Ketamine’s effect bolsters a new theory of mental illness
nautil.us
nautil.us
The sine qua non for me was an issue of Nature a few years back that focused on depression, talked about how prevalent it is, how it is a 'drain on productivity', etc. Included therein was a graph of the worst affected populations, topping the list was Afghanistan. This passed without comment. How about: 'hey, the cause of depression seems to be human misery, like war, unemployment, alienation, etc.'
But you can't sell a fucking pill to cure war and alienation, so ...
Well, no you can't because it seems a lot of people with really good life are just struck by it.
Although I believe the environment (physical, emotional, relational [edit: in recovery or/and prevention]) plays a huge role there still seems to be something extra going on.
But I still strongly agree with your point. My strongest influence on this stuff is The Biology of Belief by Bruce Lipton, who explains how it all works on a cellular and genetic level.
For the first decade or so after being diagnosed with depression I believed it could only be explained by brain chemistry or something like that. Only later in life when I learned more about healthy relationships and what does and doesn't work for me emotionally did I realize that my depression was an obvious reaction to the dysfunctional environment I was raised in.
My ignorance of the non-chemical causes of my depression made me feel I was "just struck by it". But there really was a cause in my environment. I believe this is true for many other people as well.
Depression and anxiety in particular I think are better explained as a mismatch between human adaptation and current human environment. They are signals that things are unsafe/insecure. It seems to me more wise to focus on improving our environment than on constantly blaming the brain, whether through the serotonin hypothesis or this new neuroconnectivity approach.
The main reason for this is that it's fallacious to think that your emotions are "completely independent of your life circumstances". They're symbiotic.
I was born into modest privilege and had an upbringing that was free of abuse or major trauma, and the only things that have gone severely wrong for me in life have been through my own poor decisions.
Yet I can now easily see how the depression I've experienced was due to a combination of living in a somewhat unhealthy environment and having a propensity to respond to that environment by becoming depressed and fatigued. I can now see the same applies to everyone else I know of who experiences depression.
The explanation you've given is embraced by mental health professionals as it allows them to justify attempting to cure it with pharmaceuticals and short therapy consultations, but as the data shows, that approach has a pretty low success rate.
I also agree with your point about "people reacting to things with the wrong emotions or the wrong intensity of emotion"; understanding and addressing this has been fundamental to my own recovery.
What I'm disputing is the notion that there is a clear-cut distinction between "exogenous" and "endogenous" depression, and that one is "totally unrelated" to the other. Nothing in biology - or in and truly complex system - works like that.
That said, I'm not presuming to be able to change your mind, but more pointing out that the premise your position relies on - that one's environment and one's emotional response to their environment are completely independent - is neither an undisputed scientific fact nor true in my own experience or anyone else I've observed.
While I agree that neither exist in complete isolation, it still doesn't preclude one from being the dominant cause.
Moreover, not many people would advance the same argument in regards to conditions such as schizophrenia or bipolar disorder—how clinical depression is somehow special and not deserving of the same [endogenous] understanding is beyond me.
My own view is that depression is an evolved response to negative stresses and situations, and that clinical depression is the far end of this scale. Depression is therefore your brain's way of telling you that you need get out of a bad situation. Schizophrenia seems to be akin to a flaw resulting from some evolutionary aspect of the brain's operation, perhaps due to creativity/intelligence.
How do you reconcile this with cases of clinical depression where the person's life is otherwise fantastic, and yet they suffer from crippling depression anyways—absent any negative stresses or situations?
I was in similar denial at the beginning, until I realised that these factors are important.
I'm certainly open to the possibility that depression might be possible for someone with a fantastic life, but from what I've seen that doesn't correspond with the experiences of myself and friends/family who have experienced it.
https://news.ycombinator.com/item?id=10761938
Perhaps they can provide some insight as to how.
I think the mistake here is to assume that a privileged life is a good life.
All the comments here that say things like "they had plenty of money, good looks, great career etc but were crippled by depression" make that mistake.
If there's biological factors working against a person harder than any emotional/environmental/life changes can correct for, then those techniques are ultimately rendered inadequate.
The biological factors are symbiotic with the environmental factors. One does not function in isolation from the other. If your biology is preventing you from enjoying your supposedly "good" life, you don't really have a good life at all. Depression is one way in which the mind signals that.
The way to have a life that is actually good is to bring your environment and your biology into balance.
Such techniques exist and are highly effective for people who are fortunate enough to be able to discover and adopt them (of whom I'm one).
That they're not widely accepted in the mainstream doesn't diminish from their existence or their effectiveness.
As I've said earlier, I understand your point of view as it's one I held for a long time.
Since I learned the way of thinking about it that I've been arguing here, I've been able to take meaningful action that has allowed me to overcome depression and build a life that is actually good rather than just appearing good (both to outsiders and to my delusional self).
Anyway, I won't be responding further; you've made your point well, I've made mine and I hope my comments have helped you to clarify your own thinking, as yours have mine. Thank you for the discussion, it's an important issue that I appreciate people making the effort to engage in.
Agreed. To note I had originally phrased it as an "otherwise fantastic life" but it kind of turned into a semantics argument.
>The way to have a life that is actually good is to bring your environment and your biology into balance.
My position wasn't that environmental or emotional techniques are ineffective, just that sometimes they're inadequate in face of overwhelming biological factors, necessitating biological intervention as well. But hey—I think we're finally in agreement.
>Since I learned the way of thinking about it that I've been arguing here, I've been able to take meaningful action ...
That's great. Please don't take what I said as an indictment or assault against what works for you, I certainly didn't mean it that way.
>Anyway, I won't be responding further; you've made your point well, I've made mine and I hope my comments have helped you to clarify your own thinking, as yours have mine. Thank you for the discussion, it's an important issue that I appreciate people making the effort to engage in.
Likewise. Have a good one. :)
Well the argument I was responding to was that the two are completely unrelated, so if you accept that they're not, we're mostly on the same page.
The question then is how common it is for one to be overwhelmingly dominant.
From my experiences and research, I'd suggest that like most other biological phenomena, it fits a Gaussian distribution, in which for the majority of people it would be within 75/25 in either direction.
Moreover, not many people would advance the same argument in regards to conditions such as schizophrenia or bipolar disorder
This may be where I lose you completely, but I would make the same argument for those conditions.
It's common for the manifestations of those illnesses to be triggered by an acute trauma or prolonged exposure to abuse. But of course the innate propensity to develop that condition had to be there too.
In my own experience, I exhibited bipolar tendencies years ago (as strongly as others I know who were formally diagnosed with it). Since changing both my environment and my emotional tendencies, I no longer do.
Others with schizophrenia report becoming symptom-free by following a similar approach.
I'd contend that the whole reason mainstream medicine continues to be so hit-and-miss when it comes to treating mental "illness" is that it continues to resist viewing it in this way.
While I'm not disputing that emotional techniques can be beneficial, my main point was that in certain cases, the cause of the condition is probably the result of overwhelmingly dominant biochemical or physiological factors.
Meta-analysis has shown that approximately 80% of all cases of depression are initially caused by a major life stress (1). So "exogenous" factors seem to play a large role in triggering most depression. That said, not everyone develops depression following a major life stress - people have different levels of "endogenous" stress resilience/susceptibility. "Endogenous" stress resilience can be modulated, however, by "exogenous" interventions. For example, resilience can be increased by behavioral stress inoculation or even exercise, and it can be decreased by things like sleep deprivation or illness. It can also be partially inherited (i.e., if someone's parents were "exogenously" stressed, the offspring can inherit lower levels of stress resilience through "endogenous" epigenetic changes) (2).
And though 80% of initial depressive episodes may be triggered by stress, this tight correlation between stress and depression does not persist as strongly after the first depressive episode. Essentially, once someone has been depressed a first time, they are then "endogenously" more susceptible to subsequent episodes of depression.
So, is it exogenous or endogenous? Long story short, in most cases, it's both. Even if it doesn't start as both, it becomes both. And both "exogenous" and "endogenous" contributing factors interact in an on-going dynamic process.
1. http://hammenlab.psych.ucla.edu/pubs/05stressand.pdf 2. http://www.ncbi.nlm.nih.gov/pubmed/26410355
I can tell you that my condition eventually responded dramatically to medication, and that I would not be able to live the life I live now if it were not for that medication; furthermore, that because of the medication and my experience during the years I have been on it, I can look forwards to continuing to reduce my dependence on that medication.
Depression is indeed a normal response to ongoing helplessness and despair. I probably share your experience of depression in this regard, because the 'depression' that I had been treated for for years was suddenly completely irrelevant the moment my brain finally responded to medication.
However, there are several things that this account leaves out. You can't scoff and say that depression is just an normal response any more than people can scoff and say the reason you don't want to take a shower is because you're lazy. For one, as you know, depression can be very self-perpetuating. People come to believe things that keep them depressed, ruminating on their depressed state over and over again. People always see verification and never contradiction of their worldview, even though the entire world has somehow failed to just lay down and die over the course of many thousands of years, which is what it would do if that understanding of reality was valid. And people very definitely do encounter depression that does not have a proximate external cause to justify the response; many of those Afghanis, for instance, will suffer from the bleakest of depressions for many years after the wars in Afghanistan are ended. All of these things constitute a medical condition. If you don't like the word "illness" because of how it makes you feel, I can sympathize. But that doesn't invalidate the fact that depression is something that frequently does become a genuine medical problem and frequently does require a solution beyond the reach of the person suffering from it.
Sure the propensity to feel depressed in response to a given experience may differ from person to person, but it is a product of evolution, and is far too common to be pathologised as a "disorder".
We have this assumption that a materially privileged life in a rich society should entitle us to a life of happiness, and any divergence from that is an "illness".
This ignores the fact that there is much that is unhealthy about modern western society, and the proliferation of depression among seemingly well-off people in rich societies is a natural reaction to that.
I don't know how you'd differentiate between this formally, but it seems there is a massive difference - and they need different solutions.
[ edit readability ]
My point is that it would help if this distinction permeated into the popular discourse on depression ...
[ Awareness of the distinction might make the general public more likely to question the morality of pumping up soldiers with anti-depressant drugs before they go into battle, for example ]
But she suffers off-and-on depression. Not just "I feel bad" depression. Crippling, "can't get out of bed" depression. Periodic suicidal ideation. Occasional suicide attempts.
She knows she has depression. She talks about it. And she wants to be done with it. She knows how she feels when her brain is "in balance" and how it feels when she's depressed. One of these states is much more preferable to the other.
She's tried drugs, ECT, talk therapy, etc. And, yes, she's tried ketamine. Anything that will put her back to a state where she is able to get out of bed and function, and reduce the odds of her killing herself when she's depressed.
I'm sure there are a lot of people who are depressed due to outside factors -- poverty, oppression, war, etc. But I can tell you quite certainly that there are people who have "perfect" lives who find themselves clinically depressed. And at least some of those people want to get back to a non-depressed state. This research helps them.
TL;DR: Not all people are depressed because their life sucks, nor is depression something that all people can "cure" by thinking harder or trying harder. Some people have a brain imbalance and would like to fix it so they can have a life. Literally.
I dated for 5 years a woman in the same situation as what you describe. She has money, friends, family, a roof over her head. She hasn't suffered childhood trauma or anything abnormal, but she's consistently depressed and lethargic.
I'm bipolar myself. I've been through some difficult things, but my condition makes me acutely aware of how subjective human emotions are. How much of our thinking is influenced my neurochemistry rather than rational thoughts or memories. I'm pretty stable these days, but I've had times where I would just wake up in the morning and feel happy to be alive. Energized, stress-free, and confident in my abilities. The next day, I wake up depressed and I feel like my life is shit, not worth living. A few days later I feel fine again. No major life events, no major causes of stress, just my neurochemistry being unpredictable.
I think that the overinsistence in some circles on past trauma causing mental illness is harmful. There is definitely such a thing as genetic predispositions. Some depression and mental illness just does not have a cause you can point to. It's not all about overcoming negative experiences and willing yourself out of it. Genetic defects can cause all sorts of physical problems, just think of psoriasis, asthma, acne and peanut allergies. I'm not sure why people think that the brain can't have such issues. Believe me, people with peanut allergies won't overcome that through psychotherapy and confronting their mommy issues.
But all my research and experiences support the notion that both one's experiences and one's emotional reactions to those experiences are crucial. This is why you can have some people living seemingly perfect lives and winding up depressed, and others living through war and oppression and coming out fine.
In your friend's case, the environmental factors could be: (1) pressure from outsiders to "keep up appearances", (2) the negative messages and images that proliferate through the media of war, poverty, murder, terrorism, climate change etc, (3) a world that offers so many options of how to live but little consistent guidance about what is best, (4) living in a society that can still be very difficult for women, due to career challenges, threat of abuse, paternalistic attitudes etc.
These are just hypothetical of course, given that I don't know her.
And for her to be crippled by depression in response to these or other stimuli would be as much to do with a difference in the way she responds to such things vs the "average" person.
But it may not even be unhealthy. Maybe her true calling is to work as a humanitarian helping the needy rather than doing what she's been trying to do, and her depression is her mind's way of making her realise she needs to make that kind of change.
Having gone through this process in myself and with others, when you dig deep enough, something like this always turns out to be there.
But my main point is that the mind does not and cannot function independently of a person's environment, and paths to mental wellness that really work (and they do exist), involve addressing both one's inner reactions to things and one'e outer environment.
Yet I still have episodes where I sometimes can't get out of bed, or can't bring myself to leave the house. A couple of months ago I spent three days just sitting (and occasionally sleeping) in a chair, not even getting up to eat or shower. I just simply couldn't do it.
While it's true that people can experience temporary depressive episodes due to 'exogenous' factors (e.g. the death of a loved one), it is very different to 'endogenous' depression, and requires different types of treatment. While talk therapy and time can be very helpful for people to work through difficult and temporary 'adverse circumstances', it is of little help for endogenous/biological depression.
No amount of 'talk therapy' can convince my pre-frontal cortex to operate within 'normal' parameters or to get my brain to produce appropriate quantities of neurotransmitters like serotonin, dopamine and noradrenaline. I'm reasonably sure this is a chronic illness that I will never be rid of (as I've learned from 15 years of failed treatment attempts). On the upside, there's a good chance that there is some treatment out there, coupled with sustained lifestyle changes, that will allow me to stave off the symptoms so that I can live a relatively 'normal' life. In some ways it's similar to how type 1 diabetics can survive and live normal lives with regular injections of insulin.
It's not that I don't believe your depression is endogenous, I'm just curious. I was in a similar position to you until I looked closely at my life and identified the factors that were causing my depression/CFS.
- running multiple ultramarathons with too little rest can cause depression, even if you love it. - working very hard in a job you like with too little sleep for a long time can cause depression.
In both cases it's likely your brain it just telling you that you're pushing too hard.
Some people -- like me -- find it easier to get into these mental overdrive situations, and some people might be more likely to suffer depression from the same stressors, but ultimately it seems to be the same factors at work.
I don't want to be preachy...one thing I've come to realize from many online discussions with other people suffering from depression is that almost every case is unique in some way and that the mental health community's efforts to try to group together what we're feeling into a single problem with prescribed courses of treatment is probably counterproductive. People believe that because they've experienced depression, either first- or second-hand, that they understand what all depression is like...astazangasta's comment is an example of this.
I try not to be one of those people, so what I'm offering is a suggestion, not an answer. My depression is by no means fixed, but meditation has helped me. It's one datapoint in case you want to try it.
I think that someone can be affected by somethings in their earlier life that can affect them forever. I'm not talk about repressed memories, I'm talking about the lack of positively formative experiences at critical moments of their life.
Example - what happens when say someone starts school or is a teenager at the same time their mother is undergoing menopause and their father has lost their job and they're both starting to drink? The child will feel a lack of something but not sure what. If they do think of it all, they'll think of it as partly their fault.
How can you be sure it's not WiFi radio waves messing with her brain?
Can you really rule out space aliens trying to stop her from reaching her potential?
There's a reason we use the scientific method.
Could it possibly be that there is more to life than these things?
...could it be that there is more to life than these "objective factors"?
Hacker news is pretty depressing.
It's interesting that the Ketamine research comes to the conclusion that depression is not a mental imbalance but is a product of the environment causing structural changes in the brain - this seems more in line with what eg ADD and Depression ACTUALLY are - it's not that I can't focus because I caught something from my neighbour - I can't focus because I'm berated with stimuli and I can't pick just one thing to focus on. I'm not depressed because my brain isn't producing enough seratonin, it's because I've been wore down supressing my wants and needs and extended myself trying to make other people happy or overstimulated myself or whatever.
We don't know but the picture is getting clearer - depression isn't a common cold that you need drugs for - it's more like liver disease caused from chronic drinking. Stop drinking, and let your liver recover only science just barely understands the processes of the psyche and environment that cause those physical changes in the brain yet.
Addiction itself is very much an obvious facet - it's not a degenrate behavior but a degenerative structural change to the brain that cause inner behavioral and perceptual changes that need a physical restructuring of the brain to overcome.
It will take time but science will get clearer. The problem is that there are many motives - the whole "sitting is the new smoking" awareness is evidence that we focus on the wrong things - why is this just coming out now? because there is no profit motive to fund that research.
BTW. I always considered ADD, ADHD, etc. to be a bit of a fake disease, a product of environment, but I'm no longer sure. I've been struggling with depression and anxiety for many years and responded relatively well to SSRIs which stabilized my mood and helped me quit the recurring panic attacks. The problem is not gone, but with a little more stable emotional situation I managed to figure out that what really causes most of my problems now is total lack of focus. I can't hold my attention on any kind of work-related task (the task doesn't matter; what matters is that it's work) for more than 30 seconds without compulsively seeking something else to do. Be it HN or IMs. With no easy distraction source available, I'll get anxious and sleepy. I can be perfectly well-rested but will still occasionally get sleepy at work just because I refuse to distract myself with Hacker News. A considerable amount of my mental energy goes to fighting this and forcing myself to focus. Now that I've finally dug that up from underneath the layers of anxiety, it's going to be a topic of the next conversation with my doctor.
#HNTherapy
Also, this is what I got googling for ADD[2]. What the shit?
[0] - http://slatestarcodex.com/2014/09/10/society-is-fixed-biolog...
[1] - http://lesswrong.com/lw/2as/diseased_thinking_dissolving_que...
Do you doubt the existence of autism? Dyslexia?
Probably not.
Sorry that it can't play the role in your polemic that you were hoping for.
http://www.thelancet.com/journals/lanpsy/article/PIIS2215-03...
Researchers seem to be using an infusion of 5 mg per kg of body weight. That means you don't give a bunch of pills to a patient, which in itself helps a bit to reduce risk.
There's a bit of a web-based discussion here: https://www.youtube.com/watch?v=5b6zrpd1trk
Probably not, at least not according to most of the research conducted on it so far. Like many treatments for depression — including psychotherapy — it appears to change the way the brain processes certain information and effects the connections between neurons. But it’s not clear how long these changes last, or whether chronic ketamine treatment would be needed, similar to a diabetic taking insulin.
http://psychcentral.com/blog/archives/2012/12/01/should-you-...
Ketamine has been tested in treatment-resistant bipolar disorder, major depressive disorder, and people in a suicidal crisis in emergency rooms.[26] Benefit is often of a short duration.[27] The quality of the evidence supporting benefit is generally low.[27]
The drug is given by a single intravenous infusion at doses less than those used in anesthesia, and preliminary data indicate it produces a rapid (within 2 hours) and relatively sustained (about 1–2 weeks long) reduction in symptoms in some people.
https://en.wikipedia.org/wiki/Ketamine#Depression
Ketamine may have its use for treatment resistant depression and dealing with emergencies caused by suicidal bouts because it can make depression symptoms disappear for few days, but this is only temporary as better ketamine based drugs are developed.
At least until they wear off.
https://www.washingtonpost.com/news/to-your-health/wp/2015/1...
> A new study provides some of the strongest evidence yet that using an antidepressant like Prozac, Paxil or Zoloft during the final two trimesters of pregnancy may be linked to a higher risk of autism spectrum disorder for the child, but researchers said the results should be interpreted with caution.
https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_i...
> SSRIs can cause various types of sexual dysfunction such as anorgasmia, erectile dysfunction, diminished libido, genital numbness, and sexual anhedonia (pleasureless orgasm). Sexual problems are common with SSRIs. Poor sexual function is also one of the most common reason people stop the medication. Very rarely, these effects persist after discontinuation of the medication.
Especially when suicide is one of the leading causes of death of women during the perinatal period.
The article makes it perfectly clear what the risk is, how much the increase is, and with what factors it is associated; and what the researchers caveats were about their own findings. The poster you were slamming wasn't spreading FUD or hyperbolizing; he was just simplifying. It's pretty irresponsible (and obnoxious) of you to suggest otherwise.
Maybe I'm missing it, but from that article: what's the base rate, what's the rate if a woman takes SSRIs, and what's the increase?
(And here rates are provided in X per 100,000)
I'm not playing this game with you. Obviously, the information wouldn't expressed that way in the WP article. You may recall that they're a newspaper, not a scholarly journal. So you know perfectly well that it wouldn't have expressed the information in those terms.
The article does mention exactly what the increase is. As to the base rate, the WP article doesn't use that exact term -- but they do give hard numbers for the sample sizes involved, and took care to point out that the smallness of the proportion of infants who developed autism (with or without taking SSRIs) was one of the factors that led the researchers to point out that their findings should be taken with caution.
If you want more data and specifics, read the JAMA article. If you think the researchers themselves made some basic flaw in their statistical reasoning -- and, correspondingly, you'd like to bring their reputations and their future funding channels into question -- then the burden of proof lies on you to show it. And I'm sure JAMA Pediatrics would be very interested in getting an email from you.
But if you're going to fault the WP article for not conveying every facet of detail from the research article, in as many digits of precision -- even though its overall presentation was basically fair, and on point to the level of detail that would be meaningful to its readers -- then you're basically playing head games.
Do you at least agree that the article doesn't explain what the quoted 87% increase means in a way the readership is going to understand? Can you explain what that 87% increase means?
The article had almost no relevance to this thread; it was dumped here as yet more pill-shaming bollocks; it targets a group who already have to put up with a lot of bullshit; and it's disappointing to see that kind of behaviour defended.
The original study is irresponsibly presented and poorly reported and I have no problem pointing that out.
That's not what I said. It's basically the opposite of what I said. In my initial response to you, what I was basically saying was that the article presented the key upshot of the researchers' findings, without echoing all the details. That is, it wasn't anything like the FUD piece you were making it out to be.
Do you at least agree that the article doesn't explain what the quoted 87% increase means in a way the readership is going to understand?
No. It's very clear, from my reading. I'll agree that not every reader is going to understand it, but anyone with say, median freshman-level skills in reading comprehension ought to be able to understand it.
Can you explain what that 87% increase means?
Yes. But I'm not going to do it for you.
The article had almost no relevance to this thread; it was dumped here as yet more pill-shaming bollocks;
It's fine if you want to think that. Doesn't seem relevant to what I was saying, though.
Selective Serotonin Reuptake Inhibitor. https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_i...
I'm sorry that I can't recall the source, but you should look into this.
This is why it's important to trust your care to a psychiatrist or allied mental health professional.
On that same note, people with ADHD are often missing dopamine in many parts of the brain, but ADHD isn't necessarily correlated strongly with depression. And quick dopamine-releasing drugs like amphetamine (Adderall/Dexedrine/Vyvanse), or dopamine reuptake inhibitors like methylphenidate (Ritalin/Concerta), tend not to be great treatments for depression, either. They can be a short term treatment by giving you a euphoric high the first few times you take them, or if you take big doses, but that's not a good long term treatment strategy.
SSRIs don't work very well for many people, but they do work well for many other people.
If you think depression is about just increasing serotonin in the brain, let me point out that "serotonin syndrome" is a very real risk of using antidepressants. It's essentially an overdose on serotonin. It's clear that messing with serotonin in the brain, you can give a sort of neurochemcial nudge that can help you overcome depression, but happiness is not itself the amount of serotonin in your system.
Either way, I quit using drugs and alcohol many years ago and regular exercise with exercise, tons of CBT, and lots of vigilance has helped the best. But it would be nice to have a drug on the market that would make keeping depression at bay so effortful and so much hard, consistent work.
Anecdote isn't worth much in medicine, but there really is something special about Ketamine.
For one, there are tricyclics (TCAs), which were the first antidepressants on the market, and generally are not prescribed nowadays. Another category of older antidepressants includes MAOIs, which were the first mass-market antidepressants. These are also not generally prescribed nowadays due to interactions with common types of food, although modern MAOIs such as moclobemide [1] require far less diatary restrictions than the older MAOIs did. The final major category I'll mention are SNRIs, which along with SSRIs are the most commonly prescribed first-line antidepressants.
Apart from these major categories, there are a bunch of atypical antidepressants on the market. There's bupropion, which I personally take, and which has far less side effects than SSRIs and SNRIs but may not be as effective for all patients. There's St. John's wort, which is available off prescription in many countries. There's lithium, which has recently gained popularity. In total, I would guess there are about a hundred different types of antidepressants in production around the world (including old Soviet concoctions that are not available in the West due to the huge price of getting just one of them to market).
If you're unhappy with the side effects of SSRIs, I would encourage you to look up other types of antidepressants, as they have very widely varying side effects, and most atypicals have far fewer common side effects than SSRIs and SNRIs do. In particular, I would like to point out that bupropion usually increases sex drive instead of lowering it like SNRIs and SSRIs tend to do.
Tricyclics are frequently used in attempted and completed suicide.
Being more careful with prescribing tricyclics to people with suicidal ideation would probably reduce the numbers of attempted and completed suicide.
This will wear off in a few days, but it is not side-effect free drug - there are still many unknowns.
I don't know if ketamine has high risk of causing general intelligence reduction in the long term, but there are reports of that from people who abuse the drug in recreational doses for a long period of time. So, it's definitely something to be wary about.
It's like arguing that a bug is a problem with the UI, not the code...
Ketamine inhibits the reuptake of all three major monoamines. Thus it mimics to some degree both the mechanisms of action of SNRIs (serotonin/norepinephrine reuptake inhibitor) such as venlafaxine (effexor), used to treat depression/anxiety and DNRIs (dopamine/norepinephrine) such as bupropion (wellbutrin)/methylphenidate (ritalin), which are used to treat depression/ADHD. Ketamine also impacts the acetylcholine receptors, which have been linked to anti-depressant effects, and the less-well-researched sigma receptor.
While the above interactions may contribute to the reported anti-depressant effects, some of those same interactions make it undesirable as a medication. Dopamine reuptake inhibitors and mu-opioid antagonists are notoriously abused for their euphoric effects. However, those effects are contrasted with psychotomimetic effects of ketamine's interaction with NMDA, kappa-opioid, muscarinic acetylcholine, and simga receptors.
Ultimately, it's incorrect to simply categorize ketamine as a depressant or a sedative. The body is an exceptionally complex chemical network, and you're right to be skeptical. But I think it's important that we not dismiss the positive reported effects of the drug because of the side effects that occur at various points on the dose-response curve. We may find out that by controlling dosage we can tune a beneficial level of antidepressant response without psychosis, dissociation, or amnesic effects due to hormetic effects. Or it might work exceptionally well for some otherwise treatment-resistant cases. Even if not, we'll be able to use that data to tweak the binding affinities to investigate drugs that have a better therapeutic use.
Ketamine I don't think has a huge problem with this compared to other drugs. It may be a bit of a bizarre experience but not often a tramuatizing one.
For example, would you recommend that someone with schizophrenia try it?
The FBI has a problem hiring good security experts because of their strict drug testing policies.
http://www.wsj.com/articles/SB100014240527023044227045795743...
There are many tech companies, like Pivotal Labs, that love drug testing.
And, of course, safety-reliant jobs like truck drivers, warehouse staff, etc.
Another one joked that "We used to drug test at hire, and if you didn't come up positive for ANYTHING, we'd fire you." That was based in a state where medical MJ is legal, and their drug policy was the most reasonable I'd ever seen. "What you do on your own time is your business, and we only start caring if it affects your work performance or interactions with coworkers during work hours."
Meanwhile, the place where I spent 12 years not only tested at hire, you were under the constant "threat" of "random" testing, and the same policies applied to everyone - from rig workers and truck drivers, to programmers. The only time I got "randomly" tested was after a coworker on my team had blown his "random" test... A couple of weeks later I was "randomly" selected; at least HR had a sense of humor about it. "You won the piss test lottery! Go down to XYZ as soon as you get in this morning and pee in a jar..."
This meant that my first and only time I've ever tried MJ was at the age of 40.
If you're interested in the history I found What the Dormouse Said to be pretty interesting.
http://www.amazon.com/What-Dormouse-Said-Counterculture-Pers...
Francis Crick, Kary Mullis, Steve Jobs, Feynman, and many other of the most well known scientists and engineers of the past 50 years have gotten such a personal and creative benefit from psychedelics that they have publicly spoken about it despite their schedule 1 status.
One of my girlfriend's problems is that she has low energy levels - certainly caused by previous stimulant use, and her body's inability to efficiently produce energy (ATP) by burning glucose/fructose. Before she met me, she treated this symptom (low cellular energy levels) by drinking alcohol regularly. Alcohol is an energy-rich molecule, the metabolites of which are easily burned by the insulin-resistant brain cells which have become insulin-resistant. She started drinking a month after starting methadone, a drug which is known to cause sugar cravings.
Deciding to quit methadone was easy once she realized that she hated it. But when she lost access to alcohol, her brain went into a sort of 'survival' mode, which led to her being taken to the hospital [1]...
The causes behind my girlfriend's condition are fairly obvious to me, having observed her for months now. But the hospital staff had no context for why their patient was acting the way she was, so they just treated her symptoms. The doctors at the inpatient facilities she's been at don't care about physiology either, they just reach into the pharmacy and try new drugs with the proper label ("anti-depressant", "anti-psychotic", "mood-stabilizer" - these are marketing terms, imho). She's still exhausted, but at least they're giving her the coconut oil capsules I dropped.
There is another way. My grandfather, a dentist with an interest in hypnosis, didn't remember much of his one class with psychiatrist Milton Erickson, M.D., except that Dr. Erickson was always "bitching" - about having to go to medical school, having to learn anatomy, physiology and pharmacology, etc etc, when all he really wanted to do was hypnosis (this was Dr. Erickson's method of conversational hypnosis, applied to an audience of medical professionals). The Erickson Foundation released a really cool documentary [3] last year...
[1] https://news.ycombinator.com/item?id=10639657 [2] https://www.commentarymagazine.com/articles/how-psychiatry-l... [3] http://wizardofthedesertfilm.com/
And most especially, thank you for pointing out that amazing documentary on Erickson! I've read the NLP foundation's first two books on him and they're incredible. I just picked up a copy of the DVD.
BTW, have you tried any NLP of the therapy variety with your gf? How surprised would you be to find it working as well as you can imagine? ;)
> BTW, have you tried any NLP of the therapy variety with your gf? How surprised would you be to find it working as well as you can imagine? ;)
She's come a long way since I met her. I recently found a copy of /UnHypnosis/ at a local thrift store, which she's going through: http://stevetaubman.com/unhypnosis/ - seems like it's basically applied NLP. I have most of the old NLP books, and some of the newer ones too.
My Voice Will Go With You - https://books.google.com/books?id=AEo9acmCFNUC
A few words about new theories. All new theories that can garner such enthusiasm for their presentation are invariably bolstered by something. No-one writes magazine articles about ambiguous signals from an exciting new theory. If the evidence presented is not in some way definitive, then it should be viewed as a precondition for the propagation of the theory, not evidence in favour of it. Few of us are expert judges of neurological theories, and we are not able to tell if there is anything substantial beyond the feeling that we experience that something valuable has been learned.
I know that the effects of Ketamine in treating serious episodic depression are very exciting. I feel that I understand enough to suggest that neuroplasticity is not an especially 'new' theory, or a 'theory' by itself. The neuroplastic response is real, well documented, and undisputed. What is a theory, and had not been established as fact, the last time I discussed it with someone, is that idea that the neuroplastic response is the central intermediary between the physical effect of the drug and the clinical effect of the drug. It occurs, but it had not been established that it is causal.
The central suggestion regarding the 'vaccine' effect seemed to be buried a bit in the article (unless I missed something in skimming), but it is the actual new information, which is interesting and heartening. Soldiers coming to a forward operating medical station with severe burns were treated with Ketamine rather than another anaesthetic because of its relative safety. They subsequently developed PTSD half as often as all soldiers and civilians treated for less or equally severe burns with other anaesthetics.
On the basis of the theory that PTSD and depression emerge an erosion of neurosynaptic connections, the leap is made from there to the idea that Ketamine might perhaps serve as a true 'vaccine' when people were going into high-stress situations. From my relatively uneducated perspective, this seems a bit irresponsible in two separate ways.
Firstly, the evidence is that the soldiers were 'vaccinated' against psychological disturbances associated with extreme trauma... after the initial extreme trauma had occurred. There is evidence from studies with mice that a Ketamine treatment changes their response to stressors in a way that seems both dramatic and positive. Ketamine is a common recreational drug. If we should be excited about the prospect of this response being replicated in humans, then why is there not already ample evidence that this response is replicated in humans?
Secondly, there is absolutely no reason that we should conclude that the effect of the Ketamine on the burn victims has anything to do with neuroplastic response. Ketamine is an anesthetic. It limits pain, which is traumatic. Anesthetics operate in different ways. Ketamine seems to inhibit the transmission of pain signals in the spinal cord. This prevents them from reaching the limbic system. Other forms of anesthesia may not. Ketamine is, infamously, an amnesic and a dissociative. Stress disorders require memory formation. Ketamine prevents memory formation. Other forms of anesthesia may not. And so on. In the context of the surfeit of plausible explanations for this effect, to suggest that the effect is particular evidence supporting a theory that PTSD is cured by neuroplastic regeneration of synaptic connections is not particularly responsible. It might not be terrible journalism, but it is definitely bad science, and almost certainly not something that was presented as science to the journalist.
You are correct, this is a new finding. It does not, however, come from the study looking at soldiers. In that study, ketamine was actually given after stress (not as a 'vaccine'). Those researchers also failed to replicate that effect when they looked a larger group of soldiers. The first study was done in 2008 and the second one was done in 2014. Believe me, if they had found a protective effect in humans 7 years ago, you would have heard about it by now.
The research that actually shows the ketamine might be a 'vaccine' has all come out this year (2015). And, so far, it's all only in mice. The scientific publication referred to in the Nautilus article is "Ketamine as a Prophylactic Against Stress-Induced Depressive-Like Behavior": http://www.biologicalpsychiatryjournal.com/article/S0006-322.... At least two other research teams at other universities (FSU & UC-Boulder) have independently also found similar effects, but none of that is published yet (though it was presented this year at the national Society for Neuroscience conference). In other words: yes, it's new.
Additionally, neuroscientists at Mt. Sinai, the NIMH, and UC-Boulder (among others) have found that bacteria and immune cells might also be used to 'vaccinate' against stress. Again, most of that research--though not all of it--is still not published yet, and has only been presented at conferences so far.
I also completely agree that the sedative-level dose given to soldiers after stress might have worked by blocking traumatic memory formation. It has already been established that blocking or "erasing" stress memories may prevent PTSD (here's just one example: http://www.medscape.com/viewarticle/819452).
In the studies in mice, ketamine was no longer in the animals' systems by the time they were stressed. So they were not sedated. And the researchers tested memory formation to confirm it was not affected. Thus, it seems that ketamine's protective effect in mice isn't just because memory is disrupted. That said, it is always possible they missed something.
From what I can find, it doesn't seem like anyone has even looked yet to see how this ketamine-vaccine strategy effects neuroplasticity. At this stage, it's probably best to consider the post-stress effect of ketamine in soldiers (1), the pre-stress protection in mice (2), and the neuroplastic effects of ketamine (3) as three separate things.
That said, I did find ketamine to be an extremely effective anti depressant with the primary effects being immediately noticeable and positive. I currently re-dose on ketamine every couple months and take bupropion daily--between all of these I've been able to greatly reduce fairly severe depression that went untreated and worsened over a 10+ yr period.
Possibly with a low enough dosage this would be manageable, but speaking from experience from watching people that have been on the wrong end of the stick with this one. it can do some really serious long term damage in that department.
Here's someone who was using 15 g per day: http://www.bbc.co.uk/newsbeat/article/29811499/k-bladder-the...
A therapeutic dose is 5 mg per kg. An average adult would be 80 kg, which gives a dose of 400 mg once every maybe 30 or 60 days.
I watched two documentaries in short succession: Drugs Inc's episode on Ketamine, and a few episodes of Combat Medic. Drug Incs' played up the bladder damage, the persistant dissociative feeling with abusers, and how it's just horse and cat tranquilizer that's no longer used on humans.
Combat Medic non-challantly showed medics giving ketamine to US soldiers in Afghanistan, because it's an effective and immediate anesthetic. They were subtle about it, but it was there. Our the dissonance in the media about drugs like this is indicative of fear mongering and propaganda.
The reason my initial gut felt this way is not due to any documentary or scare tactic it's purely personal experience.
I have two close friends that have taken the recreation too far. One now has permanent bladder issues and the other was lucky to get their habit in check in time. So my gut reaction was not very scientific, apologies.
I am a huge fan of legalization and science. Let people make their own mistakes and if there is a medical path that helps people I'm all for it!
Just hope that this is also part of the discussion ( harm prevention ) because there is some real risks with abuse, that personally I have witnessed first hand.
Having said that science over fear for sure, I am a fan of science over fear. I still feel more positive light than negative and am hopeful people use his for good!
At recreational doses, doctors aren't going to be prescribing anywhere near that.
FWIW - doctors are definitely using "recreational" doses in these experiments.
It would be like saying having a couple of recreational beers on a Friday causes liver failure. It doesn't. Drinking a bottle of whiskey every day for an extended period of time, perhaps.
Same with Ketamine
Ketamine and Bladder Health
In some cases, chronic ketamine use has been associated with urinary tract symptoms that can include increased frequency of urination, urinary incontinence, pain during urination, passing blood in the urine, and reduced bladder size. In several reported severe cases, surgical intervention to remove the bladder was deemed necessary by clinicians. The wide dose-response range leading to documented cases suggests that individual responses to ketamine may be idiosyncratic and unpredictable, making it unclear what level and frequency of use may lead to urinary problems.
https://www.erowid.org/chemicals/ketamine/ketamine_health.sh...
>In some cases, chronic ketamine use has been associated >In several reported severe cases
Chronic / addiction levels yes. Not recreational levels. As I put
As to ketamine and bladder problems. I used to be involved with the UK free party scene which had serious problems with ketamine in the early 2000s ( up until the supply shortage caused by the Indian clampdown a few years ago), before it was well known about the addiction / health problems it could cause (although issues were known, but it wasn't generally well known beyond a few knowledgeable people).
You would often hear that ketamine had no comedown, had no side effects. Users would start out being weekend users, then progress to daily, sniffing between 3-7 grams a day, all day - everyday. Then gradually you started hearing about stomach cramps, difficulty going to the toilet, thinking you had to go to the toilet every 10 minutes, having to urinate a jelly/jello like bloody substance. Drs had no idea what was going on and were no help. But by this stage the addiction had them completely and the only way to stop the pain was to sniff more ketamine. Eventually it led to a girl having kidneys and / or bladder removed and slowly the public conscience about the dangers of ketamine was known.
However, of all the users I knew who kept it to only weekends, used ketamine for years with none of the above mentioned health problems. Anecdotally of course and I am sure there may be edge cases I am unaware of. But recreational use of ketamine does not cause bladder problems IME
People drinking far less than that, maybe a glass or two of wine most days, are getting cirrhosis.