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Welcome to the Synaptic Tails podcast, where neurology meets practical tips in veterinary care. Hosted by Dr Emma Hancox, a Technical Vet Advisor at Dômes Pharma UK, alongside Dr Mark Lowrie of Movement Referrals.
In each episode, we explore the challenges of managing epilepsy cases in first-opinion practice - sharing clinical insights, lived experience, and practical strategies to support your patients and your team.
Season 1 introduced Dômes Pharma UK’s S.M.A.R.T. Approach to Epilepsy, offering step-by-step support on seizure management. In Season 2, we build on that foundation with even more focused conversations - tackling status epilepticus, seizure mimics, feline epilepsy, adjunctive therapies, and the power of teamwork in chronic care.
Join us as we unravel the complexities of veterinary neurology, share real-world stories, and empower you with knowledge. Together, let’s enhance the health and happiness of our canine and feline companions.
🌐 Learn more about Dômes Pharma UK: https://domespharma.co.uk
Access Vet Resources from Dômes Pharma UK at https://domespharma.co.uk/the-vet-vault/
🌐 Learn more about Movement Referrals: https://www.movementvets.co.uk
Movement Referrals is an independent, specialist veterinary hospital with practices in the North West and Midlands. Our aim is to provide high-quality but efficient Specialist referral services. We concentrate on orthopaedics and neurology, two of the most common reasons for referrals. We offer common referral procedures, such as TPLO, patellar luxation, and spinal surgery, at reasonable prices.
One of our fundamental philosophies is "getting it right first time." We not only provide more choice at better value, but we aim to objectively demonstrate our value through measuring and publishing our
Hello and welcome back to
Synaptic Tales Season two.
I'm Emma, and I'm here with
Mark Lowrie to delve into the
intricate world of canine epilepsy.
Today we are focusing on adjunctive
medications and alternative therapies.
Ready?
Mark, we might bring back that
snake oil from the first season.
Well, you know what, it depends
how long we've got, but we could
definitely get onto that and we can
go much further than that if you like.
I mean,
Epilepsy management is a balancing act
and when first line treatments don't quite
hit the mark, well, adjunctive medications
and therapies can really help us tailor
the approach to the individual patient.
And I think owners are desperate to
find that golden bullet, so to speak.
So they'll be all over the
internet trying to tell you
what to prescribe to their dog.
Oh yes, for my sins, I am in various
Facebook groups and forums as well.
But that's what we really mean by
adjunctive therapies, isn't it?
It's those that are given alongside
the more traditional treatments.
So I think let's start with those.
Obviously most of us are familiar with
the likes of phenobarbital, and we spoke a
lot about it in the first season as well.
But what happens when they're not enough?
And I think, I find clinicians in
practice are very good at starting
treatments and taking blood samples.
And if they're like me though, they
often panic when you've got your serum
concentration back and the seizures still
aren't getting better, what do we do then?
It's really frustrating and yeah, you just
want to give a nice quick fix, don't you?
So, a great question.
First, it's important to highlight
the concept of appropriate dosing.
So if serum concentrations of the main
drug you're giving is sub therapeutic,
but the seizures are well controlled.
Well, there's no need to
increase the dose, we're happy.
Yeah.
But if the seizures persist, then
adding in a second medication
can often make a big difference.
And when you say sub therapeutic, that
can actually be quite tricky, isn't it?
Because the reference ranges
from the labs are quite wide,
particularly for phenobarbital.
Yeah.
They can be.
Generally we aim for between
25 to 35 mgs per litre.
As we know, the vast majority of
patients are well controlled at these
concentrations, but the lab reference
ranges are often much wider than that.
They can go from 15, maybe up to 40.
So if you have a patient say at 15 or
18 mg per litre, although it might be in
the reference range, we still definitely
have scope to increase that dose if
the seizures aren't well controlled.
And so once it's in that range, why do we
have to keep on monitoring these bloods?
Isn't it just going to stay there?
Well, phenobarbital is effective for
about 60 to 80% of epileptic dogs
when used as a monotherapy, but it's
got this auto induction effect, which
complicates the long-term effect.
You may remember, I like
to liken it to alcohol.
So, if you've never drunk alcohol
before and you have a, you enjoy a
nice glass of wine, it gives you like
a little woozy feeling at the end.
But then if you have another glass
of wine the next night, you might
not quite get that same effect.
So you have to have that little
bit more wine to achieve effect.
And so over time you're drinking
more and more to maybe achieve that
effect you first had in the first way.
Considering when we are recording,
this is giving me echoes of my dry
January and I didn't drink anything.
And then suddenly that
first drink again is woo.
I agree.
God, dry January.
I hate dry January.
I did it and I hated it.
But yeah, so exactly that.
So February the first, you enjoyed
that drink, but you felt probably
a little bit hungover the next day
from that, from very small drink.
I'm not accusing you of being a big
drinker, but just that small amount of
alcohol would be enough to tip you over.
But the same thing's true of
phenobarbital, so you start off
with say one tablet twice a day.
And then over time the dog
will develop a tolerance to it.
So actually we need to increase
that dose with time to maintain
the same therapeutic concentration.
So it's why we always
say blood monitoring key.
Doing it every six months is a good idea.
Two weeks after any dose change
and when there's changes in seizure
frequency because the dog is going to
get tolerant and we need to put more
medication in to give that same serum
therapeutic concentration long term.
That is interesting then, so when
we have a patient that's been on
phenobarbital for a little while, is it
the progression of that disease or is
it the tolerance to, to phenobarbital
or do we not know necessarily?
I think it absolutely is both.
So I think you are getting a tolerance
to medication, but we know epilepsy
is progressive, so I wouldn't want
to single one out over the other.
But both those things are
happening probably concurrently.
Yeah.
And so moving on to the kind of
adjunctive, or therapies, potassium
bromide, I think it's a bit of an old
school drug now, but it's really useful.
What do you think about
that for adjunctive therapy?
Yeah, you mentioned it to human
medics and they sort of think of it
as some kind of witchery or something.
It was in the dark ages, it was
considered a medication used to
kind of treat witches and get 'em
out of their witch like tendencies.
But you see it pairs really well
with phenobarbital because they've
got this kind of synergistic effect.
They work together.
It's also a great option for dogs with
the liver conditions that we've mentioned
because it's excreted via the kidneys.
The disadvantages, it does take
some months to reach steady state.
So three to four months to be exact.
So if we're going to start it today, don't
expect any benefit for a good few months.
And that's where there's a little bit
of a drawback and patience is vital.
Yeah, that is quite a long time.
I've seen, of course, that you
can do loading doses as well.
So do you recommend those?
Yeah, so a loading dose can be done.
It's 600 mgs per kg divided
usually over five days.
But of course it depends on the severity
of the seizures you're dealing with.
But look, it speeds things up,
but of course it then speeds up
side effects and makes them worse.
So I generally recommend
hospitalisation for doing this, due
to the risk of sedation, the ataxia
and potentially vomiting as well.
But really keep it for those severe
cases because you will see quite
profound side effects that can
persist for some weeks or even months.
But I guess those maintenance doses,
if you've just got a long term
approach, that's fine then isn't it
just a start at the maintenance doses?
And I think if you are preempting
that you're going to need it, then
introducing it sooner rather than
later is probably the way to go.
Yeah.
And what about imepitoin?
It's another licensed option, although
it seems a little bit niched perhaps.
Well, it is.
Phenobarbital and imepitoin are
the first two licensed treatments,
so we should make that clear.
They sort of sit at the top of
that A-C-V-I-M treatment triangle.
Both are highly effective, but
have different applications.
So imepitoin, I mean, it's it's licensed
specifically for managing generalised
seizures in idiopathic epilepsy.
In contrast, phenobarbital has a little
bit more of a broader range covering
both idiopathic and structural epilepsy.
It's particularly effective for
severe conditions like cluster
seizures and status epilepticus, where
imepitoin is not the preferred choice.
And actually it would say do avoid in
situations such as cluster seizures.
And do we have any kind of
studies comparing the two at all?
There was a study about six
years ago, I think 2019.
There was a study that provided
an excellent comparison
between these two medications.
Highlighting some of the key differences.
For instance, cluster seizures were
reported in nearly 70% of dogs that were
treated with imepitoin compared to just
under 40% in the Phenobarbital group.
And over a sort of three year period,
90% of dogs on imepitoin experience
cluster seizures compared to only
about 35% of those on phenobarb.
Now, imepitoin is sometimes thought
to have fewer side effects, but
this study actually showed that
adverse effects requiring a change in
medication were actually more common
with imepitoin than with phenobarbital.
So I think it's important that when
that's raised as an advantage, it may
not always be the case in the particular
patient you're prescribing it in.
These findings, combined with the
clinical experience we have, often
position phenobarbital a little bit
more as the preferred first line
treatment, especially for severe cases.
But imepitoin still might have a
place in those cases that maybe
are far less severe and just want
to maybe try medication early on.
Okay.
It sounds like careful patient selection
then is crucial really for these drugs.
And what about levetiracetam?
It's not obviously licensed for
dogs and cats, but it's become
really popular as an add-on.
What are your thoughts on this?
Well, it's brilliant for refractory cases.
I've got no question about that,
especially because it's so well tolerated.
It's also really useful in those dogs
that have problems with liver disease.
So, if we've got any problem there, let's
give levetiracetam because it's renally
excreted and then there's pulse therapy.
So that's where you use the
levetiracetam for cluster seizures.
You can go as high as 60 mgs per kg
as an initial dose, but then giving
sort of 20 to 30 mgs per kg every
eight hours during the cluster.
We call it a cluster buster until
the episodes have actually gone.
Yeah, I think that was really useful.
I remember this patient in practice
was on phenobarbital like all the time.
Obviously this was a
border collie, classic.
But then we'd, when it seizured it had a
cluster and it did this every kind of six
to eight weeks or something like that.
And it got to the point where the owners
would just call us up and go, oh, can
we get its levy drug again please?
And then we would just
prescribe a few days.
And that's acceptable to do, isn't it?
Oh, absolutely.
And that's the perfect
time to be using it.
I think that's a great situation
where it really helps that patient.
I've read within the literature
though that levetiracetam can have
a bit of a honeymoon effect and
maybe that's why we pulse dose it.
Do you see that?
Well, I don't really believe
it's got a true honeymoon effect.
The idea that it works well for three to
six months and then loses its efficacy
isn't really supported by the evidence.
If levetiracetam seems to stop
working, it's often more about the
progression of the epilepsy or the
underlying disease, rather than the
drug itself becoming less effective.
Similar to the question you asked
earlier about phenobarbital.
I think phenobarbital becomes more
tolerated, but the epilepsy progresses,
so you have to keep increasing the dose.
The same's true here, because remember
we're introducing levetiracetam quite
late on here, and by late on, I just
mean after some months of having
used something else previously.
So
the epilepsy's already progressed and so
seizures are becoming more problematic.
I suppose what's important is to
recognise that a dose adjustment
can often restore seizure control.
So if there is a drop in efficacy,
it's worth considering whether the
dose needs to be escalated rather
than assuming the medication's failed.
I still think it remains a really useful
tool in our management of epilepsy when
you tailor it to the patient's needs.
Yeah.
And so can you have a patient
that's on, say, lower doses long
term of levetiracetam and still
pulse dose it if you need to.
I kind of want to keep it in
my back pocket, I guess for
that emergency cluster episode.
That's fine too.
I tend to be more about having
it onboard fully or not at all.
I also get some owners that maybe only
give it sort of once or twice a day, and
I actually think that's worse because I
think actually what you're doing is the
way the halflife works, you're giving it
and there's periods of the day when the
dog will be well covered by levetiracetam
and periods when they aren't well covered.
And I tend to find in those periods when
they're not well covered, that's when
what we call breakthrough seizures occur.
So actually you can end up making
seizures worse in that scenario.
So I always stick to
three times daily dosing.
Do we do slightly lower dose?
You could definitely give it a go, but I,
it's not something I've done, but I think
there, there could be a reason to do it.
Yeah.
Yeah.
And what about things like
the emergency options?
So obviously it's not like a long-term
medication, but having things like we
mentioned it in a previous episode,
rectal diazepam for instance, at home.
Is that a useful thing for owners to have?
Oh, it's a must have for
cluster seizure prone dogs.
I think they have to have
this on the shelf ready.
We can give sort of around about half to
two mgs per kg at home and you can give
it up to three times in 24 hour period.
So it's a great way to stop the
seizure progression while waiting for
the dog to either get to the clinic
or for those seizures to pass by.
And for the really refractory cases,
we sometimes turn to drugs like
gabapentin, zonisamide, or even felbamate.
Like what are your thoughts on that?
They're worth considering,
but they come with caveats.
I don't use them very
often, I'll be honest.
And I certainly see plenty of
patients that are refractory
to epileptic medication.
The caveats are high cost, limited
evidence, it's important to say many of
the studies only include small numbers
of dogs in which they show there may
be a benefit and often really quite
disappointing results in severe cases.
So they're not magic bullets,
but they can sometimes tip the
scales in the right direction.
I think that must be a really
important conversation to have
with the owners as well as just to
make sure they realise that, you
know, if phenobarbital, potassium
bromide, haven't been the magic bullet,
is it likely that this one's going to be?
Perhaps not.
That's right.
Well, we go back to the
seven wives, don't we?
But I think, yes, if you're giving an
owner a medication in addition to others
that are in place, you're probably doing
that because the seizures are frequent.
And I think if the owner's expecting
to go home, give that medication
and seizures disappear, then well,
you've got a mismatch of expectations
so definitely still remember
the client communication is key.
Perfect.
So I think in summary, just kind
of wrapping up the medications part
here, getting the most out of those
first line options like phenobarbital
and potassium bromide are really key
here and kind of only moving on to
those others if we really need to.
So moving on, talking about
alternative therapies now.
And I don't mean things that are
medications, I mean things that aren't,
and owners often come in asking
about these, but some of them can be
quite surprisingly effective, right?
They can, you know what, if you go
onto forums and you Google this and
you pretend you're trying to manage
to find the cure for your dog.
You'll have some very
unusual things that come up.
People present them all the time.
They're huge hot topics at the minute.
Not a week goes past in our
clinic where someone might mention
things like MCT oil or CBD oil.
Various things like that that they
are using and with variable results,
but certainly some with success.
So you mentioned one there, CBD oil,
it comes up a lot in consultations.
What is the evidence behind it?
Well, I suppose the big misnomer we're
saying here is, we're not saying let's
smoke cannabis and hope life's good.
That's not what we're doing.
CBD oil is, important to
say it's a non psychoactive
compound derived from cannabis.
So really important to
say it's different to THC.
So THC is the psychoactive component
of cannabis and that causes the high,
that makes cannabis an abused drug.
So we're not looking at that.
So we'll put that to bed straight away.
Definitely.
But CBD oil is sought after
for its therapeutic effects
without causing that high.
So medicinal cannabis products are
often formulated to maximize the
CBD content while minimising the THC
to reduce the psychoactive effects.
I see.
Do we have any kind of studies
in dogs looking at CBD products?
Yeah, several studies have examined CBDs,
anti-epileptic potential in dogs, it
resulted in a 33% reduction in seizure
frequency when compared to a placebo.
But interestingly though, half
the dogs in both groups, so that's
the CBD and the placebo group,
were classified as responders.
So they both achieve more than
a 50% reduction in seizures.
Wow.
That's it.
So, you're giving CBD oil and
it's helping, but you're also
giving nothing and it's helping.
There's a second study that found
that 6 out of 14 dogs treated
with CBD achieved a more than 50%
reduction in seizure frequency, in
the same dogs receiving a placebo.
So clearly CBD in that circumstance
seems to have some form of benefit.
It's quite small numbers though, I guess.
They are, and this is important,
it comes back to all of them that,
we are looking at small numbers
of dogs, not large pools of 200
epileptic dogs, which would be ideal.
But we're just not able to get these
numbers in veterinary medicine.
And then there's a third study
that looked at dogs with drug
resistant idiopathic epilepsy.
So remember these are dogs that have
epilepsy, that have been given the
conventional medication, but still are
continuing to have severe seizures.
So the owners of these dogs were given
either a placebo, the same as the
previous two studies, and they didn't
know which was given to their dog.
They were then monitored for a
period of time with seizure frequency
recorded, and then switched to the other
medication for the same period of time.
Now in this study, dogs receiving CBD
oil alongside standard epileptic drugs
had a 25% reduction in seizure days.
Whereas the placebo
group saw a 6% increase.
Total seizure frequency increased
in both groups, although the
increase was smaller in the CBD
group, like sort of 3% versus 30%.
But the one thing I note from this study
is we normally use the definition of
successful treatment being more than
a 50% reduction in seizure frequency.
And you'll note that I mentioned
reduction in seizure days.
So if we do actually look at the
50% reduction in seizure frequency,
that kind of standard benchmark as
a successful outcome, then there was
actually no significant difference
between the CBD and placebo groups.
So I feel, when we actually look
at these studies in the way we've
looked at all other anti epileptic
medications and whether they're
effective or not, then there's not
quite such strong evidence for its use.
So there are a few studies out there with
perhaps promising results at the moment,
but is there anything on the flip side
that we should warn the owners about?
So things like adverse events, for
instance, and what about dosing?
It's funny this isn't it because we
talk about medications and we're always
talking about adverse effects and
things, but I've always noticed with
owners wanting to try these alternative
therapies, they don't seem to worry
about
no, it's true
adverse effects.
Side effects were seen in all of these
studies, all three of them reported
things like ataxia, so like a drunken
walk, lethargy, vomiting, and then
significant increases in some of the
liver enzymes like, alkaline phosphatase.
Now when you hear those, that could be
a list of side effects from any of the
other conventional medications we use.
Very similar side effects to what we're
used to, to our sort of licensed choices.
Now while these early findings
are encouraging, I guess
further research is needed to
standardise the dosing of CBD oil.
We need to confirm that it is safe and
we also need to evaluate its long-term
efficacy as an adjunctive therapy or
even as a primary treatment for epilepsy.
At the moment I think the verdict's
still out, but when you have a dog with
epilepsy and you're desperate to find
a suitable treatment, I certainly think
that CBD oil is worth considering.
And, I can think of many patients where
I have used this as an alternative
or as an adjunctive medication.
I think I always worry about
the legalities of recommending
or prescribing CBD oil.
Are we allowed to as vets?
In the UK, vets cannot legally
prescribe CBD products because,
well, we don't have any veterinary
medicinal products containing CBD
that are authorised in the UK.
However, under the Veterinary Medicines
Regulations, we can prescribe human
CBD products containing cannabin
oil, so the CBD, on the cascade, if
it's deemed clinically necessary.
Okay.
As you say, if they're still refractory,
then we can think about adding that in?
Indeed.
So it's not a first line approach here.
Recommending or prescribing CBD
you've got to approach it cautiously.
The product would need to come
from a reputable source, and I
suppose it's important to ensure
that it doesn't contain THC.
So that is a controlled
substance under UK law.
And additionally when discussing CBD
with clients, it's really important
to manage expectations yet again
because you want to highlight the
limited evidence available about its
efficacy and the safety in animals.
But ultimately if a client's
keen to use CBD for their pet?
Well, we should guide them responsibly.
We should make sure they
understand the legalities and
the risks and it's always good.
Well, it's always a good idea
to document these conversations
thoroughly in the clinical notes.
Definitely.
That really puts my mind at rest.
Thank you.
What about dietary management?
What about MCT diets?
There's a lot of talk
about them at the moment.
Yeah, this is one of my favourites.
So MCT.
So Medium Chain Triglyceride diets.
Studies here, well, they show a
32% reduction in seizure frequency
with medium chain triglycerides.
The diet here that was studied
is a specific diet that I
probably should mention.
So it's the Purina Neurocare Diet.
It's a commercial option and it
basically allows you to create the same
circumstances they had under the trial.
It isn't a standalone treatment, I should
say that again, but it is a great adjunct.
And how does it work?
Well, it's a, the ketogenic diet
is something that's long been
used in humans to manage epilepsy
and this diet is inspired by the
development of the MCT diet as a
more palatable alternative for dogs.
The ketogenic diet traditionally
was like high fat diet for people.
You'd kind of see like, a typical English
breakfast would be a very good idea of
what you'd have on a ketogenic diet.
But this diet replaces some long
chain fatty acids with medium chain
triglycerides, which are far more
readily absorbed and form ketones.
And these ketones make the diet ketogenic.
So we like ketones in epilepsy because
they reduce excitatory neuronal activity.
So they're effectively calming down
all those nerves that are short
circuiting in an epileptic brain.
They improve mitochondrial function,
given a more efficient energy source
for neurons, and that improves
their stability and resilience under
stress, which basically then means
they decrease neuroinflammation.
This is really just
trying to help the brain.
There's no doubt that chronic
inflammation in the brain is a potential
contributor to seizures and ketones
really probably do reduce this through
their anti-inflammatory pathways.
I'm more worried because I think
of ketones as like diabetic
dogs and stuff like that.
Should I be worried about
using these diets or?
I think as a neurologist, I don't
want to get into the ins and outs of
ketones because you're right keto
acidosis is clearly a very bad thing,
but I think in these circumstances
where you're giving it and giving it
in the kind of doses and the amounts we
are, there isn't really a big concern.
Okay.
A dog is able to metabolise these
effectively as opposed to in some
of these, well, a diabetic state
where there are clearly more
issues with glucose consumption.
Okay.
That's good.
And is the commercial diet the
only way to feed these MCT oils?
What about if the owners
are, say, reluctant to change
the diet, for instance?
Well, there are different ways to achieve
an MCT diet in dogs with epilepsy.
The easiest for me is just
to buy a commercial diet.
But you can go and buy a high grade
MCT oil, but you really want to ensure
that it contains both caprylic acid, or
C8, and capric acid, or C10, as these
are the key medium chain fatty acids
that generate ketones efficiently.
Some even look to using coconut oil,
but it's not really quite as effective
because it has far less concentrations
of these C8 and C10 compounds.
These findings just highlight the
potential of what these MCT based
diets might actually do as an
adjunctive therapy in epilepsy.
But I should say individual responses
vary, but owners are much more receptive
to diets and if you can fix something or
at least manage something with a diet,
I think owners are much more willing
to give it a go and try it long term.
Yeah, and I think that's really important
again, that I think as vets we just
go medications and, but owners want
to have these conversations with us
and being open and upfront about, they
are possibilities, but also what are
the likely kind of outcomes of these.
Aside from MCTs, the role of
diet is really interesting to me.
And I know we've talked in a previous
episode about inflammatory bowel
disease and the fly catching behaviour,
which was really interesting to me.
But I've also seen some information about
the gut brain axis and how patients with
inflammatory bowel diseases or dietary
intolerances can have increased seizure
frequencies during flare-ups as well.
So should we be thinking more
about a holistic approach when
it comes to epilepsy cases?
I think we should, I really do.
So this is still a very much an
emerging area, and I don't think
there's anything too strong there, but
there's definitely bits of evidence
pointing towards diet being huge.
And if you can manage your gut, your
brain potentially will benefit from that.
There was quite an old study now
that I remember that I really
liked, where they looked at only
a very small handful of dogs.
And they were dogs with drug
resistant epilepsy, so they'd been on
phenobarbital and potassium bromide.
It really effective, well, at
appropriate serum concentrations, but
they weren't being that effective.
It was, the dogs were still
having frequent seizures.
But in that study, these dogs also
had some kind of allergy as well.
And the allergies were either
gut allergies or skin allergies.
So they were being managed in this
case with a hypoallergenic diet.
Now in half of these dogs, they responded
really positively to a hypoallergenic diet
and the seizures reduced significantly
and they crossed the threshold for the 50%
reduction in seizure frequency by a mile.
So it showed that there was a
real positive benefit here that
was maintained after the study.
So there's clearly stuff going on with
diet here, and I always have to say,
it might not be the hypoallergenic
diet that was helping them.
There's some other inadvertent component
of that diet that helped, but there's
clearly a lot going on with diet,
and I know lots is being done right
now, looking into this more to try
and come up with further therapies.
Maybe that will be in season three.
Don't talk about season three.
So last season we mentioned
vagal nerve stimulation, which
sounded really intriguing, but
not exactly mainstream yet.
Is there any updates on that?
Surgically implanted vagal stimulators
are really quite effective.
But they're expensive
and definitely invasive.
A simpler option is like digital
ocular compression, which can sometimes
abort seizures, but it's crude, but it
can be effective in the right hands.
You literally mean just putting
your fingers on the eyeballs?
That's exactly it.
Now, if you close your eyes
and you push your eyeballs.
He's he's doing it right now.
I'm doing it right now.
I'm doing it in both but if you push both
eyes, you'll feel, well, you don't feel
anything, but it stimulates the vagus.
And then potentially
reduces seizure frequency.
But these are crude techniques, these
are going back some years, but I
think it's simpler than going for a
surgery to have an implant put in.
Last season our treatments, were you
coming home with us going for a walk and
now it's just digital ocular pressure.
Yeah, pushing your eyeballs in.
Simple and effective.
Doesn't cost a thing.
I just want to go back to
something you mentioned before.
We were talking about CBD oils and
actually that the placebo group
had a really high response as well.
So I think the placebo effect,
we can't ignore it, can we?
Absolutely.
So studies show a significant reduction in
seizure frequency, even in placebo groups.
It highlights the importance of really
trying to control these trials to
validate any treatments efficacy.
There are studies showing the placebo
effect is there in canine epilepsy.
It's not really understood why,
but it is really interesting
that we see such a thing.
The placebo effect is when we see a
psychological or physiological response
to an intervention that doesn't
have specific therapeutic activity.
So for example, in a placebo
controlled trial, over 50% of dogs
with epilepsy receiving a placebo
showed a reduction in seizure
frequency compared to their baseline.
Nearly one third of those dogs
were then classified as responders,
meaning they experienced a more
than 50% reduction in seizures.
That is actually a
shockingly high statistic.
Well, I suppose there are a
few reasons why we might see a
placebo effect in canine epilepsy.
You may have heard of
the caregiver effect.
So when a caregiver or owner knows
their pet's receiving a treatment, they
may perceive improvements or report
fewer seizures, even if the frequency
hasn't really changed objectively.
So subjectively, they're
feeling there's some form of
improvement, but this is hard.
But it's a hard one to believe as seizures
are either present or they're not.
So the use of a rigorous diary
to document the seizures, that
should really avoid that pitfall.
Even subtle changes in the dog's
environment, routine or the
caregiver's behaviour, during the
treatment period could positively
influence seizure frequency.
The fact we see a placebo effect really
tells us how important it is to use
rigorous placebo controlled studies
to really evaluate the effectiveness
of any anti-epileptic therapy.
And it's a reminder that not all
improvements in seizure control
can necessarily be attributed
to the treatment itself.
I think that's really hard though,
speaking as a pharmaceutical
company, for us to do a placebo
controlled trial obviously has
its ethical concerns as well.
Just thought that was
an interesting point.
Well, it is.
And it doesn't stop us doing some of
these studies because I sometimes feel
this barrier prevents us from learning
more because we're saying, well that's
not a placebo controlled study, but it
may still give valuable information.
So I think it's something more to be
aware of when interpreting results,
but not necessarily a barrier
to doing some of these studies.
And I wonder if it has something
to do with the owners being
less stressed about their pets,
thinking that they're receiving
a treatment that's going to help.
Has there been any studies
looking into owner stress and
its impacts upon epilepsy?
Well, you see, that's
a fascinating question.
Quite a deep one and one that speaks,
I suppose, to that complex relationship
between pets and their owners.
So while dogs themselves obviously
aren't really aware of whether they're
receiving an active treatment or a
placebo, the owner's perception of
improvement can really play a huge role
in how they report their pet's condition.
And that has been well documented
in studies on canine epilepsy.
There is evidence suggesting that when
owners feel less stressed, perhaps because
they believe a treatment is working, well
it can influence how they interpret and
report their dog's seizure behaviour.
And this isn't to say the seizures
themselves necessarily change, but
the owners might perceive the dog
as doing better, which can impact
how we assess treatment success.
And some research has explored
the broader impacts of owner
stress in canine epilepsy.
So a stressed owner may inadvertently
contribute to a more stressful
environment for the dog, potentially then
influencing seizure frequency or severity.
But the opposite of that would be that
when owners feel more in control, say
by starting a new treatment or having
a clear management plan, it can have a
positive ripple effect for that patient.
So while the placebo effect is
often viewed as a phenomenon
tied to the treatment itself.
It's quite possible that reducing
owner stress is part of the equation.
And it's a reminder that as vets
supporting the owner, it's really
as important as supporting the
patient and helping owners feel
informed, empowered, and reassured.
We can make a real difference.
That's really interesting.
So even in the absence of a
drug, it can still yield a
significant response in some cases.
Exactly.
And it emphasises why we need
to interpret treatment responses
carefully in clinical practice.
It's not just about the medication,
it's also about that broader context of
the dog's care routine and environment.
So we've talked about owner
stress and how that can impact on
epilepsy and their dog's epilepsy.
What about the other way round?
So I've been reading that there's
some kind of link between epilepsy
and anxiety states in dogs.
And actually if we can calm down
these kind of behavioural responses,
can that help the epilepsy?
Yeah, I think that's a really good point.
we're getting more evidence that dogs
that have epilepsy have other, well, I
suppose what we call comorbidities, other
problems associated with the epilepsy.
And in the past we kind of maybe
recognised the dog was a bit more
anxious but didn't appreciate it might
be part of the epileptic condition.
So anxiety is definitely one of them.
But all sorts of behavioural
changes can be associated with this.
I've known dogs that can be a
little bit more aggressive because
of their epilepsy or they might
be a little bit more subdued.
I mean it can work both ways.
So if you're dealing with an anxious
dog, it might be that relieving
anxiety in some way can help.
Now we've mentioned this
on a previous episode.
We are vets so we reached
straight for the drugs.
Yep, that was where my mind was going
so you know, we'll open up our cupboard.
We'll see there's plenty of anxiolytic
medication out there that can maybe help.
So anxiolytic medication may be
appropriate here that we use to try
and help a dog feel calmer and less
stressed in certain environments.
So I probably wouldn't use it all the
time, but maybe in those situations where
you anticipate a stressful experience
coming up, maybe the grandchildren are
coming around for Christmas or whatever it
might be, it might help in that situation.
But I think again, by managing
epilepsy with medication and
potentially through diet, diet here
might well help, it can help anxiety.
I think we're getting to the point
where we appreciate a healthy diet
will help you have a healthy brain
through a number of mechanisms that
I can't even begin to describe.
But I think all these
things would really help.
yeah, and I think, correct me if
I'm wrong, but I read that actually
some of these anxiety type states
and behavioural comorbidities
are independent of treatment.
So sometimes we think it's because
of an adverse effect really
from things like phenobarbital.
But actually they've been
seen in treatment naive dogs
as well, isn't that right?
That's absolutely right.
And actually I had a really good
example recently where a vet had
started a dog on phenobarbital and
the seizures were really loads better.
It was a good improvement.
But actually the dog had started
to bite people when it had
never been like that before.
And the question was posed, well,
is the phenobarbital doing this?
And actually, I really strongly
believed it wasn't the phenobarbital,
it was kind of almost unmasking other
aspects of that dog's condition.
So, the dog had a tendency towards that.
And the dog's brain had maybe caused
this situation where the threshold
for biting had been lowered.
And so a difficult situation, but one
that then can be managed in other ways.
So by managing the anxiety for that dog,
we did actually see a good response.
I wouldn't blame anti epileptic
medications when we see changes
in behaviour every time.
Certainly it can happen, but I
think there's often other causes.
Yeah.
It's really interesting and again,
comes back to that holistic approach,
really looking at the whole animal,
not just focusing on one part.
So Mark, what is your final advice,
I would say, to clinicians managing
these refractory epileptic dogs?
because they can be really
quite challenging cases.
Communication.
Well, that's everything.
You've got to set realistic expectations.
So seizure reduction, not
elimination, is really the standard
goal we should be heading for.
Managing epilepsy isn't just
about the dog, it's about
supporting the family as well.
Okay.
Well said.
Well said.
I think that's probably all we
have time for in this episode.
So thanks again for listening to
Synaptic Tails and join us next
time when we turn our eyes to cats.
Until next time.
Goodbye.
Bye, Mark.
Bye for now.