Comment by webinvest | Hacker News Reader

Comment by webinvest | Hacker News Reader

> “The treatment, known as Stanford accelerated intelligent neuromodulation therapy (SAINT) or simply Stanford neuromodulation therapy, is an intensive, individualized form of transcranial magnetic stimulation. In the study, remission typically occurred within days and lasted months. The only side effects were temporary fatigue and headaches.”

> “Twenty-nine people with treatment-resistant depression participated in the study: About half received SAINT, and the rest underwent a placebo procedure that mimicked the real treatment. After five days of treatment, 78.6% of the participants in the treatment group were no longer depressed, according to several standard methods of evaluation. “It’s quite a dramatic effect, and it’s quite sustained,” said Alan Schatzberg, MD, the Kenneth T. Norris, Jr. Professor in Psychiatry and Behavioral Sciences, who was a co-author of the study.”

Makes me wonder what percentage of the placebo group improved?

> The transcranial magnetic stimulation treatment currently approved by the Food and Drug Administration requires six weeks of once-daily sessions. Only about half of patients who undergo the treatment improve, and only about a third experience remission from depression.

Within four weeks after treatment, 12 of the 14 participants who had received the treatment improved, and 11 of them met FDA criteria for remission. In contrast, only two of the 15 participants who had received the placebo met the criteria for remission

From the article further on.

The two mentioned in the article met the FDA definition of remission. It doesn’t say, how many improved in general. This is important specifically since the sample size of the trial is small.

I agree both endpoints are interesting-- but arguably remission is more important of an outcome measure than improvement.

But remission is defined by the same measure. It’s just an arbitrary threshold on the HDRS.

Sure. And improvement is doubtlessly confounded more by the placebo effect. Still, both are interestink.

It's the important & useful of the two endpoints they measured. Anything will have a positive effect on depression if it comes with a lot of high-tech vodoo and people in lab coats. Only it won't last and it will the "yeah, I guess I'm feeling better"-level of improvement.

> Only it won't last and it will the "yeah, I guess I'm feeling better"-level of improvement.

Who says it won't last? Most depressions actually do get better by themselves.

How do you think humanity has survived so far?

(Most, but not all. And even if it eventually gets better without meds, there was still a lot of suffering.)

It's quite possible humanity has survived because most people never get depressed. You need to be quite clear about definitions to have a meaningful conversation on this.

Maybe. So please ignore the part where I speculate about evolution, if you want to.

Empirically, most clinical depressions get better by themselves today.

Similarly, most alcoholics improve by themselves.

(Of course, effective treatment is still useful!)

Unfortunately your genes don’t care about whether you’re happy or not beyond your gene’s needs for survival and reproduction.

Yes. And given the prevalence of continued prevalence of depression, there might be some evolutionary benefit for the genes that also cause depression.

No clue whether it's the depression itself, or whether that's just a side-effect of something else that's useful.

Considering we are chemical based, I wonder how of it is the serotonin receptors are plugged with LSD, an effect similar to SSRI's. https://edition.cnn.com/2020/02/27/health/lsd-overdoses-case...

But what about other chemicals, Glycine contributes to an increase in 5alpha Reductase which helps reduce Cortisol one of the stress hormones. It can be used in place of sugar in hot beverages and food, how much does stress contribute to depression? https://en.wikipedia.org/wiki/5%CE%B1-Reductase#List_of_conv...

And then there is Glutathione which increases light sensitivity, could this help reduce Seasonally Affect Disorder (SAD) also known as the winter blues, knowing that it also helps management of ROS, peroxides, lipid peroxides and heavy metals? Glutamine, N-Acetyl Cysteine and Glycine help to increase Glutathione in the body.

I wonder if fMRI has a similar effect on the brain to homogenising milk, namely it softens the fat walls in milk. Is fMRI having an effect in the brain or in the vascular system with plaques that contribute to atherosclerosis, because induction hobs or magnetic induction reduces inflammation https://peerj.com/articles/929.pdf does this demonstrate that depression is caused by a variety of factors not just one's linked to serotonin even though serotonin plays a part with the immune system?

Does this also imply the possibility of the inverse, magnetically making people depressed?

This is a great comment. I've always been a little uncomfortable with the thought of this magnetic treatment in a way I couldn't put into words and this nails it.

I'm willing to trust, perhaps naively, that everyone is getting the same Prozac tablets. But how does the skill of the practitioner and maintenance of their magnetic treatment device affect outcomes? It's almost like a surgery, but I'm not sure who's actually been trained to perform it.

Which isn't to say someone shouldn't do it, just my own feelings based on limited understanding. Perhaps if I knew more I would have greater faith.

The trial used fMRI data to find a cortical area that has functional connectivity with the DLPFC. That area is then targeted with a neuronavigation system (similar to AR), that helps the clinician place the TMS coil at the right spot and the right angle. This in addition to the magnitude of the pulses being based on the patient's threshold (e.g. minimum amount of stimulation that causes motor movement when used over the motor cortex) is what is meant by "personalized".

It's also of note that the treatment takes place over multiple days and there's multiple sessions in a day. During that time, patients are continuously evaluated. This trial was also only used on patients with treatment-resistant depression (i.e. have tried many different medications and forms of therapy, some included ECT) and were screened as such. From my understanding, the treatment was explored as a "last resort" for those that could find no other medical relief, but this obviously has further implications.

Magnetic therapy makes me feel sick to my stomach for reasons that have for long been unknown to me. I'm more comfortable with the idea of undergoing electroconvulsive therapy than something that involves magnets. I'm not sure why it bothers me so much, but it does to an unusual degree.

Human emotional responses to wireless technology, even before the invention of said technology, are very interesting. Check out the wiki page for James Tilly Matthews.

Odd coincidence. The link to “pneumatic chemistry” in that article is purple because I was just reading about the history of bismuth.

Yikes, hope I'm not a hatter like this dude. Thanks for sharing, lead me to discover the Travels Through Time podcast and listened to this episode: https://www.youtube.com/watch?v=d7GdAHr7ZHU

A whole lot of treatments end up refined with time.

The FDA approved treatment is "aim at the middle of the dorsolateral prefrontal cortex". Getting more activity and connectedness improves its regulation of overall emotional activity.

This research implies that aiming instead slightly differently and a different dosing regimen may be more effective.

This is no different from any other medical treatment, where we find refinements in how and where to apply basically the same treatment to get better results.

Yes. Treatments are simply implementations of science technology at a particular time.

To get some perspective on iterations of treatment, read this account of the work of August Bier.

He pioneered spinal anesthesia, something used all of the time today for epidurals during childbirth.

His experimental treatments he both performed and had performed on him by his assistant will, at the very least, raise your eyebrows.

https://en.wikipedia.org/wiki/August_Bier#Spinal_anesthesia

Do you have the same feelings about radiation therapy for cancer?

It's all a little freaky if you think about it: even in evidence-based medicine, a whole lot of it is people making qualitative determinations and squishy adjustments to treatment, and undoubtedly getting it wrong a whole lot.

Then again, the stuff shows benefits in trial, and presumably we get most practitioners trained up and doing the thing that's the standard of care well enough...

There might be the perfect amount of paracetamol to take to treat your light headache.

But in practice people just take two 500mg tablets and call it a day. Works well enough most of the time, even though it might be 'wrong' in some platonic sense of the word. (Eg you might have been helped enough with a slightly lower dose. Or perhaps 1250mg would have been better and suppressed slightly more of the pain. Who knows?)

No, it's a very different situation since radiation therapy has such a long history at this point.

I'm just not sure what the margin for error is, the failure modes for this magnetic therapy, or what makes a good magnetic therapist.

Not a reason to stop developing it though.

Magnetic treatment has a long history... we've given billions of MRIs, no one's grown a 3rd arm.

There are plenty of doctors that rather die than treat their cancer. There was even a "recent" HN story about it. The motivation is that for a nasty one, the treatment is often worse than the disease, and they rather spend their wealth and to easy their pain and enjoy their last months of living rather than going through a very hard process that might not work, might leave them in an not that good state.

There are drug recalls: https://www.fda.gov/drugs/drug-safety-and-availability/drug-... which would invalidate your assumption about Prozac tablets.

It seems like a… blunt instrument.

That’s what gives me pause.

I concur with this, and the concern that you don't just get something for free. What is the actual mechanism at play here?

Any study can only imply the outcome of what was observed. The techniques they used required an MRI machine so you aren't going to see magnetic fields wherever you go.

They stimulate activity in a precisely chosen part of the brain. There is no inverse. They could stimulate a different part. In fact, they use the motor cortex to calibrate the stimulation level to be the lowest that produces any involuntary movement. I imagine it must be interesting for the subjects.

This reminds me of Greg Egan's creepily effective SF story "Reasons to be Cheerful", which is online here: https://www.utilitarianism.com/greg-egan/Reasons-To-Be-Cheer...

How happy would you choose be if you could consciously decide how happy to be?

For a treatment-resistant condition, 50% success rate can be worth the effort.

Hell, 5% is worth the effort if it's little enough effort or the condition is severe enough. 80% is incredible if it holds up.

Not if it utterly ruins the remaining 20%. Or results in Lewy-Body Dementia in old age, or, or.. That's my concern here.

I wonder what results you'd get if you tried a treatment which was literal torture...?

Eg. "We'll poke this red hot poker into you 10 times to cure your depression"... Many painful screams later... "So, is the depression any better now, or should we do more treatment?".. "Yes, yes, I'm pretty much cured!".

How can we be sure that this 'torture effect' isn't whats being measured here? Especially when the treatment appears to have unpleasent side effects, and the success of the treatment is measured with patient feedback...

Wouldn't the patients just opt out of the trial rather than continue and lie to the researchers? Nobody's being forced into it

You can't assume that.

Part of being depressed is you don't even have the will to resist being treated in a way that you don't like.

In fact, I'd say that feeling powerless against conditions that you don't like is the core of what depression is.

It's why someone who is depressed doesn't feel like doing anything, because they feel like no matter what they do nothing will ever change so nothing they do is ever worth the effort.

It doesn't need to be that intrusive.

Just mildly uncomfortable .. for a period of time longer than one would be willing to tolerate.

Something like being at the dentist when you have many cavities in your teeth.

You can tolerate one or two sessions. But the idea of doing it every day for two weeks straight is unbearable enough that you decide on the third day to report feeling well.

The article says 2 out 15 improved in the control group.

Likely more than 2 of 15 improved. The numbers to compare are 2 of 15 remission vs. 11 of 14 remission-- not <<unknown>> of 15 improved vs. 12 of 14 improved.

> Makes me wonder what percentage of the placebo group improved?

For future reference, assuming this is a clinical trial, data from clinical trials is available online. This is the kind of statistic that you'd be able to find.

But it must be difficult to do so, or you would have done a lmgtfy link or comment like "Just search the study title and look at table 12."

> Within four weeks after treatment, 12 of the 14 participants who had received the treatment improved, and 11 of them met FDA criteria for remission. In contrast, only two of the 15 participants who had received the placebo met the criteria for remission.

>>In contrast, only two of the 15 participants who had received the placebo met the criteria for remission.

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