Dr. David Plevin - #21 - May 10, 2025

Mike: 00:00:15

Welcome back to the Neurostimulation Podcast, where we

2

: 00:00:18

explore the science practice and future

of brain-based therapies, clinical

3

: 00:00:23

neurostimulation in particular.

4

: 00:00:25

I'm your host, Dr.

5

: 00:00:26

Michael Passmore, and today's guest

is someone whose work truly bridges

6

: 00:00:30

clinical care and academic depth.

7

: 00:00:34

Dr.

8

: 00:00:34

David Plevin is a general psychiatrist,

as well as an addiction psychiatrist, a

9

: 00:00:39

clinical academic, and a PhD candidate at

the University of Adelaide in Australia.

10

: 00:00:44

Dr.

11

: 00:00:45

Plevin's work spans everything

from clinical neuromodulation and

12

: 00:00:49

de-prescribing to addiction psychiatry.

13

: 00:00:52

He's authored numerous peer reviewed

studies, including recent systematic

14

: 00:00:56

reviews on theta burst TMS or transcranial

magnetic stimulation, ECT in medically

15

: 00:01:03

complex patients and predictors of

treatment response in depression.

16

: 00:01:07

In this conversation, we're

going to dig into the nuances of

17

: 00:01:10

transcranial magnetic stimulation.

18

: 00:01:13

It's going to be a wide ranging

and thought provoking discussion,

19

: 00:01:16

and I think you'll come away

with both clinical insights and

20

: 00:01:19

philosophical food for thought.

21

: 00:01:32

So I'm back with Dr.

22

: 00:01:33

David Plevin.

23

: 00:01:34

David, thank you so much

for joining me today.

24

: 00:01:37

I'm really excited for this conversation.

25

: 00:01:39

I'm really looking forward

to learning more about your

26

: 00:01:41

practice, your research, and yeah.

27

: 00:01:44

Thanks again for joining me today.

28

: 00:01:46

David: Thank you so much for having

me, Mike, and it was a pleasure to

29

: 00:01:48

meet you in Japan earlier in the year.

30

: 00:01:51

Mike: Yeah, exactly.

31

: 00:01:52

And we were just talking a bit about that

before rolling with the recording, Dr.

32

: 00:01:56

Plevin and I met at the Brain

Stimulation Conference in Kobe

33

: 00:02:00

Japan in February of this year.

34

: 00:02:02

And it was a great meeting.

35

: 00:02:04

It was fascinating and lots of

interesting presentations both

36

: 00:02:08

in terms of the speakers and

the posters that were presented.

37

: 00:02:11

And I was particularly

interested and fascinated with.

38

: 00:02:14

Dr.

39

: 00:02:15

Plevin's team's poster, which he

presented there, and we're gonna

40

: 00:02:18

be talking a lot about that today.

41

: 00:02:20

So yeah, indeed.

42

: 00:02:20

It was great to meet you there, David.

43

: 00:02:22

And that was certainly a

very interesting conference.

44

: 00:02:25

And so I was gonna ask then may,

maybe we can just go right into it.

45

: 00:02:28

Sure.

46

: 00:02:29

In general, you've got a very unique

and interesting clinical background,

47

: 00:02:33

working across mental health,

general psychiatry, addictions, as

48

: 00:02:37

well as clinical neurostimulation.

49

: 00:02:39

Yes.

50

: 00:02:39

So maybe you could help us to provide some

background and help people to get to know

51

: 00:02:44

you a bit in how those sorts of domains

intersect in your practice these days.

52

: 00:02:49

David: Sure.

53

: 00:02:49

I have had a varied background to

get into medicine and psychiatry in

54

: 00:02:53

the first place, having done science

and then pharmacy and then medicine

55

: 00:02:57

and in within psychiatry, I I'm not

sure what the training is in Canada

56

: 00:03:04

or elsewhere in the world, but in

Australia and New Zealand, it's a five

57

: 00:03:07

year training program after internship.

58

: 00:03:09

I did three years of it was general

psychiatry and mandatory consult liaison

59

: 00:03:15

and child & adolescent rotations.

60

: 00:03:17

And then I did two years advanced training

in addiction psychiatry at a public drug

61

: 00:03:23

and alcohol service here in Adelaide.

62

: 00:03:25

And I'm have since after

gaining fellowship, worked in

63

: 00:03:30

private practice and academia.

64

: 00:03:31

So I have a halftime role, which

links in with the private hospital at

65

: 00:03:36

which I admit patients and at which

I have my consulting suites as well.

66

: 00:03:40

And my, after seeing a talk a couple of

years back, we had Leo Chen, who's now

67

: 00:03:46

one of our supervisors Shan Siddiqi and

Joshua Brown, they were in Adelaide.

68

: 00:03:51

They gave us a presentation here at our

clinic as part of the continuing medical

69

: 00:03:56

education, essentially grand rounds, and

from that, I moved into a PhD in TMS.

70

: 00:04:03

I have an interest in

personalized medicine.

71

: 00:04:06

Going back a while when I did an

undergraduate degree in, in science,

72

: 00:04:10

I did an honors in pharmacology.

73

: 00:04:11

We were looking at the pharmacogenetics

of the peak glycoprotein, which is one

74

: 00:04:16

of the efflux transporters, and looking

at that in kidney donors, transplant

75

: 00:04:21

donors and recipients, and seeing if that

correlated with various clinical outcomes.

76

: 00:04:27

So there's a longstanding interest

in personalized medicine, and this

77

: 00:04:30

is, the latest manifestation of that.

78

: 00:04:33

Mike: Yeah that's really fascinating.

79

: 00:04:35

It is one of the things that's gotten

me very interested in neurostimulation

80

: 00:04:39

in general, the sort of the transition

and historically I think we're seeing

81

: 00:04:42

that it's going from more of a sort

of like a more general application

82

: 00:04:46

and dare I say, crude, with.

83

: 00:04:49

Back in the days of ECT with less

refinement in terms of the actual,

84

: 00:04:53

specifics and the technology

of that particular treatment.

85

: 00:04:56

Yeah.

86

: 00:04:56

And in general, becoming more refined

and personalized, as you say, with all

87

: 00:04:59

of these various different technologies

now, like the TMS and the theta burst

88

: 00:05:03

and all the different things that we're

gonna be certainly talking about today.

89

: 00:05:06

But that is fascinating and I think I

shared those interests as well with you.

90

: 00:05:11

And I think it's much needed because

whether it's medication or psychotherapy,

91

: 00:05:15

we do try and do our best for individual

patients to personalize these treatments,

92

: 00:05:19

but there's always improvements

that, that are, you know, necessary.

93

: 00:05:23

David: Oh, I agree.

94

: 00:05:24

At this stage, it's, this is part

of the fun of psychiatric practice,

95

: 00:05:28

but it does, it would be nice if

we had more of a, a scientifically

96

: 00:05:33

backed rationale for choosing a

particular medication, neurostimulation

97

: 00:05:37

treatment of psychotherapy.

98

: 00:05:38

I.

99

: 00:05:38

Or whether to say none of

the above actually work.

100

: 00:05:41

These are all useful things for an

individual and for, broader public

101

: 00:05:46

health allocation of resources as well.

102

: 00:05:49

Mike: Yeah, definitely.

103

: 00:05:50

And what's interesting and exciting is the

prospect of combining things in a targeted

104

: 00:05:54

way to achieve that personalization.

105

: 00:05:56

Yeah.

106

: 00:05:56

I'm sure.

107

: 00:05:57

I'm curious then.

108

: 00:05:58

It makes sense based on what

you were just saying in terms of

109

: 00:06:00

that story that brought you here.

110

: 00:06:02

But are there any other things that

you can that come to mind that really

111

: 00:06:05

drew you to exploring the, these

specific neuromodulation techniques

112

: 00:06:09

like TMS and ECT in your clinical work?

113

: 00:06:13

David: Look, I guess TMS is one

particularly that I've been drawn to.

114

: 00:06:17

There is a, there is a.

115

: 00:06:19

I shouldn't say in some

sense it's a novelty factor.

116

: 00:06:21

Obviously TMS has been

around since the mid: 1980

117

: 00:06:24

In Australia, it's only

been funded by Medicare.

118

: 00:06:28

So the federal government since November,

: 2021

119

: 00:06:34

of which they, their criteria are

need to have trialed medications at an

120

: 00:06:39

adequate dose for a certain period of

time, for at least three weeks each, try

121

: 00:06:44

medications of two different classes, try

psychotherapy if clinically appropriate.

122

: 00:06:50

So in a sense, it is there,

there is some novelty to it.

123

: 00:06:54

We certainly didn't have much exposure

to TMS in my psychiatry training.

124

: 00:06:58

In Adelaide, there are very

few clinical, very few TMS

125

: 00:07:03

machines in clinical practice.

126

: 00:07:04

We have one at the hospital, which I work.

127

: 00:07:06

And a friend and colleague, him

and his colleague have a service

128

: 00:07:11

where they have a machine each.

129

: 00:07:12

So there's in.

130

: 00:07:13

My city, Adelaide, which is one

point something million people.

131

: 00:07:18

There's only three machines.

132

: 00:07:19

So it is a, it is an area of

interest in the novelty sense.

133

: 00:07:23

And I suppose also in the, I think we

might've been alluding to this when

134

: 00:07:28

talking in Japan the notion of, expanding

non-pharmacological treatments and

135

: 00:07:33

biological treatment, which is nonetheless

not a pharmacological treatment.

136

: 00:07:39

I think it's something that has

a lot of interest and promise.

137

: 00:07:45

Mike: No, definitely.

138

: 00:07:45

Yeah, I remember chatting about that.

139

: 00:07:47

I think that the landscape there sounds

very similar to the one in Vancouver

140

: 00:07:51

and probably Canada in general.

141

: 00:07:54

It's fascinating, I think

because I can think back to

142

: 00:07:57

having done a week long course.

143

: 00:08:01

It was 2003 in Boston with Dr.

144

: 00:08:03

Pascal Leone and TMS and

thinking at the time.

145

: 00:08:07

Sure.

146

: 00:08:07

Of course.

147

: 00:08:08

It was mostly research oriented, but

there was emerging clinical evidence

148

: 00:08:11

in depression and thinking, gosh, this

should revolutionize practice, but,

149

: 00:08:15

20 years on, and it really hasn't.

150

: 00:08:16

And I think there's so many

interesting dynamics at play there.

151

: 00:08:20

Whether it has to do with pharmaceutical

lobby or how the governments in these

152

: 00:08:24

different countries and insurance

agencies have approached the whole issue.

153

: 00:08:28

And, but it, there's something sorely

necessary in terms of developing

154

: 00:08:32

different kinds of therapies.

155

: 00:08:33

Because I have, I'm sure you do as well.

156

: 00:08:35

We have these conversations with

colleagues and patients all the time.

157

: 00:08:38

Who, which just reflects this general

frustration with the, obviously our

158

: 00:08:42

current treatments can help some

people and they're very helpful for

159

: 00:08:45

many people, but there's a lot of

people that really have disappointing

160

: 00:08:48

outcomes or only partial improvement.

161

: 00:08:50

And so there's always hope that we

can we can achieve better outcomes

162

: 00:08:53

with some of these technologies.

163

: 00:08:55

So it is exciting for sure.

164

: 00:08:56

David: Absolutely.

165

: 00:08:58

Maybe this sort of as a slight

tangent, I suppose with, hopefully the

166

: 00:09:02

development of, novel biological, but

non-pharmacological treatments also is

167

: 00:09:07

additionally beneficial for our patients.

168

: 00:09:09

One of my clinical interests has

been in deprescribing and trying

169

: 00:09:14

to reduce polypharmacy burden.

170

: 00:09:16

The story I heard from someone

a geriatrician perhaps saying

171

: 00:09:21

to a ward round, what's the

most dangerous medication?

172

: 00:09:24

And the answer was the fifth one.

173

: 00:09:26

Mike: Yeah, for sure.

174

: 00:09:28

I, a hundred percent, it's hard to know.

175

: 00:09:30

Obviously these are complicated,

complicated questions.

176

: 00:09:33

And again, when it, the, I think I

really this term personalization.

177

: 00:09:37

I know it's catching on

and then for good reason.

178

: 00:09:38

But yeah, I think with the best of

intentions sometimes, and particularly

179

: 00:09:43

when, people practicing in urban

centers or maybe academic centers

180

: 00:09:47

where, the treatment resistant

definition often and does involve four

181

: 00:09:51

or five, six different psychotropics.

182

: 00:09:53

And again, people come to that point.

183

: 00:09:56

It, there's no it's.

184

: 00:09:57

There's this idea of the system in

quotes or, people go through the

185

: 00:10:01

system per se, and people on the way

their helpers were doing their best

186

: 00:10:05

to try to help them with symptoms and

following treatment guidelines that are

187

: 00:10:09

evidence-based and so on and so forth.

188

: 00:10:11

But at the end of the day, when as you,

I have similar concerns in a lot of

189

: 00:10:14

situations when I see someone who lands

in the hospital perhaps and is still

190

: 00:10:18

debilitated by symptoms and yet still

taking all these different medications

191

: 00:10:22

and then suffering the side effects.

192

: 00:10:23

And it's hard to tease out the residual

symptoms from the medication side effects.

193

: 00:10:27

So absolutely, I can think of many

times in a more of a tertiary care

194

: 00:10:31

setting when deprescribing and trying

to start from scratch as, as safely

195

: 00:10:35

as possible ended up being the best

thing for that particular person.

196

: 00:10:38

Yeah.

197

: 00:10:39

And probably ECT ends up being

something that, is we often tell

198

: 00:10:43

people, especially the seniors that,

and their families that we're looking

199

: 00:10:46

after that ECT as much as people.

200

: 00:10:49

Often, initially have a kind

of a they hold their breath

201

: 00:10:51

a bit because of the stigma.

202

: 00:10:53

Then in the end it's much more,

it's much better tolerated than some

203

: 00:10:56

of these cocktails of medications

that weren't working before.

204

: 00:10:59

So why don't we turn to the TMS thing?

205

: 00:11:02

'cause I was really interested

in your poster that you presented

206

: 00:11:04

at the conference in Japan.

207

: 00:11:07

What I understood from that was

that was a meta-analysis in terms

208

: 00:11:10

of predictors of response in

major depressive disorder to TMS.

209

: 00:11:16

So for viewers and listeners,

transcranial magnetic stimulation.

210

: 00:11:19

Yeah.

211

: 00:11:20

And in particular this technique

known as theta burst stimulation.

212

: 00:11:23

Do you mind helping us understand

more about that particular project?

213

: 00:11:27

David: Yeah, absolutely.

214

: 00:11:29

So all listeners, there

are different types of TMS,

215

: 00:11:32

transcranial magnetic stimulation.

216

: 00:11:35

The burst stimulation is a particular

pattern of the application of

217

: 00:11:38

magnetic pulses that replicates a.

218

: 00:11:42

Biological pattern that was observed

in rats, in, in exploratory behavior.

219

: 00:11:47

I think it's been in, in the laboratory.

220

: 00:11:50

It's associated with neuroplasticity.

221

: 00:11:52

So I believe that was the, or under,

I've assumed that's the impetus for the

222

: 00:11:57

development of the birth stimulation.

223

: 00:12:00

So this was, it ended up being

a systematic review rather

224

: 00:12:03

than a meta-analysis as such.

225

: 00:12:05

But we did look systematically

at the literature and try and

226

: 00:12:08

find out what the predictors for

response to thebus stimulation are.

227

: 00:12:13

I suppose there's a couple

of reasons for that.

228

: 00:12:16

One being I don't think anyone had

actually had previously looked at the

229

: 00:12:20

predictors of treatment response to

this particular protocol for of TMS.

230

: 00:12:26

We might given that the, theta

patterns have a particular biological

231

: 00:12:30

role issue, that there may be some

differences in response to, stimulation

232

: 00:12:35

compared to trans, to standard sort

of transcranial magnetic stimulation.

233

: 00:12:40

I guess the other thing, ideally you

might be able to say look, we can,

234

: 00:12:43

this person has these demographic

or clinical characteristics that

235

: 00:12:48

strongly correlate with their response.

236

: 00:12:50

This is great.

237

: 00:12:51

We can say let's try and get

them to the birth stimulation.

238

: 00:12:55

Or, perhaps idea, in a broader

sentence, maybe you'd say, let's

239

: 00:12:58

aim for a neuro stimulation

before pharmacology, for example.

240

: 00:13:04

Conversely too, it may be the case

that there is no, there are no

241

: 00:13:08

particular predictors of response and

the of birth stimulation can be used

242

: 00:13:12

like, trans diagnostically in a sense

for various depressive syndromes.

243

: 00:13:18

So that was the background

to the research.

244

: 00:13:20

Yeah.

245

: 00:13:22

Mike: Yeah that's really interesting.

246

: 00:13:23

Again, coming back to this whole idea

of targeted and personalized approaches.

247

: 00:13:27

Yeah.

248

: 00:13:27

As early as possible.

249

: 00:13:28

That makes a lot of sense.

250

: 00:13:30

So as far as, yeah, and I misspoke

there on the meta-analysis piece.

251

: 00:13:33

So with this being a systematic review,

so what, remind me again, and for the

252

: 00:13:38

folks who haven't seen the poster or

don't know the paper, what are some of

253

: 00:13:41

the most promising kinds of clinical or

electrophysiological markers that seem to

254

: 00:13:48

be, coming or the data pointing towards.

255

: 00:13:52

David: Yeah.

256

: 00:13:52

Of the many demographic and illness

related and treatment related and

257

: 00:13:57

electrophysiological factors that were

assessed in, that have been assessed

258

: 00:14:02

in the literature, and these were all

from clinical trials probably, not that

259

: 00:14:07

these were the, not the looking for these

predictors was the key part of the trial.

260

: 00:14:10

But they had been looked at in trials, so

among trials that assessed using it as a

261

: 00:14:17

target, the left or electoral prefrontal

cortex, which is very commonly used as

262

: 00:14:22

a treatment target treatment refractory.

263

: 00:14:24

So the more the more refractory or

one's depressive illnesses to treatment

264

: 00:14:30

the less likely they're to respond.

265

: 00:14:32

So that was a fairly large odds ratio, but

the confidence interval being quite large.

266

: 00:14:38

So to.

267

: 00:14:40

Translate that into lay terms, I suppose

it suggests there's a response, but

268

: 00:14:44

the, we can't say for certain whether

the response is, the true response is

269

: 00:14:48

just a little bit worse or a lot worse.

270

: 00:14:52

And you would expect that, I suppose

the more frequent refractory someone's

271

: 00:14:56

condition is, whether that's due to

biological factors, whether it's due to

272

: 00:14:59

social circumstances, whether it's due to

273

: 00:15:02

Fairly intractable psychological factors.

274

: 00:15:04

The more difficult we just treat

with anything, whether it's

275

: 00:15:07

psychology, whether it's pharmacology,

whether it's neurostimulation.

276

: 00:15:11

Yeah.

277

: 00:15:12

And hedonia in youth, I think that

might have been a Canadian study.

278

: 00:15:15

Just remind myself what the thing

was with anhedonia in youth.

279

: 00:15:20

I think the so the less anhedonia

in youth was associated with

280

: 00:15:23

lower depressive scores.

281

: 00:15:25

There were a few electrophysiological

variables that more consistently predicted

282

: 00:15:30

the burst response stimulation response

tapes, but the effect sizes were small.

283

: 00:15:36

So one possible mechanism of action

of the burst stimulation, and

284

: 00:15:39

these are all, I suppose these are

all speculative to some extent.

285

: 00:15:44

But it might be restoring and the

balance if there is an ex, an imbalance

286

: 00:15:50

between excitation and inhibition.

287

: 00:15:53

So EBS might enhance the inhibitory

function of particular neurons in the

288

: 00:15:59

brain, GABAergic cortical into neurons.

289

: 00:16:01

So it may be the case that a

greater, if the brain is already

290

: 00:16:07

more in an inhibitory state Yeah.

291

: 00:16:09

That might reflect more favorable

brain state in which the birth

292

: 00:16:13

stimulation can exert its effect.

293

: 00:16:15

And.

294

: 00:16:17

Certain electrophysiological parameters

that reflect greater cortical inhibition

295

: 00:16:23

do seem to be associated with response.

296

: 00:16:25

But again, they're small effect

sizes, so possibly more promise with

297

: 00:16:31

the electrophysiology rather than

with clinical or demographic factors

298

: 00:16:35

in terms of predicting a response.

299

: 00:16:38

Mike: Yeah.

300

: 00:16:39

Yeah.

301

: 00:16:39

It's interesting because, I agree I

understand from a regulatory perspective

302

: 00:16:44

that there is importance in terms

of, accessibility and having it made

303

: 00:16:48

available for the treatment resistant

depression population, at least initially.

304

: 00:16:52

But it is also interesting to think

about just opening the optionality

305

: 00:16:56

for people perhaps earlier on

in, in terms of their therapeutic

306

: 00:17:01

journey and identifying factors.

307

: 00:17:04

In terms of their phenomenology that

might signal preferential early response

308

: 00:17:09

to neurostimulation even before an SSRI.

309

: 00:17:13

That, that's just because, a person

might, for whatever reason, prefer to

310

: 00:17:17

try that first and maybe they should

be able to, especially if they have,

311

: 00:17:21

features of their particular syndrome

that bode well in terms of a, yeah.

312

: 00:17:25

Positive response.

313

: 00:17:27

So again, this personalization

question, so do you think based

314

: 00:17:30

on that, based on your study that

say we look at just standard TMS

315

: 00:17:34

versus this theta burst protocol?

316

: 00:17:36

Maybe before that, do you mind,

so if we stick with the theta

317

: 00:17:39

burst for a second, so Yeah.

318

: 00:17:40

Does that entail some, maybe you can

help us help viewers and listeners

319

: 00:17:45

and me understand the degree to which

that then would provide benefit in

320

: 00:17:49

terms of an accelerated course or

other kind of therapeutic advantages

321

: 00:17:53

for people in terms of less risk of

side effects or things like that.

322

: 00:17:57

David: The theater best?

323

: 00:17:58

That's a good question because we were

one of the hospital at which I work

324

: 00:18:02

as one of the sites in an Australian

study that was published in: 2021

325

: 00:18:06

There was a site here in Adelaide, I

think there were two sites in Melbourne

326

: 00:18:10

and one site in the Gold Coast, if,

by memory, serve, speak correctly.

327

: 00:18:13

And we looked at this study, I should

say, I wasn't part of the team at

328

: 00:18:17

that point, but the study looked

at three different types of of TMS.

329

: 00:18:22

So standard TMS, an accelerated

course of the birth stimulation at

330

: 00:18:28

one particular, I suppose intensity

of, or magnetic dose, if you will,

331

: 00:18:35

for the more technically minded lists.

332

: 00:18:37

I think it was 80% of motor threshold

and another at a higher dose.

333

: 00:18:40

So 120% of motor threshold.

334

: 00:18:43

And there was no statistical difference

between the three groups in terms of

335

: 00:18:48

clinical response, the benefit of.

336

: 00:18:51

Birth stimulation, that is,

that it can be administered in

337

: 00:18:55

a very brief period of time.

338

: 00:18:57

So whereas a, standard TMS might take

about 40 minutes or so per session.

339

: 00:19:04

The birth stimulation can be administered

in a much briefer period of time.

340

: 00:19:10

So the treatment itself might

last for a few minutes, and in an

341

: 00:19:14

accelerated fashion that can be done.

342

: 00:19:16

You can have two or three treatments

over the course of an hour.

343

: 00:19:20

So in a, in Australia Medicare funds 35

treatments for an initial course of TMS.

344

: 00:19:27

So there are benefits for patients

for services to some degree,

345

: 00:19:32

depending on how it's done in

having a more accelerated course.

346

: 00:19:35

Obviously it's, if you are having

the stimulation once a day,

347

: 00:19:39

then you would be there for.

348

: 00:19:42

Let's say five, 10 minutes

while they set it up.

349

: 00:19:44

A few minutes of treatment and

then you're off on your way.

350

: 00:19:47

And like theoretically a clinic could

be have a much more scalable service

351

: 00:19:54

than if someone's receiving a 40

minute treatment a day, for example.

352

: 00:19:58

As far as side effects, no,

I don't believe there are.

353

: 00:20:01

Some people don't tolerate

the birth stimulation as well.

354

: 00:20:05

And look some people for what,

for whatever reason, these are the

355

: 00:20:09

mysteries of the brain and the limits

of our knowledge, but some people

356

: 00:20:12

do respond better to standard TMS

rather than the birth stimulation.

357

: 00:20:19

Why that is, that's a good question,

and I'm sure that would be some useful

358

: 00:20:22

further research in looking at why

some people respond to one type of

359

: 00:20:28

TMS as opposed to the other type.

360

: 00:20:30

Mike: Yeah.

361

: 00:20:31

Yeah.

362

: 00:20:32

And I guess the idea as well is the,

in terms of patient convenience, and

363

: 00:20:36

like the standard of stand for the

Saint protocol of really having brief

364

: 00:20:41

treatments compressed into many during

a single day as opposed to spread

365

: 00:20:45

out over the course of many weeks.

366

: 00:20:47

Yes.

367

: 00:20:48

Yeah.

368

: 00:20:49

I wonder is there any evidence of

an increased risk of seizure with

369

: 00:20:52

these more intensive or abbreviated

accelerated treatment protocols?

370

: 00:20:58

David: I believe my, under my

understanding is that there are, the

371

: 00:21:03

risk of seizure with TMS is present

obviously, but it is very low.

372

: 00:21:07

Yeah.

373

: 00:21:08

Some of the standard protocols, I

can't off the top of my head, remember,

374

: 00:21:11

it might be the low frequency.

375

: 00:21:13

Unilateral TMS, so one of the

types of the standard TMS might

376

: 00:21:18

be associated with lower risk of

seizure, but that said, the risk of

377

: 00:21:22

seizure in, in general is quite low.

378

: 00:21:25

Yeah.

379

: 00:21:25

If people, you, in, some people have

had TMS even in the case of having

380

: 00:21:32

comorbid epilepsy, which would be

certainly pose an increased risk

381

: 00:21:37

of seizures, but it can be done.

382

: 00:21:39

Yeah.

383

: 00:21:41

Yeah.

384

: 00:21:41

I guess just to say that the risk of

seizures with the birth stimulation

385

: 00:21:44

is probably higher than with standard

TMS, but how high that is unclear.

386

: 00:21:49

Mike: Yeah.

387

: 00:21:50

And probably not a significant issue.

388

: 00:21:52

And that's just part of the risk benefit

consideration, but the risk of seizure

389

: 00:21:55

in general is still very low with TMS.

390

: 00:21:58

David: It has been said, and to be fair,

it was people who gonna sell TMS machines,

391

: 00:22:02

but suggested the risk of seizure with

antidepressants is higher than the

392

: 00:22:05

risk of seizures with TMS, which is a.

393

: 00:22:10

Mike: For sure.

394

: 00:22:11

Absolutely.

395

: 00:22:12

Yeah.

396

: 00:22:13

And yeah, this is the thing, and I

guess that leads to another question

397

: 00:22:16

in terms of, what you're anticipating

on the horizon in terms of combining

398

: 00:22:20

neurostimulation techniques like

this with medication and other types

399

: 00:22:24

of therapy, psychotherapy, therapy.

400

: 00:22:27

Yeah.

401

: 00:22:27

What do you have thoughts about that?

402

: 00:22:32

David: I think my understanding, and

I, this is a brief understanding or

403

: 00:22:37

rather a deep understanding, but that

team is combined with psychotherapy

404

: 00:22:40

can be particularly helpful.

405

: 00:22:42

And I do wonder, I think a lot of the

benefit of people having TMS is that

406

: 00:22:46

they get to, there is, I'll say the

placebo effect, and not in a derogatory

407

: 00:22:51

or negative sense, but in the sense that

they do have just simple supportive care

408

: 00:22:56

and get to spend an hour with a caring.

409

: 00:22:59

A clinician.

410

: 00:23:00

Each day they get to spend time

with a caring person who's taking,

411

: 00:23:05

who's doing their depression

scores before and after treatment.

412

: 00:23:08

So I think that is, even if it's not

formally part, even if you're not

413

: 00:23:12

formally doing a structured psychotherapy

or something similar during the

414

: 00:23:17

course of TMS, I think there that

component of it is a big component too.

415

: 00:23:22

I don't wanna speculate specifically as

to whether as about many medications,

416

: 00:23:28

but there is one, there, there is

some interesting new work and there

417

: 00:23:31

is a trial underway in Australia at

the moment looking at de cycline.

418

: 00:23:35

As an, I think the initial work

was out of North America, and this

419

: 00:23:38

is a larger study, which has been

hampered by the difficulties in

420

: 00:23:42

accessing the medication as well.

421

: 00:23:45

But there is, I think that the.

422

: 00:23:47

Initial studies were very promising

in terms of a markedly increased.

423

: 00:23:52

I can't remember specifically as

responsible remission, but there is

424

: 00:23:55

a, the individuals who use deicer

alongside TMS, they were, they

425

: 00:24:04

had, they just went much better.

426

: 00:24:06

But there are some interesting

avenues for pharmacology in, as

427

: 00:24:11

an adjunctive treatment with TMS.

428

: 00:24:14

Mike: Yeah.

429

: 00:24:14

No, that's it is really interesting

'cause I think that I guess it

430

: 00:24:17

makes sense in terms of, again, what

we were talking about with taking

431

: 00:24:20

advantage of as many of these types

of approaches to treatment as we can.

432

: 00:24:25

And maybe, I guess there's always

that argument around keeping things

433

: 00:24:28

simple is generally a pretty,

pretty good principle to stick by.

434

: 00:24:31

But then on the other hand, maybe some

people would, for whatever reason,

435

: 00:24:36

especially again, if we're by virtue of

the regulatory guidelines, at least for

436

: 00:24:40

now, limited to treatment resistant kinds

of patients, then we're almost forced

437

: 00:24:46

in a way to think about having, people

on medication and or psychotherapy.

438

: 00:24:49

But yeah, the piece that you mentioned

about the expectation effect or some

439

: 00:24:53

of placebo type effect is interesting

as well, because that's something that,

440

: 00:24:58

I'm seeing more and more this kind

of, and I guess historically as well.

441

: 00:25:02

It's been a thing dating back to,

decades ago, maybe even centuries

442

: 00:25:06

ago with people, a snake oil type.

443

: 00:25:09

Approach of yeah.

444

: 00:25:10

Electrical stimulation on the brain,

curing hysteria or what have you.

445

: 00:25:13

And there is that has to be considered.

446

: 00:25:15

And I think, for people who don't know who

are watching and listening that this is

447

: 00:25:18

what's really important about the extent

to which the randomization and the control

448

: 00:25:23

and the blinding of these kinds of studies

is critically important so that we can

449

: 00:25:26

make sure that this isn't just, snake

oil and not true, valid, scientifically

450

: 00:25:32

based and validated kinds of technologies.

451

: 00:25:35

That was certainly something that I got

out of hearing some of the presentations

452

: 00:25:39

and seeing some of the posters at the

conference on these even more novel

453

: 00:25:43

neurostimulation kinds of techniques,

like the focused ultrasound and

454

: 00:25:46

different things that are coming out.

455

: 00:25:50

David: Absolutely.

456

: 00:25:51

And I suppose just for the listeners

as well, there is TMS does have a real

457

: 00:25:56

therapeutic response when they have

compared active to sham TMS in trials.

458

: 00:26:01

There is a response by the same to

and with as with anything, whether it

459

: 00:26:05

be psychotherapy or pharmacotherapy,

there is the, I suppose the, or I

460

: 00:26:12

suppose, or the atmosphere in which

it's of expectation of a radiology

461

: 00:26:18

friend just described something similar.

462

: 00:26:20

When there is a big shiny machine,

people can, there is a response,

463

: 00:26:24

Mike: yeah.

464

: 00:26:25

And I just wanna just focus

in on this before I forget.

465

: 00:26:28

'cause I think it's really important

and I want people that are watching

466

: 00:26:31

and listening to just understand

the study, the results of the study.

467

: 00:26:35

So I think I just pulled up the poster

here and I'm just gonna have a look.

468

: 00:26:37

'cause I think the way that you portrayed

that visually is really helpful.

469

: 00:26:41

The three kind of areas of prediction

to data, birth stimulation response.

470

: 00:26:46

So the first was the EEG predictors,

which is interesting, right?

471

: 00:26:50

In terms of being able to do a diagnostic

test and then take that information and

472

: 00:26:54

then project to tell a person, or to help

that person decide to what extent might

473

: 00:27:00

they or might they not respond to TBS.

474

: 00:27:03

So do you mind, so maybe before that I'll

just for, just to contextualize a bit.

475

: 00:27:07

So there were three kind of areas.

476

: 00:27:08

There were the EEG predictors.

477

: 00:27:10

There were the clinical predictors

and then there were certain factors

478

: 00:27:12

that were not predictive of the

beta birth stimulation response.

479

: 00:27:15

So let's have a look first

at the EEG predictors.

480

: 00:27:17

Do you mind just walking us

through what you found in that?

481

: 00:27:21

David: So just to briefly discuss,

and this is certainly not my

482

: 00:27:25

area of expertise, but there are

electrophysiological, there are

483

: 00:27:29

these things called TMS evoked

potentials or teps, these,

484

: 00:27:34

Mike: so

485

: 00:27:34

David: my understanding is you

administer a TMS pulse and then

486

: 00:27:39

you record the electrical activity

on the scalp, essentially.

487

: 00:27:44

So these tps have a certain pattern.

488

: 00:27:47

It's a bit difficult to explain

verbally without seeing a picture.

489

: 00:27:51

But these particular patterns they

have peaks and they have troughs.

490

: 00:27:55

And the, these particular the

particular peaks and troughs can

491

: 00:28:00

be associated with inhibition or

excitation in the cortex of the brain.

492

: 00:28:05

So some of these predictors that

so basically the predictors, his.

493

: 00:28:11

Of t of the birth stimulation response

in the electrophysiological sense

494

: 00:28:16

were those predictors that suggested

there were a greater response were

495

: 00:28:21

those that were either indicated

greater inhibition or lower excitation.

496

: 00:28:29

Two of these particular peaks

are called N 45 and N 100.

497

: 00:28:34

They are associated with

with cortical inhibition.

498

: 00:28:37

And if those peaks were higher,

that was associated with the

499

: 00:28:40

birth stimulation response.

500

: 00:28:42

And conversely, another peak,

which is called Peak 60.

501

: 00:28:46

A smaller P 60 was associated

with with TBS response and P

502

: 00:28:51

60 itself is a, essentially a

marker of cortical excitation.

503

: 00:28:56

So that's the EEG predictors as

far as the clinical predictors of

504

: 00:29:01

the birth stimulation response go.

505

: 00:29:03

We did talk through a bit about anhedonia

and treatment refactor this before there

506

: 00:29:08

was another study, I believe it was

out of Taiwan, looking at a particular.

507

: 00:29:12

A particular type of data, birth

stimulation, they call prolonged

508

: 00:29:16

intermittent data, birth stimulation.

509

: 00:29:18

I think it's just a longer course

essentially that's published

510

: 00:29:21

out, that's used in a few of

these studies from Taiwan.

511

: 00:29:24

They found a few predictors anxiety

suicidality, number of anxiety

512

: 00:29:28

disorders, again, illness for raciness.

513

: 00:29:31

Interestingly that was using a different

target site called the dorson, medial

514

: 00:29:36

prefrontal cortex, which might be

associated with some I guess more

515

: 00:29:41

anxious symptoms in depression.

516

: 00:29:44

Which sort of, it's a bit of

a different target site, but I

517

: 00:29:48

guess something to be aware of.

518

: 00:29:50

And then the other thing was

there were a lot of factors

519

: 00:29:52

that just weren't predictive of

response, age, sex, or gender.

520

: 00:29:56

Life stress, psychiatric

comorbidities, alcohol use.

521

: 00:29:59

Interestingly, other

medications left or rightness.

522

: 00:30:03

The genetic of a particular gene, BDF,

brain derived neurotrophic factor, which

523

: 00:30:08

is i'm sure as with any compound in

the brain, there are many complicated

524

: 00:30:12

and difficult to understand effects.

525

: 00:30:14

But, my understanding is at least in

part, is involved in neuroplasticity.

526

: 00:30:18

A particular polymorphism of that

gene, which I assume was, has been

527

: 00:30:23

associated with less treatment response

or perhaps less neuroplasticity.

528

: 00:30:27

It didn't make any difference in

the birth stimulation response.

529

: 00:30:30

And another particular

electrophysiological

530

: 00:30:35

phenomenon frontal theater

changes was not associated with

531

: 00:30:38

the burst stimulation response.

532

: 00:30:41

Mike: Yeah, no, that's great.

533

: 00:30:42

And I realize it's challenging to

explain these complex technical

534

: 00:30:46

aspects, but what I can do is I can

just, I can, I have that photo that

535

: 00:30:51

I took of the poster, so if that's

okay with you, I can just have this.

536

: 00:30:54

Kind of posted for viewers,

at least on the YouTube side.

537

: 00:30:58

And yeah, people can check that out.

538

: 00:30:59

I can put images in the show notes as well

for the listeners on the podcast side.

539

: 00:31:04

Yeah, it's very interesting.

540

: 00:31:05

Yeah, I think the other thing is,

'cause I think I could see how the

541

: 00:31:08

more this kind of data comes out on the

technical aspects of it, the more that

542

: 00:31:12

could potentially be integrated into

some kind of a computerized algorithm.

543

: 00:31:16

That could be something that could,

especially with ai, that could analyze,

544

: 00:31:21

this sort of diagnostic information

based on an EEG and get a sense of the

545

: 00:31:24

person's clinical presentation and history

and medication trials and genetic kind

546

: 00:31:29

of information and kind of put print

out like a risk benefit analysis and

547

: 00:31:33

some recommendations around, PMS like

approaches and, placement and various

548

: 00:31:38

aspects of the technique that might be

administered, whether it's TBS or duration

549

: 00:31:43

of individual sessions, blah, blah, blah.

550

: 00:31:45

All the different potential things

that can be manipulated in terms of

551

: 00:31:48

optimizing that person's outcome.

552

: 00:31:51

David: I think that would be the dream.

553

: 00:31:53

I think we are unfortunately

still a ways off.

554

: 00:31:56

Yeah.

555

: 00:31:56

But I think that would be wonderful.

556

: 00:31:58

I suppose pharmacogenomics might be an

illustrative analogy, there, there seemed

557

: 00:32:04

to be a few, a couple of decades back

when I did an honors project in a sense

558

: 00:32:09

that this might revolutionize medication.

559

: 00:32:14

Prescribing it hasn't really

done so for various reasons.

560

: 00:32:19

I suppose it is.

561

: 00:32:20

And I'm not sure what

the status is in Canada.

562

: 00:32:22

Occasionally in Australia.

563

: 00:32:24

I haven't personally ordered any

pharmacogenetic tests for patients, but

564

: 00:32:28

occasionally people will come to me and

they will have gone to a pharmacogenetics

565

: 00:32:33

provider and they'll come with a report

saying that they, might be a poor

566

: 00:32:38

metabolizer for enzyme X or caution

might need to be taken with medication.

567

: 00:32:43

YI guess outside of a handful of

medications, it hasn't really, the, I

568

: 00:32:52

guess pharmacogenetics itself hasn't

really fulfilled those promises.

569

: 00:32:57

I suppose perhaps, certainly oncology

is not my field, but there are just

570

: 00:33:02

a vast array of new medications

that target particular, aspects

571

: 00:33:08

of the disease process, and that

might be trans diagnostic as well.

572

: 00:33:12

Perhaps that's what we are looking at.

573

: 00:33:13

So rather this is all very speculative,

but perhaps we can use something like TMS

574

: 00:33:20

in a trans diagnostic fashion perhaps,

and ideally we can help to funnel a

575

: 00:33:26

particular treatment towards a person

who will benefit from it particularly.

576

: 00:33:31

But I guess also having the humility

to recognize that it might still be

577

: 00:33:37

some time before these things can

translate into to clinical practice.

578

: 00:33:42

Mike: Yeah.

579

: 00:33:43

Definitely.

580

: 00:33:44

But it is, it's exciting, it's promising.

581

: 00:33:45

It's, it'll be interesting to

see to what extent that the

582

: 00:33:48

artificial intelligence aspect can

accelerate these kinds of things.

583

: 00:33:53

In the next five to 10 years, I expect

that there will be some acceleration

584

: 00:33:56

that'll really foster the whole

personalization kind of project.

585

: 00:34:01

'cause I think that's,

it's definitely necessary.

586

: 00:34:03

It would hopefully involve a

bit less trial and error and a

587

: 00:34:05

little bit less educated guessing.

588

: 00:34:08

David: Yeah.

589

: 00:34:08

1, 1, 1 study that we are hoping to

conduct soon would be essentially using

590

: 00:34:14

artificial intelligence both to hopefully

to predict treatment response to TMS,

591

: 00:34:19

otherwise to track treatment response.

592

: 00:34:21

One of the engineers at Adelaide

University has developed a software

593

: 00:34:25

package that, somehow integrates a

number of artificial intelligence tools.

594

: 00:34:30

Various features are extracted from a Zoom

video, and they include facial features,

595

: 00:34:37

they include bio acoustic features,

they include linguistic features.

596

: 00:34:41

So we will be looking at that and that

potentially provides the opportunity for

597

: 00:34:48

rapid and automated not only tracking

of treatment response over time and I

598

: 00:34:55

guess potentially more objective as well.

599

: 00:34:56

But then possibly these things also have a

benefit of predicting treatment response.

600

: 00:35:01

And very interestingly, in the

sphere of facial features, there

601

: 00:35:06

are a handful of studies from the

late seventies, early eighties that

602

: 00:35:12

have that looked at facial EMG.

603

: 00:35:16

For a couple of the facial muscles,

the corrugator muscle and the

604

: 00:35:19

zygomatic muscle, which is involved

in lifting the lip corners upwards

605

: 00:35:24

and outwards, basically smiling.

606

: 00:35:26

Some of these studies suggest that

the electrical activity of these,

607

: 00:35:31

of one or other of these muscles may

actually indicate that someone is

608

: 00:35:36

more likely to respond to treatment.

609

: 00:35:39

So there is some historical precedent

and I guess watch this space.

610

: 00:35:46

Mike: Yeah that's really interesting.

611

: 00:35:47

Anything that can be done to just yeah.

612

: 00:35:50

Help our treatments be

as efficient as possible.

613

: 00:35:52

Absolutely.

614

: 00:35:53

And as targeted as possible.

615

: 00:35:54

For sure.

616

: 00:35:55

How about do you mind if we turn

for a minute, if we turn to your

617

: 00:35:59

expertise in addiction medicine

and substance use disorders?

618

: 00:36:03

Yeah.

619

: 00:36:04

I'm just curious to know if you're, you

have a sense, my, my sense of it isn't

620

: 00:36:07

is that, there's not really obviously

there's a lot of comorbidity with mood

621

: 00:36:11

disorders and substance use disorders.

622

: 00:36:13

And hopefully the neurostimulation

techniques that are targeted towards

623

: 00:36:18

treating things like depression

would then also help for folks who

624

: 00:36:22

have some comorbidity with say,

alcohol use disorder, for example.

625

: 00:36:26

But what's your sense of whether

or not there's any promise or even

626

: 00:36:29

current, clinical application that I'm

not aware of, but maybe you are for.

627

: 00:36:35

Treating substance use disorders

with any kind of particular

628

: 00:36:38

neurostimulation technique, either

now or potentially in the future?

629

: 00:36:43

David: I am not.

630

: 00:36:44

I think similarly, there certainly

has been a lot of research, as with

631

: 00:36:48

many things that's just on the, on

the border of being promising or not.

632

: 00:36:53

I guess a, addiction is a difficult

area and I suppose, we talk about

633

: 00:36:58

the biopsychosocial model and

psychiatry and that is particularly

634

: 00:37:01

pertinent in addiction as well.

635

: 00:37:02

There are certainly biological components

to addiction, but there are also

636

: 00:37:07

psychological components, whether it be,

the negative reinforcement of drinking,

637

: 00:37:13

for example, to relieve withdrawal

symptoms, whether it be using substances

638

: 00:37:18

to ameliorate negative emotional states.

639

: 00:37:23

There are social.

640

: 00:37:24

Components of addiction are huge as well.

641

: 00:37:27

There was a study looking at

returned US soldiers from Vietnam

642

: 00:37:32

of the soldiers who were addicted

to heroin when they were in Vietnam.

643

: 00:37:37

I'm not sure what definition they

used, but only 10% of them to that

644

: 00:37:41

sort of state of addiction upon

within a certain period of time after

645

: 00:37:45

they return to the United States.

646

: 00:37:47

So there are, I don't think that means

we should avoid or give up on, on

647

: 00:37:55

biological treatments for addiction, but

648

: 00:37:57

It is only one part of it.

649

: 00:37:58

And the evidence I've seen so

far is it's not enough to bring

650

: 00:38:03

it into clinical practice.

651

: 00:38:05

Mike: Yeah.

652

: 00:38:06

Yeah, no, that makes sense.

653

: 00:38:07

I'm, and I really appreciate that

you bring up this notion of the

654

: 00:38:10

bio-psychosocial model because

I think with these technologies

655

: 00:38:14

there's almost a natural inclination.

656

: 00:38:16

It's totally understandable, but there's

a natural inclination for a degree

657

: 00:38:20

of hype and hyperbole and some sense

that these technologies are gonna be

658

: 00:38:24

a magic bullet of sorts for people.

659

: 00:38:26

And I think that, when it comes to,

obviously what probably attracts folks

660

: 00:38:30

like you and I to go into the field in the

first place is the idea of each individual

661

: 00:38:34

person is their own unique individual.

662

: 00:38:36

And they bring their own unique set of

circumstances that, that bear on not

663

: 00:38:42

only the development of the condition

that they're coming or to coming to

664

: 00:38:46

see, a clinician for help with, but

also then that would have to inform.

665

: 00:38:52

Logically than the management options.

666

: 00:38:54

And I think part of the risk, with

certain neurostimulation techniques

667

: 00:38:57

is that they perhaps are unfairly

seen as a magic bullet or a panacea.

668

: 00:39:03

I've certainly heard from mentors when

it comes to ECT that it's not a panacea.

669

: 00:39:08

'cause I think most clinicians will have

had times when they've had, outcomes

670

: 00:39:11

for from ECT that seem miraculous.

671

: 00:39:14

And so of course then that's

gonna generate excitement.

672

: 00:39:16

And then perhaps yes, an over application,

which is perhaps what happened in

673

: 00:39:21

the, the dark days in quotations when,

there, the stigma that came out of

674

: 00:39:24

this sort of broad application for

things that probably wasn't actually,

675

: 00:39:29

now that it's more targeted and

refined in terms of its application.

676

: 00:39:32

So yeah, I think that, to prevent

that, I suppose it's important to

677

: 00:39:36

understand that yes, these disorders

are complicated and there's.

678

: 00:39:41

A number of different factors

in all these domains that have

679

: 00:39:45

to be taken into consideration.

680

: 00:39:46

And it's not just, it's not

likely to be just, data of birth

681

: 00:39:49

TMS or whatever new invention.

682

: 00:39:53

It's not to say that it's

a bad idea to innovate.

683

: 00:39:56

No, not sure.

684

: 00:39:56

Try to find new treatments,

but it's just to maybe take it

685

: 00:39:59

with a grain of salt as well.

686

: 00:40:01

David: I think so, and I completely

agree and I guess on a metaphysical

687

: 00:40:06

level I think we there, we, with

the human brain and human behavior,

688

: 00:40:13

we very quickly come to the limits

of what we can possibly know.

689

: 00:40:18

I don't think we will ever I don't

think it's any more possible for a

690

: 00:40:21

human to understand how matter can

result, how, the relationship between

691

: 00:40:27

a physical brain and the subjective.

692

: 00:40:29

Sense of a, an emotion or a

thought than it is for, a dog

693

: 00:40:35

to do algebra, for example.

694

: 00:40:37

So I think we are, we run up against

a wall, which I think is, which

695

: 00:40:42

doesn't mean we can't find out as

much as we can, but we do have to have

696

: 00:40:46

humility and yeah, no, absolutely.

697

: 00:40:48

Respect that mystery, yeah.

698

: 00:40:50

Mike: Yeah.

699

: 00:40:50

Sorry I cut you off, but yeah.

700

: 00:40:51

Respect the mystery.

701

: 00:40:52

Is that what you said?

702

: 00:40:53

I agree.

703

: 00:40:54

Yeah.

704

: 00:40:54

Yeah.

705

: 00:40:54

It's really fascinating and I'm so

glad that the conversation's going

706

: 00:40:57

in this direction because it makes me

think that one of the maybe intangible

707

: 00:41:02

benefits of the whole push for.

708

: 00:41:06

Finding a neurostimulation technique

that is not only therapeutic and can

709

: 00:41:10

help people who have perhaps been

disappointed by legacy treatments like

710

: 00:41:14

the medications and or psychotherapy.

711

: 00:41:16

But it speaks to this idea that

maybe what we're learning through

712

: 00:41:20

studying neurostimulation technique

can actually tell us a bit more

713

: 00:41:23

about consciousness itself.

714

: 00:41:24

And so how certain contemporary theories

of consciousness, which historically

715

: 00:41:29

have been maybe limited by, the

neurotransmitter model of how thought

716

: 00:41:37

and consciousness kind of arises,

particularly as it relates to mental

717

: 00:41:40

illness might not be the full story.

718

: 00:41:43

Or maybe there's more I've read

about a little bit about this.

719

: 00:41:46

By no means an expert, but just, novel

theories like maybe, electromagnetic

720

: 00:41:51

theories of consciousness itself,

rather than or, rather than the

721

: 00:41:55

typical kind of neurotransmitter

and action, potential neuronal

722

: 00:41:59

function that is well established.

723

: 00:42:00

And I'm not dismissing that by any

means, but I'm just saying that

724

: 00:42:02

there are these very interesting

new theories of consciousness that

725

: 00:42:06

kind of might dovetail well with how

we're finding that neurostimulation

726

: 00:42:09

techniques actually seem to alter

consciousness in a therapeutic manner.

727

: 00:42:15

David: Again, this is not my area

of expertise, but I think it's it

728

: 00:42:17

has you opens fascinating doors and

leads to very interesting questions.

729

: 00:42:22

And I agree.

730

: 00:42:22

I think the neurotransmitter model is,

it is certainly not, I guess it's, is

731

: 00:42:28

where a lot of biological research has

focused over the decades as a consequence

732

: 00:42:32

of the, the fairly spectacular success

of some medications in some cases.

733

: 00:42:38

But it does have its limitations.

734

: 00:42:39

And on a, I guess a semi formed thought

of how is, perhaps we are just, whilst

735

: 00:42:45

you can look at neurotransmitters

on one level, perhaps we're just

736

: 00:42:50

looking at the wrong level, of the

organism, of the human organism.

737

: 00:42:54

A person with mania or depression or

psychosis has nothing wrong with their

738

: 00:43:00

neutrons or protons, for example.

739

: 00:43:02

It would be ridiculous to look at, I

don't know, doing a neutron study in,

740

: 00:43:06

in somewhere with depression, maybe

neurotransmitters again and not the

741

: 00:43:11

right level that we need to look at.

742

: 00:43:12

And maybe it does tie in with

those electrophysiological factors,

743

: 00:43:15

electromagnetic factors, these

are all very speculative thoughts.

744

: 00:43:20

Perhaps that is the.

745

: 00:43:22

You can, to use an analogy, if

you took a glass of water from

746

: 00:43:26

a giant wave, you would say

there's nothing wrong with it, but

747

: 00:43:29

Could still destroy a beach

regardless of whether there's anything

748

: 00:43:32

wrong at the equivalent of the

neurotransmitter level in in that

749

: 00:43:35

Mike: analogy.

750

: 00:43:37

Yeah, for sure.

751

: 00:43:38

But I think, again, getting back to

the idea of less tangible factors

752

: 00:43:41

and the bio-psychosocial approach.

753

: 00:43:43

We, what we, one of the things we

do know from decades of research

754

: 00:43:46

on the psychotherapeutic side is

that common factor of a positive

755

: 00:43:49

therapeutic relationship, yes.

756

: 00:43:51

So I think at the end of the day, I know

I have these discussions with colleagues

757

: 00:43:54

who, and we share frustration about

after the sixth and seventh medication

758

: 00:43:58

trial and umpteenth hospitalization,

and the person's still not doing well,

759

: 00:44:01

but at the end of the day, what we can

still offer is just that presence and

760

: 00:44:04

that support and that encouragement

and just trying to instill hope.

761

: 00:44:07

Yes.

762

: 00:44:07

So I think that's still gonna go a

long way, regardless of what biological

763

: 00:44:11

treatments that we're able to offer and

they should dovetail and for good reason.

764

: 00:44:14

David: I agree.

765

: 00:44:15

And I think that's, I don't think our

job is at risk of being usurped by AI at

766

: 00:44:21

any point, because AI cannot replace that

interpersonal content, which does have a.

767

: 00:44:29

There is a spiritual component, that

cannot be replaced by an AI telling

768

: 00:44:34

you X, Y, or Z, or giving you advice

or saying, have you approached it

769

: 00:44:40

in this manner, even if it could be,

the next Sig Freud and give you the

770

: 00:44:44

perfect formulation or what have you.

771

: 00:44:48

Mike: Yeah, for sure.

772

: 00:44:48

There's gonna be, there obviously,

again, I think that there's a lot

773

: 00:44:52

of promise and utility for the AI

therapy kinds of options that are

774

: 00:44:56

emerging, and that's, it is what it is.

775

: 00:44:58

But I think that there's gonna be, there's

still gonna be an uncanny valley, so

776

: 00:45:03

to speak, that's gonna separate this

sort of natural human intuition that

777

: 00:45:07

is, is inherently there with direct

interactions, whether it's in person

778

: 00:45:11

or remotely like this, I think, yeah.

779

: 00:45:13

Yeah.

780

: 00:45:15

So that's great.

781

: 00:45:16

We're running out of time, so I thought

maybe, we could wrap up with me asking,

782

: 00:45:19

based on your research and your clinical

practice, what would be some things that

783

: 00:45:23

you foresee in terms of research in TMS

and the what's on the horizon in terms

784

: 00:45:29

of clinical application, whether it's

TBS, like the birth stimulation or the

785

: 00:45:34

Saint Stanford accelerated protocols.

786

: 00:45:37

Where do you think that the

field is going in these terms?

787

: 00:45:40

David: That's a good question.

788

: 00:45:40

So I think one, one, I suppose one is

adjunctive treatments like deicer and I

789

: 00:45:48

don't want to become overly biological.

790

: 00:45:51

It may be a adjunctive psychological

treatments or other treatments that can

791

: 00:45:54

be really useful in this sphere as well.

792

: 00:45:56

I think the saint and I know the

Saint Protocol and I think the East

793

: 00:46:02

coast version of that, the eight

protocol where they had adjusted.

794

: 00:46:06

Where they had as far as I understand

compared the Saint Protocol as much

795

: 00:46:09

as possible to another pro to sorry,

they compared the Saint Protocol to

796

: 00:46:14

an I as much as possible identical

protocol, except not using a functional

797

: 00:46:18

MRI to locate the target site.

798

: 00:46:21

I think these things are quite,

potentially quite fascinating,

799

: 00:46:25

just having a very rapid treatment.

800

: 00:46:29

They, I guess to, to be

a bit of a Debbie Downer.

801

: 00:46:31

I suppose they, it still leads to

the issues of access to treatment and

802

: 00:46:35

it's very difficult for any clinic

to say there's one machine that

803

: 00:46:38

costs, let's say $80,000 Australian.

804

: 00:46:43

That machine will be taken

up for a week by one patient.

805

: 00:46:47

But anyway, I think that's an

interesting area of research,

806

: 00:46:49

another area which, certainly I'm

not I'm sure the research is there.

807

: 00:46:53

I'm not as familiar with it, but.

808

: 00:46:56

Looking at, other conditions

outside of depression.

809

: 00:46:58

I know that, OCD certainly one, there's

been a lot of work on, and I think

810

: 00:47:02

I understand that there is some very

conflicting studies or there's controversy

811

: 00:47:07

about the best target site and so on.

812

: 00:47:10

So I think there are, the future is

very interesting for this actually one

813

: 00:47:16

study that's not directly related to

psychiatry, but certainly related to CNS.

814

: 00:47:20

There is pheno phenomena.

815

: 00:47:23

There is a study at Adelaide University,

which I don't have anything personally

816

: 00:47:27

to do with, but it's looking at

TMS two manage neurotoxicity from

817

: 00:47:32

certain chemotherapies for cancer.

818

: 00:47:34

So I think TMS as a technology

can certainly expand beyond

819

: 00:47:39

the psychiatric sphere.

820

: 00:47:40

I'll be honest to say, I'm not sure

what other people are currently

821

: 00:47:44

doing with it in practice as

opposed to in research, but I think.

822

: 00:47:49

It is a, an excellent and

fascinating technology.

823

: 00:47:54

Mike: Definitely.

824

: 00:47:55

Yeah, definitely.

825

: 00:47:55

Dr.

826

: 00:47:56

Plevin, thank you so much for

spending time with me today and for

827

: 00:47:59

a really interesting discussion.

828

: 00:48:01

I certainly learned a lot and I'm sure

our audience is really educated now

829

: 00:48:06

and informed in terms of your research

and your clinical experience, and

830

: 00:48:09

hopefully everyone has found this to be

as interesting a discussion as I have.

831

: 00:48:13

So thank you once again, really

appreciate your time and your

832

: 00:48:17

interest and your expertise.

833

: 00:48:18

David: Thank you.

834

: 00:48:19

I really been a pleasure talking

to you and I really appreciate the

835

: 00:48:22

opportunity to come on your podcast.

836

: 00:48:25

Mike: Yeah, that's great and

we'll look forward to catching

837

: 00:48:27

up again at a future conference.

838

: 00:48:28

Hopefully.

839

: 00:48:29

David: That sounds excellent.

840

: 00:48:30

Thank you.

841

: 00:48:31

Mike: Okay, have a great rest of the day.

842

: 00:48:32

Cheers.

843

: 00:48:33

Thanks,

844

: 00:48:33

David: you too, Mike.

845

: 00:48:33

See you.

846

: 00:48:34

Mike: Bye-bye.

847

: 00:48:34

Okay, bye-bye.

848

: 00:48:35

Thanks a lot, David.

849

: 00:48:35

Bye.

850

: 00:48:36

That was Dr.

851

: 00:48:37

David Plevin offering us a rare

blend of scientific rigor and

852

: 00:48:41

reflective clinical wisdom.

853

: 00:48:43

Whether it was his exploration and

explanation of his team's research in

854

: 00:48:48

terms of electrophysiological and clinical

predictors of theta burst stimulation in

855

: 00:48:53

transcranial magnetic stimulation, or his

perspectives on things like de-prescribing

856

: 00:48:58

in mental health treatment and addictions.

857

: 00:49:02

There really is a lot there to

reflect on as we all work to better

858

: 00:49:05

understand the brain and how to care

best for those who are suffering.

859

: 00:49:10

If you enjoyed today's episode,

please like and subscribe.

860

: 00:49:13

Leave a review or comments in the

comment section, and don't forget

861

: 00:49:18

to share this with a friend, family

member, or a colleague, somebody who

862

: 00:49:22

you think might be interested and might

benefit from understanding more about

863

: 00:49:26

neurostimulation, as we discussed today.

864

: 00:49:29

You can find links to Dr.

865

: 00:49:30

Plevin's research, I'm going to put images

and other links about his study that we

866

: 00:49:36

talked about in the show notes, so please

do check those out as well as links to

867

: 00:49:40

his clinical and academic programs at

the University of Adelaide in Australia.

868

: 00:49:45

Other resources that I thought

might be useful, I'll put

869

: 00:49:47

in the show notes as well.

870

: 00:49:49

So thanks again for joining us.

871

: 00:49:50

I really appreciate your time,

your interest, and your attention.

872

: 00:49:54

It's important to me.

873

: 00:49:55

I realize that there are many other

things that you could be doing,

874

: 00:49:57

and I'm honored that you would

be spending time listening to or

875

: 00:50:01

watching the Neurostimulation Podcast.

876

: 00:50:03

So until next time, take care,

stay curious and be well.