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Ketamine's effect on depression may hinge on hope

med.stanford.edu

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Re: Ketamine's effect on depression may hinge on hope

#31

Post by 3cats-in-a-coat »

It's shocking how much of medicine is just based on trust and word of mouth. Studies made decades ago that turn out completely wrong and not reproducible. We flatter ourselves that we're enlightened and based on science, but the more you dig the more you realize it's all a game of trial and error and fighting cultural wars to get your "remedy" out there and profit.

It's rather shocking to someone who's not familiar with the inner workings of the pharma industry and medicine in general.

In particular in psychiatry, we have working theories about how the various agents work to achieve anti-depressive or anti-psychotic effects, which are taken as the gospel or proven fact. And then those models turn out absolutely wrong. And we have to face the fact we're prescribing drugs to sick people we have no clue how and why they work. And whether they work at all, often.

It's especially the case when a given drug must be taken for months before any effect is seen. It's essentially impossible to control for other variables over MONTHS of someone's life. You can easily convince them they feel slightly better now because they've been months on end taking Zoloft. They may've easily been better if they hadn't taken it.

Re: Ketamine's effect on depression may hinge on hope

#32

Post by omginternets »

Waterluvian wrote: post #23
omginternets wrote: post #7

Beyond the importance of controlling the placebo effect, I am worried that a lot of the drug-depression research is overlooking an important possibility: that the thing about ketamine/psilocybin/etc that is helping with depression is not some latent property of the molecule, but rather the actual transcendent experience of the trip. In other words, the trip is the point, not the mechanistic neuro-tinkering [0]. Impor…

A very fascinating thought to consider. Though I struggle not to be equally suspect than this is also just hopeful thinking.

>Though I struggle not to be equally suspect than this is also just hopeful thinking.

I think we all do. Certainly, I struggle with that as well. I think this is an inherent property of undecidable questions (contrary to most well-formed scientific theories, which are valuable precisely because they can distinguish themselves from hopeful thinking).

Here's something to consider: some kind of hopeful thinking may be a fundamental psychological need. When I saw the title of this HN post, I had thought that perhaps this was the question that ketamine researchers were considering, but alas not.

Re: Ketamine's effect on depression may hinge on hope

#33

Post by Waterluvian »

omginternets wrote: post #32
Waterluvian wrote: post #23

Earlier quoted context omitted.

A very fascinating thought to consider. Though I struggle not to be equally suspect than this is also just hopeful thinking.

>Though I struggle not to be equally suspect than this is also just hopeful thinking. I think we all do. Certainly, I struggle with that as well. I think this is an inherent property of undecidable questions (contrary to most well-formed scientific theories, which are valuable precisely because they can distinguish themselves from hopeful thinking). Here's something to consider: some kind of hopeful thinking may be a…

Now that is an idea that resonates with me.

It feels like a slightly abstract application of “it’s the journey not the destination.”

Re: Ketamine's effect on depression may hinge on hope

#34

Post by kallistisoft »

scythe wrote: post #4

This is not the first trial of ketamine used under clinical anaesthesia to disguise its effects. A previous study using similar methods in 2018 found the usual effects of surgery: a transient increase in depressive symptoms. I'm no expert but my inclination is to blame this on postoperative pain. https://www.sciencedirect.com/science/article/pii/S000709121... The confidence interval in the new study includes zero, al…

> It's not clear if ketamine — or anything else — should be expected to work normally when it is administered to patients under general anesthesia. General anesthesia has profound effects on the functioning of the nervous system.

Very much this! Additionally when discussing ketmaine it's method of action (NMDA receptor antagonist) specifically could be disrupted by the effects of another anesthetic compound.

Re: Ketamine's effect on depression may hinge on hope

#36

Post by omginternets »

b33j0r wrote: post #21
omginternets wrote: post #7

Beyond the importance of controlling the placebo effect, I am worried that a lot of the drug-depression research is overlooking an important possibility: that the thing about ketamine/psilocybin/etc that is helping with depression is not some latent property of the molecule, but rather the actual transcendent experience of the trip. In other words, the trip is the point, not the mechanistic neuro-tinkering [0]. Impor…

Agree. I have heard stories of people who “had one treatment and never smoked/put their elbows on the dinner table ever again.” My experiences seemed to benefit more from watching David Attenborough and feeling a connection to life. I’d interpret the dad of a family of mountain lions as an analogue of my dad, etc. Seeing events as taking place in a dissociated context. All that introspection is what I found useful ab…

>Yeah, sounds silly.

It only sounds silly to our modern sensibilities, which I am increasingly considering regressive on the specific question of "what is a life well-lived".

To a pre-modern society that considers e.g. dreams to be vehicles of important meaning, religiousity to be a good thing in measure, idle time to be a gift and introspection to be one of the major points of existence, it doesn't sound silly at all. It sounds wise.

I'm a scientist by training and an engineer by trade, but as an empiricist, I am forced to admit that my life has gotten better by making room for the irrational, superstitious, obliquely-associative, self-contradictory omginternets to exist. Make of that what you will ;)

Re: Ketamine's effect on depression may hinge on hope

#37

Post by NickM »

dv_dt wrote: post #17
omginternets wrote: post #7

Beyond the importance of controlling the placebo effect, I am worried that a lot of the drug-depression research is overlooking an important possibility: that the thing about ketamine/psilocybin/etc that is helping with depression is not some latent property of the molecule, but rather the actual transcendent experience of the trip. In other words, the trip is the point, not the mechanistic neuro-tinkering [0]. Impor…

Another issue is the variability of depression as a diagnosis itself. An admittedly anecdotal set of my encounters with people who take or have taken anti-depressants is most are on changing set of prescriptions because nothing works continuously and a high percentage of them are ones which no anti-depressant drug worked and were fixed by a different diagnoses for something like adhd. How does one evaluate if a new d…

An admittedly anecdotal set of my encounters with people who take or have taken anti-depressants is most are on changing set of prescriptions because nothing works continuously and a high percentage of them are ones which no anti-depressant drug worked and were fixed by a different diagnoses for something like adhd.

An alternative explanation for this is that if you keep giving people different drugs and different diagnoses eventually they will feel better for unrelated reasons and will assume the current diagnosis/drug combo is what “fixed” them.

Re: Ketamine's effect on depression may hinge on hope

#38

Post by sli »

JohnMakin wrote: post #15
Forgotthepass8 wrote: post #6

If that House MD arc ends up being ahead of its time...

Which one?

I didn't watch a lot of House MD but I believe I know what's being referred to.

There was an arc where House was administered ketamine as part of a treatment for his leg and he started walking without his cane, suggesting that his condition was being caused by psychological trauma long after his leg had physically recovered.

Re: Ketamine's effect on depression may hinge on hope

#39

Post by acchow »

omginternets wrote: post #7

Beyond the importance of controlling the placebo effect, I am worried that a lot of the drug-depression research is overlooking an important possibility: that the thing about ketamine/psilocybin/etc that is helping with depression is not some latent property of the molecule, but rather the actual transcendent experience of the trip. In other words, the trip is the point, not the mechanistic neuro-tinkering [0]. Impor…

Much of the benefit of psychedelics is the introspection, which you can do sober as well (although the depth of the reflection is magnified and qualitatively different while tripping).

This is confirmed by the linked study (which shows that placebo-ketamine is also very effective).

Re: Ketamine's effect on depression may hinge on hope

#40

Post by progmetaldev »

I'm more interested in the effects of Ketamine on anxiety. I know that it's not as effective, but haven't seen any statistics specifically related to anxiety. I have gotten my Ketamine through Mindbloom, and just need to schedule my treatment and follow up dates. My depression effects are due to my suffering through anxiety for over 20 years (started in 1999). My anxiety also seemed to correlate with 2 bad trips from LSD in the late 90s, that resulted in my being hospitalized and injected with Thorazine to abort the trip. While I have had some depression from divorce and breakups, those bouts aren't lasting the way my anxiety is, and persists in day to day life. I imagine it is related to my being hospitalized at night for LSD, but I do not suffer anxiety unless I drive at night. I have seen various psychiatrists, psychologists, therapists, and have undergone biofeedback and cognitive behavioral therapy with limited success. I find that when my life as a whole is less stressful, my anxiety at night is less pronounced and sometimes non-existent.
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