Study: Electroshock therapy more successful for depression than ketamine
today.uconn.edu
today.uconn.edu
The space is also at the precipice of a whole new class of psychedelics coming online - MDMA, psilocybin, and more are all 1-5 years out (working through FDA drug trials), and hold promise of both faster results (versus 6-8 months of trialing traditional antidepressants) and fewer downside risks (versus weight gain, sex drive, etc. issues with antidepressants and memory loss, headaches, etc. with ECT and TMS).
Bottom line, if you're suffering and considering those treatments, I highly recommend finding a local center and at least learning more about options available to you.
Edit: If anyone wants to talk, advice, etc., email is in my profile.
The effects of psychedelics are profound to a person who hasn't experienced them, which is the vast majority of people today. I think, when a person goes through a powerful experience they've never had, it makes them a lot more suggestive, which in turn makes therapies more effective. Will this still be the case if psychedelics usage is normalized? When a person knows what to expect out of the drug will they still remain as suggestible to therapy?
My own experience with psychedelics tells me no: once you become familiar with the effects the "high" loses some of it's properties that make it a useful tool for introspection.
I haven't done psychedelics in a purely therapeutic setting so there may be something to my observation that I'm missing completely.
I can’t speak to other hallucinogens but I would imagine the situation is the same there. The day after an acid trip isn’t a new neurochemical environment because of the powerful hallucinations the day before, it is something else.
> My own experience with psychedelics tells me no: once you become familiar with the effects the "high" loses some of it's properties that make it a useful tool for introspection.
My own experiences run directly counter to this assertion.
What is a "new neurochemical environment" exactly? I've had many acid comedowns, and they have all been affected by how the high was - emotionally, mentally, and physically. What do you mean by "its something else"?
https://hubermanlab.com/sleep-toolkit-tools-for-optimizing-s...
There are so many small things you can do, and they get summarised here. Drugs are just one dimension.
Shoot me a DM if you want to try it out - happy to send one your way.
I am curious to read why this is bad. My doc thinks this is perfectly fine
Melatonin is naturally secreted by the pineal gland, which like other hormones gets downregulated when taken exogenously over long periods of time.
There’s also studies showing a downregulation in dopamine and seratonin with long term use of melatonin.
- https://impossible.co/blogs/health/magnesium-and-sleep - https://impossible.co/blogs/health/l-theanine-for-sleep
[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866161/ [1] https://onlinelibrary.wiley.com/doi/full/10.1002/brb3.1423
Seems way too dangerous for home use.
https://www.bmj.com/content/364/bmj.k5233
This article is arguing ECT as acute treatment for resistant depression. In most, if not all, cases a patient would become eligible for ketamine treatment at the same time if not sooner than ECT. Memory loss directly due to ECT is the reason most people are strongly against using it. Treatment options are based on minimizing risks, not guaranteeing success. Unless ketamine is contraindicated, it will always be a safer treatment than ECT.
1. You are under general anesthesia 2. The dosage of electricity is very low when compared to how it was done before. 3. The electrical currents are far more focused
Stuff like personality changes or loss of creativity is no longer a risk factor. Risks tend to be those associated with general anesthesia and mild memory loss around the treatment.
I had over 2 rounds of 15 treatments over a 6 month period. I haven't had a serious relapse in the 5 years since. I had tried every SSRI and SNRI my insurance would cover. I had been in therapy for over a decade. I was suicidal. ECT saved my life.
How does the memory loss manifest? Are you aware that you lost time, like can you feel that you did experience time pass for X amount of days, but you just don't remember what took place? Or is the feeling that the time never passed at all, like it was Monday and you woke up on Friday, but it felt like it was actually Tuesday morning, and you have no intuitive feeling that a week passed at all?
ECT is an inpatient procedure that need one anesthesiologist and one psychiatrist plus nurses to administer, two to three times weekly for three to four weeks.
Who pays for the healthcare, definitely want to try the former and use the latter only if the former works poorly.
IRRC both of them cannot compare to psychotherapy, which has far higher effectiveness at the cost of far more resources.
The whole point of this, and numerous other articles is that this statement is objectively false.
If you have treatment resistant depression, PTSD, etc that treatment includes therapy.
Which is why ketamine and ECT are being investigated - for plenty of people these treatments have resolved things such that they do not need medical or therapy based treatment.
> which has far higher effectiveness at the cost of far more resources.
I'm guessing this is a typo, but given the cost of 1+ hours a week at easily $100-200/hr, for years - often without any limit at all - I'd be curious what the total cost is. This is especially important in this case as ECT, ketamine, etc treatments are _required_ to demonstrate efficacy, whereas psychotherapy has no such requirements.
There's been plenty of research over the years that has found pretty underwhelming outcomes from therapy based treatment outside of specific areas - more extreme are the therapy group/out-patient scams which have been shown very clearly to only work for groups of people with exactly the same trauma, and even then, only specific types of trauma.
It's a real problem in mental health treatment that only treatments that require the use of drugs and/or "surgical" procedure are required to provide evidence that they actually work.
I’ll take milder effects over pain and memory loss, thanks.
No mention of longevity of effect, or specific studies and who paid for them.
The other "side effects" are generally part of its desirable properties ;)
I imagine the physical effects of ECT must be very harsh and difficult for the body.
It’s like saying that a side effect of drinking alcohol is feeling drunk.
For better or for worse.
The disassociation is often a desired effect, it can be incredibly enjoyable.
> Most people diagnosed with depression are offered an oral antidepressant (in combination with psychotherapy) as a first-line treatment option. But _if oral antidepressants don’t help_, or _if the person is at imminent risk of hurting themselves_, there are other, more rapid treatment options: ECT, and more recently ketamine or esketamine.
> “ECT is consistently more successful than ketamine” at helping _patients with serious depression_
> “We need to improve public awareness of ECT for _treatment-resistant depression_.”
(emphasis mine)
I hadn't thought about that in years, but it was my first thought when I saw the headline, I was thinking that was just so obsolete. Indeed, longevity of effect, or specific studies and who paid for them.
Yikes.
ECT as used well into the 80s, possibly even the 90s, was pretty much aversion therapy - essentially just: "you'll behave properly or we'll torture you".
In CA at least the rules for use of ECT nowadays are extremely strict, and required frequent confirmation of understanding of what you think you are doing, what is involved, why you are doing it, etc administered by a party not involved in the treatment.
> I was thinking that was just so obsolete.
Why? The studies for ECT for treatment resistant depression show that it _is_ effective for more than 50% of candidates who undergo it. Note that these are treatment resistant cases, e.g. people for which there is by definition a 100% failure rate for every other option.
> Indeed, longevity of effect, or specific studies
For some people ECT appears to provide a permanent relief. Some it provides significant improvement for extended (e.g. years) periods, and for some it does not do anything.
I can't point to specific studies because at this point there are so many, and that they all have very similar outcomes of more than 50% of recipients having extended or permanent (presumably within bounds of time) improvement in symptoms.
> and who paid for them.
Generally it's government funded institutions, but I get the general "evil business" conspiracy vibe from this comment. It's important to realize that ketamine and ECT aren't things that you can make profitable. If they work for a given patient they both have extended periods where the patient is not likely to need any treatment, if ever again - the general worst case for a profit driven treatment.
Your ability to have a high profit margin is limited by ketamine being a generic drug in the US, and being cheap and easy (in terms of drugs) to manufacture. ECT on the other hand has a large array of costs that can't be avoided, but that also aren't profit centers: you need hospital facilities due to the general anesthesia, an anesthesiologist, the actual doctor, nurses, and a third party to audit and interview patients.
If it has changed sufficiently to be essentially unrecognizable vs prior practice, that is probably a good thing... Still, knowing what I do about neuroscience from a minor in college, it still seems like heavy artillery barrages to deal with an insect infestation, or burn the village to save it. The real work of the brain & nervous system happens in hundreds of subtle interactions within cells and in the synapses, the patterns of the synapses, etc, and this is just a global sledgehammer. It'll likely have measurable effects, although 50% seems pretty much like toss-a-coin Russian Roulette with your brain. Perhaps an OK bet in true desperation, but...
The aversion therapy element is gone entirely - it is always performed under general anesthesia, the patient must consent explicitly, and the patient consent and understanding must be checked regularly by a third party.
> The real work of the brain & nervous system happens in hundreds of subtle interactions within cells and in the synapses, the patterns of the synapses, etc, and this is just a global sledgehammer.
Modern ECT is performed with low voltages applied to specific regions, as this and every other paper involves goes into the details of.
> It'll likely have measurable effects, although 50% seems pretty much like toss-a-coin Russian Roulette with your brain.
The success rate is greater than 50%, but it's also fairly dismissive to act like there's no cost involved in the alternative. For example, would you be saying "sure there's a 50% chance this cancer cure will save your life, but it has a bunch of terrible side effects, so it's basically Russian roulette"
> Perhaps an OK bet in true desperation, but...
Again with the dismissiveness.
Neither ECT nor ketamine are considered for anything other than extreme cases for which all alternatives have failed, so weighing the side effects of these treatments against the symptoms of mild and/or treatable conditions is kind of shitty?
I get it, due to personal experience you are biased against ECT, and so whether a bunch of research demonstrates that it can be beneficial is not relevant to you. But you don't get to then act like the alternative is some kind of panacea free from these side effects that are apparently so bad.
However, I don't recall even implying or "act[ing] like the alternative is some kind of panacea", and I don't hold such a position, and I don't say there is no cost in the alternative.
In fact, it is likely that both are major problems, and will at some point be considered barbaric (as will the cancer chemotherapy you mentioned).
All three are deliberate massive disruptions to the entire system, not at all targeting the actual problem, and in fact any benefit is simply a welcome side-effect. An analogy would be a problem in some towns in the midwest US, and ECT is like hitting the zone with a Magnitude 9.3 earthquake and Ketamine/Chemo is like hitting the zone with a massive flood. Sure, the problem may go away, but...
The best advances are being made in immunological cancer treatments, which are far more targeted, and looking far more effective.
Eventually, we'll be able to know more to know which small subset among the 100 billion neurons and ~quadrillions of synapses to target. Meanwhile, considering either ECT or systemic drugs as much more than a few steps up vs applying leeches is just wrong. I haven't seen a shred of research that indicates understanding of exactly what brain structures are being targeted, and why nevermind what neurons, for ECT or the systemic drugs, and quite a bit on basically empirical, 'well we do this and it gets a desired effect X% of the time'. Sure, that is way better than nothing, and it is all we have, but it is NOT anything like the desired end state of diagnosing IN DETAIL and EXACT problem and it's detailed mechanism, and then repairing it.
I definitely prefer that over losing memories but I have not tried ECT.
As if the often pleasant, often interesting, often terrifying yet short term and proven harmless side-effects of Ketamine can even compare to the ECT! I would like to see how _much_ better ECT is, given all the factors. Additionally, one can do quick, repeat treatments with ketamine. I'm sure doctors would caution repeatedly getting hooked up to an ECT machine.
Ketamine in recreational use has equally documented side effects, some quite severe. Extreme circumstances that have caused irreparable damage are rare, but not unheard of.
There are also numerous other anecdotes from people that have undergone numerous session of ECT with minor side effects.
I'm not for or against ECT or ketamine, I just find the language used and conclusions reached from so little evidence extremely dangerous.
As far as I know, bladder damage is the only actual physical effect of ket
https://en.wikipedia.org/wiki/Townes_Van_Zandt#Early_life
I heard a Radio Lab episode in which a sufferer of chronic depression said that he hyperventilated before ECT to minimize memory effects.
You also don't just get "hooked up to an ect machine" - it's well established that ECT as used historically was almost entirely aversion therapy - modern ECT does not ever occur on a conscious patient, and because of how it was used historically there are extremely strict controls on patient consent and patient awareness of what they are consenting to - all questionnaires, surveys, consents, etc are taken by a third party that is not part of the treatment.
> The overall pooled SMD for depression symptoms for ECT when compared with ketamine was −0.69 (95% CI, −0.89 to −0.48; Cochran Q, P = .15; I2 = 39%), suggesting an efficacy advantage for ECT compared with ketamine for depression severity.
> Both ketamine and ECT had unique adverse effect profiles (ie, ketamine: lower risks for headache and muscle pain; ECT: lower risks for blurred vision, vertigo, diplopia/nystagmus, and transient dissociative/depersonalization symptoms).
Perhaps you'd reach the same conclusion as you did, and I think the paper puts it best:
> Although ECT may be more efficacious than ketamine in the acute phase, treatment options should be individualized and patient-centered, considering different adverse effect profiles and patient preferences.
Feeling a little loopy from a hefty Ket dose and having permanent brain damage from being shocked are so far removed from each other that it is an actual failing in different regards.
Drugs may figuratively fry your brain, but it is certainly better than literally frying your fuckin brain.
A keyword was left from the title / headline.
https://www.dea.gov/sites/default/files/2020-06/Ketamine-202...
Any discussion of efficacy that doesn’t include side effects is quackery.
> The side effect profiles of the two treatments differed, with ECT more likely to cause headaches, muscle pain and memory loss, while ketamine was more likely to cause dissociative symptoms, vertigo and double vision.
The vertigo and double vision last a little while, possibly the rest of the day. They're not long term or serious. The memory loss from ECT can be long-term for some people.
I've personally found ketamine to help a lot with my mental health issues. It's great and I'd highly recommend at least giving it a shot in a therapeutic setting. I'm sure it's interesting recreationally as well, though I've never tried it that way.
Would you try it? If you've not got much to lose, why not? It's not as if suicide is suddenly no longer an option afterwards.
Don't think that's necessarily the case.
It's just that sometimes, the easiest and least confrontational way to stop a treatment with serious side effects is to claim that the treatment is no longer needed.
Studies should find ways to control for such problems.
Watch people get sleep problems, a few days of that, and then the mental health issues kick in.
Or cause sleep problems (stimulants or environmental), then see mental health issues produced.
The opposite can happen (mental health problem leads to sleeping problems) but in my circles I haven’t seen that as often. Of course then the mental health issues compound.
Fucking with your sleep is not healthy.
But if you’re sleeping 18 hours a day, that’s not just a cause of depression, it’s an effect.
It's been 12 years since her ECT for post partum depression and she still has memory losses and a completely changed personality (agression is one).
> “Every single study directly reports ECT works better than ketamine. But _people are still skeptical of ECT, perhaps because of stigma_,” Rhee says, or negative depictions in films such as “One Flew Over the Cuckoo’s Nest” and shows such as “Stranger Things.” “_We need to improve public awareness of ECT for treatment-resistant depression_.”
If we read the article carefully, we can see that the headline (as all headlines are) is lacking in nuance:
> Most people diagnosed with depression are offered an _oral antidepressant (in combination with psychotherapy) as a first-line treatment option_. But _if oral antidepressants don’t help, or if the person is at imminent risk of hurting themselves_, there are other, more rapid treatment options: ECT, and more recently ketamine or esketamine.
Firstly, oral antidepressants and psychotherapy are still the firstly line of defence, and for the majority of people enough. As it is, ketamine or esketamine is nowhere near close - has nowhere near enough evidence and longitudinal studies - to replace SSRIs and psychotherapy as the first line. Unfortunately modern medicine isn't advanced enough to fully understand what's going on with oral antidepressants (we have theories, but the majority evidence is simply statistics), let alone (es) ketamine and ECT. As a result, if oral antidepressants are not effective it can often be difficult to effectively prescribe treatment. Naturally a consequence of this is increased risk, from procedures that may not have much if any benifits, not even including the very real chances of a misdiagnosis!
If we look at the cited paper's abstract, the message is even more clear
> Question: Is ketamine as effective as electroconvulsive therapy (ECT) in patients with _major depressive episode_?
> Findings: This systematic review and meta-analysis of 6 trials with 340 patients suggests that ECT may be superior to ketamine in improving depression severity. Findings also suggest that ketamine and ECT each have unique adverse effect profiles.
> The overall pooled SMD for depression symptoms for ECT when compared with ketamine was −0.69 (95% CI, −0.89 to −0.48; Cochran Q, P = .15; I2 = 39%), suggesting an efficacy advantage for ECT compared with ketamine for depression severity.
> Both ketamine and ECT had unique adverse effect profiles (ie, ketamine: lower risks for headache and muscle pain; ECT: lower risks for blurred vision, vertigo, diplopia/nystagmus, and transient dissociative/depersonalization symptoms).
> Meaning: Although ECT may be more efficacious than ketamine in the acute phase, _treatment options should be individualized and patient-centered, considering different adverse effect profiles and patient preferences._
Both (Es)Ketamine and ECT are useful and sometimes literally life saving therapies for those with treatment resistant depression. Like any treatment some respond effectively and may never have to undergo future treatment whilst others may require constant support. The stigma around ECT and the uninformed experience and use of anecdotes is dangerous, and ignores the reality that there are no good answers, at least with our current medical knowledge.
I would advise not drawing any conclusions from limited evidence, and if they want to see more personal anecdotes explore both the positive and negative comments at /r/ECT and /r/TherapeuticKetamine
Vitamin B-9 has to do with DNA synthesis... My source for physiology told me that even the mutants get enough Vitamin B-9 from an adequate diet, it's just poor methylators who rely on fortified food who are screwed. Deplin is the prescription form of Vitamin B-9. It's approved as an add-on therapy, for when patients don't respond well to the prescriptions that never work.
Usually 'mental health' diagnoses are manifestations of stress: emotional stress is the big one, but malnourishment is often a factor too. Stressed brains use more energy thinking about the stress all the time.
ECT should be retired from use. I heard once that brain damage causes the brain to increase production of the steroid allopregnanolone. The beneficial effect of the SSRI's seem to also be related to increased allopregnanolone, NOT to boosting serotonin levels.
I wonder if my friend's guardian [0] could consent to her getting electrocuted.
[0] https://news.ycombinator.com/item?id=33307982
Edit: She remembers being depressed for as far back as her memories go. Someone on twitter says food fortification didn't really take off until the 1980's. Before then you had to explicitly buy "wonder bread" to get fortified flour, now you can basically assume white flour is fortified white flour.
Outside of very specific circumstances during hospitalization, doctors can't actually force you to take any medication.
As soon as the doctors got their order for involuntary treatment in November 2015, they cornered my friend and injected her with a time-release version of haloperidol, then released her to her mother's house.
A day and a half later her mom called the psychiatrists, who said to take my friend to a real ER. My friend told the real doctors at the real ER that she was NOT suicidal. She told me how the haloperidol had 'hit her like a truck', and she tried everything she could think of to counteract the agony: alcohol, cocaine, heroin, dextromethorphan (aka cough syrup), etc.
All the anti-dopamine drugs are terrible. Some of the second-generation drugs that are forced on people are much worse than plain old haloperidol. The poor doctors are just implementing their training. Tragic.
My observation is that agony-inducing drugs are not actually helpful for substance abuse.
To be charitable and more specific, If you are stable enough there's nothing technically stopping you from not taking prescribed medication and self medicating - as long as you remain stable enough to not warrant involuntary treatment. The obvious risk is if your prescribed medication (or a combination of prescribed and self prescribed medication) is making an impact, you could get worse.
From this comment it sounds like there's a lot you're leaving out of this story, but I'd like like be caucious of making generalising statements from specific personally related scenarios.
There's more than can be covered in a little comment.
I have the psychiatrists' September 2015 affidavits, filed in support of their petition for involuntary treatment. They say, essentially, "patient expects us to believe she was psychotic because she was drinking 2 bottles of liquor a day, and using cocaine. We know this is not the case because we previously got her 'stabilized' in 2008 and 2010 on haloperidol. She obviously does not appreciate that she is broken and requires anti-psychotics for the rest of her life."
My videos from August 2015 prove that she was actually fine before she ran out of alcohol, and that whatever deterioration the doctors think they're treating is entirely caused by palliative psychiatric drugs.
Sometimes these situations turn out tragically because the patient was involuntarily given drugs, sometimes they turn out tragically because the patient wasn't.
I'm surprised they went with a time release injection -- from the sounds of it, when you say "time release" you mean on the order of 30-90 days, not "12 hours". I'd have expected them to just work on stabilization and then moving to an outpatient program. I'm very surprised they'd have used it without any history of it being effective.
In a more recent tale with a family member undergoing an involuntary stay, I'd have wished they'd used a longer term haloperidol injection.
There's not a one size fits all solution, and it's hard to balance legislation around personal freedoms vs recognizing when the patient is a harm to themselves/others, or even capable of making informed rationale decisions.
> My observation is that agony-inducing drugs are not actually helpful for substance abuse.
Haloperidol isn't for substance abuse, so I wouldn't expect it to perform well at it.
When she got captured again, their thinking was "she's obviously back here because she didn't take her haloperidol". They never asked me about her alcohol consumption.
Whitaker's book points out that the Quakers' asylums fed people 4 meals a day and provided activities. iirc around 80% of the patients recovered to the point where they could leave the asylum. Think that was covered in Mad In America.
The psychotic patients who do the best, long term, are those who are never treated with antipsychotics. Those who do second best are those who are tapered off antipsychotics promptly. Those who do the worst are those who are maintained on antipsychotics in perpetuity.
Haloperidol has one of the highest rates of side-effects[1], like permanent movement disorders, in its class, and it is neurotoxic[2]. Movement disorders like tardive dyskinesia don't seem like a good time.
Second generation antipsychotics typically have lower affinities for dopamine receptors compared to older drugs, thus lowering the severity of side-effects associated with dopamine blockade. They have much lower risks of causing movement disorders. They also bind to dopamine receptors differently than the strongly antagonist first generation antipsychotics. Some of them are partial agonists, inverse agonists, and full agonists with lower affinities at dopamine receptors, so they have less "anti-dopamine" activity than haloperidol and older antipsychotics do.
I agree with you that these drugs have terrible side-effects, but I'd argue that being loaded with haloperidol is one of the worse options to be treated with when it comes to bad side-effects. There's immediate release inectable versions of olanzapine, ziprasidone and clozapine, all second generation antipsychotics, but I suspect they cost more than haloperidol.
I think aripiprazole (Abilify) is the least-bad of the antipsychotics. None of them work when the psychosis is actually caused by malnutrition, cocaine, meth amphetamine, or alcohol.
Injection of these drugs is a form of violence.
From here[1]:
> What happens if the respondent isn’t compliant with the treatment order?
> It’s up to the judge but the idea is that non-compliance with a court order equates to contempt of court and is punishable by jail time. This is where the “teeth” or consequences are introduced for someone refusing to comply with the treatment plan. However, we have found that many counties do not enforce treatment orders with jail time.
When the option is to be compliant with treatment or be held in contempt of court, that sounds like force.
That's a fascinating insight. Recent medical research implicates neuroinflammation in the pathogenesis of depression [0][1]. Steroids generally have anti-inflammatory properties. Allopregnanolone specifically has anti-neuroinflammatory effects [2][3].
It's amazing, inflammation appears to be implicated in all manner of diseases and conditions.
[0] https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.14720 [1] https://www.frontiersin.org/articles/10.3389/fncel.2021.6910... [2] https://www.sciencedirect.com/science/article/pii/S009130221... [3] https://www.sciencedirect.com/science/article/pii/S235228951...
What's perplexed me is why this mechanism would occur in evolutionary terms, or if it's really just a byproduct.
My breakthrough 'intervention' was frying whole wheat donuts in coconut oil. Coconut oil is brain food for alcoholics.
[0] https://en.wikipedia.org/wiki/Prostaglandin#Biosynthesis
According to wikipedia, Vitamin B-9 is broken down by our bodies into a family of compounds called "THF", which:
1. Help synthesize DNA,
2. Help repair/modify DNA,
3. Help create the amino acid "Methionine", which is a precursor to other amino acids, and is thus important for the synthesis of many proteins inside the body,
4. Activate Vitamin B12.
A deficiency in Vitamin B-9 can lead to a loss of appetite, weakness, heart palpitations, headaches, irritability, and anemia. Also interesting to note that a deficiency in Vitamin B-12 will cause the body to overcompensate and convert a large portion of Vitamin B-9 into the form that metabolizes Vitamin B12, which leads to a condition that mimics a deficiency of Vitamin B9.
One of these days, when I have enough free time, I want to develop a particle-level simulation of the human body, so that medical students, doctors, and curious laymen can see these processes in action on their personal computers. If I combine that with an affordable at-home blood test/diagnostic system, we will have a mechanism to bring affordable healthcare to every single person in the country. And perhaps a reliable method to find the true cause of a patient's depression, before prescribing them SSRI's or other psychiatric drugs.
Another product in this cycle is SAMe (S−adenosyl methionine), which has been marketed for decades as supplement for improving depression.
[1] https://www.creative-proteomics.com/services/methionine-cycl...
Essentially, enough detail to get a list of symptoms and bodily sensations, and predict the outcome of any potential blood test or urinalysis. Or, alternatively, enough detail to take the results of a blood test/urinalysis, and predict the state of every single tissue in the body.
There's some interesting work on "organs on a chip" e.g. arrays of microfluidic cell cultures that allows some experimentation on a combination of a few types of tissue modeling an organ or some aspect of it, but even that's already pushing the state of art and not fully mature at the moment; doing something similar for many (much less all or most) organs is something that doesn't work yet; and these "organs on a chip" are useful because pure simulation is even less mature and is unable to do what these cell cultures can.
The goal you state is interesting, relevant, and potentially achievable, but it's still some decades away.
Consider protein folding. This occurs millions of times per second in the thirty trillion cells in the human body. We only just now built a machine learning model that can predict some of the conformations of individual proteins.
The crazy thing is that protein folding is the easiest problem in biology. Nice clean training data, static high resolution targets. Cell biology is not that. Cells are noisy and constantly changing, and its insanely difficult to even measure what they're doing. Like every time we try to determine how many different types of cells there are, we come up with a different, larger number than before. The reason for this is that all our measurements of the number of proteins, RNA, and other chemicals in cells are bad, like looking through a distorted broken lens.
Complicating all this is that biology is is insanely coupled across both spatial and temporal scales. Consider the KRAS protein. Its one of the most commonly mutated genes in cancer. The most common mutations in KRAS amount to about a dozen atoms being out of place in the protein, due to a single base change in DNA. This nanoscale change in a single cell propagates up to tumors that interfere with bulk physiology and result in death. Or, more specifically for the brain, consider huntington’s disease. Theres a section of DNA thats repeated in a gene called huntingtin. If you have less than 36 copies of the repeat, the you're fine. More than 36 results in a brain disease that typically takes 30-50 years to even manifest.
So, all that to say that simulating this is insanely hard. Like, you’re trying to write a simulation for a system where we dont know what it’s made of or how its individual parts work. Also, we just empirically know that changing the arrangement of a few atoms can result in massive changes that lay dormant for decades before they suddenly appear.
Likely you wouldn't need/want a particle level simulation, but a kinetics level model. Just with kinetics you could draw simulations of "particle concentrations" or other fun things to show medical students, etc, but without the need to simulate the actual chemicals. Though eventually hopefully we could do that too! The AlphaFold breakthrough is a huge advance toward that IMHO.
> If I combine that with an affordable at-home blood test/diagnostic system, we will have a mechanism to bring affordable healthcare to every single person in the country. And perhaps a reliable method to find the true cause of a patient's depression, before prescribing them SSRI's or other psychiatric drugs.
Just getting all the kinetics together would be amazing. You could essentially do what you're talking about of calculating most likely causes (not just correlations). Though brain chemistry != entirety of depression or whatnot. Still just getting even the top 20 chemical cycles mapped from blood tests could be pretty awesome and help bring light to a huge range of conditions.
In my opinion, medicine currently is at a 1.0-1.5 order effects level. As in we can diagnose first order ailments pretty well. But second order effects? Not really, though I said 1.5 in that medical researchers and doctors are slowly figuring out some limited second order effects, like "X medicine with Y gene" or "X medicine with Y medicine" can have good or bad effects.
We're certainly not talking about 3rd order effects.. We have the math, we have the statistics, but it's just hard maths and stats.
Although alphafold is a breakthrough, this is less optimisation, more chaos theory.
My project's scope is more along the lines of:
1. Taking a look at Roche's list of all biochemical pathways in the human body[0].
2. Creating a 3D model of a human body, assuming that all the molecules in the body interact only in the way that the chart prescribes.
3. Create a database of symptoms and sensations in the body, and use the 3D model to determine all the possible ways that the biochemical pathways could go awry in order to create the ailment.
The way I envision it, the model is simply going after low-hanging fruit.
I'm all for your particle-level simulation of the human body, I've had thoughts along similar lines (but unfortunately lack the skills and knowledge to implementation something like this).
To cite this, and the medical consensus of professionals and other studies:
> Meaning: Although ECT may be more efficacious than ketamine in the acute phase, _treatment options should be individualized and patient-centered, considering different adverse effect profiles and patient preferences._
(emphasis mine)
ECT is not for everyone, but a last option when all else fails.
Electroconvulsive Therapy (ECT) is a safe and effective evidence-based medical treatment. ECT is endorsed by the APA when administered by properly qualified psychiatrists for appropriately selected patients.
https://www.psychiatry.org/File%20Library/About-APA/Organiza...
You’re welcome to disagree with the APA, or point out that the APA only represents a small fraction of psychologists, or question whether this is really a consensus opinion.
The APA isn’t god.
But I don’t think you can say things like “No, not even close” and expect to be taken seriously.
The problem is the side effects. The memory loss is really rough. Based on my background as a software programmer, my psychiatrist (who has recommended and done ECT for other people) recommended very strongly against ECT for me and said I should try ketamine instead.
Learn some neuroscience.
https://www.ucl.ac.uk/news/2022/jul/no-evidence-depression-c...
https://www.ucl.ac.uk/news/2022/jul/analysis-depression-prob...
Here's an analogy: If I took Nordic people and gradually shrank the architecture, chairs, and desks around them across a few generations, such that most would have to unnatural bowing of the head and curvature of the spine, they would experience enormous agony - back pains, neck pains, etc (like "depression"). They would even correctly identify that they are suffering due to a genetically inherited length of their skeleton. Now imagine that in such a world, the "medical solution" is to remove a couple of vertebrae to make them shorter or take some pills that anesthetize the neck muscles. Let's even say all that happens without side effects. Many a patient would be happy for the agony to go away.
And yet, I still think this is completely the wrong approach. I have deep compassion for depressed people. I believe they should be very careful trusting a system that "shrunk the architecture" so to speak and offers a form of brain chemistry interference as a "solution".
In my opinion, depressed people should attempt to remember that it is almost mathematically impossible that they are the descendants of dozens of generations of depressed adults. They would be far better served, in my opinion, to try to recall and recreate the ancestral adaptive environment (the bigger chairs and taller ceilings).