilepsy can regard be

regarded as uncomplicated but for one

out of three patients that's not the

case medications do not control seizures

and one out of three people and for this

group their epilepsy is disabling they

experience frequent seizures disrupting

daily life medication side effects and

there is often a long term impact which

is evident for people with uncontrolled

seizures so yes it

is important for us to look at the

impact of depression and other

psychiatric disease on the treatment and

outcomes in epilepsy and vice versa

there are many questions still to be

answered about the intersection of

epilepsy and mental house but right now

I'm going to turn things over to my

colleague dr. Goodell who will walk you

through the key things to know when it

comes to medical therapy and epilepsy

what I really want to talk about is a

big 30,000 foot view of what are some of

the issues that we have with our

different anti-seizure medications and

by the way I will probably go back and

forth and terminology between

antiepileptic drug and the new preferred

term anti-seizure medication so we we

talked about with it there what our

therapeutic goal what are we trying to

do the mantra is very simple no seizures

no side-effects okay that may not always

be possible or so at our while that's

the the ultimate goal I think are true

therapeutic goal is what can we do to

maximize efficacy minimizing seizures

and also minimizing the appearance of

adverse drug effects and also what we

try to do is looking at the different

qualities of these drugs which I'll talk

about we're going to try to mix and

match a little bit about how we pick

certain drugs for certain patients so

let's go to the next slide that one of

the other things I think is very

important and one of the things I try to

teach students is again a simple mantra

the brain and the mind are in fact the

same organ and I think sometimes we silo

things out too much but what we really

grow to understand over say the last 20

years is that there is an

interconnection between differing mood

disorders you already heard Elaine talk

earlier about this overlap of

psychiatric conditions well some of

these actually we now know can influence

the severity of epilepsy and sometimes

the epilepsy can influence the severity

of different psychiatric disease and

another way to look at this is and we'll

go to the next slide is that seizures

may be just one

phenotypic expression of what epilepsy

is so take a more holistic view of what

epilepsy is not just that seizure again

with this slide is just sort of a

elaborating a bit on that first brain

slide is that we do know that you know

these other neurologic pathways in the

brain things that innervate our frontal

cortex our ability to have executive

function and thought in impulse control

areas of the brain that affect mood and

we know again we've already talked about

mood and epilepsy mood disorders in

epilepsy sometimes go hand in hand it's

not a coincidence we now know that

through dopamine pathways and search

nergic and others that there is a

logical reason and that explanation for

this and in fact some of our

anti-seizure medications may in fact

make some of these conditions better

next slide please

so back to 30,000 foot view the common

property of our anti-seizure medications

is we can suppress and hopefully stop

seizures it'd be nice that they were all

that simple and straightforward but we

do know that many of these drugs have

differing pharmacokinetic properties

meaning how are our guts and our livers

and our kidneys process and handle them

we know that there are different side

effects and toxicities as a individual

drugs and as a class and also very very

importantly many of these drugs are

associated with multiple drug


okay so again what our next slide please

what our ultimate goal is knowing that

that general pharmacology and I'll going

a little bit deeper in here well how do

we tailor this and how do we try to mix

and match it and strike some balance

next slide hopefully this is a graphic

showing the introduction of new drugs

yes I hope yes so we have made in some

respects we've made a lot of progress in

other respects we've not made very much

what do I mean by that if we go back in

time back to the 19th century and early

20th century we did have drugs that work

they did suppress seizures unfortunately

they were also associated with profound

cognitive impairment and other types of

metabolic effects and then you see there

was sort of this glorious period in the

in the 60s and 70s and 80s where we had

a number of new drugs that were

introduced on many of these proved to

have a little bit better efficacy in

terms of seizures than the older drugs

but what we also found began a

recognition of is that all these drugs a

lot of them had other baggage meaning

meaning mainly side effects and drug

interactions well then as we entered the

decade of the brain in the 90s and now

continuing on into the new millennium

the new century that we have a number of

newer molecules really what the focus of

this generation that so-called third

generation has been has been - what can

we do to minimize side-effects and

minimize drug interactions and when

that's where I mean we've made a lot of

progress sadly however in terms of

efficacy we're stubbornly the same let's

go to the next slide and what do I mean

by that when we look at seizure control

on there's some data that's you know

it's you know back in the 2000-2001 on

data but and sadly it still holds true

that if I ask the question if we have a

brand new diagnosed patient with

epilepsy and of all those drugs that I

just showed you if we take the first

drug off the shelf we're going to bat

about 50% meaning that we're going to

make get our seizure free right it's our

goal we're going to make maybe maybe

half that will be seizure free okay what

if we switch to the second drug

we're going to pick up maybe another 10

to 13 percent will make them seizure

free after that things start looking

grim we are now on a different

trajectory and by international

definition once you fail to anti-seizure

medications given an optimal dose as you

are pharmaco resistant meaning you have

a a different trajectory perhaps at a

different you know expectation for

future drug trials now does that mean we

stop no it means we keep we keep itching

we keep finding new drugs but the point

that I want to leave you with and let's

go to the next slide is um we need to be

aggressive early on and if art you know

knowing uncontrolled seizures and the

risk of sudden unexpected death and a

lot of these things we may be able to

alter debt trajectory there's some

interesting science that says it's very

very early aggressive control of

seizures maybe maybe maybe we can

influence that long-term effect but if

nothing else it is vitally important we

do whatever we can as soon as we can to

get as best control as we can so the

thing I would leave you with the message

I would leave you with even though these

statistics look grim the grimmer

statistic in my estimation is that many

patients go years with uncontrolled

seizures maybe only trying one or two

drugs we need to have every tool in our

toolkit available to us and we need to

have a plan for patients to reasonably

quickly assess whether these drugs work

and if not try different drugs or

potentially different combinations of

those drugs ok let's go to the next

slide please so it could be a whole

nother two or three hours of lectures on

the pharmacology of answering the

question how do anti-seizure medications

work on the the real answer that is we

don't entirely know for many of these

drugs generally speaking what they're

doing is we're trying to suppress that

excessive electrical activity in neurons

and by doing that one of our main

mechanisms if we think about you know

from again a 30,000 foot view

we know that seizures seem to be the

synchronous electrical discharge caused

by excessive neuro excitatory activity

in the brain and that's mainly mediated

by the chemical glutamate so many of our

anti-seizure medications work to dampen

down the release of that glutamate it

also may be that some of our anti-sea

our seizures are due to inefficient

breaking or inhibition and that's

meaning mediated mainly through gaba and

many of our anti-seizure medications or

to enhance or augment gaba so what does

that translate to then in terms of you

know the bigger picture of picking drugs

then if we look at seizure types you

know and break up the epilepsy seizures

into focal seizures the old language I

would have been partial onset seizures

or generalized seizures most of our

medicines that we have available to us

will work for focal seizures most but

not all will work for generalized

seizures and whether that's a primary

generalized epilepsy which tends to be a

genetic epilepsy or a secondary

generalized convulsion most of our drugs

will treat those to one extent or

another but not all and then there are

those patients that you know we clearly

cannot come up with an epilepsy focus we

can't come up with a mechanism and we'd

return those broad-spectrum drugs and we

have a handful that can treat a variety

of things okay so let's go to the next

slide so to summarize we have a variety

of targets available that the different

drugs work on on I will tell you again

that this is painting a very broad and

very simplistic picture of what I just

told you we're learning almost everyday

that many of these drugs have other

mechanisms or may be a combination of

mechanisms multiple mechanisms that some

of these medicines have that may be

contributing the really interesting

thing is

we can have two patients that look alike

that look the same have the same type of

seizure and may respond very differently

to these different medicines so again we

can only take mechanism of action so far

now well I don't necessarily have slides

on here is I'm sure everybody has heard

about cannabidiol CBD or cannabis for

epilepsy I'm certainly happy to answer

questions at the end but the one thing I

want to leave you with we don't really

know what CBD is doing to treat seizures

but what I can tell you with pretty much

a degree of certainty is whatever this

drug is doing it's working very

differently from any of our other

anti-seizure medications again maybe we

can explore that in discussions next

slide please

so why is any of this important well for

the first drug for your decision of what

drug to pick the furry for that patient

that presents to you does mechanism of

action important I would say no it's

important however when that first

medicine fails remember I told you about

half of those patients or more it's not

going to work taking a drug that works

with a what we think is a different

mechanism is a more rational approach

may not be the only approach but it is

one rational approach to trying to

optimize drug therapy it may also give

us a little bit of insight into let's go

to the next slide please

it may give us a little bit of insight

into side-effects okay and you know once

we know what the seizure type is once

we've you know selected our drug knowing

what that mechanism is and what we can

expect what we also know about our

patient what other kind of medical or

psychiatric or psychological morbidities

they have the mechanisms sometimes can

give us some insight as to what a drug

may be a beneficial thing to try or may

in fact be a negative thing next slide


hopefully again this one's entitled

things to consider so what can I tell

you that let's let's switch to

psychiatric and cognitive and other

types of side effects most of our sadly

most of our anti-seizure medications can

influence cognitive function to one

degree or another I will tell you

there's a lot of drugs and drug

companies out there that will tell you

their drug is absolutely free of

cognitive side effects I that may be

true and a lot of patients there are

still patients that are going to tell

you that they can't think very clearly

or things seem foggy but there are drugs

that are clearly worse there I will also

tell you I think it's a general rule of

thumb whenever possible monotherapy the

more medicines we add on on we may add

on to drugs that have supposedly minimal

cognitive effects but we add them

together and now we have a patient who's

complaining to us behavior some of our

anti-seizure drugs may amplify or make

worse certain types of behavior like

irritability or aggressiveness um an

example for that might be the drug

lovest racetam of potentially pyramidal

by compa that may actually make things

worse there are some anti-seizure

medicines that may actually dampen that

down and in fact have uses very valid

and good demonstrated uses in psychiatry

so the thing that I'd like you to keep

in mind about this again I would love to

be able to tell you some drugs and I'll

give you some general guidelines here

but know that anything can happen with

any drugs but I do want to move on let's

go to the next slide and about side

effects I do want to be able to give you

some broad strokes of what kind of

things to think about so let's go to the

next slide please

common side effects of anti-seizure

medications so there's a lot of

different things these drugs can cause

and there's a couple different sort of

ways I want you to think about this

first of all there's allergic reactions

and what do I mean by allergic reactions

the thing that I'm really concerned

about our hypersensitivity things that

we would see with say rash

as being probably the most profound

example that the one that's easy to see

some of our drugs in some patients can

cause significant rash some of our older

medicines such as dilantin or tegretol

or lamictal

can not only cause rash they may cross

react so in other words a patient who is

allergic to Dale and may be allergic to

lamictal in some cases these can cause

very significant problems we have dose

related side-effects things again like

this cognitive thinking problems with

balance and dizziness on board or WLAN

sometimes those things are dose related

we may not see it at a low dose but we

may up the dose again to maximize

efficacy and that's where we begin to

see side-effects and then we may have

like the way I like to call media sync

radical things things we can't

necessarily pick up a lot of problems

for example birth defects um some of

these not all drugs even those that have

been associated with birth defects

caused caused it and every woman who

takes things like problems with red

blood cell formation liver problems

those types of things a weight gain um

maybe a idiosyncratic some patients are

susceptible to them others aren't okay

let's go to the next slide please

mood and behavior side effects and we'll

go to the next next one so I think I've

touched on a lot of this already um what

are some of those mood and behavioral

side effects here are the common things

here's the stuff that is the most

commonly reported probably the ones that

are the most besides the concentration

difficulties and again what I have a lot

of patients tell you is it is sometimes

don't feel as sharp they just can't

think as clearly um and that goes for

you from just being a little bit fuzzy

to they're really they have memory

issues they can't remember why they got

up to walk into a different room or what

they were doing long term memory seems

to be intact it's that short-term memory

the other thing is irritability on some

patients and this can go anywhere from

irritability frankly all the way up to

to psychosis into extreme agitation some

of our medicines that have been commonly

associated with that would be things

like Lovett or asset a more keppra and

pyramidal or if I combi a newer

generation medicine very good

efficacious drugs both of them but they

can cause irritability I'd love to be

able to tell you that we have a test

that we can predict who that's going to

occur in and again we simply the science

isn't there yet but the really the

things that are that are you know

sometimes the most concerning and

troubling to me and the things that I we

need to screen for constantly is

depression and anxiety again these are

common comorbidities in our patients

with epilepsy but we have learned over

the years that some of our drugs can

make this worse and let's go to the next

slide talking a little bit about that

what are some of the drugs that we think

can cause more depression and

potentially even in a patient that has

never had a history depression some of

our drugs several which is by gaba train

which is going to be used more in

children rarely in adults gaba trill

which is a drug called TIA gabbing gaba

uptake inhibitors this is not used very

very often at all anymore at least by

neurologists but it can it can cause

depression sonograms Anissa might a

commonly used medicine um we have

learned over time that this is a drug

especially in a patient with a little

bit of history a depression can make it

worse but the one that's really of

concern to me is a drug that's been

around for now well over a hundred years

and I got to tell you it works really

really well but it's phenobarbital

phenobarbital is a very good drug from

an efficacy point of view but you use it

I would use it in extreme caution be

concerned in a patient with a history of

depression and I've already talked about

Khepera how about anxiety you know we

don't talk about anxiety as much as we

should in terms of mood disorder it's

sort of the unexplored

area of epilepsy I've already mentioned

a couple drugs velvet all is a drug we

don't use that much in except in very

very very refractory patients but again

keppra and it's cousin previa these are

drugs not only it's not just the

irritability patients may not come to

you necessarily complaining of

irritability but they just will tell you

that they're anxious so they'll use

terms that this audience may be more

familiar with than me to describe that

and understand that these drugs can

clearly do that okay let's shift gears

let's go to the next slide

antidepressants and epilepsy and the

next slide I think I may have we talked

about this earlier sort of the

pleomorphic expressions of depression

and epilepsy okay and as I tried to

mention earlier that mood the seizures

are just one phenotypic expression of

epilepsy is we've learned more that our

patient there may be other all those

other neurotransmitter systems are

referred to that we can see a lot of

different expressions and some are of

more importance than others are more

prominent I should say and others

depression major depression but here's

the thing that's really that I think

trips a lot of people up not all of our

patients that come to us are going to be

complaining our fifth criteria for major

depressive disorder some of them have

something that I like to term interictal

dysthymic disorder a better way to look

at this is they just seem bummed out

these are the patients that don't really

fit the criteria for major depression

but they're just

they're just not that happy and they're

the ones that you know they may have

some apathy as well that they express we

don't necessarily classify them some of

our instruments would not diagnose them

as having depression I think that's sad

because a lot of these patients then go

untreated and we never used to think

this until some work a few years ago

that you know bipolar disorder we also

see an overexpression of bipolar

disorder in our patients with epilepsy

okay next let's skip the next slide if

we could the brain from the MRI slide

and go to the one that's a correlation

between hippocampal volume and

depression um if we have that slide up I

want to make just one point I want to

get back to the physiology here because

sadly sometimes I hear folks say that um

well of course patients with epilepsy

are depressed

wouldn't you be depressed if you had a

chronic disease like this well the

answer is yes but also it's very

important for us to understand again

it's the brain in the mind say Morrigan

the physiology this was some actually

rather groundbreaking work from a few

years ago that um looked at hippocampal

volumes and duration of untreated

depression and we also now have this

similar looking data in other epilepsy

patients that show that that hippocampal

the hippocampus where we know that um a

lot of refractory focal seizures

originate from from mesial temporal

sclerosis that that causes epilepsy we

now know that's also related to

depression so again these two disorders

are actually physiology that explains

this let's go to the next slide

so earlier on Elena talked about the

crossover again or the comorbidity of

depression and epilepsy um let me take

that one couple layers deeper now and

this is the prevalence of depression in

epilepsy and what you'll notice here is

very interesting you know if you look at

the general population and you look at

our percent of patients that are well

controlled by that I mean seizure free

the instant depression appears to be

maybe numerically a little bit higher

than the general population but look at

those patients with pharmacal resistant

epilepsy meaning they have failed at

least to any seizure medications the

prevalence is far far higher let's go to

the next slide so what do we now know so

what is this what does this tell us well

what we think now again it used to be we

thought it was a one-way street you had

epilepsy and perhaps you developed a

psychiatric disorder what we now know

there is emerging human data again from

imaging studies looking at our

hippocampus there's animal stuff really

interesting data it looks like it's a

two-way street that not only does

epilepsy having epilepsy predispose you

to depression but we now have some very

interesting data that having depression

having an active depression may be a

risk factor for epilepsy itself again

all those pathways that I briefly

touched on these all are interacting

with each other so let's go to the next

slide please so what does that tell us

from a practical there are Q 2 point of

view what that tells us is we now have

interesting information that perhaps

using antidepressants ok drug not only

can maybe treat that depression but

maybe the use of antidepressants may in

fact be beneficial in treating epilepsy

so what I mean by that is sometimes

we'll have patients that have bad

seizures or having uncontrolled seizures

and they're depressed

we can't gain control of their seizures

until we get some kind of remission for

their depression so sometimes being

aggressive and proactive in our

antidepressant treatment is important

for us to gain control so again brain of

the mind say

Morrigan it also makes the argument

where psychiatry psychology need to work

together so let's go to the next slide

so what does that mean for our patients

it means not only drugs drugs are not

always the right answer more and more

and in our clinic we're trying to

incorporate CBT cognitive behavioral

therapy and sometimes combination above

to optimally treat not just that mood

disorder but to treat seizure disorders

okay so let's go to the next slide

please our aims overall aims of

pharmacotherapy treat everything okay we

can't treat them as in silo things

anymore we need to look at treatment get

remission of all symptoms of depression

and anxiety we need to not be afraid to

use antidepressant medicines and our

patients with epilepsy um we may need to

adjust the dose maybe not with patients

on enzyme inducing drugs but we need to

be aggressive with treatment of both of

those okay so um I think I have I'm

going to if we could now for the in chat

sake of time I'd like to go down to the

slide please Ryan I think it's 47 risk

of suicidal ideation so what about

suicide here's what we know this is

something we've become acutely aware of

in the last few years the risk of we

know that you know if you look in the

general population what the risk of

suicide is or and not only ideation but

actual attempts people with epilepsy

it's a lot higher let's please go to so

let's talk a little bit deeper about

that let's can we go to the slide number

49 the PS about FDA alert on suicidality

great so what do we know we know a

couple things on the FDA went back and

looked at this um a few years back and

interestingly enough there was an

overall risk imposed from the placebo

control trials that have been published

for increased risk for suicide allottee

in patients receiving anti-seizure

medications as compared

to placebo now that created a lot of

panic with a lot of people because if

you don't understand that statistic it

says people interpret that that there's

an 80% risk of suicidality no there's an

increased risk and what that really

means is yes there are more suicidal

events if you will in patients with

these anti-seizure medicines but again

the numbers are still very low all right

so people a lot of patients early on

we're very scared of this they thought I

don't want to take these medicines

because of the potential risk for

suicide we need to reassure our patients

know that there is an increased risk on

but there's also the benefit like we've

just been talking about the incredible

benefit of treating these seizures

themselves okay so we need to be able to

reassure patients what can I tell you

about the be different antiepileptic

medications anti-suicide anti-seizure

medications if we go to slide 50 here's

what I can tell you there's no real

clear winner or loser here we don't

really have overall any drug that's

better or worse if you look at this

slide I've got a little red circle

around lamotrigine that's not to imply

that lamotrigine causes more suicidality

I think the explanation for that is we

tend to treat more patients with mood

disorders with lamotrigine because it

has been shown it's FDA approved and

bipolar disorder and it's also been

shown to have some mood elevating

effects in our patients with epilepsy

okay so the bottom line here is patients

with mood disorders be that depression

anxiety irritability we need to look at

the whole picture we need to look at

good control of seizures as being one

very good treatment for that and then

but we do need to think about the

different medications and what they

possibly can bring to the table here

okay very quickly let's go to slide 53 I

want to talk about drug interactions

I will tell you that the pharmacokinetic

there are pharmacokinetic interactions

with these different medicines some of

our drugs are enzyme inducing medicines

meaning they rev up the activity of

these drug metabolizing enzymes some are

inhibitors meaning they can slow down

the activity of some of these enzymes

some do do both from a practical point

of view what does that mean one of the

things it means is that can affect sex

hormones some of these remember are sex

hormones testosterone estradiol are

metabolized by these same drug

metabolizing enzymes this may explain

why some of our patients have depressed

libido and sexual activity vitamin D

vitamin D is metabolized by these

enzymes and vitamin D levels we've shown

in some of those enzyme inducing

medications can actually be depressed

and this may be a risk factor for

developing osteoporosis slide 54 please

next slide so again there's a number of

our older and the drugs that seem to be

the most caused common culprits if you

will for this are our older medicines

such as tegretol phenobarbital they

lanten and when we rarely use any more

primidone so carbamazepine phenobarbital

senator phenytoin and primidone besides

those effects on our own endogenous

hormones we have to think about other

medicines that this may impact and those

other medicines can be anticoagulants in

our young women or think of oral

contraceptive pills we can decrease the

activity and they may have an impact on

antidepressants and antipsychotics and

very importantly in our of cancer

patients these have been shown to


reduce the efficacy of antineoplastic

treatment we go too quickly to the next

slide number 55 again just as just

realized in this so thinking about our

psychotropic medications both the

typical and a lot of the atypical

antipsychotics these enzyme inducers and

reduce serum concentrations

I think first clearly for showing um in

terms of schizophrenia

that probably has an impact whether it's

affecting the antidepressant activity of

those drugs is a question we still don't

know we go to slide 56 we do know that

some of these drugs like valproic acid

may actually do the opposite and we have

evidence that valproic acid which we may

be using for bipolar patients and mood

disorders may actually raise the

concentration of some of these drugs

so in summary here um there's a variety

of things we need to pay attention to

and think about in in terms of how we

pick these drugs

pharmacology mechanism clearly one thing

side-effect profile I think we need to

be thinking more about the behavioral

effects and mood effects than we do and

then finally drug interactions we need

to always be asking the question if the

other medicines I'm using aren't working

or maybe causing problems that I

wouldn't anticipate are my anti-seizure

medications interfering thanks Barry

we're gonna spend a bit of time now

reviewing medication adherence in

epilepsy and risks that are present for

a person living with epilepsy so one of

the greatest problems in treating

illness is the failure of patients to

take medications they are prescribed

correctly and in some cases at all the

average percentage of patients who fail

to take medications as prescribed was

estimated by the World Health

Organization to be right around 50% now

studies have helped to determine the

behaviors or actions of patients after a

prescription is provided to them and

what we've learned is that about 1/4 of

patients do not take medications at all

so they receive a prescription but then

they don't go out and get it filled

about 28% or just slightly over 1/4 stop

taking their medication before a

prescription runs out and 22% so almost

a quarter so almost one in four patients

take less than the dose prescribed

and here in STEM education we know is

multi-dimensional phenomena and it's

determined by the interplay of different

factors and they're termed dimensions by

the World Health Organization

now these sets of factors include social

and economic factors healthcare system

related factors condition related

factors therapy related factors and

patient related factors if we examine

closely and break down these dimensions

and appreciate the sentiments that

patients share there are several

barriers to inherence to consider

complexity so there are too many pills I

can't keep them straight cost memory

problems not understanding why a

medication is required for some people

when they feel well they stop taking

medications not recognizing the

preventative aspect of the medication

they are taking that allows them to feel

well and this can sometimes be the case

in epilepsy people think well you know I

haven't had a seizure in six months I I

don't really think I need to keep taking

my medication another contributing

factor in epilepsy is embarrassment and

stigma which can lead people to not

taking medications from a psychiatric

disease standpoint depression in and of

itself can contribute to poor adherence

so you can imagine how the combination

of comorbid disease might affect

adherence health literacy is also a key

barrier you know and as providers we

have an obligation to try to overcome

this issue by ensuring the appropriate

education and counseling and supports

are available around medications finally

belief systems whether individual

or cultural can influence behavior when

it comes to adherence if we take a

closer look at non adherence and

neurologic and psychiatric diseases you

can see that both for epilepsy and

depression non-adherence sits at

approximately 40% and studies that

looked at medication non-adherence

specifically in epilepsy compared to

other chronic medical conditions

determine that non adherence was a

problem from between about one-quarter

and two-thirds of patients now in

epilepsy studies have also demonstrated

that non adherence results in increases

in emergency room visits

hospitalizations and injuries related to

more motor vehicle accidents

additionally compared with adherent

behavior so compared with people who

take those medications if someone

doesn't take their medication if their

non-adherent that's associated with a

three-fold increase in risk of death an

increased per patient emergency room an

inpatient hospital costs now why are

adherence and removing barriers to

adherence so important in epilepsy well

because we know that a person living

with epilepsy faces increased risks that

includes seizure emergencies and

complications from seizures accidents

and drowning drug reactions suicide and

sudden unexpected death in epilepsy

which is referred to as SUDEP just for a

moment on Sudha Sudha occurs when a

person with epilepsy who is in their

usual state of health dies unexpectedly

and no other obvious cause of death is

found it affects one out of a thousand

people with epilepsy each year

and for people with poorly controlled

seizures the risk is even higher recent

clinical guidelines have shared that for

people who have more than three

generalized tonic-clonic seizures a year

and people who have seizures which occur

at night the risk is further elevated so

it's very important that patients who

have been prescribed anti-seizure

medications follow their doctor's

directions and take their medications

regularly and reliably the risk for

breakthrough seizures when medication

regimens are not followed are high if

you were caring for a patient with

comorbid disease and they share a

history of non adherence counseling

around these risks and immediate

referral back to their neurologist is

vital there may be a reason cost or

side-effect that's led them to not

taking their medication and this should

be explored and solutions implemented

whether it be a trial of a different

medication that needs to happen or an

appeal to an insurance company

non-adherence in epilepsy can result in

injury in death and really needs

immediate attention we're going to move

on now to review seizure first aid and

have dr. Goodell introduce to you

another type of medication used in

epilepsy called rescue therapy the three

basic principles of seizure first aid

include staying with the person keeping

the person safe and in the appropriate

circumstances turning a person on their

side stay safe side are a good simple

guideline for thinking about seizure

first aid the other key concept you'll

want to take away is related to timing a

seizure the other key concept you'll

want to take away is related to timing a

seizure and the importance of doing so

with the critical number of five minutes

as a guide to your respond

let's walk through what you can do in

the event of being present when someone

is having a seizure recognizing that

there are many different types of

seizures and you'll need to tailor your

response appropriately

however the common principles we just

discussed always apply if you are

present when a person is experiencing a

seizure you want to stay with that

person remain calm and keep those around

you calm check for a medical ID and use

your watch or your phone to begin timing

the seizure you're going to want to keep

the person safe so move harmful sharp or

hard objects out of the way and if they

happen to wander during their type of

seizure try to gently guide them away

from dangerous situations like traffic

or terrain that is rocky or uneven where

they may fall and injure themselves if

the person loses consciousness you want

to gently guide them to the floor or

ground turn the person on to their side

to help clear saliva and keep the airway

open put something soft like a jacket or

a sweatshirt under their head and loosen

any tight clothing like ties or scarves

that may be around the neck never put

anything in the person's mouth and don't

offer food or medication unless they're

completely awake and aware you never

want to restrain a person during a

seizure holding someone down during a

seizure does not stop movements that

accompany a seizure the movements will

stop when the seizure ends and most

seniors last between several seconds and

a few minutes after the seizure ends

stay with them until they are fully

alert and aware offers some reassuring

words and let them know in simple terms

what has happened and that they are okay

and safe if necessary offered a call a

loved one to help them return back to

their home safely

most seizures are not medical

emergencies but there are instances

where 911 should be called these include

if a seizure lasts longer than five


if a person has repeated seizures if

there is any difficulty with breathing

if the person is injured during a

seizure or is pregnant or is in medical

distress if a person does not return to

their usual state after a seizure 911

should be called for seizures that occur

in water 911 always be called as a

medical evaluation is always required if

this is someone's very first seizure

they should be transported to the

emergency room for an evaluation you are

going to want to share information about

how long the seizure lasted and the

description of what you notice during

the seizure when emergency personnel

arrived to help remember timing the

seizure is important in sharing that

information is also important timing the

seizure is important because guidelines

have established that if a convulsive

generalized tonic-clonic seizure with

the loss of consciousness is prolonged

lasting more than five minutes it is

defined as status epilepticus a seizure

emergency this also applies if a person

has repeat seizures over a prolonged

period not recovering between seizures

911 be called in both cases and with

that information in hand I'm going to

turn things back to dr. Goodell who will

introduce you to another set of

medications used in emergency settings

both inside and outside of the hospital

public so um get back to a little bit of

the pharmacology we talked about um you

know that the you know drugs are either

working to decrease that excitatory

activity or they're working to in

and that inhibitory activity what do we

know about in acute seizures so someone

is having either of cluster seizures or

cute recurrences or things that also

make us really worried that they're

going to go on and develop status

epilepticus we want to stop that that

process really quickly and soon we have

very good evidence going back years that

a class of drugs the benzodiazepines

meaning things like valium and ativan

and ver said so diazepam lorazepam

midazolam all of these benzodiazepines

we know from years of experience if we

give them quickly that they can stop a

seizure the problem is most of these

drugs are given in the hospital setting

are given IV that may not be possible or

won't be possible in say a kid in school

or somebody in at home or in the

workplace so over the last couple years

were on the last few years we've known

we sometimes send patients home with

oral tablets of a drug like valium or

ativan to cutely stop a seizure but

again that drug has got to get absorbed

and it takes a while so there's a whole

new delivery system the formulations of

these older medicines that are now

starting to come to market you're going

to see them over the next couple years

there for a long time we have a rectal

on a device or administration of Valium

of diazepam it goes under the name diet

staff now it works works really well but

as you might imagine rectal delivery is

not practical or convenient or desirable

in a number of situations especially say

in a school setting or in the workplace

there is now a development for on both

would called buccal um administration

there's going to be a little strips that

you actually going to either put on the

tongue or on the side of the cheek that

rapidly dissolve and give this drug very

quickly the first one they'll be coming

to market is actually an intranasal

version of a drug called midazolam so

it's actually like a nasal spray

you'll squirt this thing in anybody can

give it it's very simple to give and

it's been shown to get absorbed very

very very rapidly and terminate seizures

so we have a whole new

not necessarily a new class of medicines

but just new ways of giving us both in

the nose and in the side of the cheek

that I think are really going to be

important for us in the acute management

of patients thanks so much very this

brings us to the final part of today's

webinar we wanted to be sure to share

with you that there are a number of

resources you can turn to after today's

session to continue learning about

epilepsy and medications used to treat

epilepsy resources for providers and

patients and links to these resources

can be found on epilepsy comm or by

calling our Epilepsy Foundation 24/7

help line this presentation and the list

of resources you see on this slide will

be available for viewing on epilepsy

comm I would like to thank dr.

Manderscheid for supporting and guiding

this work in behavioral health and

epilepsy and for giving us the

opportunity to be here with all of you

today I'd also like to offer special

thanks to dr. goodell for sharing his

time and his incredible wealth of

knowledge and experience with us this


and for his steadfast support of the

Epilepsy Foundation and the epilepsy

community at large

dr. goodell thanks so very much I want

to thank each of you for your interest

and attention today and we hope you'll

join us in the future as we continue to

share with you regular webinar learning

sessions that are focused on the

intersection of epilepsy and mental and

behavioral health you can find updates

for new learning opportunities on the

landing page at epilepsy comm and via

Twitter Facebook and LinkedIn thanks so

much everyone