4 ms·

Impossible that it would receive ethical approval, and for good reason, but it would be fantastic if such a study could be conducted as a double blinded placebo

by dangom 5y ago

Impossible that it would receive ethical approval, and for good reason, but it would be fantastic if such a study could be conducted as a double blinded placebo-controlled clinical trial. The fact the patient knows she has a myriad of doctors looking at her, and that she had to undergo an extremely invasive and unique procedure means we cannot separate the intervention from the response.

bertil 5y ago
My partner is defending her PhD on using Deep Brain Stimulation (DBS) i.e. a comparable device with constant current, to address severe OCD next Friday. Results are impressive (and published) on a small sample of ten patients. There’s at least three research programs that I know of (and probably a couple more if I had read the bibliography properly rather than just fix the formatting issues) with a dozen patients, some for OCD, other for other psychiatric issues. The approach is widely effective on neurological issues (Parkinson’s notably). Her lab have scheduled double-blind trials as soon as the next patient is operated, which I think is next month, with a protocol that includes 1. implanting the device, 2. only activating the electric current for half for six months, and 3. have another psychiatrist, blinded to whether the device is active, test its effect. There was an ethical debate on testing the device without Cognitive behavioural therapy (CBT) at the same time: CBT has a meaningful impact, and no doctor would imagine not prescribing that too, but scientifically, having patients with and without CBT, with and without DBS, etc. would allows to measure the effect of the each alone and together. I learned about this seemingly different approach (I suspect the device is similar, but the current is triggered differently, from the vulgarisation — haven’t read the academic papers) recently, but I’d be surprised if most of the protocols didn’t extend without much complications.
- caycep 5y ago
  Where are they implanting it in her trial? There's a big and somewhat raucous debate on 5 different (brain) targets so far, but imaging/tractography has come a long way since they started doing it. for the CBT thing...could they just use a crossover trial design?
  - bertil 5y ago
    Big debate around that, apparently — and one vs. more locations, etc. I should remember the exact area after having to draw so many version of the interaction graphs, but not on the top of my head — did check: Bed Nucleus of Stria Terminalis. I know one of her coauthor has doubt that the location matters that much (we are talking places that are less than a centimetre apart, at the very center of the brain for anyone who isn't up to date on their basal ganglia) and suspects that current works because it actually affects the whole area. Telling neurosurgeons that millimetres are not a matter of life-and-death apparently didn’t go too well at the latest conference… and honestly, it sounds a bit nerdy from the outside, but I’m really impressed by how much they care, and very happy that they do. There’s been progress on imaging, but given the image quality and resolution, the very small number of patients for whom it didn’t work to compare against, I’d be surprised if they can make non-obvious judgements like “it can work as long as one of those is electrified” vs. “it works because anywhere of that area has some current of at least that much” vs. “it works because everywhere in that area has current above a low threshold, but you need to put more if you use electrodes in only some location”. > crossover trial design Good idea, definitely my recommendation (I implemented a lot of tests with that for on-line AB-tests to account for novelty effects); I think it has been discussed and was used before, but I remember a story of patients who got very concerned over loosing the sanity they had finally gained, and begged to get the current back. The risk of regression might lead to worst outcomes. That’s the different with say, tremors from Parkinson’s: sure they are impossible to live with, but if you are confident they can be switched on and off, they become an annoying party trick. Same as a prosthetic leg: you need it to walk but if you have to take it off, you can. Mental health doesn't have the same tangibility: you are not yourself anymore without it? It’s hard to explain but it drives a lot of the trickier ethical questions in psychiatry. Check the literature because I could have made the patients up, or it could be a speculation from the ethics committee. But as the device gets more common, there will be better stats & methodology. I suspect that, to get from a research exception to a diagnostic recommendation, they will need to do investigate to recommend either switching it off in case of concern, how, how fast, which levels, when to stop lowering, etc.) or advise against any reduction, or recommend having the device removed… Crossover could be helpful in that context.
- edge17 5y ago
  Is this something like TMS? I know people that do this, apparently the results are very good.
  - caycep 5y ago
    No, it's a stimulating electrode implanted surgically in selected brain targets. The difference is: TMS is inaccurate/broad/hard to target, and wears off either when you shut off the TMS or a few days to weeks later. Think a weaker version of ECT. DBS allows focus on specific brain targets, and the effect lasts for the lifetime of the electrodes/device.
- DenisM 5y ago
  This probably deserves its own HN post.
smt88 5y ago
> Impossible that it would receive ethical approval > The fact the patient knows she has a myriad of doctors looking at her, and that she had to undergo an extremely invasive and unique procedure means we cannot separate the intervention from the response. Deep brain stimulation has undergone many such trials[1]. I'm not sure why this would be such an ethical barrier when we have much more risky and permanent procedures (various surgeries, for example) that can undergo ethical trials. Methodology summary from trial linked below: "We conducted a 6-month double-blind, randomized, sham-controlled crossover study in implanted patients with previous severe TRD who experienced full remission after chronic stimulation. After more than 3 months of stable remission, patients were randomly assigned to 2 treatment arms: the ON-OFF arm, which involved active electrode stimulation for 3 months followed by sham stimulation for 3 months, and the OFF-ON arm, which involved sham stimulation for 3 months followed by active stimulation for 3 months." 1. https://pubmed.ncbi.nlm.nih.gov/25652752/ https://pubmed.ncbi.nlm.nih.gov/25652752/
caycep 5y ago
typically this is done via sham stim. i.e. implant both groups, but don't turn on the control group for the blinded phase. Helps that DBS technique has had 40 years or so to refine itself so its adverse-effect rate is reasonably well known and established. See methods section https://n.neurology.org/content/88/16_Supplement/P5.016 https://n.neurology.org/content/88/16_Supplement/P5.016
amelius 5y ago
There are animal models for depression.

by dangom 5y ago

bertil 5y ago

My partner is defending her PhD on using Deep Brain Stimulation (DBS) i.e. a comparable device with constant current, to address severe OCD next Friday. Results are impressive (and published) on a small sample of ten patients. There’s at least three research programs that I know of (and probably a couple more if I had read the bibliography properly rather than just fix the formatting issues) with a dozen patients, some for OCD, other for other psychiatric issues. The approach is widely effective on neurological issues (Parkinson’s notably). Her lab have scheduled double-blind trials as soon as the next patient is operated, which I think is next month, with a protocol that includes 1. implanting the device, 2. only activating the electric current for half for six months, and 3. have another psychiatrist, blinded to whether the device is active, test its effect. There was an ethical debate on testing the device without Cognitive behavioural therapy (CBT) at the same time: CBT has a meaningful impact, and no doctor would imagine not prescribing that too, but scientifically, having patients with and without CBT, with and without DBS, etc. would allows to measure the effect of the each alone and together. I learned about this seemingly different approach (I suspect the device is similar, but the current is triggered differently, from the vulgarisation — haven’t read the academic papers) recently, but I’d be surprised if most of the protocols didn’t extend without much complications.

caycep 5y ago
Where are they implanting it in her trial? There's a big and somewhat raucous debate on 5 different (brain) targets so far, but imaging/tractography has come a long way since they started doing it. for the CBT thing...could they just use a crossover trial design?
- bertil 5y ago
  Big debate around that, apparently — and one vs. more locations, etc. I should remember the exact area after having to draw so many version of the interaction graphs, but not on the top of my head — did check: Bed Nucleus of Stria Terminalis. I know one of her coauthor has doubt that the location matters that much (we are talking places that are less than a centimetre apart, at the very center of the brain for anyone who isn't up to date on their basal ganglia) and suspects that current works because it actually affects the whole area. Telling neurosurgeons that millimetres are not a matter of life-and-death apparently didn’t go too well at the latest conference… and honestly, it sounds a bit nerdy from the outside, but I’m really impressed by how much they care, and very happy that they do. There’s been progress on imaging, but given the image quality and resolution, the very small number of patients for whom it didn’t work to compare against, I’d be surprised if they can make non-obvious judgements like “it can work as long as one of those is electrified” vs. “it works because anywhere of that area has some current of at least that much” vs. “it works because everywhere in that area has current above a low threshold, but you need to put more if you use electrodes in only some location”. > crossover trial design Good idea, definitely my recommendation (I implemented a lot of tests with that for on-line AB-tests to account for novelty effects); I think it has been discussed and was used before, but I remember a story of patients who got very concerned over loosing the sanity they had finally gained, and begged to get the current back. The risk of regression might lead to worst outcomes. That’s the different with say, tremors from Parkinson’s: sure they are impossible to live with, but if you are confident they can be switched on and off, they become an annoying party trick. Same as a prosthetic leg: you need it to walk but if you have to take it off, you can. Mental health doesn't have the same tangibility: you are not yourself anymore without it? It’s hard to explain but it drives a lot of the trickier ethical questions in psychiatry. Check the literature because I could have made the patients up, or it could be a speculation from the ethics committee. But as the device gets more common, there will be better stats & methodology. I suspect that, to get from a research exception to a diagnostic recommendation, they will need to do investigate to recommend either switching it off in case of concern, how, how fast, which levels, when to stop lowering, etc.) or advise against any reduction, or recommend having the device removed… Crossover could be helpful in that context.
edge17 5y ago
Is this something like TMS? I know people that do this, apparently the results are very good.
- caycep 5y ago
  No, it's a stimulating electrode implanted surgically in selected brain targets. The difference is: TMS is inaccurate/broad/hard to target, and wears off either when you shut off the TMS or a few days to weeks later. Think a weaker version of ECT. DBS allows focus on specific brain targets, and the effect lasts for the lifetime of the electrodes/device.
DenisM 5y ago
This probably deserves its own HN post.

smt88 5y ago

> Impossible that it would receive ethical approval > The fact the patient knows she has a myriad of doctors looking at her, and that she had to undergo an extremely invasive and unique procedure means we cannot separate the intervention from the response. Deep brain stimulation has undergone many such trials[1]. I'm not sure why this would be such an ethical barrier when we have much more risky and permanent procedures (various surgeries, for example) that can undergo ethical trials. Methodology summary from trial linked below: "We conducted a 6-month double-blind, randomized, sham-controlled crossover study in implanted patients with previous severe TRD who experienced full remission after chronic stimulation. After more than 3 months of stable remission, patients were randomly assigned to 2 treatment arms: the ON-OFF arm, which involved active electrode stimulation for 3 months followed by sham stimulation for 3 months, and the OFF-ON arm, which involved sham stimulation for 3 months followed by active stimulation for 3 months." 1. https://pubmed.ncbi.nlm.nih.gov/25652752/ https://pubmed.ncbi.nlm.nih.gov/25652752/

caycep 5y ago

typically this is done via sham stim. i.e. implant both groups, but don't turn on the control group for the blinded phase. Helps that DBS technique has had 40 years or so to refine itself so its adverse-effect rate is reasonably well known and established. See methods section https://n.neurology.org/content/88/16_Supplement/P5.016 https://n.neurology.org/content/88/16_Supplement/P5.016

amelius 5y ago

There are animal models for depression.