Tackling depression with ketamine

[Burnt Offerings]

The economic/social context to these developments is repulsive, of course, but I do find the pharmacological aspects of this topic to be interesting. The role of NMDA receptors in depression is interesting to me.

 

[Felonious Monk]

(Ketamine is vile in the US healthcare industry's lore.)

Could you describe a little more what you mean by that? I get the general idea but you seem to be referring to something in particular.

I agree with you about the other parts, but as the treatment becomes more mainstream I don't think they would need an anesthesiologist at all times, since they're careful to say it's only 10% of that dosage.

 

[Burnt Offerings]

It seems to have less of a bad reputation than phencyclidine, LOL

 

[MyDoorsAreOpen]

Could you describe a little more what you mean by that? I get the general idea but you seem to be referring to something in particular.

I agree with you about the other parts, but as the treatment becomes more mainstream I don't think they would need an anesthesiologist at all times, since they're careful to say it's only 10% of that dosage.

In my experience working within the US healthcare system, ketamine is considered a bit of an embarrassment whose proper place has been reduced to two situations:
1) Emergency field surgery and wilderness medicine, when you have a person in (or about to undergo) severe pain, and you have absolutely nothing else, and
2) Procedural sedation for children, especially for popping a dislocated joint back into place.

In short, it's very hard for a drug with a common listed side effect of psychosis (!) to gain much respectability, because for most straight laced Joe Schmos, that's an absolutely unacceptable side effect, no matter the benefits.

By gently bringing up the possible benefits of ketamine in conversation with fellow healthcare providers, it has become clear to me that this drug is largely regarded as being in the same category as chloramphenicol -- a crude anachronism of a drug that belongs relegated to desperate situations in the third world, and that no sane human being would want to either take themselves, or administer to another human being.

 

[Jabberwocky]

If ketamine helps treat depression, why can’t doctors prescribe it?

If ketamine helps treat depression, why can’t doctors prescribe it?

ntidepressants are among the most commonly prescribed drugs throughout the western world. In fact, they are prescribed more than any other drug for Americans aged 18 to 44, and they are now taken four to five times more frequently than in the early 90s. In the UK, antidepressant use has doubled over the past decade. Either more people are depressed, more people are talking about their depression, or doctors now think they have got a pill that will help.

What are these drugs? Unlike the antidepressants of 30 years ago, they are considered “clean” and well-tailored. They target a certain neurochemical and leave the rest of the brain alone. (Old-school antidepressants were notorious for their scattershot effect.)

First-line antidepressants are almost exclusively what are called selective serotonin reuptake inhibitors (SSRIs), with the emphasis on “selective”. That means they keep serotonin in the connections between neurons (the synapses, where all the action is) far longer than it would normally remain. Serotonin is a neurochemical that appears to moderate the information travelling between neurons. The theory is that depression grows from too much information, consisting mainly of self-criticism, negative memories and negative expectations, cycling in an endless loop. More serotonin should diminish this unhelpful deluge.

But do SSRIs actually work? Despite great promise, the big picture reveals a mixed bag of results – and opinions. Many studies have revealed extremely limited effectiveness for SSRIs when compared with placebos. These disappointing results drew attention to studies conducted by the pharmaceutical companies, in which poor results were systematically buried. (Did we really trust the drug makers to present an unbiased picture?) Yet other well-controlled studies suggest that SSRIs do help depressed people at least some of the time. The final verdict? SSRIs help some people on a good day, according to some studies and not others. Most experts agree that it would be a very good thing to find other drugs that work more reliably.

Along comes ketamine. Ketamine has been around since the early 1960s, when it became available as an anaesthetic for use with humans and animals. Its psychotropic (mind-altering) effects were soon discovered. Ketamine changed people’s perception of themselves and the world around them to a degree comparable to LSD and other psychedelics. Thus began its career as a street drug and its designation as a controlled substance. You know how the reasoning goes: we can’t let people go around changing their reality. Nevertheless, it has been used as a party drug for decades, often under the nickname “K”.

Ketamine’s potential for fighting depression has been studied for years. Current reviews conclude that it is highly effective against depression – a promising new medicine, but potentially dangerous, both physically (you can lose your balance) and psychologically (it can produce psychotic-like states). But how does it work?

The main neurotransmitter for communicating between brain cells is glutamate. Little bundles of glutamate molecules, sent from one neuron to the next, tell each neuron how rapidly to fire – a very important message. But glutamate molecules have to enter the receiving cell through a doorway designed to welcome them. And one of the main doorways is called the NMDA receptor.

Thanks to swarms of glutamate molecules shooting into NMDA receptors all over the brain, an incredibly complex, incredibly subtle network of firing neurons creates our sense of reality. When the brain is functioning normally, the pattern of firing neurons matches what is going on in the world outside your brain. If you happen to be schizophrenic, then not so much.

What ketamine does is block many of those NMDA receptors, so the glutamate molecules have nowhere to land. Consequently, the network that fashions reality starts to fall apart. The harmony of synchronised neurons breaks down, and your perception of the world starts to drift. That’s why ketamine is called a “dissociative”. Ketamine has been used on the battlefield where wounded soldiers can dissociate from their pain. So ketamine’s main contribution is to free you from what’s in front of your face.

Nobody knows exactly how ketamine nails depression. Yet I don’t think it’s so mysterious. When people are depressed, they undergo the same cycling thought patterns over and over again: I’m no good. Nobody really likes me. I don’t deserve to be happy. I’m too selfish, too greedy, too unpleasant. It’s called rumination. What’s more, the negative self-thoughts reinforced through rumination promote feelings of sadness, shame and hopelessness, while those feelings reinforce the spiralling negative thoughts. A vicious circle indeed.

What ketamine might do is break the cycle, perturb the relentless repetition of depressive self-appraisals. The “reality” that you are a bad, worthless person gets fragmented, because ketamine fragments everything you think you know. Ketamine permits you to sojourn into different psychological realities. That is one of the risks associated with clinically dispensed ketamine, but for depressives, a little holiday from the daily grind of pessimism might be a welcome relief.

It would be great if ketamine-based treatment moves beyond its interminable research phase: is it really safe? Can we be absolutely sure? Let’s not forget that booze can also make you lose your balance, and it’s quite legal. And depression itself can generate psychosis, often for lengthy periods. Ketamine doesn’t look so bad on balance.

I would like to see ketamine become available, at least through the safeguards of the doctor-patient relationship, to the millions who suffer depression. But there is a lesson to be learned from ketamine’s protracted debut. We are so afraid of the drugs people take for fun, to feel good, or at least to feel different for a few hours, that we ban them almost reflexively and punish those who use them. Why? What’s so bad about adults taking a vacation from the imperious reality we call “normal” – a reality that, sorry to say, isn’t decreed by God or nature but by culture, by a semi-arbitrary history of conventions? We should divert some of our hyped-up fear of abuse potential into a societal experiment, a sandbox, so to speak, for exploring the benefits of various popular drugs – drugs (such as ketamine, marijuana, ecstasy and psilocybin) that are illegal because people sometimes want to take them. Surprise, surprise: these drugs might just help people feel better.

https://www.theguardian.com/comment...reat-depression-illegal-drugs-antidepressants

Frustrating to see how ketamine is still having to be presented more as a recreational substance or "drug of abuse" and not the legitimate medical treatment it has in fact become (even if it's psychiatric application is still technically considered "investigative" by many in the mainstream - but this is how they treated MDMA after it was demonized for decades, so I'm not surprised).

The way its infusions are used to treat stuff like depression bares very, very, very little (if anything really, other than the antidepressant effects) in common with how it is used recreationally.

Still, happy to see this kind of thing in mainstream press.

 

[MyDoorsAreOpen]

I know this article was from the UK, but I can only speak for the USA: Even with it being much less widely known as a drug of abuse in this country, our healthcare system hates ketamine. It's got a reputation as a crude and dangerous tool of last resort, which barely fit for administration to human beings.

Technically with an unrestricted DEA license, I can prescribe ketamine for depression. Or for any condition that, in my medical judgment, it has efficacy in treating. But I've never dared to do such a thing, because I simply do not want (nay, cannot afford) the unwanted negative attention this would bring me. Doing so would raise eyebrows at every level; I might as well be hanging an IV drip of chloramphenicol for a bacterial infection, or entering a trauma room with a bone saw. I don't need insurance companies refusing to cover it. I don't need pharmacists calling my office refusing to fill it. I don't need irate patient family members who've done too much googling, confronting me for treating their loved one with a large animal tranquilizer or a rave drug.

The subjective psychoactive effects of ketamine are very hard to describe even to someone who has used it before, let alone to someone who's never used a dissociative. I'm aware that doses efficacious for depression are below fully dissociative. But some people are more sensitive to drugs than others. And some patients take much more than their prescribed dose for any number of reasons. I do not need a lawsuit from a patient who is mentally scarred from an unwanted mystical experience, or attempted to navigate the demands of their day to day world in a dissociated state with disastrous consequences. "Your Honor, ladies and gentleman of the jury, let the evidence show that Dr. MDAO deviated markedly from the standard of care, with disastrous consequences to the patient's health and safety. Case closed."

There are doctors in the US who prescribe ketamine for depression. Their clinics typically do little else. They do not take insurance, and they are not cheap. Typically it is administered IV onsite. The patient needs to have someone else present to drive or otherwise escort them home after each treatment. I'm sure they have to sign all sorts of waivers. Overhead expenses for these clinics are probably substantial, given the continuous vital sign monitoring of every patient undergoing treatment (per anesthesia protocol), and the multiple levels of security and documentation necessary to be compliant with DEA standards for onsite receipt, inventorying, handling, storing, administering, and disposal of a controlled substance. (You can bet the DEA, and the IRS, never take their eyes off any such a business.) If the doctor who runs the clinic is not an anesthesiologist, pile on another expense for hiring a full-time nurse anesthetist or anesthesiologist, to do little more than sit around and wait for something to go wrong, to the tune of a six figure salary. I'm sure doctors who run ketamine clinics also pay top dollar to have a specialized medical attorney on retainer, starting in the planning phases long before the first patient is ever treated, which makes startup costs prohibitive. Cash and controlled substances onsite means no expenses can be spared when it comes to building security, either.

TL;DR: American physicians can choose to treat depression with ketamine, but at least today, they are making a choice to live on the edge medicolegally, and that's not a set of challenges many in a profession that selects for risk-aversion have a taste for.

 

[cj]

I know this article was from the UK, but I can only speak for the USA: Even with it being much less widely known as a drug of abuse in this country, our healthcare system hates ketamine. It's got a reputation as a crude and dangerous tool of last resort, which barely fit for administration to human beings.

Technically with an unrestricted DEA license, I can prescribe ketamine for depression. Or for any condition that, in my medical judgment, it has efficacy in treating. But I've never dared to do such a thing, because I simply do not want (nay, cannot afford) the unwanted negative attention this would bring me. Doing so would raise eyebrows at every level; I might as well be hanging an IV drip of chloramphenicol for a bacterial infection, or entering a trauma room with a bone saw. I don't need insurance companies refusing to cover it. I don't need pharmacists calling my office refusing to fill it. I don't need irate patient family members who've done too much googling, confronting me for treating their loved one with a large animal tranquilizer or a rave drug.

The subjective psychoactive effects of ketamine are very hard to describe even to someone who has used it before, let alone to someone who's never used a dissociative. I'm aware that doses efficacious for depression are below fully dissociative. But some people are more sensitive to drugs than others. And some patients take much more than their prescribed dose for any number of reasons. I do not need a lawsuit from a patient who is mentally scarred from an unwanted mystical experience, or attempted to navigate the demands of their day to day world in a dissociated state with disastrous consequences. "Your Honor, ladies and gentleman of the jury, let the evidence show that Dr. MDAO deviated markedly from the standard of care, with disastrous consequences to the patient's health and safety. Case closed."

There are doctors in the US who prescribe ketamine for depression. Their clinics typically do little else. They do not take insurance, and they are not cheap. Typically it is administered IV onsite. The patient needs to have someone else present to drive or otherwise escort them home after each treatment. I'm sure they have to sign all sorts of waivers. Overhead expenses for these clinics are probably substantial, given the continuous vital sign monitoring of every patient undergoing treatment (per anesthesia protocol), and the multiple levels of security and documentation necessary to be compliant with DEA standards for onsite receipt, inventorying, handling, storing, administering, and disposal of a controlled substance. (You can bet the DEA, and the IRS, never take their eyes off any such a business.) If the doctor who runs the clinic is not an anesthesiologist, pile on another expense for hiring a full-time nurse anesthetist or anesthesiologist, to do little more than sit around and wait for something to go wrong, to the tune of a six figure salary. I'm sure doctors who run ketamine clinics also pay top dollar to have a specialized medical attorney on retainer, starting in the planning phases long before the first patient is ever treated, which makes startup costs prohibitive. Cash and controlled substances onsite means no expenses can be spared when it comes to building security, either.

TL;DR: American physicians can choose to treat depression with ketamine, but at least today, they are making a choice to live on the edge medicolegally, and that's not a set of challenges many in a profession that selects for risk-aversion have a taste for.

That's sad. More and more I find myself using illegal drugs not because its fun but because getting the legal help I need is too much hassle. I wonder how much of this is big pharma preserving the cash cow that are SSRIs. I mean they seem to be written for everything these days. They tried to give my dad Paxil for back pain :/.

 

[MyDoorsAreOpen]

That cash cow was slaughtered and eaten a long time ago, cj. SSRIs are all generic now, and pretty cheap.

The reason ketamine meets so much resistance is because psychosis (what the medical industry calls / considers its subjective effect set) is an absolutely unacceptable side effect to anyone concerned about risk management.

The only way I could see any prep of ketamine getting FDA approved for patient self-dosing for depression, is if it were combined with another drug that blocks ketamine's subjective effect at certain concentrations, and the prep were formulated with a ratio such that this threshold concentration of the second drug would align with the lowest dose of ketamine capable of producing a dissociated state in >90% of people. Piracetam would actually be a good choice for this second drug; I can attest it weakens ketamine's funner effects considerably, is only active in gram level dosages, and it presence in the combo could easily be spun by the marketing team as being there for "brain repair", rather than as an abuse deterrent.

 

[falsifiedhypothesi]

Yeah ok SSRI's are cheap, so what? His point was that they are overprescribed for pretty much anything. So possible psychosis is unacceptable but suicidal thoughts and behavior caused by SSRI's are? SSRI "discontinuation syndrome" aka withdrawals are acceptable even if the drug didn't help the patient? Ketamine wouldn't have the problem of withdrawal when taken in the spaced out dosages required to treat depression.

 

[Cj1231990]

My cats not sure if he's happy with his ketamine . Says it's not the same as it was before ,

 

[Cj1231990]

I'm not advocating anything I'm only here but I have seen people who are truly unwell with depression in a hospital setting (they come in stay in bed smoke don't speak to Anyway truly unwell folks ,women not said a word for days, gets given a pregablin tablet wrote up by head doctor and viola . Magic nothing was working but that brought her round. Did it last I don't know .

What I do know is ketamine can be useful in depression but I believe also with bad habits and addiction,

It maybe far more complex but basically i think it can bring round change via what I believe is a near death experience. How long does this last I don't know.

addiction can cause depression it's not what causes it but I think there's a link there about change in the brain.

 

[Cj1231990]

I wanted to add that Different things work for different people. The point is ketamine isn't prescribed for depression atm and it's not going to be anytime soon. Best bet is get help for depression by talking to people and if your happy to try these sort of things to help your symptoms do it as safely as possible.

All about the harm reduction.

Not sure about any other antidepressants that could be as safe as what ketamine could potentially be if it where to be understood better and dosages done to the specific individual.

 

[LucidSDreamr]

Depression isn't quite on the same level of sympathy as physical pain (which is also under assault). We allow opioids to exist because pain is bad enough and widespread enough to make opioids allowable. Depression is not as widespread, therefore I think the battle to have an "addictive" drug like ketamine become a mainstream treatment is an uphill one.

 

[falsifiedhypothesi]

^Depression might not be as widespread as physical pain but is certainly very prevalent, by no means negligible.

 

[cj]

^Depression might not be as widespread as physical pain but is certainly very prevalent, by no means negligible.

That's not true. D r pressing is the number one cause for people being on disability in the US. 1 in 3 people will experience a mental health disorder in just 1 year. That means depression may be the most common phychiatric diagnosis.

 

[Jabberwocky]

That cash cow was slaughtered and eaten a long time ago, cj. SSRIs are all generic now, and pretty cheap.

The reason ketamine meets so much resistance is because psychosis (what the medical industry calls / considers its subjective effect set) is an absolutely unacceptable side effect to anyone concerned about risk management.

The only way I could see any prep of ketamine getting FDA approved for patient self-dosing for depression, is if it were combined with another drug that blocks ketamine's subjective effect at certain concentrations, and the prep were formulated with a ratio such that this threshold concentration of the second drug would align with the lowest dose of ketamine capable of producing a dissociated state in >90% of people. Piracetam would actually be a good choice for this second drug; I can attest it weakens ketamine's funner effects considerably, is only active in gram level dosages, and it presence in the combo could easily be spun by the marketing team as being there for "brain repair", rather than as an abuse deterrent.

Shit, I'd just be happy to see ketamine therapy being more accessible and covered by insurance, I could care less if I have to go to a doctor's office to spend the day getting it done under medical supervision.

I've been looking into this treatment option myself. Short of getting into a study or paying a bunch of money, it seems like it is pretty difficult to get. I am looking into whether insurance will cover it, but frankly I'm not too enthusiastic.

I never found piracetam to dampen the effects of drugs like ketamine or DXM myself, although it didn't seem to hurt either (if any there were simply marginally fewer side effects I'd notice, though this applies more to DXM than ketamine). Or perhaps this is what you were referring to?

 

[falsifiedhypothesi]

That's not true. D r pressing is the number one cause for people being on disability in the US. 1 in 3 people will experience a mental health disorder in just 1 year. That means depression may be the most common phychiatric diagnosis.

I can't speak for the statistic but I generally agree. Although 1 in 3 will have a mental disorder it doesn't mean it's depression although I'm sure it's the plurality, if not very close.

 

[alpha_centauri]

Yeah ok SSRI's are cheap, so what? His point was that they are overprescribed for pretty much anything. So possible psychosis is unacceptable but suicidal thoughts and behavior caused by SSRI's are? SSRI "discontinuation syndrome" aka withdrawals are acceptable even if the drug didn't help the patient? Ketamine wouldn't have the problem of withdrawal when taken in the spaced out dosages required to treat depression.

Because Ketamine is garbage that's why. A lot of people do not have good reactions to it or while on it, and this includes people have have low amounts of it for anesthesia.

SSRIs have been studied for decades, have no major horrible or even dangerous side effects like Ketamine or the old TCAs do, and are effective at treating depression, anxiety, OCD, and other mental illnesses when used alone or with therapy.

The majority of people who take SSRIs do not have suicidal thoughts or behaviours, do not have any sort of actual 'withdrawals' as you do from benzos, opiates, or alcohol, and SSRIs are not addictive like Ketamine is.

 

[Crankinit]

The reason ketamine meets so much resistance is because psychosis (what the medical industry calls / considers its subjective effect set) is an absolutely unacceptable side effect to anyone concerned about risk management.

I've seen this before and I have to admit I don't understand it at all.

I've fortunately never experienced psychosis (except for the mild "amphetamine induced paranoia" variety, if you want to count that). But I have seen multiple people in active psychotic states, known people who suffer from psychotic disorders and read accounts of psychotic breaks, and it all seemed about as far from the experience ketamine induces as you can get while still being in the same general field of "altered states of consciousness."

Likewise, my knowledge of neurochemistry is fairly amateur, but my understanding is that the two phenomenon (ketamine intoxication and psychosis) aren't even related to the same sets of neurotransmitters (psychosis seems at least related to excessive dopamine production, while ketamine is an NMDA antagonist).

So what's the deal?

 

[kingshawaiian]

The reason ketamine meets so much resistance is because psychosis (what the medical industry calls / considers its subjective effect set) is an absolutely unacceptable side effect to anyone concerned about risk management.

I can firsthand say IME this can happen- was given ketamine as part of an anesthetic protocol several years ago and straight up attacked a nurse for no reason whatsoever. However I do not believe this to be the norm, I am likely one of a very small percentage of the population who reacts in this way to administration of this drug.