1 00:00:00,050 --> 00:00:03,260 Hello and welcome back to Synaptic Tales Season two. 2 00:00:04,069 --> 00:00:07,159 I'm Emma, and I'm here with Mark Lowrie to delve into the 3 00:00:07,159 --> 00:00:09,140 intricate world of canine epilepsy. 4 00:00:09,829 --> 00:00:13,970 Today we are focusing on adjunctive medications and alternative therapies. 5 00:00:14,433 --> 00:00:14,763 Ready? 6 00:00:14,763 --> 00:00:17,973 Mark, we might bring back that snake oil from the first season. 7 00:00:18,873 --> 00:00:21,303 Well, you know what, it depends how long we've got, but we could 8 00:00:21,303 --> 00:00:24,093 definitely get onto that and we can go much further than that if you like. 9 00:00:24,253 --> 00:00:24,463 I mean, 10 00:00:24,463 --> 00:00:28,753 Epilepsy management is a balancing act and when first line treatments don't quite 11 00:00:28,753 --> 00:00:33,253 hit the mark, well, adjunctive medications and therapies can really help us tailor 12 00:00:33,403 --> 00:00:35,076 the approach to the individual patient. 13 00:00:35,076 --> 00:00:40,326 And I think owners are desperate to find that golden bullet, so to speak. 14 00:00:40,326 --> 00:00:43,416 So they'll be all over the internet trying to tell you 15 00:00:43,566 --> 00:00:44,826 what to prescribe to their dog. 16 00:00:44,976 --> 00:00:49,296 Oh yes, for my sins, I am in various Facebook groups and forums as well. 17 00:00:49,506 --> 00:00:53,046 But that's what we really mean by adjunctive therapies, isn't it? 18 00:00:53,076 --> 00:00:57,126 It's those that are given alongside the more traditional treatments. 19 00:00:57,126 --> 00:00:58,656 So I think let's start with those. 20 00:00:59,286 --> 00:01:03,036 Obviously most of us are familiar with the likes of phenobarbital, and we spoke a 21 00:01:03,036 --> 00:01:05,076 lot about it in the first season as well. 22 00:01:05,076 --> 00:01:07,356 But what happens when they're not enough? 23 00:01:07,896 --> 00:01:12,208 And I think, I find clinicians in practice are very good at starting 24 00:01:12,208 --> 00:01:14,668 treatments and taking blood samples. 25 00:01:14,668 --> 00:01:18,988 And if they're like me though, they often panic when you've got your serum 26 00:01:18,988 --> 00:01:23,428 concentration back and the seizures still aren't getting better, what do we do then? 27 00:01:23,538 --> 00:01:27,028 It's really frustrating and yeah, you just want to give a nice quick fix, don't you? 28 00:01:27,028 --> 00:01:28,358 So, a great question. 29 00:01:28,478 --> 00:01:32,078 First, it's important to highlight the concept of appropriate dosing. 30 00:01:32,378 --> 00:01:37,328 So if serum concentrations of the main drug you're giving is sub therapeutic, 31 00:01:37,778 --> 00:01:39,548 but the seizures are well controlled. 32 00:01:39,788 --> 00:01:42,248 Well, there's no need to increase the dose, we're happy. 33 00:01:42,608 --> 00:01:42,878 Yeah. 34 00:01:43,208 --> 00:01:46,568 But if the seizures persist, then adding in a second medication 35 00:01:46,688 --> 00:01:48,023 can often make a big difference. 36 00:01:48,998 --> 00:01:53,468 And when you say sub therapeutic, that can actually be quite tricky, isn't it? 37 00:01:53,468 --> 00:01:56,768 Because the reference ranges from the labs are quite wide, 38 00:01:56,768 --> 00:01:57,903 particularly for phenobarbital. 39 00:01:58,598 --> 00:01:58,928 Yeah. 40 00:01:58,928 --> 00:01:59,708 They can be. 41 00:01:59,758 --> 00:02:04,048 Generally we aim for between 25 to 35 mgs per litre. 42 00:02:04,528 --> 00:02:08,248 As we know, the vast majority of patients are well controlled at these 43 00:02:08,248 --> 00:02:12,448 concentrations, but the lab reference ranges are often much wider than that. 44 00:02:12,448 --> 00:02:15,088 They can go from 15, maybe up to 40. 45 00:02:15,838 --> 00:02:20,548 So if you have a patient say at 15 or 18 mg per litre, although it might be in 46 00:02:20,548 --> 00:02:25,498 the reference range, we still definitely have scope to increase that dose if 47 00:02:25,498 --> 00:02:27,208 the seizures aren't well controlled. 48 00:02:28,118 --> 00:02:33,553 And so once it's in that range, why do we have to keep on monitoring these bloods? 49 00:02:33,553 --> 00:02:35,053 Isn't it just going to stay there? 50 00:02:35,863 --> 00:02:41,203 Well, phenobarbital is effective for about 60 to 80% of epileptic dogs 51 00:02:41,203 --> 00:02:45,493 when used as a monotherapy, but it's got this auto induction effect, which 52 00:02:45,493 --> 00:02:47,263 complicates the long-term effect. 53 00:02:47,263 --> 00:02:49,693 You may remember, I like to liken it to alcohol. 54 00:02:49,723 --> 00:02:52,303 So, if you've never drunk alcohol before and you have a, you enjoy a 55 00:02:52,333 --> 00:02:55,453 nice glass of wine, it gives you like a little woozy feeling at the end. 56 00:02:55,503 --> 00:02:57,273 But then if you have another glass of wine the next night, you might 57 00:02:57,273 --> 00:02:58,653 not quite get that same effect. 58 00:02:59,073 --> 00:03:01,983 So you have to have that little bit more wine to achieve effect. 59 00:03:02,013 --> 00:03:04,413 And so over time you're drinking more and more to maybe achieve that 60 00:03:04,413 --> 00:03:05,733 effect you first had in the first way. 61 00:03:05,883 --> 00:03:09,003 Considering when we are recording, this is giving me echoes of my dry 62 00:03:09,003 --> 00:03:11,523 January and I didn't drink anything. 63 00:03:11,523 --> 00:03:13,793 And then suddenly that first drink again is woo. 64 00:03:13,843 --> 00:03:14,203 I agree. 65 00:03:14,203 --> 00:03:15,223 God, dry January. 66 00:03:15,223 --> 00:03:16,213 I hate dry January. 67 00:03:16,213 --> 00:03:17,293 I did it and I hated it. 68 00:03:17,293 --> 00:03:18,433 But yeah, so exactly that. 69 00:03:18,433 --> 00:03:20,953 So February the first, you enjoyed that drink, but you felt probably 70 00:03:20,953 --> 00:03:24,433 a little bit hungover the next day from that, from very small drink. 71 00:03:24,433 --> 00:03:27,553 I'm not accusing you of being a big drinker, but just that small amount of 72 00:03:27,553 --> 00:03:28,783 alcohol would be enough to tip you over. 73 00:03:29,233 --> 00:03:31,693 But the same thing's true of phenobarbital, so you start off 74 00:03:31,693 --> 00:03:33,313 with say one tablet twice a day. 75 00:03:33,643 --> 00:03:36,103 And then over time the dog will develop a tolerance to it. 76 00:03:36,103 --> 00:03:38,833 So actually we need to increase that dose with time to maintain 77 00:03:38,833 --> 00:03:40,813 the same therapeutic concentration. 78 00:03:41,053 --> 00:03:43,963 So it's why we always say blood monitoring key. 79 00:03:44,063 --> 00:03:45,713 Doing it every six months is a good idea. 80 00:03:45,773 --> 00:03:49,043 Two weeks after any dose change and when there's changes in seizure 81 00:03:49,043 --> 00:03:52,583 frequency because the dog is going to get tolerant and we need to put more 82 00:03:52,583 --> 00:03:56,993 medication in to give that same serum therapeutic concentration long term. 83 00:03:57,353 --> 00:04:01,238 That is interesting then, so when we have a patient that's been on 84 00:04:01,318 --> 00:04:06,398 phenobarbital for a little while, is it the progression of that disease or is 85 00:04:06,398 --> 00:04:10,248 it the tolerance to, to phenobarbital or do we not know necessarily? 86 00:04:10,268 --> 00:04:11,408 I think it absolutely is both. 87 00:04:11,408 --> 00:04:14,258 So I think you are getting a tolerance to medication, but we know epilepsy 88 00:04:14,258 --> 00:04:17,288 is progressive, so I wouldn't want to single one out over the other. 89 00:04:17,288 --> 00:04:19,868 But both those things are happening probably concurrently. 90 00:04:20,148 --> 00:04:20,438 Yeah. 91 00:04:21,578 --> 00:04:26,003 And so moving on to the kind of adjunctive, or therapies, potassium 92 00:04:26,003 --> 00:04:30,533 bromide, I think it's a bit of an old school drug now, but it's really useful. 93 00:04:30,533 --> 00:04:32,543 What do you think about that for adjunctive therapy? 94 00:04:33,038 --> 00:04:35,378 Yeah, you mentioned it to human medics and they sort of think of it 95 00:04:35,378 --> 00:04:36,848 as some kind of witchery or something. 96 00:04:36,898 --> 00:04:40,308 It was in the dark ages, it was considered a medication used to 97 00:04:40,308 --> 00:04:43,458 kind of treat witches and get 'em out of their witch like tendencies. 98 00:04:43,586 --> 00:04:46,826 But you see it pairs really well with phenobarbital because they've 99 00:04:46,826 --> 00:04:48,351 got this kind of synergistic effect. 100 00:04:48,381 --> 00:04:49,371 They work together. 101 00:04:49,941 --> 00:04:53,931 It's also a great option for dogs with the liver conditions that we've mentioned 102 00:04:53,931 --> 00:04:55,581 because it's excreted via the kidneys. 103 00:04:55,631 --> 00:04:58,661 The disadvantages, it does take some months to reach steady state. 104 00:04:59,021 --> 00:05:01,511 So three to four months to be exact. 105 00:05:01,511 --> 00:05:05,651 So if we're going to start it today, don't expect any benefit for a good few months. 106 00:05:05,761 --> 00:05:09,091 And that's where there's a little bit of a drawback and patience is vital. 107 00:05:09,341 --> 00:05:10,871 Yeah, that is quite a long time. 108 00:05:10,871 --> 00:05:11,221 I've seen, of course, that you can do loading doses as well. 109 00:05:13,701 --> 00:05:15,021 So do you recommend those? 110 00:05:15,111 --> 00:05:16,551 Yeah, so a loading dose can be done. 111 00:05:16,621 --> 00:05:19,831 It's 600 mgs per kg divided usually over five days. 112 00:05:19,891 --> 00:05:23,011 But of course it depends on the severity of the seizures you're dealing with. 113 00:05:23,341 --> 00:05:26,221 But look, it speeds things up, but of course it then speeds up 114 00:05:26,221 --> 00:05:27,571 side effects and makes them worse. 115 00:05:27,571 --> 00:05:31,306 So I generally recommend hospitalisation for doing this, due 116 00:05:31,306 --> 00:05:34,876 to the risk of sedation, the ataxia and potentially vomiting as well. 117 00:05:35,596 --> 00:05:38,986 But really keep it for those severe cases because you will see quite 118 00:05:38,986 --> 00:05:42,176 profound side effects that can persist for some weeks or even months. 119 00:05:42,296 --> 00:05:45,506 But I guess those maintenance doses, if you've just got a long term 120 00:05:45,726 --> 00:05:49,476 approach, that's fine then isn't it just a start at the maintenance doses? 121 00:05:49,526 --> 00:05:51,956 And I think if you are preempting that you're going to need it, then 122 00:05:52,046 --> 00:05:54,536 introducing it sooner rather than later is probably the way to go. 123 00:05:54,686 --> 00:05:54,956 Yeah. 124 00:05:55,796 --> 00:05:57,336 And what about imepitoin? 125 00:05:57,356 --> 00:06:02,056 It's another licensed option, although it seems a little bit niched perhaps. 126 00:06:02,606 --> 00:06:03,121 Well, it is. 127 00:06:03,276 --> 00:06:07,326 Phenobarbital and imepitoin are the first two licensed treatments, 128 00:06:07,326 --> 00:06:08,556 so we should make that clear. 129 00:06:08,786 --> 00:06:12,266 They sort of sit at the top of that A-C-V-I-M treatment triangle. 130 00:06:12,576 --> 00:06:15,776 Both are highly effective, but have different applications. 131 00:06:16,106 --> 00:06:20,286 So imepitoin, I mean, it's it's licensed specifically for managing generalised 132 00:06:20,306 --> 00:06:22,226 seizures in idiopathic epilepsy. 133 00:06:22,886 --> 00:06:26,156 In contrast, phenobarbital has a little bit more of a broader range covering 134 00:06:26,156 --> 00:06:28,736 both idiopathic and structural epilepsy. 135 00:06:28,929 --> 00:06:32,289 It's particularly effective for severe conditions like cluster 136 00:06:32,289 --> 00:06:36,579 seizures and status epilepticus, where imepitoin is not the preferred choice. 137 00:06:36,579 --> 00:06:40,689 And actually it would say do avoid in situations such as cluster seizures. 138 00:06:40,824 --> 00:06:44,109 And do we have any kind of studies comparing the two at all? 139 00:06:44,569 --> 00:06:47,449 There was a study about six years ago, I think 2019. 140 00:06:47,519 --> 00:06:49,949 There was a study that provided an excellent comparison 141 00:06:49,949 --> 00:06:51,479 between these two medications. 142 00:06:51,559 --> 00:06:53,419 Highlighting some of the key differences. 143 00:06:53,749 --> 00:06:58,399 For instance, cluster seizures were reported in nearly 70% of dogs that were 144 00:06:58,399 --> 00:07:03,139 treated with imepitoin compared to just under 40% in the Phenobarbital group. 145 00:07:03,949 --> 00:07:08,419 And over a sort of three year period, 90% of dogs on imepitoin experience 146 00:07:08,419 --> 00:07:12,309 cluster seizures compared to only about 35% of those on phenobarb. 147 00:07:13,309 --> 00:07:18,169 Now, imepitoin is sometimes thought to have fewer side effects, but 148 00:07:18,169 --> 00:07:21,199 this study actually showed that adverse effects requiring a change in 149 00:07:21,199 --> 00:07:25,219 medication were actually more common with imepitoin than with phenobarbital. 150 00:07:25,939 --> 00:07:29,299 So I think it's important that when that's raised as an advantage, it may 151 00:07:29,299 --> 00:07:31,969 not always be the case in the particular patient you're prescribing it in. 152 00:07:32,849 --> 00:07:36,789 These findings, combined with the clinical experience we have, often 153 00:07:36,819 --> 00:07:39,609 position phenobarbital a little bit more as the preferred first line 154 00:07:39,609 --> 00:07:42,249 treatment, especially for severe cases. 155 00:07:42,369 --> 00:07:46,329 But imepitoin still might have a place in those cases that maybe 156 00:07:46,329 --> 00:07:50,079 are far less severe and just want to maybe try medication early on. 157 00:07:50,514 --> 00:07:50,874 Okay. 158 00:07:51,644 --> 00:07:55,994 It sounds like careful patient selection then is crucial really for these drugs. 159 00:07:56,264 --> 00:07:57,914 And what about levetiracetam? 160 00:07:58,334 --> 00:08:01,304 It's not obviously licensed for dogs and cats, but it's become 161 00:08:01,304 --> 00:08:03,044 really popular as an add-on. 162 00:08:03,044 --> 00:08:04,049 What are your thoughts on this? 163 00:08:04,859 --> 00:08:07,349 Well, it's brilliant for refractory cases. 164 00:08:07,349 --> 00:08:10,769 I've got no question about that, especially because it's so well tolerated. 165 00:08:11,429 --> 00:08:14,639 It's also really useful in those dogs that have problems with liver disease. 166 00:08:14,669 --> 00:08:18,059 So, if we've got any problem there, let's give levetiracetam because it's renally 167 00:08:18,059 --> 00:08:21,239 excreted and then there's pulse therapy. 168 00:08:21,339 --> 00:08:24,189 So that's where you use the levetiracetam for cluster seizures. 169 00:08:24,549 --> 00:08:28,389 You can go as high as 60 mgs per kg as an initial dose, but then giving 170 00:08:28,389 --> 00:08:31,839 sort of 20 to 30 mgs per kg every eight hours during the cluster. 171 00:08:32,349 --> 00:08:35,114 We call it a cluster buster until the episodes have actually gone. 172 00:08:35,519 --> 00:08:37,019 Yeah, I think that was really useful. 173 00:08:37,069 --> 00:08:41,509 I remember this patient in practice was on phenobarbital like all the time. 174 00:08:41,839 --> 00:08:44,389 Obviously this was a border collie, classic. 175 00:08:44,899 --> 00:08:49,599 But then we'd, when it seizured it had a cluster and it did this every kind of six 176 00:08:49,599 --> 00:08:51,009 to eight weeks or something like that. 177 00:08:51,639 --> 00:08:55,629 And it got to the point where the owners would just call us up and go, oh, can 178 00:08:55,629 --> 00:08:57,969 we get its levy drug again please? 179 00:08:57,969 --> 00:08:59,679 And then we would just prescribe a few days. 180 00:08:59,679 --> 00:09:00,979 And that's acceptable to do, isn't it? 181 00:09:01,079 --> 00:09:01,769 Oh, absolutely. 182 00:09:01,859 --> 00:09:03,659 And that's the perfect time to be using it. 183 00:09:03,659 --> 00:09:06,149 I think that's a great situation where it really helps that patient. 184 00:09:07,209 --> 00:09:10,749 I've read within the literature though that levetiracetam can have 185 00:09:10,749 --> 00:09:14,049 a bit of a honeymoon effect and maybe that's why we pulse dose it. 186 00:09:14,499 --> 00:09:15,699 Do you see that? 187 00:09:15,909 --> 00:09:18,829 Well, I don't really believe it's got a true honeymoon effect. 188 00:09:19,189 --> 00:09:22,409 The idea that it works well for three to six months and then loses its efficacy 189 00:09:22,429 --> 00:09:24,769 isn't really supported by the evidence. 190 00:09:25,289 --> 00:09:29,039 If levetiracetam seems to stop working, it's often more about the 191 00:09:29,039 --> 00:09:31,979 progression of the epilepsy or the underlying disease, rather than the 192 00:09:31,979 --> 00:09:33,659 drug itself becoming less effective. 193 00:09:33,989 --> 00:09:36,569 Similar to the question you asked earlier about phenobarbital. 194 00:09:36,569 --> 00:09:40,669 I think phenobarbital becomes more tolerated, but the epilepsy progresses, 195 00:09:40,669 --> 00:09:42,139 so you have to keep increasing the dose. 196 00:09:42,469 --> 00:09:45,649 The same's true here, because remember we're introducing levetiracetam quite 197 00:09:45,799 --> 00:09:49,699 late on here, and by late on, I just mean after some months of having 198 00:09:49,699 --> 00:09:51,109 used something else previously. 199 00:09:51,109 --> 00:09:51,379 So 200 00:09:51,739 --> 00:09:55,969 the epilepsy's already progressed and so seizures are becoming more problematic. 201 00:09:56,959 --> 00:09:59,629 I suppose what's important is to recognise that a dose adjustment 202 00:09:59,629 --> 00:10:01,759 can often restore seizure control. 203 00:10:01,759 --> 00:10:05,029 So if there is a drop in efficacy, it's worth considering whether the 204 00:10:05,029 --> 00:10:09,589 dose needs to be escalated rather than assuming the medication's failed. 205 00:10:10,549 --> 00:10:14,509 I still think it remains a really useful tool in our management of epilepsy when 206 00:10:14,509 --> 00:10:16,549 you tailor it to the patient's needs. 207 00:10:16,774 --> 00:10:17,074 Yeah. 208 00:10:17,734 --> 00:10:21,864 And so can you have a patient that's on, say, lower doses long 209 00:10:21,864 --> 00:10:25,584 term of levetiracetam and still pulse dose it if you need to. 210 00:10:25,584 --> 00:10:28,104 I kind of want to keep it in my back pocket, I guess for 211 00:10:28,104 --> 00:10:30,614 that emergency cluster episode. 212 00:10:30,614 --> 00:10:31,539 That's fine too. 213 00:10:31,589 --> 00:10:35,459 I tend to be more about having it onboard fully or not at all. 214 00:10:35,909 --> 00:10:38,999 I also get some owners that maybe only give it sort of once or twice a day, and 215 00:10:38,999 --> 00:10:42,779 I actually think that's worse because I think actually what you're doing is the 216 00:10:42,779 --> 00:10:45,269 way the halflife works, you're giving it and there's periods of the day when the 217 00:10:45,269 --> 00:10:48,509 dog will be well covered by levetiracetam and periods when they aren't well covered. 218 00:10:48,899 --> 00:10:51,569 And I tend to find in those periods when they're not well covered, that's when 219 00:10:51,989 --> 00:10:53,609 what we call breakthrough seizures occur. 220 00:10:53,849 --> 00:10:56,879 So actually you can end up making seizures worse in that scenario. 221 00:10:56,879 --> 00:10:59,159 So I always stick to three times daily dosing. 222 00:11:00,089 --> 00:11:01,349 Do we do slightly lower dose? 223 00:11:01,379 --> 00:11:04,319 You could definitely give it a go, but I, it's not something I've done, but I think 224 00:11:04,319 --> 00:11:05,789 there, there could be a reason to do it. 225 00:11:05,839 --> 00:11:06,139 Yeah. 226 00:11:06,409 --> 00:11:06,649 Yeah. 227 00:11:06,763 --> 00:11:09,853 And what about things like the emergency options? 228 00:11:09,888 --> 00:11:14,623 So obviously it's not like a long-term medication, but having things like we 229 00:11:14,623 --> 00:11:17,983 mentioned it in a previous episode, rectal diazepam for instance, at home. 230 00:11:17,983 --> 00:11:19,933 Is that a useful thing for owners to have? 231 00:11:20,308 --> 00:11:22,618 Oh, it's a must have for cluster seizure prone dogs. 232 00:11:22,618 --> 00:11:24,928 I think they have to have this on the shelf ready. 233 00:11:25,268 --> 00:11:29,588 We can give sort of around about half to two mgs per kg at home and you can give 234 00:11:29,588 --> 00:11:31,568 it up to three times in 24 hour period. 235 00:11:31,568 --> 00:11:35,608 So it's a great way to stop the seizure progression while waiting for 236 00:11:35,608 --> 00:11:38,518 the dog to either get to the clinic or for those seizures to pass by. 237 00:11:39,043 --> 00:11:43,863 And for the really refractory cases, we sometimes turn to drugs like 238 00:11:44,253 --> 00:11:47,793 gabapentin, zonisamide, or even felbamate. 239 00:11:47,943 --> 00:11:49,743 Like what are your thoughts on that? 240 00:11:50,173 --> 00:11:52,993 They're worth considering, but they come with caveats. 241 00:11:53,043 --> 00:11:55,143 I don't use them very often, I'll be honest. 242 00:11:55,223 --> 00:11:57,743 And I certainly see plenty of patients that are refractory 243 00:11:57,743 --> 00:11:59,293 to epileptic medication. 244 00:11:59,723 --> 00:12:03,633 The caveats are high cost, limited evidence, it's important to say many of 245 00:12:03,633 --> 00:12:06,993 the studies only include small numbers of dogs in which they show there may 246 00:12:06,993 --> 00:12:11,693 be a benefit and often really quite disappointing results in severe cases. 247 00:12:12,473 --> 00:12:15,523 So they're not magic bullets, but they can sometimes tip the 248 00:12:15,523 --> 00:12:16,843 scales in the right direction. 249 00:12:17,578 --> 00:12:20,158 I think that must be a really important conversation to have 250 00:12:20,158 --> 00:12:23,041 with the owners as well as just to make sure they realise that, you 251 00:12:23,041 --> 00:12:25,008 know, if phenobarbital, potassium 252 00:12:25,038 --> 00:12:31,048 bromide, haven't been the magic bullet, is it likely that this one's going to be? 253 00:12:31,258 --> 00:12:31,858 Perhaps not. 254 00:12:31,858 --> 00:12:32,308 That's right. 255 00:12:32,308 --> 00:12:34,078 Well, we go back to the seven wives, don't we? 256 00:12:34,268 --> 00:12:38,698 But I think, yes, if you're giving an owner a medication in addition to others 257 00:12:38,703 --> 00:12:42,033 that are in place, you're probably doing that because the seizures are frequent. 258 00:12:42,033 --> 00:12:44,733 And I think if the owner's expecting to go home, give that medication 259 00:12:44,733 --> 00:12:48,033 and seizures disappear, then well, you've got a mismatch of expectations 260 00:12:48,043 --> 00:12:51,253 so definitely still remember the client communication is key. 261 00:12:51,853 --> 00:12:52,393 Perfect. 262 00:12:52,873 --> 00:12:56,683 So I think in summary, just kind of wrapping up the medications part 263 00:12:56,683 --> 00:13:01,333 here, getting the most out of those first line options like phenobarbital 264 00:13:01,333 --> 00:13:05,263 and potassium bromide are really key here and kind of only moving on to 265 00:13:05,263 --> 00:13:06,793 those others if we really need to. 266 00:13:07,303 --> 00:13:11,233 So moving on, talking about alternative therapies now. 267 00:13:11,803 --> 00:13:16,456 And I don't mean things that are medications, I mean things that aren't, 268 00:13:16,636 --> 00:13:19,926 and owners often come in asking about these, but some of them can be 269 00:13:19,926 --> 00:13:21,576 quite surprisingly effective, right? 270 00:13:22,026 --> 00:13:25,416 They can, you know what, if you go onto forums and you Google this and 271 00:13:25,416 --> 00:13:27,786 you pretend you're trying to manage to find the cure for your dog. 272 00:13:28,026 --> 00:13:30,246 You'll have some very unusual things that come up. 273 00:13:30,246 --> 00:13:31,596 People present them all the time. 274 00:13:32,046 --> 00:13:34,146 They're huge hot topics at the minute. 275 00:13:34,146 --> 00:13:36,546 Not a week goes past in our clinic where someone might mention 276 00:13:36,546 --> 00:13:38,706 things like MCT oil or CBD oil. 277 00:13:38,746 --> 00:13:42,403 Various things like that that they are using and with variable results, 278 00:13:42,403 --> 00:13:43,848 but certainly some with success. 279 00:13:44,533 --> 00:13:48,913 So you mentioned one there, CBD oil, it comes up a lot in consultations. 280 00:13:49,183 --> 00:13:50,473 What is the evidence behind it? 281 00:13:50,523 --> 00:13:53,583 Well, I suppose the big misnomer we're saying here is, we're not saying let's 282 00:13:53,583 --> 00:13:55,203 smoke cannabis and hope life's good. 283 00:13:55,683 --> 00:13:56,643 That's not what we're doing. 284 00:13:57,253 --> 00:14:00,873 CBD oil is, important to say it's a non psychoactive 285 00:14:00,873 --> 00:14:02,583 compound derived from cannabis. 286 00:14:02,683 --> 00:14:05,413 So really important to say it's different to THC. 287 00:14:05,473 --> 00:14:09,493 So THC is the psychoactive component of cannabis and that causes the high, 288 00:14:10,003 --> 00:14:11,623 that makes cannabis an abused drug. 289 00:14:11,653 --> 00:14:12,793 So we're not looking at that. 290 00:14:12,853 --> 00:14:14,593 So we'll put that to bed straight away. 291 00:14:14,713 --> 00:14:15,133 Definitely. 292 00:14:15,183 --> 00:14:18,243 But CBD oil is sought after for its therapeutic effects 293 00:14:18,303 --> 00:14:19,863 without causing that high. 294 00:14:20,013 --> 00:14:23,613 So medicinal cannabis products are often formulated to maximize the 295 00:14:23,613 --> 00:14:29,373 CBD content while minimising the THC to reduce the psychoactive effects. 296 00:14:29,908 --> 00:14:30,188 I see. 297 00:14:30,688 --> 00:14:34,708 Do we have any kind of studies in dogs looking at CBD products? 298 00:14:35,473 --> 00:14:40,614 Yeah, several studies have examined CBDs, anti-epileptic potential in dogs, it 299 00:14:40,838 --> 00:14:45,953 resulted in a 33% reduction in seizure frequency when compared to a placebo. 300 00:14:46,823 --> 00:14:50,213 But interestingly though, half the dogs in both groups, so that's 301 00:14:50,213 --> 00:14:53,853 the CBD and the placebo group, were classified as responders. 302 00:14:53,853 --> 00:14:57,813 So they both achieve more than a 50% reduction in seizures. 303 00:14:58,068 --> 00:14:58,398 Wow. 304 00:14:58,398 --> 00:14:58,751 That's it. 305 00:14:58,751 --> 00:15:01,921 So, you're giving CBD oil and it's helping, but you're also 306 00:15:01,921 --> 00:15:03,361 giving nothing and it's helping. 307 00:15:03,481 --> 00:15:07,021 There's a second study that found that 6 out of 14 dogs treated 308 00:15:07,021 --> 00:15:12,111 with CBD achieved a more than 50% reduction in seizure frequency, in 309 00:15:12,111 --> 00:15:14,031 the same dogs receiving a placebo. 310 00:15:14,061 --> 00:15:18,441 So clearly CBD in that circumstance seems to have some form of benefit. 311 00:15:19,101 --> 00:15:20,681 It's quite small numbers though, I guess. 312 00:15:20,789 --> 00:15:23,574 They are, and this is important, it comes back to all of them that, 313 00:15:23,631 --> 00:15:26,901 we are looking at small numbers of dogs, not large pools of 200 314 00:15:26,901 --> 00:15:28,431 epileptic dogs, which would be ideal. 315 00:15:28,510 --> 00:15:31,264 But we're just not able to get these numbers in veterinary medicine. 316 00:15:32,164 --> 00:15:35,704 And then there's a third study that looked at dogs with drug 317 00:15:35,704 --> 00:15:37,354 resistant idiopathic epilepsy. 318 00:15:37,354 --> 00:15:40,744 So remember these are dogs that have epilepsy, that have been given the 319 00:15:40,744 --> 00:15:44,554 conventional medication, but still are continuing to have severe seizures. 320 00:15:45,274 --> 00:15:48,274 So the owners of these dogs were given either a placebo, the same as the 321 00:15:48,274 --> 00:15:52,504 previous two studies, and they didn't know which was given to their dog. 322 00:15:52,954 --> 00:15:56,014 They were then monitored for a period of time with seizure frequency 323 00:15:56,014 --> 00:16:01,214 recorded, and then switched to the other medication for the same period of time. 324 00:16:01,494 --> 00:16:06,179 Now in this study, dogs receiving CBD oil alongside standard epileptic drugs 325 00:16:06,209 --> 00:16:09,329 had a 25% reduction in seizure days. 326 00:16:10,079 --> 00:16:13,559 Whereas the placebo group saw a 6% increase. 327 00:16:14,292 --> 00:16:17,082 Total seizure frequency increased in both groups, although the 328 00:16:17,082 --> 00:16:21,912 increase was smaller in the CBD group, like sort of 3% versus 30%. 329 00:16:22,632 --> 00:16:26,022 But the one thing I note from this study is we normally use the definition of 330 00:16:26,022 --> 00:16:30,522 successful treatment being more than a 50% reduction in seizure frequency. 331 00:16:30,822 --> 00:16:34,542 And you'll note that I mentioned reduction in seizure days. 332 00:16:35,352 --> 00:16:38,892 So if we do actually look at the 50% reduction in seizure frequency, 333 00:16:38,892 --> 00:16:42,762 that kind of standard benchmark as a successful outcome, then there was 334 00:16:42,762 --> 00:16:46,872 actually no significant difference between the CBD and placebo groups. 335 00:16:47,502 --> 00:16:51,212 So I feel, when we actually look at these studies in the way we've 336 00:16:51,212 --> 00:16:53,552 looked at all other anti epileptic medications and whether they're 337 00:16:53,552 --> 00:16:57,662 effective or not, then there's not quite such strong evidence for its use. 338 00:16:57,912 --> 00:17:02,202 So there are a few studies out there with perhaps promising results at the moment, 339 00:17:02,772 --> 00:17:06,222 but is there anything on the flip side that we should warn the owners about? 340 00:17:06,222 --> 00:17:09,852 So things like adverse events, for instance, and what about dosing? 341 00:17:10,312 --> 00:17:13,552 It's funny this isn't it because we talk about medications and we're always 342 00:17:13,552 --> 00:17:16,342 talking about adverse effects and things, but I've always noticed with 343 00:17:16,342 --> 00:17:19,122 owners wanting to try these alternative therapies, they don't seem to worry 344 00:17:19,332 --> 00:17:19,542 about 345 00:17:19,542 --> 00:17:20,232 no, it's true 346 00:17:20,372 --> 00:17:20,892 adverse effects. 347 00:17:20,911 --> 00:17:24,671 Side effects were seen in all of these studies, all three of them reported 348 00:17:24,671 --> 00:17:29,395 things like ataxia, so like a drunken walk, lethargy, vomiting, and then 349 00:17:29,395 --> 00:17:33,325 significant increases in some of the liver enzymes like, alkaline phosphatase. 350 00:17:33,775 --> 00:17:36,505 Now when you hear those, that could be a list of side effects from any of the 351 00:17:36,505 --> 00:17:38,155 other conventional medications we use. 352 00:17:38,155 --> 00:17:42,655 Very similar side effects to what we're used to, to our sort of licensed choices. 353 00:17:42,679 --> 00:17:45,735 Now while these early findings are encouraging, I guess 354 00:17:45,825 --> 00:17:49,755 further research is needed to standardise the dosing of CBD oil. 355 00:17:50,135 --> 00:17:53,645 We need to confirm that it is safe and we also need to evaluate its long-term 356 00:17:53,645 --> 00:17:58,865 efficacy as an adjunctive therapy or even as a primary treatment for epilepsy. 357 00:17:59,295 --> 00:18:02,165 At the moment I think the verdict's still out, but when you have a dog with 358 00:18:02,165 --> 00:18:06,545 epilepsy and you're desperate to find a suitable treatment, I certainly think 359 00:18:06,545 --> 00:18:08,405 that CBD oil is worth considering. 360 00:18:08,405 --> 00:18:12,125 And, I can think of many patients where I have used this as an alternative 361 00:18:12,125 --> 00:18:14,045 or as an adjunctive medication. 362 00:18:14,255 --> 00:18:18,185 I think I always worry about the legalities of recommending 363 00:18:18,185 --> 00:18:20,315 or prescribing CBD oil. 364 00:18:20,405 --> 00:18:21,770 Are we allowed to as vets? 365 00:18:22,275 --> 00:18:26,805 In the UK, vets cannot legally prescribe CBD products because, 366 00:18:26,805 --> 00:18:30,585 well, we don't have any veterinary medicinal products containing CBD 367 00:18:30,585 --> 00:18:32,085 that are authorised in the UK. 368 00:18:33,285 --> 00:18:37,605 However, under the Veterinary Medicines Regulations, we can prescribe human 369 00:18:37,605 --> 00:18:42,615 CBD products containing cannabin oil, so the CBD, on the cascade, if 370 00:18:42,615 --> 00:18:44,595 it's deemed clinically necessary. 371 00:18:45,675 --> 00:18:45,945 Okay. 372 00:18:46,305 --> 00:18:49,605 As you say, if they're still refractory, then we can think about adding that in? 373 00:18:49,875 --> 00:18:50,385 Indeed. 374 00:18:50,385 --> 00:18:52,335 So it's not a first line approach here. 375 00:18:52,705 --> 00:18:56,185 Recommending or prescribing CBD you've got to approach it cautiously. 376 00:18:56,605 --> 00:18:59,635 The product would need to come from a reputable source, and I 377 00:18:59,635 --> 00:19:02,275 suppose it's important to ensure that it doesn't contain THC. 378 00:19:02,515 --> 00:19:04,985 So that is a controlled substance under UK law. 379 00:19:05,375 --> 00:19:08,615 And additionally when discussing CBD with clients, it's really important 380 00:19:08,615 --> 00:19:11,825 to manage expectations yet again because you want to highlight the 381 00:19:11,825 --> 00:19:16,145 limited evidence available about its efficacy and the safety in animals. 382 00:19:16,725 --> 00:19:20,430 But ultimately if a client's keen to use CBD for their pet? 383 00:19:20,490 --> 00:19:22,200 Well, we should guide them responsibly. 384 00:19:22,400 --> 00:19:24,510 We should make sure they understand the legalities and 385 00:19:24,510 --> 00:19:26,670 the risks and it's always good. 386 00:19:26,760 --> 00:19:29,160 Well, it's always a good idea to document these conversations 387 00:19:29,160 --> 00:19:30,090 thoroughly in the clinical notes. 388 00:19:30,885 --> 00:19:31,485 Definitely. 389 00:19:31,535 --> 00:19:33,035 That really puts my mind at rest. 390 00:19:33,035 --> 00:19:33,485 Thank you. 391 00:19:34,085 --> 00:19:35,675 What about dietary management? 392 00:19:35,725 --> 00:19:37,705 What about MCT diets? 393 00:19:37,705 --> 00:19:39,595 There's a lot of talk about them at the moment. 394 00:19:40,385 --> 00:19:41,955 Yeah, this is one of my favourites. 395 00:19:41,975 --> 00:19:43,330 So MCT. 396 00:19:43,330 --> 00:19:45,760 So Medium Chain Triglyceride diets. 397 00:19:45,850 --> 00:19:50,800 Studies here, well, they show a 32% reduction in seizure frequency 398 00:19:50,840 --> 00:19:52,970 with medium chain triglycerides. 399 00:19:53,570 --> 00:19:56,660 The diet here that was studied is a specific diet that I 400 00:19:56,660 --> 00:19:57,560 probably should mention. 401 00:19:57,560 --> 00:19:59,450 So it's the Purina Neurocare Diet. 402 00:19:59,870 --> 00:20:04,070 It's a commercial option and it basically allows you to create the same 403 00:20:04,070 --> 00:20:06,050 circumstances they had under the trial. 404 00:20:06,590 --> 00:20:10,580 It isn't a standalone treatment, I should say that again, but it is a great adjunct. 405 00:20:11,180 --> 00:20:12,470 And how does it work? 406 00:20:12,520 --> 00:20:16,300 Well, it's a, the ketogenic diet is something that's long been 407 00:20:16,300 --> 00:20:20,090 used in humans to manage epilepsy and this diet is inspired by the 408 00:20:20,090 --> 00:20:24,650 development of the MCT diet as a more palatable alternative for dogs. 409 00:20:25,060 --> 00:20:28,630 The ketogenic diet traditionally was like high fat diet for people. 410 00:20:28,630 --> 00:20:32,865 You'd kind of see like, a typical English breakfast would be a very good idea of 411 00:20:32,865 --> 00:20:34,575 what you'd have on a ketogenic diet. 412 00:20:34,615 --> 00:20:38,245 But this diet replaces some long chain fatty acids with medium chain 413 00:20:38,275 --> 00:20:42,325 triglycerides, which are far more readily absorbed and form ketones. 414 00:20:43,278 --> 00:20:45,708 And these ketones make the diet ketogenic. 415 00:20:45,708 --> 00:20:51,048 So we like ketones in epilepsy because they reduce excitatory neuronal activity. 416 00:20:51,258 --> 00:20:55,068 So they're effectively calming down all those nerves that are short 417 00:20:55,068 --> 00:20:56,988 circuiting in an epileptic brain. 418 00:20:57,618 --> 00:21:01,368 They improve mitochondrial function, given a more efficient energy source 419 00:21:01,368 --> 00:21:04,998 for neurons, and that improves their stability and resilience under 420 00:21:04,998 --> 00:21:08,958 stress, which basically then means they decrease neuroinflammation. 421 00:21:09,018 --> 00:21:10,968 This is really just trying to help the brain. 422 00:21:11,173 --> 00:21:14,203 There's no doubt that chronic inflammation in the brain is a potential 423 00:21:14,203 --> 00:21:18,583 contributor to seizures and ketones really probably do reduce this through 424 00:21:18,583 --> 00:21:20,263 their anti-inflammatory pathways. 425 00:21:20,263 --> 00:21:23,503 I'm more worried because I think of ketones as like diabetic 426 00:21:23,503 --> 00:21:24,793 dogs and stuff like that. 427 00:21:24,833 --> 00:21:26,873 Should I be worried about using these diets or? 428 00:21:27,393 --> 00:21:30,213 I think as a neurologist, I don't want to get into the ins and outs of 429 00:21:30,213 --> 00:21:34,243 ketones because you're right keto acidosis is clearly a very bad thing, 430 00:21:34,633 --> 00:21:37,718 but I think in these circumstances where you're giving it and giving it 431 00:21:37,898 --> 00:21:41,148 in the kind of doses and the amounts we are, there isn't really a big concern. 432 00:21:41,148 --> 00:21:41,288 Okay. 433 00:21:41,738 --> 00:21:44,498 A dog is able to metabolise these effectively as opposed to in some 434 00:21:44,498 --> 00:21:46,658 of these, well, a diabetic state where there are clearly more 435 00:21:46,658 --> 00:21:48,358 issues with glucose consumption. 436 00:21:48,443 --> 00:21:48,733 Okay. 437 00:21:48,868 --> 00:21:49,318 That's good. 438 00:21:50,008 --> 00:21:53,898 And is the commercial diet the only way to feed these MCT oils? 439 00:21:54,268 --> 00:21:56,548 What about if the owners are, say, reluctant to change 440 00:21:56,548 --> 00:21:57,703 the diet, for instance? 441 00:21:58,168 --> 00:22:02,368 Well, there are different ways to achieve an MCT diet in dogs with epilepsy. 442 00:22:02,368 --> 00:22:05,068 The easiest for me is just to buy a commercial diet. 443 00:22:05,458 --> 00:22:10,498 But you can go and buy a high grade MCT oil, but you really want to ensure 444 00:22:10,498 --> 00:22:17,068 that it contains both caprylic acid, or C8, and capric acid, or C10, as these 445 00:22:17,068 --> 00:22:20,638 are the key medium chain fatty acids that generate ketones efficiently. 446 00:22:21,058 --> 00:22:24,618 Some even look to using coconut oil, but it's not really quite as effective 447 00:22:24,618 --> 00:22:29,113 because it has far less concentrations of these C8 and C10 compounds. 448 00:22:30,118 --> 00:22:33,478 These findings just highlight the potential of what these MCT based 449 00:22:33,478 --> 00:22:36,478 diets might actually do as an adjunctive therapy in epilepsy. 450 00:22:36,928 --> 00:22:41,998 But I should say individual responses vary, but owners are much more receptive 451 00:22:41,998 --> 00:22:46,168 to diets and if you can fix something or at least manage something with a diet, 452 00:22:46,258 --> 00:22:50,098 I think owners are much more willing to give it a go and try it long term. 453 00:22:50,713 --> 00:22:56,113 Yeah, and I think that's really important again, that I think as vets we just 454 00:22:56,113 --> 00:23:00,733 go medications and, but owners want to have these conversations with us 455 00:23:00,733 --> 00:23:04,523 and being open and upfront about, they are possibilities, but also what are 456 00:23:04,523 --> 00:23:07,013 the likely kind of outcomes of these. 457 00:23:07,468 --> 00:23:11,218 Aside from MCTs, the role of diet is really interesting to me. 458 00:23:11,218 --> 00:23:15,328 And I know we've talked in a previous episode about inflammatory bowel 459 00:23:15,328 --> 00:23:19,048 disease and the fly catching behaviour, which was really interesting to me. 460 00:23:19,538 --> 00:23:24,128 But I've also seen some information about the gut brain axis and how patients with 461 00:23:24,128 --> 00:23:29,138 inflammatory bowel diseases or dietary intolerances can have increased seizure 462 00:23:29,138 --> 00:23:31,658 frequencies during flare-ups as well. 463 00:23:32,048 --> 00:23:35,378 So should we be thinking more about a holistic approach when 464 00:23:35,378 --> 00:23:36,848 it comes to epilepsy cases? 465 00:23:37,178 --> 00:23:38,708 I think we should, I really do. 466 00:23:38,708 --> 00:23:42,538 So this is still a very much an emerging area, and I don't think 467 00:23:42,538 --> 00:23:46,318 there's anything too strong there, but there's definitely bits of evidence 468 00:23:46,318 --> 00:23:48,358 pointing towards diet being huge. 469 00:23:48,538 --> 00:23:53,188 And if you can manage your gut, your brain potentially will benefit from that. 470 00:23:53,558 --> 00:23:56,018 There was quite an old study now that I remember that I really 471 00:23:56,018 --> 00:23:58,568 liked, where they looked at only a very small handful of dogs. 472 00:23:58,618 --> 00:24:02,158 And they were dogs with drug resistant epilepsy, so they'd been on 473 00:24:02,398 --> 00:24:04,258 phenobarbital and potassium bromide. 474 00:24:04,258 --> 00:24:08,248 It really effective, well, at appropriate serum concentrations, but 475 00:24:08,248 --> 00:24:09,538 they weren't being that effective. 476 00:24:09,538 --> 00:24:11,488 It was, the dogs were still having frequent seizures. 477 00:24:11,908 --> 00:24:15,908 But in that study, these dogs also had some kind of allergy as well. 478 00:24:16,018 --> 00:24:19,258 And the allergies were either gut allergies or skin allergies. 479 00:24:19,288 --> 00:24:23,968 So they were being managed in this case with a hypoallergenic diet. 480 00:24:24,748 --> 00:24:29,088 Now in half of these dogs, they responded really positively to a hypoallergenic diet 481 00:24:29,088 --> 00:24:33,588 and the seizures reduced significantly and they crossed the threshold for the 50% 482 00:24:33,588 --> 00:24:36,268 reduction in seizure frequency by a mile. 483 00:24:36,268 --> 00:24:39,718 So it showed that there was a real positive benefit here that 484 00:24:39,718 --> 00:24:41,218 was maintained after the study. 485 00:24:41,698 --> 00:24:45,598 So there's clearly stuff going on with diet here, and I always have to say, 486 00:24:45,598 --> 00:24:47,908 it might not be the hypoallergenic diet that was helping them. 487 00:24:47,908 --> 00:24:51,148 There's some other inadvertent component of that diet that helped, but there's 488 00:24:51,148 --> 00:24:54,658 clearly a lot going on with diet, and I know lots is being done right 489 00:24:54,658 --> 00:24:57,658 now, looking into this more to try and come up with further therapies. 490 00:24:58,158 --> 00:24:59,868 Maybe that will be in season three. 491 00:25:00,648 --> 00:25:02,058 Don't talk about season three. 492 00:25:03,542 --> 00:25:07,112 So last season we mentioned vagal nerve stimulation, which 493 00:25:07,112 --> 00:25:10,682 sounded really intriguing, but not exactly mainstream yet. 494 00:25:10,682 --> 00:25:11,792 Is there any updates on that? 495 00:25:12,065 --> 00:25:16,775 Surgically implanted vagal stimulators are really quite effective. 496 00:25:17,195 --> 00:25:19,895 But they're expensive and definitely invasive. 497 00:25:20,315 --> 00:25:24,245 A simpler option is like digital ocular compression, which can sometimes 498 00:25:24,245 --> 00:25:28,475 abort seizures, but it's crude, but it can be effective in the right hands. 499 00:25:28,967 --> 00:25:31,847 You literally mean just putting your fingers on the eyeballs? 500 00:25:32,112 --> 00:25:32,832 That's exactly it. 501 00:25:32,957 --> 00:25:35,277 Now, if you close your eyes and you push your eyeballs. 502 00:25:35,297 --> 00:25:36,707 He's he's doing it right now. 503 00:25:36,707 --> 00:25:37,247 I'm doing it right now. 504 00:25:37,247 --> 00:25:40,137 I'm doing it in both but if you push both eyes, you'll feel, well, you don't feel 505 00:25:40,137 --> 00:25:42,087 anything, but it stimulates the vagus. 506 00:25:42,467 --> 00:25:45,227 And then potentially reduces seizure frequency. 507 00:25:45,227 --> 00:25:49,087 But these are crude techniques, these are going back some years, but I 508 00:25:49,087 --> 00:25:51,667 think it's simpler than going for a surgery to have an implant put in. 509 00:25:51,717 --> 00:25:57,087 Last season our treatments, were you coming home with us going for a walk and 510 00:25:57,087 --> 00:26:00,087 now it's just digital ocular pressure. 511 00:26:01,137 --> 00:26:02,097 Yeah, pushing your eyeballs in. 512 00:26:02,147 --> 00:26:02,987 Simple and effective. 513 00:26:02,987 --> 00:26:03,857 Doesn't cost a thing. 514 00:26:04,757 --> 00:26:07,187 I just want to go back to something you mentioned before. 515 00:26:07,457 --> 00:26:11,657 We were talking about CBD oils and actually that the placebo group 516 00:26:11,927 --> 00:26:13,907 had a really high response as well. 517 00:26:13,907 --> 00:26:17,597 So I think the placebo effect, we can't ignore it, can we? 518 00:26:18,152 --> 00:26:18,392 Absolutely. 519 00:26:19,097 --> 00:26:25,097 So studies show a significant reduction in seizure frequency, even in placebo groups. 520 00:26:25,227 --> 00:26:28,367 It highlights the importance of really trying to control these trials to 521 00:26:28,367 --> 00:26:30,257 validate any treatments efficacy. 522 00:26:30,937 --> 00:26:34,687 There are studies showing the placebo effect is there in canine epilepsy. 523 00:26:35,077 --> 00:26:37,987 It's not really understood why, but it is really interesting 524 00:26:37,987 --> 00:26:39,247 that we see such a thing. 525 00:26:39,457 --> 00:26:43,377 The placebo effect is when we see a psychological or physiological response 526 00:26:43,377 --> 00:26:47,217 to an intervention that doesn't have specific therapeutic activity. 527 00:26:47,847 --> 00:26:52,347 So for example, in a placebo controlled trial, over 50% of dogs 528 00:26:52,347 --> 00:26:56,397 with epilepsy receiving a placebo showed a reduction in seizure 529 00:26:56,547 --> 00:26:58,347 frequency compared to their baseline. 530 00:26:58,927 --> 00:27:02,587 Nearly one third of those dogs were then classified as responders, 531 00:27:02,857 --> 00:27:07,147 meaning they experienced a more than 50% reduction in seizures. 532 00:27:07,717 --> 00:27:10,837 That is actually a shockingly high statistic. 533 00:27:11,287 --> 00:27:14,037 Well, I suppose there are a few reasons why we might see a 534 00:27:14,037 --> 00:27:16,287 placebo effect in canine epilepsy. 535 00:27:17,007 --> 00:27:18,987 You may have heard of the caregiver effect. 536 00:27:19,047 --> 00:27:24,057 So when a caregiver or owner knows their pet's receiving a treatment, they 537 00:27:24,057 --> 00:27:29,337 may perceive improvements or report fewer seizures, even if the frequency 538 00:27:29,337 --> 00:27:31,227 hasn't really changed objectively. 539 00:27:32,037 --> 00:27:34,347 So subjectively, they're feeling there's some form of 540 00:27:34,347 --> 00:27:37,017 improvement, but this is hard. 541 00:27:37,077 --> 00:27:40,347 But it's a hard one to believe as seizures are either present or they're not. 542 00:27:40,397 --> 00:27:44,817 So the use of a rigorous diary to document the seizures, that 543 00:27:44,817 --> 00:27:46,887 should really avoid that pitfall. 544 00:27:47,437 --> 00:27:51,337 Even subtle changes in the dog's environment, routine or the 545 00:27:51,337 --> 00:27:55,017 caregiver's behaviour, during the treatment period could positively 546 00:27:55,017 --> 00:27:56,607 influence seizure frequency. 547 00:27:57,387 --> 00:28:02,397 The fact we see a placebo effect really tells us how important it is to use 548 00:28:02,397 --> 00:28:06,897 rigorous placebo controlled studies to really evaluate the effectiveness 549 00:28:07,437 --> 00:28:09,327 of any anti-epileptic therapy. 550 00:28:10,077 --> 00:28:13,707 And it's a reminder that not all improvements in seizure control 551 00:28:13,887 --> 00:28:16,977 can necessarily be attributed to the treatment itself. 552 00:28:18,402 --> 00:28:21,032 I think that's really hard though, speaking as a pharmaceutical 553 00:28:21,032 --> 00:28:25,892 company, for us to do a placebo controlled trial obviously has 554 00:28:25,892 --> 00:28:27,452 its ethical concerns as well. 555 00:28:28,310 --> 00:28:29,582 Just thought that was an interesting point. 556 00:28:29,657 --> 00:28:30,077 Well, it is. 557 00:28:30,077 --> 00:28:33,527 And it doesn't stop us doing some of these studies because I sometimes feel 558 00:28:33,527 --> 00:28:36,947 this barrier prevents us from learning more because we're saying, well that's 559 00:28:36,947 --> 00:28:41,147 not a placebo controlled study, but it may still give valuable information. 560 00:28:41,147 --> 00:28:44,207 So I think it's something more to be aware of when interpreting results, 561 00:28:44,207 --> 00:28:46,617 but not necessarily a barrier to doing some of these studies. 562 00:28:46,808 --> 00:28:49,988 And I wonder if it has something to do with the owners being 563 00:28:49,988 --> 00:28:53,828 less stressed about their pets, thinking that they're receiving 564 00:28:53,828 --> 00:28:55,178 a treatment that's going to help. 565 00:28:55,688 --> 00:28:59,348 Has there been any studies looking into owner stress and 566 00:28:59,348 --> 00:29:01,058 its impacts upon epilepsy? 567 00:29:01,688 --> 00:29:03,378 Well, you see, that's a fascinating question. 568 00:29:03,378 --> 00:29:07,098 Quite a deep one and one that speaks, I suppose, to that complex relationship 569 00:29:07,098 --> 00:29:08,628 between pets and their owners. 570 00:29:09,078 --> 00:29:11,658 So while dogs themselves obviously aren't really aware of whether they're 571 00:29:11,658 --> 00:29:16,428 receiving an active treatment or a placebo, the owner's perception of 572 00:29:16,428 --> 00:29:20,088 improvement can really play a huge role in how they report their pet's condition. 573 00:29:20,538 --> 00:29:23,958 And that has been well documented in studies on canine epilepsy. 574 00:29:24,528 --> 00:29:29,118 There is evidence suggesting that when owners feel less stressed, perhaps because 575 00:29:29,118 --> 00:29:32,748 they believe a treatment is working, well it can influence how they interpret and 576 00:29:32,748 --> 00:29:34,378 report their dog's seizure behaviour. 577 00:29:35,058 --> 00:29:38,988 And this isn't to say the seizures themselves necessarily change, but 578 00:29:38,988 --> 00:29:42,828 the owners might perceive the dog as doing better, which can impact 579 00:29:42,888 --> 00:29:44,878 how we assess treatment success. 580 00:29:46,098 --> 00:29:49,368 And some research has explored the broader impacts of owner 581 00:29:49,368 --> 00:29:51,378 stress in canine epilepsy. 582 00:29:52,205 --> 00:29:56,555 So a stressed owner may inadvertently contribute to a more stressful 583 00:29:56,555 --> 00:30:02,285 environment for the dog, potentially then influencing seizure frequency or severity. 584 00:30:03,305 --> 00:30:06,665 But the opposite of that would be that when owners feel more in control, say 585 00:30:06,665 --> 00:30:11,255 by starting a new treatment or having a clear management plan, it can have a 586 00:30:11,255 --> 00:30:13,415 positive ripple effect for that patient. 587 00:30:14,435 --> 00:30:17,195 So while the placebo effect is often viewed as a phenomenon 588 00:30:17,375 --> 00:30:18,845 tied to the treatment itself. 589 00:30:19,640 --> 00:30:23,540 It's quite possible that reducing owner stress is part of the equation. 590 00:30:23,540 --> 00:30:27,620 And it's a reminder that as vets supporting the owner, it's really 591 00:30:27,800 --> 00:30:31,850 as important as supporting the patient and helping owners feel 592 00:30:31,850 --> 00:30:34,580 informed, empowered, and reassured. 593 00:30:34,580 --> 00:30:35,960 We can make a real difference. 594 00:30:37,100 --> 00:30:38,390 That's really interesting. 595 00:30:39,020 --> 00:30:42,770 So even in the absence of a drug, it can still yield a 596 00:30:42,770 --> 00:30:44,810 significant response in some cases. 597 00:30:45,020 --> 00:30:45,680 Exactly. 598 00:30:45,680 --> 00:30:48,620 And it emphasises why we need to interpret treatment responses 599 00:30:48,800 --> 00:30:50,840 carefully in clinical practice. 600 00:30:51,290 --> 00:30:55,820 It's not just about the medication, it's also about that broader context of 601 00:30:55,820 --> 00:30:58,725 the dog's care routine and environment. 602 00:30:59,013 --> 00:31:03,813 So we've talked about owner stress and how that can impact on 603 00:31:03,813 --> 00:31:05,283 epilepsy and their dog's epilepsy. 604 00:31:05,703 --> 00:31:07,623 What about the other way round? 605 00:31:08,013 --> 00:31:12,843 So I've been reading that there's some kind of link between epilepsy 606 00:31:12,873 --> 00:31:15,393 and anxiety states in dogs. 607 00:31:15,393 --> 00:31:18,933 And actually if we can calm down these kind of behavioural responses, 608 00:31:18,933 --> 00:31:20,613 can that help the epilepsy? 609 00:31:21,243 --> 00:31:22,368 Yeah, I think that's a really good point. 610 00:31:22,450 --> 00:31:26,410 we're getting more evidence that dogs that have epilepsy have other, well, I 611 00:31:26,410 --> 00:31:31,230 suppose what we call comorbidities, other problems associated with the epilepsy. 612 00:31:31,620 --> 00:31:34,740 And in the past we kind of maybe recognised the dog was a bit more 613 00:31:34,740 --> 00:31:38,100 anxious but didn't appreciate it might be part of the epileptic condition. 614 00:31:38,640 --> 00:31:40,380 So anxiety is definitely one of them. 615 00:31:40,380 --> 00:31:43,470 But all sorts of behavioural changes can be associated with this. 616 00:31:43,520 --> 00:31:46,970 I've known dogs that can be a little bit more aggressive because 617 00:31:46,970 --> 00:31:49,490 of their epilepsy or they might be a little bit more subdued. 618 00:31:49,550 --> 00:31:50,750 I mean it can work both ways. 619 00:31:50,800 --> 00:31:54,520 So if you're dealing with an anxious dog, it might be that relieving 620 00:31:54,520 --> 00:31:56,050 anxiety in some way can help. 621 00:31:56,080 --> 00:31:58,300 Now we've mentioned this on a previous episode. 622 00:31:58,300 --> 00:32:00,790 We are vets so we reached straight for the drugs. 623 00:32:01,090 --> 00:32:02,580 Yep, that was where my mind was going 624 00:32:02,630 --> 00:32:03,860 so you know, we'll open up our cupboard. 625 00:32:03,860 --> 00:32:07,600 We'll see there's plenty of anxiolytic medication out there that can maybe help. 626 00:32:07,600 --> 00:32:11,600 So anxiolytic medication may be appropriate here that we use to try 627 00:32:11,600 --> 00:32:16,280 and help a dog feel calmer and less stressed in certain environments. 628 00:32:16,280 --> 00:32:19,430 So I probably wouldn't use it all the time, but maybe in those situations where 629 00:32:19,430 --> 00:32:23,540 you anticipate a stressful experience coming up, maybe the grandchildren are 630 00:32:23,540 --> 00:32:27,590 coming around for Christmas or whatever it might be, it might help in that situation. 631 00:32:27,920 --> 00:32:31,700 But I think again, by managing epilepsy with medication and 632 00:32:31,700 --> 00:32:36,120 potentially through diet, diet here might well help, it can help anxiety. 633 00:32:36,120 --> 00:32:38,940 I think we're getting to the point where we appreciate a healthy diet 634 00:32:38,970 --> 00:32:42,080 will help you have a healthy brain through a number of mechanisms that 635 00:32:42,135 --> 00:32:43,695 I can't even begin to describe. 636 00:32:44,295 --> 00:32:45,825 But I think all these things would really help. 637 00:32:45,915 --> 00:32:50,055 yeah, and I think, correct me if I'm wrong, but I read that actually 638 00:32:50,055 --> 00:32:54,490 some of these anxiety type states and behavioural comorbidities 639 00:32:55,000 --> 00:32:57,670 are independent of treatment. 640 00:32:58,420 --> 00:33:01,950 So sometimes we think it's because of an adverse effect really 641 00:33:01,950 --> 00:33:03,600 from things like phenobarbital. 642 00:33:03,600 --> 00:33:06,470 But actually they've been seen in treatment naive dogs 643 00:33:06,470 --> 00:33:07,220 as well, isn't that right? 644 00:33:07,775 --> 00:33:08,465 That's absolutely right. 645 00:33:08,465 --> 00:33:10,925 And actually I had a really good example recently where a vet had 646 00:33:10,925 --> 00:33:15,005 started a dog on phenobarbital and the seizures were really loads better. 647 00:33:15,055 --> 00:33:15,955 It was a good improvement. 648 00:33:16,285 --> 00:33:19,675 But actually the dog had started to bite people when it had 649 00:33:19,675 --> 00:33:20,875 never been like that before. 650 00:33:21,265 --> 00:33:24,505 And the question was posed, well, is the phenobarbital doing this? 651 00:33:24,535 --> 00:33:27,230 And actually, I really strongly believed it wasn't the phenobarbital, 652 00:33:27,230 --> 00:33:30,510 it was kind of almost unmasking other aspects of that dog's condition. 653 00:33:30,510 --> 00:33:32,910 So, the dog had a tendency towards that. 654 00:33:32,910 --> 00:33:35,890 And the dog's brain had maybe caused this situation where the threshold 655 00:33:35,890 --> 00:33:37,070 for biting had been lowered. 656 00:33:37,070 --> 00:33:40,790 And so a difficult situation, but one that then can be managed in other ways. 657 00:33:40,790 --> 00:33:44,540 So by managing the anxiety for that dog, we did actually see a good response. 658 00:33:44,880 --> 00:33:48,000 I wouldn't blame anti epileptic medications when we see changes 659 00:33:48,000 --> 00:33:49,620 in behaviour every time. 660 00:33:49,740 --> 00:33:52,350 Certainly it can happen, but I think there's often other causes. 661 00:33:52,605 --> 00:33:52,845 Yeah. 662 00:33:52,995 --> 00:33:56,175 It's really interesting and again, comes back to that holistic approach, 663 00:33:56,175 --> 00:34:00,100 really looking at the whole animal, not just focusing on one part. 664 00:34:00,150 --> 00:34:05,420 So Mark, what is your final advice, I would say, to clinicians managing 665 00:34:05,420 --> 00:34:07,670 these refractory epileptic dogs? 666 00:34:07,670 --> 00:34:09,710 because they can be really quite challenging cases. 667 00:34:10,760 --> 00:34:11,300 Communication. 668 00:34:11,720 --> 00:34:12,710 Well, that's everything. 669 00:34:13,010 --> 00:34:15,440 You've got to set realistic expectations. 670 00:34:15,530 --> 00:34:20,810 So seizure reduction, not elimination, is really the standard 671 00:34:20,810 --> 00:34:22,040 goal we should be heading for. 672 00:34:22,580 --> 00:34:25,640 Managing epilepsy isn't just about the dog, it's about 673 00:34:25,640 --> 00:34:27,290 supporting the family as well. 674 00:34:27,785 --> 00:34:28,085 Okay. 675 00:34:28,175 --> 00:34:28,775 Well said. 676 00:34:28,775 --> 00:34:29,255 Well said. 677 00:34:30,065 --> 00:34:33,065 I think that's probably all we have time for in this episode. 678 00:34:33,065 --> 00:34:37,355 So thanks again for listening to Synaptic Tails and join us next 679 00:34:37,355 --> 00:34:39,785 time when we turn our eyes to cats. 680 00:34:39,935 --> 00:34:40,835 Until next time. 681 00:34:41,315 --> 00:34:41,855 Goodbye. 682 00:34:41,855 --> 00:34:42,305 Bye, Mark. 683 00:34:42,530 --> 00:34:43,280 Bye for now.