WEBVTT - Can we improve PTSD treatments? 0:00:00.009 --> 0:00:02.950 This podcast was made on the lands of the Wurundjeri people. 0:00:03.220 --> 0:00:06.360 The Woi-wurrung and the Bunurong. We would like to pay respects 0:00:06.369 --> 0:00:09.270 to their elders, past and present and emerging. 0:00:14.420 --> 0:00:17.950 From the Melbourne School of Psychological Sciences at the University 0:00:17.959 --> 0:00:20.389 of Melbourne. This is PsychTalks. 0:00:22.299 --> 0:00:25.239 Hi and welcome back to Psych Talks, a series that 0:00:25.250 --> 0:00:30.620 explores exciting new research in psychology and neuroscience. I'm Cassie Hayward, 0:00:30.629 --> 0:00:33.990 an Associate Professor here at the University of Melbourne's School 0:00:34.000 --> 0:00:38.330 of Psychological Sciences. Today I'm without my usual co-host professor 0:00:38.340 --> 0:00:40.489 Nick Haslam. But I am going to be joined by 0:00:40.500 --> 0:00:44.360 a fabulous guest, Professor Kim Felmingham. Kim is going to 0:00:44.369 --> 0:00:48.400 unpack for us her fascinating research into post-traumatic stress disorder, 0:00:48.409 --> 0:00:52.349 otherwise known as PTSD. We'll learn what kind of treatments 0:00:52.360 --> 0:00:55.430 are being used now and about promising new developments that 0:00:55.439 --> 0:00:58.709 might help those affected by this disorder. So stay tuned. 0:01:02.610 --> 0:01:04.470 Kim, welcome to PsychTalks. 0:01:04.569 --> 0:01:06.400 Thanks, Cassie. Thanks for having me. 0:01:07.080 --> 0:01:10.209 The main thing we're going to talk about today is PTSD, 0:01:10.510 --> 0:01:13.040 but I think it's one of those clinical terms that's 0:01:13.050 --> 0:01:17.549 kind of seeped into the vernacular of just casual language 0:01:17.549 --> 0:01:21.290 like anxiety or OCD. And I think when people use 0:01:21.300 --> 0:01:24.279 it in that everyday way, they are probably not using 0:01:24.290 --> 0:01:27.268 it in its proper clinical definition. So, I thought to 0:01:27.279 --> 0:01:30.489 set the scene today, you could set us straight with 0:01:30.500 --> 0:01:33.459 a proper clinical definition of PTSD. 0:01:33.949 --> 0:01:37.669 There is quite a stringent definition of PTSD the way 0:01:37.680 --> 0:01:40.089 that we define it, and there's been a lot of 0:01:40.099 --> 0:01:44.220 controversy over this over the years. First up is what 0:01:44.230 --> 0:01:47.457 is the nature of the trauma that you've experienced? Because 0:01:47.457 --> 0:01:51.444 uniquely amongst the psychological disorders, we actually know the aetiology 0:01:51.455 --> 0:01:55.125 of how it starts. It starts with a trauma experience, 0:01:55.135 --> 0:01:58.845 but the trauma experience actually has to be one where 0:01:58.855 --> 0:02:03.595 you are either witnessing or you're directly experiencing life threat 0:02:03.605 --> 0:02:07.375 to yourself or someone else or significant threat to your 0:02:07.385 --> 0:02:12.494 own physical integrity is what the core definition of is. 0:02:12.845 --> 0:02:16.035 We are recognising emotional abuse as part of that if 0:02:16.044 --> 0:02:19.600 it's repeated bullying and you've grown up in a really 0:02:19.610 --> 0:02:23.419 aversive environment, but often that goes along with physical abuse 0:02:23.429 --> 0:02:26.910 as well. The only exception to that is people who 0:02:26.919 --> 0:02:32.839 are observing traumatic incidents say they are first responders or 0:02:32.850 --> 0:02:35.619 they are looking at a lot of horrible graphic imagery, 0:02:35.630 --> 0:02:40.580 and it's a cumulative trauma. That's now also recognised as trauma. So, 0:02:40.589 --> 0:02:44.979 you need to experience that to actually qualify for the diagnosis. 0:02:45.139 --> 0:02:48.294 I think way that the word "trauma" is used has 0:02:48.304 --> 0:02:52.755 been overused. Increasingly, so people will say that their divorce 0:02:52.764 --> 0:02:55.134 is traumatic, and it is, it can be life shattering. 0:02:55.145 --> 0:02:58.195 But it's not the clinical definition we use of trauma 0:02:58.205 --> 0:03:01.484 for PTSD. And then, you know, we have a very 0:03:01.494 --> 0:03:05.315 clear set of symptoms, so we have re-experiencing symptoms. So, 0:03:05.324 --> 0:03:09.785 you either need to be having intrusive memories, nightmares, flashbacks 0:03:09.794 --> 0:03:14.913 or distress and physiologic reactivity to trauma reminders. So you're triggered. 0:03:15.630 --> 0:03:19.690 You need to have avoidance of those triggers and thoughts 0:03:19.699 --> 0:03:22.740 and memories. And then there's a whole range of negative 0:03:22.750 --> 0:03:26.750 cognitions and mood. A lot of those overlap with depression 0:03:26.758 --> 0:03:30.948 and generalised anxiety as well. But there are some that 0:03:30.960 --> 0:03:35.559 are quite unique to PTSD. So having emotional numbing, not 0:03:35.570 --> 0:03:40.360 being able to feel love or happiness, positive emotions is one. 0:03:40.369 --> 0:03:45.160 There's social withdrawal, negative thoughts about yourself and just feeling 0:03:45.169 --> 0:03:49.919 really intense negative emotion. And then we've got our hyperarousal symptoms, 0:03:49.929 --> 0:03:53.539 so they are often overlapping with other anxiety disorders. So 0:03:53.550 --> 0:04:01.059 sleep disturbance, irritability, concentration difficulties, but also more unique to 0:04:01.070 --> 0:04:05.610 PTSD is hypervigilance for danger. So, you're constantly looking around 0:04:05.619 --> 0:04:09.660 expecting something terrible is going to happen, scanning for threat 0:04:09.669 --> 0:04:12.500 and also an exaggerated startle response. 0:04:12.889 --> 0:04:15.809 But to meet the definition, they have to have something 0:04:15.820 --> 0:04:18.332 on the trauma side and something on the symptom side. 0:04:18.332 --> 0:04:18.403 Yes, you do. 0:04:18.403 --> 0:04:21.399 So, you could have people who experience- are a first 0:04:21.410 --> 0:04:24.829 responder or who experience something but don't end up having 0:04:24.839 --> 0:04:25.618 those symptoms. 0:04:26.339 --> 0:04:26.531 Absolutely. 0:04:26.531 --> 0:04:28.820 And some people who have those symptoms but haven't had 0:04:28.829 --> 0:04:30.709 the trauma to set it off. 0:04:30.720 --> 0:04:32.589 So, I think something that's missed a lot of the 0:04:32.600 --> 0:04:36.589 time is having a trauma experience doesn't equal PTSD. In fact, 0:04:36.600 --> 0:04:39.660 only about 10 to 15% of people who have a 0:04:39.670 --> 0:04:43.649 trauma develop PTSD. So, really, the story is one of 0:04:43.660 --> 0:04:48.880 resilience and recovery. But there's some traumas that are associated 0:04:48.890 --> 0:04:53.299 with higher rates of PTSD, so sexual abuse, combat experience, 0:04:53.320 --> 0:04:58.730 refugee experience and interpersonal violence far more. And if you've 0:04:58.738 --> 0:05:02.100 had childhood or cumulative trauma, you've got a higher risk 0:05:02.109 --> 0:05:06.390 as well. But what's fascinating is about 70 or 80% 0:05:06.399 --> 0:05:10.559 of us, probably 70% is more realistic, will experience these 0:05:10.570 --> 0:05:15.230 types of traumas, Criterion A trauma, but only 10 or 15% 0:05:15.238 --> 0:05:19.329 of us actually develop PTSD, and we don't really have 0:05:19.339 --> 0:05:22.709 a good answer as to why. What's the difference? What 0:05:22.720 --> 0:05:26.279 are the differentiating factors? We've got a range of risk factors, 0:05:26.290 --> 0:05:29.500 but we don't have a definitive answer yet. I wish 0:05:29.510 --> 0:05:30.070 we did. 0:05:30.928 --> 0:05:34.428 And of that definition, when we think of the clinical definition, 0:05:34.440 --> 0:05:39.260 what proportion of the population would meet that clinical definition 0:05:39.269 --> 0:05:40.209 in Australia? 0:05:40.440 --> 0:05:43.079 So, it's around 7%. So it's actually one of the 0:05:43.089 --> 0:05:48.640 more common psychological conditions and the real issue with PTSD. 0:05:48.649 --> 0:05:52.130 Once it gets going, it doesn't resolve by itself, so 0:05:52.140 --> 0:05:56.190 it can last for decades, and it can really impact 0:05:56.200 --> 0:06:00.450 on people's functioning terribly. It can really decimate their relationships, 0:06:00.459 --> 0:06:05.750 their occupational functioning, their social functioning, their sense of identity 0:06:05.760 --> 0:06:11.969 and self. It's really highly comorbid with depression, significant suicidality, 0:06:12.040 --> 0:06:15.969 substance abuse. So, you know, people really need to be able to 0:06:15.980 --> 0:06:20.910 access evidence-based treatments. It typically doesn't get better on its own. 0:06:21.279 --> 0:06:25.230 And I guess with some of those scenarios you mentioned: combat, 0:06:25.959 --> 0:06:29.880 there might be a stigma around seeking support, sexual assault. 0:06:29.890 --> 0:06:33.380 There might be shame associated. So I guess one of 0:06:33.390 --> 0:06:38.109 the challenges is convincing those people that they do need 0:06:38.119 --> 0:06:38.859 the treatment. 0:06:38.988 --> 0:06:42.640 Yes, really interesting. There's a lot of stigma, especially in 0:06:42.649 --> 0:06:47.738 first responder and combat veterans around. You know, there's some 0:06:47.750 --> 0:06:51.679 ideas of PTSD reflecting weakness. It actually isn't. It's a 0:06:51.690 --> 0:06:56.019 completely understandable response to the level of the trauma you've 0:06:56.029 --> 0:07:00.349 experienced or the cumulative nature of that trauma. One of 0:07:00.359 --> 0:07:05.739 the biggest predictors of developing PTSD is having cumulative exposure 0:07:06.070 --> 0:07:09.089 ahead of time. So, yes, it is a real challenge. 0:07:09.100 --> 0:07:11.929 But there are really effective treatments out there. So the 0:07:11.940 --> 0:07:14.380 hardest thing for me as a clinician is getting someone 0:07:14.390 --> 0:07:17.209 walking in the door, and they are 60 they've had 0:07:17.220 --> 0:07:21.119 these symptoms nightly nightmares for 40 years, you know? And 0:07:21.130 --> 0:07:24.910 I did. I treated a veteran who was 72 and 0:07:24.920 --> 0:07:28.989 he'd had symptoms for 48 years or 42 years. And 0:07:29.000 --> 0:07:33.290 within 10 weeks he didn't have any PTSD symptoms with treatment, 0:07:33.750 --> 0:07:36.149 but he just didn't have the access to the treatment. 0:07:36.160 --> 0:07:39.165 Was it access? Or was it a lack of kind 0:07:39.174 --> 0:07:40.904 of wanting to seek treatment? 0:07:40.915 --> 0:07:44.464 Good question. So what really happened for him was that 0:07:44.475 --> 0:07:48.065 he withdrew, and he was able to actually withdraw. He 0:07:48.075 --> 0:07:51.494 lived on a farm out in a rural setting. The 0:07:51.505 --> 0:07:54.945 work he did didn't involve interacting with anyone. And so 0:07:54.954 --> 0:07:57.904 he managed to create a world which felt safe for him. 0:07:57.915 --> 0:08:00.934 But he was still suffering from the symptoms. There was 0:08:00.945 --> 0:08:03.575 a lot of shame and stigma around it as well. 0:08:03.584 --> 0:08:06.739 And what really broke it for him was when he retired, 0:08:06.750 --> 0:08:10.690 the symptoms actually got worse. And he then went to 0:08:10.700 --> 0:08:14.540 a veterans' self-help group and a few Men's Sheds. And 0:08:14.549 --> 0:08:17.779 then he discovered that other men were also having these symptoms, 0:08:17.790 --> 0:08:20.679 and that undercut a bit of the shame and stigma 0:08:20.989 --> 0:08:24.339 and that then fed his way through to actually getting 0:08:24.350 --> 0:08:28.640 into seeing psychologists and getting some effective help. 0:08:28.899 --> 0:08:31.450 When you do get someone in for treatment when they've 0:08:31.459 --> 0:08:33.739 admitted that they need some help and they've gotten over 0:08:33.750 --> 0:08:37.010 those barriers to get in, what is the typical therapy 0:08:37.020 --> 0:08:40.299 for PTSD at the moment? And how successful is it? 0:08:40.440 --> 0:08:46.520 Yes. So, look, we've got a range of evidence-based treatments now. Predominantly, 0:08:46.530 --> 0:08:51.469 they all involve some element of processing trauma memories, which 0:08:51.479 --> 0:08:54.320 we so we have one sort of gold standard treatment 0:08:54.330 --> 0:08:58.989 is called prolonged exposure. It's got about 100-over 100 randomised control 0:08:59.000 --> 0:09:03.659 trials of evidence of its efficacy. It involves imaginal exposure 0:09:03.669 --> 0:09:07.330 where you're actually, rather than pushing the memories out, because 0:09:07.340 --> 0:09:10.229 we think that's what maintains PTSD. The more you push 0:09:10.239 --> 0:09:13.500 them out, the more they come back in. And so 0:09:13.510 --> 0:09:17.159 it involves inviting the memories in and going through them 0:09:17.169 --> 0:09:20.869 in detail with the therapist and talking them through. The 0:09:20.880 --> 0:09:23.729 old idea was that the mechanism of that was that 0:09:23.739 --> 0:09:27.770 led to a habituation or reduction of arousal. But we 0:09:27.780 --> 0:09:30.729 now know that that's really not the case. It's more 0:09:30.739 --> 0:09:34.848 about you get corrective information as doing that, which actually 0:09:34.859 --> 0:09:38.179 can then correct some of the difficult beliefs. So a 0:09:38.190 --> 0:09:42.155 classic example is, say, someone who's been sexually assaulted and has 0:09:42.164 --> 0:09:44.723 a lot of shame and self-blame that they didn't fight 0:09:44.734 --> 0:09:48.914 back. In that, they may have blocked, or their memory is 0:09:48.924 --> 0:09:51.974 typically fragmented. So, as we go back through the memory, 0:09:52.065 --> 0:09:56.255 remembering just how powerless they were or that the person 0:09:56.265 --> 0:09:59.604 had a weapon, actually, can be incredibly helpful, or that 0:09:59.614 --> 0:10:02.445 they had a freeze response, which is just a survival 0:10:02.455 --> 0:10:05.804 reflex that they didn't choose, that actually can really help 0:10:05.815 --> 0:10:09.179 them undercut the shame and the self-blame. And so it's 0:10:09.190 --> 0:10:12.049 corrective in that sort of way. We also then do 0:10:12.059 --> 0:10:16.380 in vivo exposure, which is gradually overcoming your avoidance to 0:10:16.390 --> 0:10:18.859 triggers but doing it in a very gradual way. So 0:10:18.869 --> 0:10:22.400 say someone has had a car accident and they, you know, 0:10:22.770 --> 0:10:24.689 don't want to get back into a car. We'll start 0:10:24.700 --> 0:10:26.380 by just getting them to sit in the car in 0:10:26.390 --> 0:10:30.580 the driveway until their anxiety comes down. Nothing bad happens. 0:10:30.590 --> 0:10:33.869 It's an example of extinction learning or being able to 0:10:33.880 --> 0:10:37.479 learn to reduce your fear in that context. Then you 0:10:37.489 --> 0:10:40.109 might start getting them to just reverse their car up 0:10:40.119 --> 0:10:43.409 and down the driveway until they feel confident enough. And 0:10:43.419 --> 0:10:45.919 then it might be just driving around the local streets, 0:10:46.479 --> 0:10:49.130 quiet back roads at a really quiet time, and then 0:10:49.140 --> 0:10:52.369 you are progressing gradually up to them resuming driving. 0:10:52.440 --> 0:10:55.039 And how successful are those treatments? 0:10:55.049 --> 0:11:00.270 So those treatments we would have probably between 50 and 60% 0:11:00.280 --> 0:11:04.179 of people have a good response to that treatment, so 0:11:04.190 --> 0:11:07.429 they are no longer PTSD. But you know, that means 0:11:07.440 --> 0:11:11.095 we've got 40 or 50% of people who don't and again, 0:11:11.095 --> 0:11:16.159 if you've got childhood trauma or more complex PTSD, the 0:11:16.169 --> 0:11:18.809 response rate is less than that, but there's a lot 0:11:18.820 --> 0:11:20.809 of complexities involved there. 0:11:20.820 --> 0:11:24.530 How does that compare to treatment for, say, depression or 0:11:24.539 --> 0:11:26.210 generalised anxiety or other...? 0:11:26.219 --> 0:11:29.289 It's pretty much on a par actually. So you know 0:11:29.299 --> 0:11:33.228 most of our psychological treatments are actually within that ballpark. 0:11:33.309 --> 0:11:38.729 You know, pharmacotherapy will have an equivalent success rate as well. 0:11:38.739 --> 0:11:42.090 Except when you go off the pharmacotherapy, you typically can 0:11:42.099 --> 0:11:47.650 relapse more than more of these psychological CBT interventions. And look, 0:11:47.659 --> 0:11:50.848 PTSD is one of the harder conditions to treat. Given 0:11:50.859 --> 0:11:54.689 the complexity and severity of the disorder, it's, I think 0:11:54.700 --> 0:11:58.299 it's actually a pretty good response rate. But being a clinician, 0:11:58.309 --> 0:12:00.429 what keeps you up at night is the other 40 0:12:00.440 --> 0:12:03.599 or 50% what's going on there and how do we 0:12:03.609 --> 0:12:07.209 improve it? There are some other evidence based treatments, so 0:12:07.219 --> 0:12:10.909 EMDR is one that has got equivalent efficacy to our 0:12:10.919 --> 0:12:12.510 exposure treatments. 0:12:12.760 --> 0:12:15.599 Kim. When you say EMDR, can you just give us 0:12:15.609 --> 0:12:17.349 a little snapshot of what that is? 0:12:17.799 --> 0:12:23.510 So, it stands for Eye Movement Desensitisation Reprocessing and again, 0:12:23.520 --> 0:12:26.556 it's been an intervention that's been around for about 20 0:12:26.565 --> 0:12:31.065 or 30 years, and it was evolved from Francine Shapiro's work, 0:12:31.075 --> 0:12:34.716 and there was a lot of controversy about it initially. 0:12:34.726 --> 0:12:38.074 But look, now they've done randomised control trials, and they 0:12:38.085 --> 0:12:42.905 do show that it's got equivalent efficacy for relative to 0:12:42.916 --> 0:12:47.622 some of our exposure-based treatments. So I think clinicians prefer 0:12:47.631 --> 0:12:50.381 to use it, and many clients prefer to use it 0:12:50.392 --> 0:12:52.702 because you don't have to talk through the details of 0:12:52.711 --> 0:12:57.660 the trauma memory. But, the thing we don't know which 0:12:57.671 --> 0:13:00.192 really lit a lot of the controversy about EMDR is 0:13:00.211 --> 0:13:03.141 what is the mechanism of it we really don't understand. 0:13:03.151 --> 0:13:07.439 It's a really weird therapy to do. So, you get 0:13:07.450 --> 0:13:10.270 an image of the trauma memory in mind. And whilst 0:13:10.280 --> 0:13:13.539 you keep it in mind, the therapist either does some 0:13:13.549 --> 0:13:17.919 bilateral hand movements. So moves their fingers backwards and forwards. 0:13:17.929 --> 0:13:24.299 Or they might have hand stimulators that stimulate each hand bilaterally. 0:13:24.549 --> 0:13:27.559 Or you might do tapping. And the idea is that 0:13:27.570 --> 0:13:31.099 that is going to desensitise the memory. Now there's been 0:13:31.109 --> 0:13:37.809 so many hokumm theories, "Ooh you know it's the intrahemispheric alpha rhythms, 0:13:37.820 --> 0:13:41.419 and they link, you know they mimic REM sleep comes 0:13:41.429 --> 0:13:47.650 into play here," but, you know, I think there isn't any really convincing evidence. 0:13:47.659 --> 0:13:50.580 And in fact, some people have done randomised control trials 0:13:50.590 --> 0:13:54.729 with and without the eye movements and found equivalent efficacy. So, 0:13:54.739 --> 0:13:58.569 it's not necessarily per se about the eye movements or 0:13:58.580 --> 0:14:03.449 the interhemispheric element. The most cogent theory, perhaps, I've found, 0:14:03.460 --> 0:14:07.909 is it's about memory reconsolidation again. So, the idea is, 0:14:07.919 --> 0:14:11.348 if you bring any memory back to mind, it's labile, 0:14:11.359 --> 0:14:14.289 which means that whatever you do in a certain period 0:14:14.299 --> 0:14:17.760 of time, it can be changed. So the idea is, 0:14:17.770 --> 0:14:19.979 if you bring this image to mind of the memory, 0:14:19.989 --> 0:14:23.059 it's back in a labile state. And then, if you 0:14:23.070 --> 0:14:27.239 are actually doing finger waggling and tapping, it's a dual task, 0:14:27.469 --> 0:14:32.020 and our memory and our attentional systems are limited capacity processes. 0:14:32.250 --> 0:14:35.710 So therefore, you are using up cognitive resources to be 0:14:35.719 --> 0:14:39.880 tracking fingers or to be doing a dual task. And 0:14:39.890 --> 0:14:42.239 the theory is that that then means you've got less 0:14:42.250 --> 0:14:47.000 brain processes or resources to reconsolidate the memory. So it's 0:14:47.010 --> 0:14:50.770 laid back down less strongly is the theory, and we 0:14:50.780 --> 0:14:53.859 also have cognitive processing therapy, which has really good evidence 0:14:54.729 --> 0:14:58.190 that doesn't necessarily involve working with trauma memories. But it's 0:14:58.200 --> 0:15:02.510 much more about the cognitions and beliefs about self. So 0:15:02.520 --> 0:15:05.340 you'd use that for someone with a very shame based 0:15:05.780 --> 0:15:10.989 PTSD who don't have many reexperiencing symptoms, for example. 0:15:11.000 --> 0:15:13.489 One thing I hear about in the kind of less 0:15:13.500 --> 0:15:16.690 evidence-based space, I guess, in the health podcast space, this 0:15:16.700 --> 0:15:20.960 emerging use of drugs like MDMA for treating PTSD a 0:15:20.969 --> 0:15:24.719 lot of acronyms there but basically using a pharmacologically supervised 0:15:24.729 --> 0:15:27.760 dose of what has traditionally been a recreational drug. What 0:15:27.770 --> 0:15:29.969 does the research actually say about that as a treatment? 0:15:30.719 --> 0:15:35.299 So, in terms of MDMA that's probably got, it's progressed 0:15:35.309 --> 0:15:38.994 furthest along. So, they've done the phase three trials. But 0:15:39.005 --> 0:15:41.825 the issue with it is that they've only been done 0:15:41.835 --> 0:15:44.864 largely by the one group of researchers. So we need 0:15:44.875 --> 0:15:50.205 independent replications, and you know there isn't sufficient evidence. The 0:15:50.215 --> 0:15:53.284 TGA approved it too early. The FDA has knocked it 0:15:53.294 --> 0:15:56.869 back because they think there's insufficient evidence and there are 0:15:56.880 --> 0:16:00.940 some real challenges in doing randomised control trials. You can't 0:16:00.950 --> 0:16:05.380 blind a control condition, and that actually is quite concerning 0:16:05.390 --> 0:16:09.700 because some of those early trials did have major expectancy 0:16:09.710 --> 0:16:13.700 effects in the participants. So some participants were flying themselves 0:16:13.710 --> 0:16:17.539 self-funding themselves to fly across the US to engage in 0:16:17.549 --> 0:16:21.400 these trials. So, they already came in with an expectancy. 0:16:21.409 --> 0:16:24.546 It was going to save them. Many desperate people, desperate 0:16:24.556 --> 0:16:28.625 for a cure for PTSD, which is understandable. And so, 0:16:28.635 --> 0:16:33.226 those expectancies weren't measured adequately enough. So that's one real 0:16:33.236 --> 0:16:36.656 flaw with the designs. And we need those independent replications 0:16:36.666 --> 0:16:40.585 from independent groups and probably in people who've got even 0:16:40.596 --> 0:16:44.666 a bit of cynicism about it and measuring the expectancy effects. 0:16:44.676 --> 0:16:47.145 The other thing, I think with the psychedelics that's a 0:16:47.156 --> 0:16:49.926 real limitation is this is not going to be a 0:16:49.935 --> 0:16:53.502 panacea for treating people. It's not going to be widely 0:16:53.512 --> 0:16:57.952 disseminated because it's such an expensive therapy. The estimates at 0:16:57.961 --> 0:17:01.471 the moment are it will cost between 10 and $20,000 0:17:01.481 --> 0:17:04.151 for a treatment. And if you think about it, you've 0:17:04.161 --> 0:17:08.761 got double the clinician time as a standard treatment for PTSD. 0:17:08.771 --> 0:17:10.602 And the other thing is, we don't have head to 0:17:10.612 --> 0:17:13.972 head randomised control trials of how well does it work 0:17:13.982 --> 0:17:17.370 compared to prolonged exposure, for example? So why would you 0:17:17.381 --> 0:17:22.416 suggest people do psychedelic therapies or MDMA assisted therapies? if 0:17:22.427 --> 0:17:25.886 they might respond better to prolonged exposure, which is cheaper 0:17:25.896 --> 0:17:27.817 and can be done in 10 weeks. So I think 0:17:27.827 --> 0:17:31.656 we are at a very premature area or level. But look, 0:17:31.666 --> 0:17:35.476 the pharmacological adjuncts has been around for about 10 or 0:17:35.487 --> 0:17:41.476 15 years, now. They've tried cortisol, yohimbine, oxytocin, MDMA. They've 0:17:41.487 --> 0:17:45.016 done D-cycloserine so they've done a whole range of them. 0:17:45.026 --> 0:17:49.163 And actually, when you look at the meta-analytic evidence, it's 0:17:49.173 --> 0:17:55.062 pretty uninspiring, and they haven't really found large effects. So 0:17:55.073 --> 0:17:58.484 I think there's a lot of fascination and interest. And 0:17:58.494 --> 0:18:03.593 certainly there's too much hype about MDMA and psychedelics. I'm 0:18:03.604 --> 0:18:06.894 sick of reading newspaper articles, and the damaging thing is 0:18:06.904 --> 0:18:10.723 that actually hurts vulnerable people because people with PTSD and 0:18:10.734 --> 0:18:14.963 trauma are incredibly vulnerable. They are living with a terrible condition, 0:18:15.280 --> 0:18:18.180 and then they are desperately seeking treatment. And then that 0:18:18.189 --> 0:18:21.829 compounds the expectancy bias, I think in the research. 0:18:22.390 --> 0:18:24.020 And so just to go back on something you said 0:18:24.030 --> 0:18:27.140 about they couldn't do blind trials. So you can't do 0:18:27.150 --> 0:18:30.099 a placebo with a hallucinogen or- 0:18:30.349 --> 0:18:34.290 No, it's impossible to have blind because of the effects 0:18:34.300 --> 0:18:36.819 of the MDMA because of the effects. If you're using 0:18:36.829 --> 0:18:40.239 psilocybin the person knows they've taken it and they're getting 0:18:40.250 --> 0:18:44.395 that active dose relative to a placebo. And the placebos 0:18:44.405 --> 0:18:47.665 they've trialled so far really aren't that effective. So in 0:18:47.675 --> 0:18:50.724 the maps trials that they've done, they used a very 0:18:50.734 --> 0:18:53.385 low dose of MDMA. But it was so low, it 0:18:53.395 --> 0:18:54.645 was really not. 0:18:55.204 --> 0:18:56.665 The person taking it would know they weren't getting the full dose? 0:18:58.494 --> 0:19:01.005 Yes, pretty much, pretty much. And look, you know, three 0:19:01.015 --> 0:19:04.814 of the MDMA papers have just been retracted. Actually, there 0:19:04.824 --> 0:19:08.604 have been really serious adverse events in those trials, like 0:19:08.614 --> 0:19:12.609 one patient was sexually assaulted, and they've included that data 0:19:12.619 --> 0:19:15.050 in some of those papers, so they've been retracted. But 0:19:15.060 --> 0:19:18.530 there's even now evidence coming out. They didn't measure serious 0:19:18.540 --> 0:19:22.920 adverse events well enough. So, there is reports of increased 0:19:22.930 --> 0:19:26.839 suicidal ideation and also people also saying they didn't want 0:19:26.849 --> 0:19:29.969 to report they had PTSD still, because they didn't want 0:19:29.979 --> 0:19:33.885 to threaten this new frontier of mental health treatment. So, 0:19:33.895 --> 0:19:38.375 there's these demand characteristics, so it's really inflating the effects. 0:19:38.385 --> 0:19:41.795 So I think we just need to do good critical science. 0:19:41.805 --> 0:19:44.514 You know, it's an exciting new potential. I'm all for 0:19:44.525 --> 0:19:48.015 getting new treatments for PTSD, but we need to do 0:19:48.025 --> 0:19:48.635 the science well. 0:19:48.645 --> 0:19:51.405 Yeah, I think it definitely highlights the need for that 0:19:51.415 --> 0:19:55.729 evidence-based research. And I know you've done some pretty groundbreaking 0:19:55.739 --> 0:20:01.890 work around other treatments for PTSD. Maybe around exercise therapy? 0:20:01.900 --> 0:20:04.089 Do you want to walk us through some of that research? 0:20:04.599 --> 0:20:06.750 Yeah, so look, the exercise stuff really came from my 0:20:06.760 --> 0:20:11.719 work in neuroscience, So I- there was some research coming out. 0:20:11.729 --> 0:20:15.349 There's a neurotrophin in the brain called BDNF: Brain Derived 0:20:15.359 --> 0:20:19.875 Neurotrophic Factor, and it enhances synaptic plasticity. It's critical for 0:20:19.885 --> 0:20:23.194 learning and memory. So, one of the theories about the 0:20:23.204 --> 0:20:26.915 exposure therapy is it involves this fear extinction process, which 0:20:26.925 --> 0:20:31.275 is unlearning your fear response that is being connected to 0:20:31.285 --> 0:20:35.084 stimuli or triggers in the environment. So, exposure therapy, you're 0:20:35.094 --> 0:20:37.333 bringing the memory into your mind, and you are in 0:20:37.344 --> 0:20:40.974 a safe therapy context and nothing bad happens, so you 0:20:40.984 --> 0:20:45.159 can learn to regulate your fear or extinguish it. So anyway, 0:20:45.170 --> 0:20:49.159 there was some evidence from animal work that BDNF actually 0:20:49.170 --> 0:20:53.319 enhanced fear extinction learning. And so we then took that 0:20:53.329 --> 0:20:57.359 into our human trials. So we- I do fear extinction research, 0:20:57.369 --> 0:21:00.129 giving people electric shocks, which is a bit mean, but 0:21:00.189 --> 0:21:05.920 why not? So, we found that people with BDNF, low 0:21:05.930 --> 0:21:10.300 levels of it had poorer extinction learning with PTSD and 0:21:10.310 --> 0:21:13.469 we were doing a clinical trial of prolonged exposure in 0:21:13.479 --> 0:21:16.550 PTSD patients. And again, we found those people who had 0:21:16.560 --> 0:21:21.050 lower levels of BDNF had poorer response to exposure therapy. 0:21:21.079 --> 0:21:25.430 So we had a really nice translation from animal science 0:21:25.439 --> 0:21:30.900 to human psychophysiology and neuroscience through to actual clinical trials. 0:21:30.910 --> 0:21:32.000 Which doesn't happen all the time. 0:21:32.010 --> 0:21:35.319 It's extremely rare and so we then went "Well, this 0:21:35.329 --> 0:21:39.670 is exciting. So how do we actually increase BDNF if 0:21:39.680 --> 0:21:43.599 we can increase BDNF before they go into the therapy session? 0:21:43.810 --> 0:21:47.369 Can we enhance the extinction learning?" And maybe that's going 0:21:47.380 --> 0:21:52.150 to enhance treatment outcomes for people. So, the best way 0:21:52.160 --> 0:21:56.869 to enhance BDNF is actually through aerobic exercise moderately intense 0:21:56.880 --> 0:22:01.229 to intense aerobic exercise. So that's how we devise this trial, 0:22:01.239 --> 0:22:04.469 which we've just randomised about 80 people and we are 0:22:04.479 --> 0:22:08.010 aiming to get about 110. It has taken five years 0:22:08.020 --> 0:22:12.650 off my life, but it's really exciting and worthwhile. So 0:22:12.660 --> 0:22:15.250 what we are basically doing is getting people to come in, 0:22:15.260 --> 0:22:18.890 and they do 20 minutes of moderate to intense exercise 0:22:19.130 --> 0:22:21.930 they are quite sweaty, and then they go into the 0:22:21.939 --> 0:22:26.280 therapy room and do standard prolonged exposure for 10 sessions. So, 0:22:26.290 --> 0:22:27.449 they do that across 10 weeks. 0:22:27.459 --> 0:22:29.129 And they do the exercise before each session? 0:22:29.479 --> 0:22:31.869 They do the exercise before every session. So the idea 0:22:31.880 --> 0:22:35.118 is that will enhance their BDNF and then their fear 0:22:35.118 --> 0:22:38.762 extinction learning will be better during the exposure, so we 0:22:38.772 --> 0:22:42.411 haven't unblinded it. We don't know what the results are 0:22:42.422 --> 0:22:45.203 as yet, but one thing that's really intriguing- 0:22:45.493 --> 0:22:48.562 So just, by unblinding you mean the clinician knows whether 0:22:48.571 --> 0:22:49.392 they've exercised or not? 0:22:49.593 --> 0:22:51.843 Yeah so it's fully, fully, and so we can't analyse 0:22:51.853 --> 0:22:54.272 the results. We really don't know until we get to 0:22:54.282 --> 0:22:57.003 the end of the trial. But what we have been 0:22:57.012 --> 0:23:00.723 tracking is people's dropout rates. And, you know, we've had-. 0:23:00.906 --> 0:23:05.576 Prolonged exposure, has fairly high about 25% dropout rates. Normally, 0:23:05.676 --> 0:23:09.446 we've actually been getting quite a complex childhood trauma group 0:23:09.455 --> 0:23:11.926 of people coming through. It wasn't by design. It's just 0:23:11.936 --> 0:23:14.484 who has come into the trial. So the dropout rates 0:23:14.494 --> 0:23:17.285 are even higher, which is to be expected. They are 0:23:17.296 --> 0:23:22.014 doing a very challenging therapy with really complex trauma. But 0:23:22.026 --> 0:23:25.296 the exercise group has got half of the dropout rates 0:23:25.705 --> 0:23:28.910 and that wasn't something we predicted, and I've got no 0:23:28.920 --> 0:23:29.739 idea why. 0:23:29.849 --> 0:23:32.500 Are they feeling- Is it because they are feeling more 0:23:32.510 --> 0:23:34.219 benefits from the therapy or we don't know yet? 0:23:34.229 --> 0:23:36.969 I don't know. Is it that they have another thing, 0:23:36.979 --> 0:23:38.780 that they'll get out of it as well as doing 0:23:38.790 --> 0:23:42.770 these challenging therapies? So that's what's keeping them going. Another 0:23:42.780 --> 0:23:45.979 theory might be that because they are doing the exercise, 0:23:45.989 --> 0:23:49.390 they are burning off some of the intensity of the 0:23:49.400 --> 0:23:53.359 anxiety before coming in so they can tolerate the exposure better. 0:23:53.530 --> 0:23:57.680 People who already exercise, who are runners or whatever who 0:23:57.689 --> 0:24:04.599 do this exercise. Will they have better effects of clinical therapy? 0:24:04.890 --> 0:24:05.530 Interestingly 0:24:05.609 --> 0:24:07.290