What if we could vaccinate against depression or PTSD?
December 21, 2015 12:45 PM   Subscribe

Depression is the most common mental illness in the United States, affecting 30 percent of Americans at some point in their lives. But despite half a century of research, ubiquitous advertising, and blockbuster sales, antidepressant drugs just don’t work very well. The science magazine Nautilus explores the use of ketamine to treat depression and prevent PTSD.

Antidepressants ... treat depression as if it were caused by a chemical imbalance: Pump in more of one key ingredient, or sop up another, and you will have fixed the problem. But the correspondence between these chemicals (like serotonin) and depression is relatively weak. An emerging competitive theory, inspired in part by ketamine’s effectiveness, has it that psychiatric disease is less about chemical imbalance than structural changes in the brain—and that a main cause of these changes is psychological stress. The theory describes stress grinding down individual neurons gradually, as storms do roof shingles. This, in turn, changes the nature of their connections to one another and the structure of the brain. Ketamine, along with some similar molecules, acts to strengthen the neuron against that damage, affecting not just the chemistry of the brain but also its structure.

Mental hospitals don’t usually see patients until they break: a brain shaped by vulnerable genes, wrecked by the stress of loss or trauma. This isn’t how it works with other sicknesses: heart disease, cancer, AIDS. Detected early, these conditions can often be managed. Crises averted. If Sanacora and like-minded researchers are right, we may be on the cusp of a sea change that allows for a similar approach to mental health. The new approaches may prevent mental illness before it hits, by delivering a vaccination for the mind.
posted by Bella Donna (78 comments total) 50 users marked this as a favorite
 
Also, previously, previously and previously.
posted by Bella Donna at 12:49 PM on December 21, 2015 [1 favorite]


Haven't clicked through yet, but anecdotally, my depression was at its lowest in the years I was using ketamine recreationally.
posted by feckless fecal fear mongering at 1:04 PM on December 21, 2015 [6 favorites]


Cough, don't forget shrooms, cough
posted by showbiz_liz at 1:10 PM on December 21, 2015 [15 favorites]


We'd already have the answers to a lot of these questions if research wasn't prohibited.
posted by cjorgensen at 1:12 PM on December 21, 2015 [35 favorites]




Shut up and take my money.

Actually, shut up and fund research.
posted by Splunge at 1:44 PM on December 21, 2015 [12 favorites]


Vaccinate against PTSD and Depression?

Sounds like a military dream project.
posted by psycho-alchemy at 2:25 PM on December 21, 2015 [3 favorites]


Slight tangent, but uh, if you suffer from depression and don't watch You're the Worst, you really should. The second season is largely about it in a way that veers wildly between sad, funny, and awful to behold.
posted by DirtyOldTown at 2:29 PM on December 21, 2015 [8 favorites]


An emerging competitive theory, inspired in part by ketamine’s effectiveness, has it that psychiatric disease

I think it's valuable that the medical establishment tries to develop better psychiatric interventions, but what bothers me is that the circular and metaphorical language they rely on tells me they aren't interested in deep understanding or epistemology, despite their claims in the media about "theories". For example, if they want to theorize about "structural" features due to "stress", why not bite the bullet and move from "psychiatric disease" (genetic/personality defects) to "psychiatric injury" (more epidemiologically focused and explicitly concerned with what is socially inflicted) model? Again, this ketamine stuff may help, but I wish in general more doctors were more philosophically or scientifically rigorous.
posted by polymodus at 2:32 PM on December 21, 2015 [26 favorites]


Again, this ketamine stuff may help, but I wish in general more doctors were more philosophically or scientifically rigorous.

The whole Ben Carson Pyramids cycle raised some questions for me. Are doctors not taught to be scientifically rigorous? Why do the degrees take so long then?
posted by solarion at 2:39 PM on December 21, 2015 [2 favorites]


The whole Ben Carson Pyramids cycle raised some questions for me. Are doctors not taught to be scientifically rigorous? Why do the degrees take so long then?

Med and pre-med are mostly rote memorization and hand-eye coordination.
posted by kafziel at 2:42 PM on December 21, 2015 [16 favorites]


Doctors are professionals, not researchers. There are lots of reasons for the length of a medical degree, but it's not because they're working on a thesis or anything like that.
posted by Joe in Australia at 2:45 PM on December 21, 2015 [12 favorites]


Anecdotally, ketamine is a dissociative, and as such it can bring trauma to the surface if you already have PTSD. Dissociation is a major symptom of PTSD, which is the brain's way of dealing with trauma in the moment it's happening. After the trauma has passed, people with PTSD may dissociate when triggered, which can happen with ketamine without the psychological trigger. It sucks when you're doing a bump and all of a sudden the world around you turns sinister.
posted by krinklyfig at 3:15 PM on December 21, 2015 [4 favorites]


oh hell no.
posted by Wemmick at 3:23 PM on December 21, 2015 [1 favorite]


?
posted by feckless fecal fear mongering at 3:33 PM on December 21, 2015


From the article, it sounds like the therapeutic doses of ketamine are sufficiently small to avoid the K-hole. Even if they weren't, I am pretty sure there would be some people whose PTSD is so frequently and reliably triggered and so completely unresponsive to existing treatments that they would still volunteer for a trial, should such a thing ever come about.

Thanks for the post, as well as the round-up of earlier posts on the topic. I found that really interesting and it actually offers me a bit of hope.
posted by Athanassiel at 3:33 PM on December 21, 2015 [2 favorites]


I think I saw a documentary about this called Serenity.
posted by asok at 3:35 PM on December 21, 2015 [4 favorites]


This was a really interesting article. Thanks for posting it.

Incidentally, it's so incredibly hard for me to imagine a life without depression that it might as well be discussing the impending prospect of individual, on-demand space travel.
posted by mudpuppie at 3:36 PM on December 21, 2015 [21 favorites]


The whole Ben Carson Pyramids cycle raised some questions for me. Are doctors not taught to be scientifically rigorous? Why do the degrees take so long then?
This is an aside, but the guy's running for president as a Republican. The only to ways to win are to be stupid, or to pretend to be stupid. I don't think this is a good basis upon which to critique the medical/science establishment.
posted by klanawa at 3:40 PM on December 21, 2015 [3 favorites]


I recently started a new job in a process chemistry group and one of our hot projects is ketamine. I was surprised when someone first told me about it, but it's clear that it's a big deal these days. We had a presentation last week about the actual administration of the drug -- it's done in the presence of a medical professional.
posted by Peter J. Prufrock at 3:41 PM on December 21, 2015 [3 favorites]


Mudpuppie, if you're not prone to addiction, I might recommend it. The days afterward were nothing short of glorious. I could feel emotions, taste food again, do normal people things! Living was beyond enjoyable.

I have an addictive personality and I did end up having a problem with novel dissociatives for a while, but thankfully that seems mostly behind me.
posted by Valued Customer at 3:42 PM on December 21, 2015 [2 favorites]


I'm all for new meds, and this is good and important work, because there is no reason why people should suffer - it doesn't make you better. But I want to just say that this:
Suicides, 90 percent of them among the mentally ill, take 40,000 Americans every year—more than murder or car crashes. Since 2005, the suicide rate among U.S. war veterans has nearly doubled; in the first half of 2012, more service members died by suicide than in combat. Few medical failures are more flagrant than psychiatry’s impotence to save these people.
Detracts from something that it's important to remember. We do not have a flagrant medical failure. We have a flagrant social failure, and a flagrant political failure. Improve the meds, for all our sakes, but also remember that most of the stress that damages people is inflicted, deliberately or callously, by other people, often those who have most responsibility to protect those they harm.

Of course, medicines like this can potentially be an important tool in ending the cycles of injury and abuse that underpin so much mental illness, and we need every tool we can get our hands on. I feel like crying for those I love for whom such advances will come too late.
posted by howfar at 3:50 PM on December 21, 2015 [48 favorites]


I have struggled with depression for a long time, amongst other emotional and devlopmental issues that I'm still trying to get a handle on well into my 30s. Having seem some of the accounts of the benefits, I am so incredibly interested in the idea of therapeutic dosages of Ketamine and other drugs that have been traditionally used for "recreational" purposes. Strictly at therapeutic dosages -- I'm not at all interested in something like Ketamine at recreational dosages, because I've personally never found recreational drugs all that appealing - but with everything I've read about the use of Ketamine for treating depression, it seems so promising, and I would be seriously tempted to look into the black market if it wasn't for all of the risks associated with that sort of transaction. I may bring this up with my Dr, just to see what could come of it - but it sounds like that may not be a particularly easy thing to arrange.

Everything in this article and others I've read starts to paint a picture that makes more sense - I had an incredibly traumatic childhood, and it had never occurred to me that it was a potential cause of mental issues as opposed to just sort of co-existing alongside it. It seems like the risks of a therapeutic dose in a professional setting are minimal to none - I don't see what there would be to lose.

It's a shame that Ketamine and other psychoactive substances are so demonized - It should surprise nobody that the same drugs that affect the brain can be used for either recreational or therapeutic purposes, and it seems like restricting research into them is beyond counterproductive and actually holding back much of the insight we could have on the brain and mental illness.
posted by MysticMCJ at 3:52 PM on December 21, 2015 [9 favorites]


The Poverty Clinic, by Paul Tough, which ran in the New Yorker, is related in some ways and an amazing read: As she listened to Sullivan, Burke found herself inching toward a diagnosis that, a year earlier, would have struck her as implausible. What if Sullivan’s anxiety wasn’t merely an emotional side effect of her difficult life but the central issue affecting her health? According to the research Burke had been reading, the traumatic events that Sullivan experienced in childhood had likely caused significant and long-lasting chemical changes in both her brain and her body, and these changes could well be making her sick, and also increasing her chances of serious medical problems in adulthood. And Sullivan’s case wasn’t unusual; Burke was seeing the same patterns of trauma, stress, and symptoms every day in many of her patients. Agreed, howfar. We have a flagrant social failure.
posted by Bella Donna at 4:01 PM on December 21, 2015 [9 favorites]


Mudpuppie, if you're not prone to addiction, I might recommend it. The days afterward were nothing short of glorious. I could feel emotions, taste food again, do normal people things! Living was beyond enjoyable.

I have an addictive personality and I did end up having a problem with novel dissociatives for a while, but thankfully that seems mostly behind me.


Question 2, though, is where do we get any?
posted by kafziel at 4:24 PM on December 21, 2015


Find a raver.
posted by feckless fecal fear mongering at 4:35 PM on December 21, 2015 [3 favorites]


I know that the involvement of big business in potentially life-saving drugs is not really a new thing. But after reading the article, I've found I keep musing in a ranty kind of way all over again about the stupidity of the capitalist system on things so basic and profoundly necessary as a healthy life. The whole thing about treatments like lithium and ketamine being under-explored and under-tested because there's no possibility of money in it is just maddening. Pun intended.
posted by Athanassiel at 4:36 PM on December 21, 2015 [4 favorites]


Question 2, though, is where do we get any?

Great question. I'd advise against getting it off the streets, because it may be something else entirely. There are definitely ways to procure it online, though it's considerably harder than it was a few years ago. I guess I'll get back to you on that one.
posted by Valued Customer at 4:43 PM on December 21, 2015


Some time back I ran across a study that used the neural-network model of depression to look at explaining SSRI's long-term effectiveness as being based on amplifying the signal at weakened junctions enough to allow the brain's natural learning process to regrow dendrites and reinforce those junctions, so that even after the SSRI is discontinued the repaired junctions remain. I only skimmed it so there's probably a lot I'm missing there, but this seems complementary, not competitive, with this idea in this pullquote about ketamine providing protection to stress-weakened dendrites to halt or reverse their erosion.

So the positive interpretation is there might be some robust new attention being paid to this theory of depression that might pan out well. But the world-weary (and rather depressed) interpretation is that I wish to God and all the Angels and maybe a few of the better-behaved demons, that these mental illness stories in pop sci magazines would stop pitting treatments against each other in a winner-take-all for which pill is the Real True Medicine that actually solves the problem, and which ones were all just a fake illusion that wasn't doing any good anyway. Like they have to kick the old dog a few times when parading around the new puppy.
posted by traveler_ at 4:51 PM on December 21, 2015 [10 favorites]


I wish there was something out there like this. People recommend therapy in these scenarios, but psychotherapy really doesn't focus on things like PTSD, or abusive childhoods, or the darker sides of humanity. It's mostly about upper middle class white people problems, like coping with getting a huge raise, or junior's not taking to his violin lessons, or this person doesn't like me. I can understand that: being a therapist isn't all that lucrative, and who wants to deal with the really messy, depressing problems out there?

There's also a serious lack of quality in therapists since the bar is set so low for who can become a social worker or counselor. I can't tell you how many stories I've heard of abusive or poor quality therapists who do more harm than good and cost money to do it. And the people who say therapy helped them, a lot can't even explain how it helped, "it just did".

So if there were ever a medical intervention to help prevent people from having to get involved in the the messy, shady world of therapy, I'd be all for it.
posted by gehenna_lion at 5:05 PM on December 21, 2015 [5 favorites]


Uh, point of order, I was in therapy for suicidal depression and BPD, which aren't exactly confined to upper middle class white people--I'm only one of those things.
posted by feckless fecal fear mongering at 5:12 PM on December 21, 2015 [21 favorites]


Few medical failures are more flagrant than psychiatry’s impotence to save these people.

Lots of oncologists' patients die. Usually not described in vaguely sexual terms as "impotence".
Lots of renal docs' patients die. Usually not described in vaguely sexual terms as "impotence".
Lots of cardiologists' patients die. Usually not described in vaguely sexual terms as "impotence".
etc

Psychiatry is held to a different standard from much of medicine. This probably stems from some deep stigma attached to behavioral medicine, which is felt to have different agency for patients in their relation (autonomy and dependence) with their doctors. You could get all psych-y about this... Anyway, this stigma is built in to the health care delivery systems at a basic level. For example, the Medicaid IMD Exclusion. If you really want to treat people preventatively for depression, anxiety and psychosis before they have to return to emergency rooms repeatedly, removing this discrimination is the single biggest intervention that could help.

As for ketamine? Seems to work, and definitely safe in isolated use as long-term use in dosages of 2 mg/Kg for procedural sedation demonstrate. However, long-term or chronic use has definite toxic effects of unknown significance on the brain's GABAergic regulation system that may result in initiation or predisposition to psychosis. No other drug is without harms, especially psychotropic medicines, so why should ketamine or any other NMDAR blocker be different? The issue is who is more or less vulnerable to ketamine injury, how to quantify and qualify that injury, and how to categorise the NNH and NNT for a specific syndrome and demographic/person.
posted by meehawl at 5:19 PM on December 21, 2015 [12 favorites]


> psychotherapy really doesn't focus on things like PTSD, or abusive childhoods, or the darker sides of humanity.

My psychotherapy has dealt with all of these things - and has helped greatly. And has never once focused on "upper middle class white people problems" - and that is the case for most people I know. I know, anecdotal, but so are your "stories."

Are you basing this off of experience? Because there's a toxic myth surrounding therapy that you pretty much tossed out there verbatim, but I've found that there is little basis for that myth. That's the same sort of myth that has had people judging me rather harshly when the topic of therapy comes up - This is a perception I've been fighting for years, and one of the reasons I almost never bring it up.

Now, there are some substandard folk out there, that's true. I also believe that therapy requires the person who is attending it to make a concerted effort to actually be honest, which isn't always easy.

However, you are doing the entire field - as well as many who has gone to therapy - a disservice with your broad characterization.
posted by MysticMCJ at 5:20 PM on December 21, 2015 [30 favorites]


I was in therapy for serious stuff, too, and I was exploited by one, and sexually harassed by another (shown pictures of erect penises, he asked me if I was "into men", etc). And there's not much you can do about it except file a complaint that goes nowhere.

So it's really a luck of the draw, I guess. The mental health community sure as heck doesn't care what happens to you.
posted by gehenna_lion at 5:20 PM on December 21, 2015 [2 favorites]


I'm sorry you had those experiences, gehenna_lion, because no one should have to go through them. But, please don't dismiss the experiences of many, many other people here who have worked through non-upper-middle-class shit with a helpful therapist (even if it took getting to the 4th or 5th therapist) based on your own limited (and awful) experience.

There are also a number of people here who work in the mental health community. Reducing the entire profession to dealing with "upper middle class white people problems," and dismissing the people reading this thread who are mental health professionals as uncaring as a whole, is really uncaring and unfair to actual people who are reading your actual words.
posted by mudpuppie at 5:37 PM on December 21, 2015 [12 favorites]


gehenna_lion, I'm sorry you had such terrible luck with therapists. I haven't been happy with all of my therapists but the ones I've seen became therapists because they truly wanted to help people. I know that's not true for every therapist (or every teacher, or every fill-in-the-blank), but I promise you that there are good, caring, skilled therapists in the world. I so wish you'd gotten one of those instead. Which, I agree, is about a billion times more challenging if you are poor or working class or struggling financially in any way.

meehawl, do you happen to know why the Medicaid IMD Exclusion came into being? Thanks for the link, I had no idea. I knew our mental healthcare situation was fucked but jeez!
posted by Bella Donna at 5:39 PM on December 21, 2015 [1 favorite]


[One comment deleted. gehenna_lion, I'm sorry those things happened. It's not okay to pick a fight about it with people here, though; we've been over this before. Please drop this now.]
posted by LobsterMitten (staff) at 5:55 PM on December 21, 2015


I will neither confirm nor deny taking Special K, or that it was really fucking cool.
posted by Cool Papa Bell at 5:55 PM on December 21, 2015 [3 favorites]


Ketamine remains my most fucked up drug experience. It hit me while I was in the shower, I couldn't figure out how to turn off the tap. It took me about half an hour to crawl from the shower to the living room because I kept getting trapped and tangled in my carpet. It was a low pile rug. We kept listening to the Weezer blue album because none of us could figure out how to change the CD. Good times.
posted by Hazelsmrf at 6:16 PM on December 21, 2015 [3 favorites]


I sort of wish these articles would stop being written. Write one when there is actually hope of an effective, affordable, not-illegal treatment without devastating side-effects, but until then, stop writing yet another version of, "scientists say this drug you will never ever ever get your hands on may be the one that could keep you alive. if you could get your hands on it. which you can't."

I had a conversation with a very nice doctor the other day, who was very kind and very concerned about the amount of distress I am in. And when she offered to put me on something I had to say no, look, I know what's out there, none of it works, not well enough, or not long enough, or not without some destructive effect. And she looked as though I'd hurt her feelings, but she recouped quickly, reminding me that new drugs are coming out all the time. And what was I supposed to say? All the really interestingly hopeful pills are ones you can't prescribe me. Forget all the illegal stuff, you can't even prescribe SREs, they're not available here because we can only take drugs that will make somebody a profit. All you are going to prescribe is yet another kind of SSRI, and if I ask for a referral to therapy, all I am going to get is another well-meaning therapist handing me another copy of Feeling Good and telling me to do homework about cognitive distortions.

I hate articles like this. I hate that there is some fantasy-land out there, some psychotropic Narnia where people find medications that help them control the pain and fear and sorrow, but I cannot ever seem to be in the right place with the right doctor or the right insurance to get there.
posted by mittens at 6:19 PM on December 21, 2015 [35 favorites]


What are SREs? I googled but still lost.
posted by Hazelsmrf at 6:22 PM on December 21, 2015


Serotonin reuptake enhancer (tianeptine). Seemed promising, but unavailable in the US.
posted by mittens at 6:26 PM on December 21, 2015


Vaccinate against PTSD and Depression?

Sounds like a military dream project.


Sounds like the dream of every veteran who struggles with their mental health.
posted by bile and syntax at 6:26 PM on December 21, 2015 [7 favorites]


If the US Armed Forces really wanted this to be available to vets, it would be before New Years Eve.
posted by gottabefunky at 6:51 PM on December 21, 2015 [1 favorite]


stop writing yet another version of, "scientists say this drug you will never ever ever get your hands on may be the one that could keep you alive. if you could get your hands on it. which you can't.

Amen to that.
posted by gottabefunky at 6:52 PM on December 21, 2015 [1 favorite]


I had heard a report on this a few weeks back on NPR, and it got me incredibly excited. I was also excited to read in the article provided here that 50 doctors in the US are already offering Ketamine infusions. Granted, these puppies cost $300-$1000, but I think we are well on our way to something quite viable.

In the meantime, I'm not going to consider myself an expert in therapy, but I'll say I've been working my ass off the last 10 or so years to bring about some sort of wholeness and healing. With regard to PTSD, I will offer that EMDR (Eye Movement Desensitization and Reprocessing) was quite effective for me, as was shifting the focus of my therapy from a CBT approach to a Family Systems Theory approach. I also benefited from a low dose of Prozac - though it didn't make everything sunshine, lollipops and rainbows, it sure as hell did give me a nice little buffer so that I could keep putting one foot in front of the other.

I'm particularly grateful to hear about the effect constant stress can have on the brain. Only now am I a year out of a four year long major depressive state - and I still feel the effects of the depression. I am no longer depressed, thankfully, but I am not the same person that I was. I don't know what the hell it is that lingers still. Apathy? In any event, I'm quite irritated by it, but I feel quite limited by it at the same time. It's pretty damn annoying.

As an aside, for whatever it may be worth, the best approach I ever found with regard to finding a well-respected therapist, is to call around and ask for referrals, and see whose name comes up repeatedly. Odds are good that you have stumbled upon a quality someone.
posted by round2 at 7:15 PM on December 21, 2015 [5 favorites]


Generally, if you take antibiotics given to you for an infection by a jerk doctor, they are pretty close to as effective as antibiotics given to you by a supportive doctor. This starts to crumble when you get multiple systems involved - there's definitely research suggesting that miscarriages, diabetes etc can be better managed or reduced in severity through support+treatment than treatment alone, but therapy is weird. It's one person connecting to another person in a therapeutic relationship. Comparing it to biochemical treatment is totally apples to - well, tomatoes. Sorta fruit-related but maybe more a vegetable?
posted by dorothyisunderwood at 7:45 PM on December 21, 2015


Agreed wishing they wouldn't publish these things until it is available everywhere. It just further alienates me and makes me feel hopeless to read about drugs that might work that I'll never see. The mental health system here has decided after I went inpatient for my PTSD that I'm banned from therapy as talking about trauma is "unhelpful" for me. So I'm stuck here with flashbacks and dissociation and a psych nurse that suggests meds everytime I see her even tho those same doctors that tell me "not talking" is better tell me that there is no medication for me to try that will work. Tried them all. She seems hurt that I reject them. So don't taunt me with articles about types of therapy and drugs that are miraculous cures when those of us with "the most extreme abuse I've ever heard" (according to my last therapist who thought going inpatient would get me extra help) can't even get anything but CBT garbage that we've done 10000x before and medications that don't work.
posted by kanata at 8:08 PM on December 21, 2015 [4 favorites]


I am probably underinformed, but hasn't Johnson & Johnson been pushing esketamine hardcore? It's curious that some folks see this as an alternative to big pharma promoting dubious drugs as miracle cures that haven't shown long-term efficacy, when to me it just looks like the same-old same-old.
posted by thetortoise at 8:10 PM on December 21, 2015 [3 favorites]


I had heard a report on this a few weeks back on NPR, and it got me incredibly excited. I was also excited to read in the article provided here that 50 doctors in the US are already offering Ketamine infusions. Granted, these puppies cost $300-$1000, but I think we are well on our way to something quite viable.


Without the research to back up what is the correct patient selection, dose and duration of therapy, those doctors are opportunistic snake oil salesmen until proven otherwise.
posted by chiquitita at 8:45 PM on December 21, 2015 [1 favorite]


No taunt intended, kanata. Can't imagine the difficulty and pain of your situation.
posted by Bella Donna at 8:52 PM on December 21, 2015 [1 favorite]


I find it frustrating that the only options you can get a hold of are the ones where the side effects are generally guaranteed to be there and bad and it's 50/50 at best whether or not it'll work at all, and yet that's pretty much the only option anyone will give you these days.
posted by jenfullmoon at 9:06 PM on December 21, 2015


I am probably underinformed, but hasn't Johnson & Johnson been pushing esketamine hardcore? It's curious that some folks see this as an alternative to big pharma promoting dubious drugs as miracle cures that haven't shown long-term efficacy, when to me it just looks like the same-old same-old.

I mean the drug itself has been around forever obviously and there's definitely research into it's use for mental illness predating J&J trying to get their fancy new formulation approved - can't say how much though. I've tried various doses of ketamine and methoxetemine, erm, very off label and I think they work as an antidepressant - probably only for a couple weeks per dose though. You know what I think really has potential though is buprenorphine. But I wouldn't bet on that becoming mainstream any time soon.
posted by atoxyl at 9:30 PM on December 21, 2015 [1 favorite]


I am probably underinformed, but hasn't Johnson & Johnson been pushing esketamine hardcore? It's curious that some folks see this as an alternative to big pharma promoting dubious drugs as miracle cures that haven't shown long-term efficacy, when to me it just looks like the same-old same-old.

Yep. Same old unscientific biopsychiatry, and it looks like the new ketamine push is aimed at letting the pharma manufacturers replace their old off-patent antidepressants with new ketamine analogs. (Generic ketamine will likely likely remain Schedule III, which is awfully convenient for profits.) Mark my words, they're hoping for a new batch of dubiously effective and overmarketed blockbusters. It's no coincidence that Dr. Sanacora has gotten money from Naurex and J&J, among others.

Also this bit of ridiculousness:

The researchers tested several types of stress, including one in which subject mice are “bullied” by more aggressive mice for two weeks. After this daily hazing, mice ordinarily develop the rodent equivalent of PTSD and depression: freezing in a new space, refusing to interact with other mice, and not moving in a forced swim test. But the mice “vaccinated” before the bullying fared far better: They didn’t act depressed afterward.

"Vaccinated" against bullying? See, the problem with mental "illnesses" like depression and PTSD is that we don't have a solid biological explanation for the conditions (we don't even know if they are biologically caused, which is something I'm deeply skeptical about). Thus, since we don't have a known biological pathology to target, all the animal models for psychiatric conditions must involve some external disturbance such as social stress or trauma. But of course, once we get the drugs approved they're sold to the public as treating some underlying chemical, genetic, or other biological pathology. It's absurd.
posted by Wemmick at 9:35 PM on December 21, 2015 [8 favorites]


I kind of worry, as someone who was drugged sometimes as a child so that I "wouldn't remember" being raped and assaulted, that the vaccine analogy as this research is being reported will just give people ideas that if you give a kid this drug then you're absolved of moral responsibility, so go get some. It sounds awful but then a lot of the root causes of PTSD are.

I can see its value for ER doctors and first responders and soldiers though. If it leads to advances in actual after-the-fact treatment that would be awesome.

Wemmick, it's been a while since I was up on the research but the last time I was obsessing over it there were differences in brain structure correlated to PTSD, so I'm not sure where you're getting the idea that there's no biological pathology to target. Unless you mean that PTSD is a normal response to stress. But some forms of cancer may be a normal response to high doses of radiation - eliminating the radiation is a big deal, but you can still treat the cancer. Or another analogy, stress can impact on blood pressure which can impact on cardiovascular health, but we don't take drugs for blood pressure out of the loop because we don't quite know why some people's stress kills them and others' don't. Unless I'm misunderstanding your "causes" there.
posted by warriorqueen at 6:09 AM on December 22, 2015 [2 favorites]


hasn't Johnson & Johnson been pushing esketamine hardcore?

Reading the clinicaltrials.gov pages about it is tremendously exciting. Lordy. So many studies. How does one become a guinea pig? (or "bullied mouse" if that is more apropos?)
posted by mittens at 6:11 AM on December 22, 2015 [2 favorites]


I kind of feel like treating depression as a purely medical issue is overlooking a lot, as a few people have referenced above. I have depression of some form, and I have been on every anti-depressant, mood stabiliser, and anxiolytic you care to mention, as well as a laundry list of anti-psychotics and other more exotic drugs. None have helped at all. Nor has any form of therapy or psychologists' intervention had a significant impact. I am completely convinced that I know exactly what would cure me though - a decent job, a decent place to live, decent access to the resources to be able to actually live a life rather than merely survive.
posted by Dysk at 6:33 AM on December 22, 2015 [9 favorites]


we don't even know if they are biologically caused, which is something I'm deeply skeptical about)

Gotta agree with Wemmick here. I feel like quoting Tina, "What's biology got to do with it?" Big Pharma wants you to think "biology" plays a role in causing mental "illnesses", that way they keep us in the dark about benefits of nutraceuticals, acupuncture, homeopathy and different supplements. My advice would be to try flax seed.
posted by todayandtomorrow at 6:55 AM on December 22, 2015


I don't want to speak for Wemmick, but I think their point is that social stress is a very clear part of the research, often the main part where research on animals is concerned since we can't, like, talk with them and ask how they're doing, but this side of things is often entirely omitted in how the the drugs are marketed and explained to lay audiences, in favor of quasi-biological yet not well-supported explanations like the one everybody remembers from all the SSRI commercials. I am pretty much the furthest thing from anti-psychiatry-- been using antidepressants of one kind or another for the last 15 years-- but there is a very real point here.
posted by thetortoise at 7:05 AM on December 22, 2015 [2 favorites]


Our models are dangerous no matter what we do. If we divide mind from body, we end up stuck with talking therapies that do not address the physical harms of our disease. If we focus on pills, we ignore how social structures can cause so much pain--the lack of decent housing and jobs, as dysk points out. If we see depression as a war between big pharma and ourselves, we open ourselves to treatments that have not been tested for safety and effectiveness (as the many useless bottles of supplements here on my desk will attest).

I am ready for...I almost want to call it a spiritual model of depression, but that is not what I mean. Maybe I mean a demonic model of depression. I want to know who this shadow-self is, that is capable of sabotaging me at every turn--who seems to learn from everything I do, so no matter how many correct steps I take, there is always this yawning chasm of blackness before me. I have a decent job! I have decent housing! So now the shadow changes strategies, and reminds me how awful it would be if it were all taken away. How appropriate it would be, since I do not deserve any of it. I feel as beaten now in my seemingly successful middle age as I did as a child when actual blows fell. But who is it that is doing the beating? I want a theory of depression that answers the question, not with diagrams of my amygdala, not with the blithe ignorant confidence of the doctor with his prescription pad, but a full-bodied j'accuse.

I sense that answer is not to come. So I have to settle for whatever the next medication is, even though none of them have worked. But it is so frustrating to have done everything one is told to do, and still be left with this pain.
posted by mittens at 7:16 AM on December 22, 2015 [11 favorites]


if I ask for a referral to therapy, all I am going to get is another well-meaning therapist handing me another copy of Feeling Good and telling me to do homework about cognitive distortions.

I'm so sorry that that's been your experience, and it was very nearly mine as well. I don't have depression, but I do have PTSD, and EMDR therapy was a lifesaver for me. My regular therapist (with whom, yes, I've talked about some upper middle class stuff like work stress, but mostly we've discussed the abuse that caused my PTSD) had to refer me to a specially-trained therapist for me to do EMDR, and it helped in ways that talk therapy and cognitive behavioural therapy just didn't. From what I've read on Pubmed it has good results for most PTSD populations but not, for some reason, veterans (though the veteran study was just one study and it might have been flawed in some way I'm not well-educated enough to spot). It might not be for you or the others above who have found therapy to be useless, but in my opinion it's worth trying if you have specific traumas you need to work through.
posted by joannemerriam at 8:35 AM on December 22, 2015


> I am completely convinced that I know exactly what would cure me though - a decent job, a decent place to live, decent access to the resources to be able to actually live a life rather than merely survive.

This is very likely the situation for a lot of people- and while it's extremely important, I don't think that it's the root cause for everyone. The "shadow" that mittens mentioned just above me is a great example of something that goes well beyond just fulfilling those basic needs.

I believe that when we consider the overall concept of mental health as a society, we are very good at conflating being in a bad state of life with more "biological" depression, and also with trauma - Three very different causes for a similar effect, that may or may not be intertwined. This is where many of the gaps in mental health are most apparent- we have these blunt approaches that may or may not work, regardless of the cause.

But there's something else that comes with this... the toxic belief that we are medicating ourselves into a false sense of happiness or to convince themselves that they are happy as some form of societal conformity or control.

I would be interested to see some sort of study for how that actually plays out for people - what I've typically seen (all anecdotal, of course) is that when people who are unhappy mostly due to circumstance look towards medication for a solution, that if anything, if there is some sort of "clinincal depression" or similar, the medication may help them see through the fog and give them a better awareness of what is specifically making them unhappy or more energy to deal with things that actually can be addressed, but it's not a magic "i'm going to make myself happy with my miserable life" pill. I've never known anyone who has been in that sort of scenario to stay on a medication long term. Anecdotal, I know.

Of course, not every situation can be addressed on ones own (despite what the conservative narrative may be). It's not going to fix scraping by week to week via a job that you hate that you are just barely able to hang on to, but need, for example. If you are in a bad situation that is bad no matter what, there's a strong temptation to find a medical "escape" via large doses of anti-anxiety medication, for example. And certainly, many do this.

Handling pharmaceuticals as profit engines is incredibly problematic, and something I feel to be at the root of so many of the issues here. The advertising of very potent drugs such as Abilify - an anti-psychotic - directly to the masses through TV and other mediums is a huge, huge problem, and goes well beyond unethical to what I view as criminal. Additionally, the profit model behind pharmaceuticals incentivizes getting as many people as possible on whatever new medication can be patented. That is something that has seriously damaged the field, in my opinion - and I think it has been responsible for a good many people being on medication that they have had no business being on.

In a perfect world, there would not be medical professionals prescribing these as casually as we do today. This is a large problem, and I'm fairly sure that the profit model driving this and other problems is largely responsible for many of the negative views of psychiatrics and mental health in general. We've also been historically poor at dealing with these problems in the past - The horrible history of lobotomies used as wide-spectrum treatments isn't too long ago.

However, I think writing off the idea of any sort of biological or physical cause as a possibility is unwise. It's very telling that many conditions actually do correlate with structural changes in the brain - certain lobes being smaller, different readings from fMRIs or PET scans, or in the case of this article, changes in dendrite structure. There are definitely cases where there is a clear issue with brain structure that is closely related to the condition itself. We certainly don't have all of the answers, but we are getting closer. In my same ideal world where medications aren't overprescribed, you'd be ale to get a fMRI or PET scan if you were struggling with a condition, and you would be able to identify what you need (and what you didn't). Of course, we are lacking many of those models (and any sort of scan is way too expensive for most insurance providers.) We ultimately need to have a better way of reading what is going on and what the treatment should be, just as you would get an x-ray or ultrasound to better understand physical pain within the body and know how to treat it. That's one of the largest gaps we have - and I believe it's something that will come, hopefully in my lifetime.

Mental health is a poorly understood field in general that has been tainted by the institutional abuses of the past, as well as by the desire for profit. It's also a field where there have been many developments for the positive, and many people who wouldn't be able to have a good or even someone normal life otherwise are able to treat and manage conditions, and live much fuller lives as a result. The narrative of a pill as a cure to "unhappiness" and the reality of being able to treat things that were not treatable in the past should not be mixed.
posted by MysticMCJ at 8:39 AM on December 22, 2015 [4 favorites]


I'm excited that alternative treatments are being explored, and that there is recognition that some of the treatments we have now don't always work very well.

I've tried ketamine once in the past, and it was useful for what I was experiencing then. More importantly, I really could have used the treatment to help me through the brief emotional blip I experienced last week, instead of a short-term heavy duty sedation that impeded my ability to process anything and damaged my sense of competency. And if ketamine wasn't the answer, maybe something else would have been.

I feel like my disability and this sense of inadequate treatment places me in a tough situation when discussing potential treatments, or the politics surrounding mental health. "intractable mental disorders" are encapsulated within the mental health belief system, which serves as a way of rendering my concerns as void. It makes me hesitant to speak.

I'm angry about that and I hate the psych system so hard - even with the supportive professionals I have involved with my care. I have support, but I don't have appropriate treatment or solutions.

(That's because I'm on the spectrum, and like so many other people have described, I've also been handed a dozen other diagnosis, because despite neuropsychological testing in both adulthood and childhood, this diagnosis can't possibly be right, because my presentation doesn't fit within general practitioners (limited experience/training) autism box.

Which means that I'm placed in a slightly different box, and often receive treatments that -surprise! -don't have the expected result. I'm harmed by this, and not alone. There's been several posts on this recently, closely fits - but I'm degressing, and my anger/pain over what happened this past week doesn't belong here.)

*This post is about novel treatments and maybe hope for people currently struggling. There are huge hurdles in the field for this because in addition to being a science, it's also a profession, one that functions as a bureaucracy (and we all know there are things bureaucracies do and don't do well).

Unfortunately, the people who utilize the system do so because they feel something is "wrong", different, or not working. These issues often neatly fit into psych-boxes where prescribed treatments work, despite the individuals feeling they are what we derisively call "special snowflakes".

A term that can also be used to dismiss or gaslight 'edge cases' or people who feel the current professional assessments are inaccurate. Which can increase the stagnation in developing new treatments.

My hope is for greater awareness that alternative treatments should be explored and accepted within the practicing part of the mental health community. Fitting treatments to the person, not the presumed disorder.
posted by bindr at 9:04 AM on December 22, 2015 [6 favorites]


The serious stress of modern life in the west: fixing the results with a pill, but leaving the root causes in place.
posted by i_am_joe's_spleen at 10:29 AM on December 22, 2015 [1 favorite]


I've had recurring severe depression since I was a kid. I'm really thankful for SSRIs, which are an effective bandaid, but only a beginning. My body, at this point, doesn't seem to be able to function without an SSRI, so that pretty much sucks. A 4 month vacation from meds just about did me in recently. It's my cohort that will demonstrate what happens with long term use of SSRIs, if anyone's paying attention.

I've met many caring mental health workers, but only a small handful who are particularly skilled or even pretty competent, and they have had varying levels of training/ certification. A couple have been dangerously unskilled and not really ethical in one case. Insurance reimbursements have been driven down, and that doesn't help, even as insurances are now required to at least fund mental health care, which is an improvement. At least in the US, our lives are less conducive to health; communities and families are fragmented and we are easily isolated.

Back on meds, I'm better able to cope, so that's a plus. I'd love to be able to legally test drive ketamine, uneasy about any illegal options; life's complicated enough. A hug and my sincerest sympathy, empathy, compassion and best wishes to anybody who wants/ needs any of that. MeFi has been a community for me, wouldn't want to be without it.
posted by theora55 at 10:45 AM on December 22, 2015 [2 favorites]


Three very different causes for a similar effect

Yes, thank you. I always find the direction that some of these last comments have been going kind of offensive as someone who does not have any "reasons" to point to for my history of anxiety/OCD/depression. At the same time I wouldn't dare to suggest I have it better than people who *do* have some clear trauma or harder lives than me - like, I don't complain about my lot in life it's just that my experience supports biological/heritable causation far better than anything else. And since the ketamine studies here are including both depression and PTSD they are very explicitly bringing multiple possible causes into the picture.
posted by atoxyl at 11:06 AM on December 22, 2015 [3 favorites]


This is something I wonder about, reading some of the comments, and apologies for derailing from ketamine a bit but I am curious. Some of you have mentioned PTSD; I don't have it, and it's not like doctors never had a chance to diagnose me when I've picked up a bunch of other diagnoses, but I often feel like my depression has remained treatment-resistant for so long in part because of early traumatic experiences and long-term stuff where I had little control, as well as the plain stress of not being neurotypical in a world designed for neurotypical people. Is processing trauma more of a spectrum thing, or more either/or and what I am talking about is qualitatively different from PTSD? i.e., when we talk about stress/trauma giving rise to mental illness and when we talk about PTSD, are we talking about two different things? I mean, I should probably make an AskMe, but y'all seem unusually well-informed and articulate on these subjects.
posted by thetortoise at 1:05 PM on December 22, 2015 [1 favorite]


Just tossing my two cents in... and to show how what we call "depression" is different for everybody... I am very fortunate in that I have never suffered a, as polymodus called it, "psychiatric injury". My depression and anxiety are largely chemical based. Everybody's body absorbs and creates chemicals slightly differently. The way mine does it just happens to cause depression and anxiety.

My assumption is that this is a very large reason why the concept of "depression" is tragically misunderstood. The concept itself is too vague, there is no real definition of what is and what is not "depression". How in the world could a single drug, or type of therapy, or treatment, or anything really, treat such a nebulous concept?
posted by Blue_Villain at 1:25 PM on December 22, 2015


when we talk about stress/trauma giving rise to mental illness and when we talk about PTSD, are we talking about two different things?

Yes, we are, at least at this point in time (and I'm using "we" to mean "mental health professionals" here, though I've also had PTSD). PTSD is an anxiety disorder with specific symptoms, and a client would need to have the required number of those symptoms in order to meet criteria for a diagnosis of PTSD.

Non-PTSD stress and trauma can kind of wear down someone's resilience, if that makes sense. Like how it's easier to get sick when you haven't been sleeping or eating well (I think that's not just an urban legend?) -- if your mind is spending all its energy warding off a lot of stressors, you have fewer resources available to use positive coping mechanisms to ward off depressive symptoms before they turn into full-blown depression.

I think, however, that as more research goes into trauma and its effects, criteria and diagnoses may change. For a long time it was assumed that PTSD only happened to combat veterans. There's been a recent-ish shift in realizing that other trauma (especially sexual assault) could be, and often is, a trigger for it, and I'm starting to sense (in articles like the linked one) a shift toward recognizing trauma as cumulative. Which makes me think we may officially move away from the idea that one big life-threatening trauma is what leads to PTSD, and therefore toward a different understanding of how trauma affects mental health. The proposed diagnosis of Complex PTSD is starting to move toward that idea.
posted by jaguar at 1:33 PM on December 22, 2015 [2 favorites]


Yes, some of the comments bother me as well, and they are things I hear all the time... Never mind the fact that I am doing exactly what I want to do, I have a healthy relationship, and I've improved my life considerably, andI am constantly working towards happiness, and on my perception of it - I'm clearly lying to myself, according to many people, and must be still fundamentally unhappy. The thing is, it's not unhappiness - it's something much more different. You can truly know you are happy, and still be fundamentally removed from your experience of the world around you in ways that may resemble unhappiness on the outside.

It's really had to take a symptoms-based approach for mental health, because being in a bad situation and having a fundamentally different physical brain structure can actually manifest in some of the same ways - which should be no surprise, given the brains role in our bodies. The approach we have now is so primitive, because there's little concrete analysis to go off of - It is almost all subjective.

Like, imagine that someone is constantly crying, but you can't talk to that person, and you can't actually see the eye itself - All you see is the tears. If you can't talk to that person, you have no idea if that's an emotionally driven thing. If you can't physically examine the eye, you have no idea if it's a physical issue with the eye, or an issue with the tear duct, or anything else. All you can do is throw a treatment at it, and see if it the tears stop or not. Working to cure the emotional pain does no good if that's not the root cause.... and at the same time, eyedrops aren't going to do any good if there is a ton of emotional pain. Tears probably aren't the best analogy, so my apologies on that, but it would also be like trying to treat a broken bone when you have no way to see if it even is broken, and don't entirely know what a bone is in the first place. Many practitioners use the vision analogy when they are discussing psychiatrics vs. purely talk therapy - We don't simply tell someone to "try harder" if they have really severe astigmatism or are extremely nearsighted, we prescribe glasses or contacts, or we perform surgery - and in some cases, exercising the eyes (i.e. certain types of non-drug therapy) can improve the eyes, but certainly not all cases. I've never felt like that was the best analogy, though, because we can test for nearsightedness, and it doesn't typically get confused with a bunch of other conditions.

What we do with mental health is a somewhat inverted version of my tears or broken bones analogy - We don't have much concrete to look at, there are very few objective ways to look at this from the outside -- we are mostly reliant on the feelings and history of a person. I'm struggling with how to best articulate the concept, but what it comes down to is this - The way that a physical disease, injury, or condition presents tends to allow for lots of hard data to diagnose, and doesn't tend to manifest in a similar way as our day-to-day emotions may. Mental conditions tend to be the exact opposite - Little-to-no hard data, diagnosed almost entirely by emotion and discussion - so for someone on the outside, it's very easy to write it off as "just sadness, get in a better position in life" or "you need to not take the human condition so much to heart" or "you need to move on" or other similar things. We can understand the concept of near-sightedness as it's easy to simulate, describe, and understand, but imagine if it wasn't - For someone who can't experience it the same way, it may seem unfathomable that you'd ever have to do anything other than squint or shade your eyes to see things better.

There are a million holes in all of these ways I'm trying to explain it - and that's the ultimate problem, is that mental health is something we just fundamentally don't understand well at all.
posted by MysticMCJ at 1:37 PM on December 22, 2015 [1 favorite]


(Better copy of the DSM-V criteria for PTSD. I didn't realize the one I posted above was shortened/paraphrased.)
posted by jaguar at 1:48 PM on December 22, 2015


Btw when I said "have it better" I meant "have it worse!" Sorry - that could read very differently than I intended it.
posted by atoxyl at 3:43 PM on December 22, 2015


This is very likely the situation for a lot of people- and while it's extremely important, I don't think that it's the root cause for everyone. The "shadow" that mittens mentioned just above me is a great example of something that goes well beyond just fulfilling those basic needs.

I would like to stress that I very much only speak for myself when I say that I think my depression can be cured by substantial improvements to the conditions of my life. I think depression is a broad church, with many different causes and many different treatment strategies that work for different people. I just know that the same drugs and therapies that I have seen help so many of my peers do nothing for me, and that my motivation, self-esteem, self-worth, and ability to meaningfully experience happiness and envisage a future - any future - for myself have been present when my material conditions have been better, and only then. And the worst thing is, I feel (and am) utterly unable to do anything to improve my situation while my situation is crap. I look at a job application form and become effectively paralysed or break down crying - either way, I cannot, cannot fill it out. I did some freelance work months ago, and to get paid I had to fill out a three-page document. THREE PAGES. That's not much, really, considering most of it was tick boxes and questions. But here I am writing yet another longish comment on MetaFilter, while that document lies unfilled in a drawer somewhere, and I still haven't been paid and am consequently behind on my rent. And even thinking about that basically breaks me. Yet when I was working full time in a halfway decent job I was filling out complicated tax returns for working in a country I wasn't living in and dealing with shit I just cannot now and could not before that like it was nothing - cooking, eating, cleaning, looking after myself, basic life admin shit.

I'm sorry if my comments belittled or erased anyone's experience, or was another straw in a bundle of social pressures and narratives on anyone's back, truly. I just know that I have been told a thousand times that what I need is medical intervention, and no medical intervention in over a decade of trying has done anything other than maybe have some side-effects like dry mouth or headaches or whatever.

It's not the same for everyone, and I never meant to imply it was. If I did, then I apologise profusely.


(That's because I'm on the spectrum, and like so many other people have described, I've also been handed a dozen other diagnosis, because despite neuropsychological testing in both adulthood and childhood, this diagnosis can't possibly be right, because my presentation doesn't fit within general practitioners (limited experience/training) autism box.

Oh god yes this also.
posted by Dysk at 3:59 PM on December 22, 2015 [1 favorite]


do you happen to know why the Medicaid IMD Exclusion came into being

Deinstitutionalization was the overt reason (blocking funding for any long-term care facility with more than 16 beds effectively accomplished this). But many of the abuses and poor care present in the system of mass institutionalization stemmed in large part from a systemic desire not to meaningfully fund mental health care. So the covert reason was to avoid paying for something which on some deep level felt wrong for many people. Trying to avoid paying for it explicitly is also called "care in the community", which it paradoxically fails to accomplish.
posted by meehawl at 5:13 PM on December 22, 2015


> mental health is something we just fundamentally don't understand well at all.

We don't, but we understand a good amount of the underlying chemistry. Specifically, we understand it enough to say that Ketamine is an NMDA receptor antagonist (and to describe what an NMDA receptor is). We are also able to move a few atoms around to make a similar-but-different-enough-to-get-a-patent molecule which biochemical companies are wiling to pursue, for better or worse.

Given that there are phase ii clinical trials underway for esketamine, it will hopefully be available in 5-10 year, assuming trials pan out, though that's no help right now, unfortunately.

> Granted, these puppies cost $300-$1000

Not a bad markup, given that Ketamine wholesales south of $20 a gram, and that's probably enough for a full round of "infusions".
posted by fragmede at 8:26 PM on December 22, 2015


Btw esketamine is not a different drug - it's just enanantiopure S-ketamine. J&J's special innovation is a nasal spray formulation, or something.
posted by atoxyl at 8:34 PM on December 22, 2015


Just to add that that some of the people offering this as IV "infusions" may be wrapping it in a cloak of sciency medicalism. Ketamine works really well for emergency sedation of agitation using intramuscular once-off injections, and its rapid antidepressive effects seem well replicated in similar intramuscular injections. You don't need all the paraphernalia of infusions, but when people are paying through the nose, that may be what they expect...
posted by meehawl at 6:01 AM on December 23, 2015


Cough, don't forget shrooms, cough

Why I Take Psychedelic Mushrooms For My Health
posted by homunculus at 9:54 PM on December 24, 2015 [1 favorite]


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