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Oral ketamine for treatment-resistant depression

(I should have made it more clear in my earlier post that I am talking only about treatment resistant depression: depression that has persisted for a very long time and has not responded to other treatments.)

I got my info from a combination of sources, motivated by my personal experience. After 30+ years of extreme depression, I had lost nearly everything important to me and was virtually disabled. I volunteered for a ketamine study at the National Institutes of Health, and a single infusion completely relieved all of my symptoms within a few hours. It is the most important thing that has ever happened to me, so for the past year I've been studying the research, talking to doctors and scientists, getting additional treatment, and comparing notes with other people like me. My comments above are based on face-to-face conversations at NIH with some of the leading ketamine researchers (Dr. Zarate, et al); reading every word of every published ketamine research paper I have found; attending conferences and watching webinars of all the major researchers (Drs. Murrough, Chrystal, Duman, Sanacora, et al); talking to experienced ketamine doctors (Dr. Brooks, Dr. Sajben, et al) who have decades of experience with the drug itself and over the past few years have treated hundreds of depression patients with this new protocol; carefully monitoring my own personal response to various ketamine doses and ROAs; and constant cross-talk with many other people like me who have actual ketamine experience (medical treatment, not recreational use).

So that's why I think what I think about ROA. I've absorbed a lot of info, but do not feel comfortable attempting to explain the details about WHY the antidepressant effect are so dependent on ROA and rate. Some of the deeper details are beyond me, anyway, because they require an understanding of neurology, neuropharmacology, and other knowledge I lack. My personal experience certainly shapes my view, but I have confidence in my assertion about ROA+rate because I've also developed relationships with expert doctors and expert patients and I've grown to trust them. Most of that trust comes from many long talks with practicing doctors -- not researchers -- who are using ketamine to heal real live patients, including a veteran anesthesiologist with 40 years of ketamine experience. And many more, even longer talks with people like me who were suffering acute misery, felt dramatic relief from a single infusion in a clinical trial, and have since received ongoing clinical treatment via a variety of ROAs. Some of us have achieved partial relief from intranasal, but we all agree the relief from IV was vastly superior.

In discussing ROA with the people above, many of them have pointed out that ketamine has been around for 50+ years and is very widely used, and if any old ROA worked on depression it would have been noticed decades earlier. In the 90s some doctors began using it off-label to treat CRPS/RPS and other extreme physical pain ailments. Through trial and error, they found that sub anesthetic IV doses really helped. Those patients often suffer from depression, too, and doctors noticed that some of them felt happier when their pain was relieved. It's not surprising they were depressed given their extreme pain, and it's not surprising they felt happier afterward. But someone eventually made the leap to ask if they were happier solely due to their pain relief, or if maybe the ketamine helped the depression independently. The earliest scholarly studies were done at Yale circa 2000.

Regarding your doctor, I agree with Foreigner. She sounds very under-informed to me. The idea of dosing orally for depression and her comment about it "building up" in your system make me really question her level of knowledge. I commend her for being willing to consider it for off-label depression use, but compared to all the people I listed above, she is far off in left field. I'd hate to see either of you give up on ketamine treatment or discourage others from considering it, if you have a non-response to oral. Perhaps you could encourage her to speak to one of the experienced ketamine doctors listed on the Ketamine Advocacy Network website?

In case it's useful, here's a list of doctors who offer ketamine treatment for pain: http://neurotalk.psychcentral.com/thread148368.html. I'm sure some of them are also offering the depression IV protocol, or would be willing to.

Regarding the cost of infusion, there is no consistency in pricing yet. Keep in mind that a doctor who offers IV ketamine has to cover some pretty high costs. I did research to see what it would cost to open a "ketamine clinic" in my state and was astonished at the costs involved. If you are a doctor who wants to use a dissociative anesthetic for an off-label use on a severe mental illness with a high suicide rate, be prepared to pay malpractice premiums in the hundreds of thousands of dollars per year. Your office will need to have at least one dedicated treatment room, outfitted with specialized equipment usually found only in large facilities (infusion pumps, treatment chairs, monitoring equipment, etc.), nursing and admin support (maybe), etc. I'm not going to defend or condemn anyone's pricing here, but I can say that the $900 you were quoted is at the extreme top end of the scale. You might find someone cheaper, but if you have to travel to see them and pay for a hotel, the overall cost might be no better. Arctica, feel free to PM me if you want to discuss details about my infusion doctor.
 
Don't want to derail the thread but my girlfriend is going to start ketamine infusion next month for pain resulting from a severe auto accident. 200 mgs infused /4hrs. She is currently using a lumbar sympathetic block with minimal benefit and that , she says, is diminishjng. She is depressed and her doctor seems to think the ket will be an effective treatment.
Her insurance at first said the ketamine infusion was experimental and would pay only 10%. They have come around to doing a 70 - 30 split. Her cost will be *84.00 per infusion X 12 weeks.
 
Thanks for that info, Bukwheat. So her doctor charges $280 total per infusion? I have suspected that the lowest cost for depression IV will eventually come from pain management doctors who have experience treating CRPS/RSD with ketamine and whose practices are already set up for IV procedures. Your info seems to support that. The doctors I am tracking are mostly focused on depression, and don't have established pain mgmt practices. Among them, $300 is the lowest per-infusion cost I found. Keep in mind my info is incomplete. Are you able to share the name of her doctor?

In general, it seems doctors who currently offer ketamine IV treatment for depression fall into 3 categories:

1. pain management
These folks are already experienced with ketamine, and with IV protocols. Depression IV treatment is a natural extension of what they already do, and they have the infrastructure to support it without additional investment.

2. anesthesiologists
They have, by far, the most hands-on experience with ketamine, because it has been FDA-approved for anesthetic use for over 50 years, and it is very widely used for that purpose.

3. psychiatrists
Many of them have not physically touched a patient or performed a procedure since med school, and they might contract with someone else to actually perform the infusion (like an internist or a chemo clinic). The psychiatrist would place the order for the infusion and you would be under his/her care, but the hands-on work would be done by someone else, maybe in a different location.

If you see a pain mgmt doc or anesthesiologist, don't expect to receive psychiatric care from them. If you have a miraculous response to ketamine, they are not trained to help you navigate the profound sense of relief you might feel. If you are a non-responder, they are not trained to help you cope with severe disappointment.

Keep in mind that psychiatrists will be financially impacted if ketamine becomes widely adopted and their most difficult treatment-resistant depression patients suddenly experience rapid relief. I have interviewed a lot of psychiatrists about ketamine over the past year, many of whom were completely in the dark until I reached out to them. I try to be sensitive to the fact that ketamine represents a dramatic change from everything they have practiced for decades regarding depression, and might require them to weigh patient suffering vs. their own interests. Most people would be apprehensive about something that challenges the foundation of their training, beliefs, professional success, etc. They're only human.
 
She saw him at Boone Hospital in Columbia MO. I don't know his name but I won't leave you hanging for long.
 
Ketadvocate she saw Dr. Patel. He has a partner, Dr. Nobel. Best of luck in weaving you way through our healthcare system.
 
Foreigner said:
In terms of harm reduction, it's probably best to do this under the guidance of a doctor, but to be 100% honest, your doctor doesn't sound like he knows what he's talking about. Some of his comments that you've shared here are totally off base, from the part about aterial delivery, to olney's lesions, etc.
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Thanks for all the posts, guys. I'll post more later. Just to be clear, there are actually 2 doctors in my story, not one. The woman is my current psychiatrist, the man is the doctor who has a local clinic charging $900 for infusions. I had a single consult with the infusion doc, and see the woman shrink weekly. I think there's agreement all around (including the opinion of the woman psychiatrist) that the infusion clinic doctor either doesn't know what he's talking about or is hyping the hell out of it trying to make a buck. Did I mention he reported a 95% success rate? The woman psychiatrist doesn't know very much about ketamine treatment, but readily admits this and goes back to the primary sources and current literature to answer her questions. She is the one who gave me the prescription for the lozenges after agreeing that the clinic costs were outrageous. We are trying to put our heads together to come up with a more cost-effective solution.
 
dopamimetic said:
Really ... may I ask what country you are living in? Can't imagine even a pharmacy handing out Ketamine, I guess if it were available, I could get it scripted too (but was hard enough to find a doc like that.. we have one of the most expensive health care systems in the world, but concerning psychoactives they are very restrictive like in many places). Intranasal Ket on Prescription? Wow..
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I'm in the United States, where doctors are allowed to prescribe any FDA-approved drug for any use they see fit (called off-label usage). Ketamine is an FDA-approved drug, and has been for a long time. In fact, it's even on the World Health Organization's short list of essential drugs that every country should have available. To the best of my knowledge, intranasal ketamine is not available anywhere (although J&J apparently has it in clinical trials now), but a compounding pharmacy could probably make some up, depending on patent laws. It's kind of like Botox, which was FDA-approved for the treatment of eye movement disorders, but plastic surgeons don't get in trouble if they use it to treat wrinkles instead.
 
Until yesterday, I had been taking 200 mg at night (4 x 50 mg troches) via a buccal/oral route. I had only been taking them at night over a period of a couple hours, and found that I got an immediate antidepressant effect maybe in the first half hour, but the initial effect wears off quickly and leaves you wanting to re-dose. I found that the residual anti-depressant effects lasted into the next morning and afternoon. I do feel a little intoxicated on it, so I've not been taking it during the day when I have work, etc. I do think I am becoming somewhat tolerant to it taking it daily.

Within a week, my depression had lifted to the point where I felt like I could listen to music again(!), at least while I was still noticing the primary effects. Music has felt too emotionally charged and painful, even for songs that don't really have strong associations for me.

In an effort to keep the initial effects longer, I started taking "Ketamine SR" 200 mg as a single dose last night. It's a sustained release formulation in capsules made by a local compounding pharmacy. I was curious, so I broke a capsule open to see what was inside. It was a lot of fluffy white powder (no little balls) that looked like significantly more than 50 mg to me, eyeballing it. I think it's some sort of cellulose polymer powder that turns into a gel on contact with water. I didn't get any information about the expected half-life, etc. Does anyone have any information on this kind of SR formulation that could hazard a guess? I didn't really get a buzz last night when I took it, so I'm not sure if this isn't an effective ROA or if the onset was gradual enough that I didn't notice. I will give this a shot for another couple days to see how it goes. I don't think I would have a problem taking the SR version during the work day. The pharmacy is also working on an intranasal version to try, but I don't have it in hand yet.

I had a QEEG done recently as part of a neurofeedback workup, and some of my beta activity was anywhere from 2.5 to 6(!) standard deviations above the mean, which apparently translates into extreme anxiety for most. I've had anxiety symptoms since I was very young (maybe 3), but feel like it's relatively well-controlled with benzos as needed compared to the depression, which is debilitating. I am not sure if the depression is simply a result of my brain burning out after expending so much energy on PTSD-like levels of anxiety, or something different. I have been on antidepressants for most of the last 20 years after starting Prozac for depressive symptoms in 8th grade or so. I also have significant theta-beta reversal, which is apparently related to genetically inherited depression and bipolar disorder (although I'm pretty sure I have unipolar depression).

Ketamine's initial buzz feels like an emotional burn salve to me, not so different from the effect of other dissociative anesthetics, like nitrous. I'm wondering if the antidepressant effect is related to quenching the ridiculous amount of excitatory neurotransmitters I must have circulating, at least for a few hours. It's unclear to me if the residual effect is related to my brain having a few hours each day to expend less energy and heal and then coasting on the results for the next day (or 2 weeks for those on an infusion schedule), or if the residual non-buzz effect is important as well. Does anyone else have any theories regarding the antidepressant mechanism of action here?
 
For the record, I also have the following genetic variants, which might have resulted in the depressive symptoms and/or my poor medication response. However, I gave Deplin (L-methylfolate) a trial for about 6 months earlier this year, and eventually discontinued it because it didn't seem to make a difference. Previously, I've tried many other antidepressants and other psych drugs, often in combinations and at heroic dosages, including SSRIs (Lexapro, Zoloft, Prozac, Paxil), SNRIs (Cymbalta, Wellbutrin, Effexor), mood stabilizers (Lamictal, lithium), TCAs (Elavil, Tofranil), atypical antipsychotics (Seroquel, Abilify, Risperdal), and others (Wellbutrin, Viibryd, Buspar, liothyronine, levothyroxine, trazodone) with poor or no response. I haven't tried any MAOIs. Of the above, Wellbutrin was probably the drug that I responded to/tolerated best.

dtPKm.png
 
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Update: The "sustained release" ketamine capsules were a no-go. They were 50 mg caps mixed with (I think) methylcellulose polymer powder. I was taking 4 at bedtime as a single oral dose. I was getting very nauseated around 6:30 in the morning, and vomiting. I am not sure what was going on, but my suspicion is that I was allergic to the Barbie-pink coloring of the gelatin capsule (I tried uncapping the pills, but couldn't deal with swallowing slime balls on a queasy stomach). Alternately, maybe a 200 mg oral dose on an empty stomach was too much compared to the same dose over multiple hours by a buccal/oral ROA. Even on a 200 mg single dose of the extended release, I never felt any sort of "buzz," which I notice on a 50 mg buccal dose.

I've switched back to 200 mg as 4 x 50 mg troches spread over a few hours in the evening, and am feeling much better.

The compounding pharm floated the idea of suppositories, a vaginal cream (no thanks and no thanks), and subcutaneous injections. What's the difference between IM and SQ ketamine? My shrink would be on board with an SQ ROA.

ETA: I had a maculopapular rash/nausea/vomiting on Viibryd, which is apparently FD&C Red #40
 
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You may have already read this, but here's a link that suggests the appropriate oral dose for depression is 0.5 mg/kg body weight. Of course, this is only based on two single cases. http://www.mayo.edu/research/clinical-trials/CTS-00103950

By the way, I'm a writer who has a published article asking "Is ketamine the next Prozac?" I did not write that, my editor did. Thoroughly embarassing. Editors have a way of mucking things up that can be even worse than writers. That's saying a lot
 
I started taking Prozac at 13 when Prozac was the new Prozac, and still under patent. But ketamine knocks Prozac into next week. If things even out, I might eventually be old enough to tell Cuckoo's Nest stories about how back in the day when people were acutely suicidal or nearly completed suicide, they would lock you up on a psych ward for 72 hours and check on you every 5 to 15 minutes to make sure you weren't harming yourself, and then they'd kick you to the curb ("sorry, your insurance won't allow you to stay longer") with a brand new SSRI prescription that wasn't going to kick in (if it worked at all) for another 3-4 WEEKS. Pretty grim.

I started around 0.3 mg/kg (I was taking these at home, basically unsupervised, so we wanted to aim low). I'm now at about 2.4 mg/kg, which is still a lot lower than some of the oral dosages in the ketamine pain studies (I think). I'm still struggling with dosing, and it's definitely a work in progress. I should have an intranasal formulation in hand in the next couple days, which I'm greatly looking forward to, as it doesn't have the norketamine conversion issues of oral administration, is probably easier on your bladder, and will probably cut the amount I'll need significantly (mg for mg), which will hopefully reduce side effects.
 
Neilwagner1 said:
You may have already read this, but here's a link that suggests the appropriate oral dose for depression is 0.5 mg/kg body weight. Of course, this is only based on two single cases. http://www.mayo.edu/research/clinical-trials/CTS-00103950

By the way, I'm a writer who has a published article asking "Is ketamine the next Prozac?" I did not write that, my editor did. Thoroughly embarassing. Editors have a way of mucking things up that can be even worse than writers. That's saying a lot
Click to expand...

All the same, if you have a link to share, I'd like to read it.
 
My most recent game plan had been to try to switch to SQ injections, but there is apparently a lot of red tape associated with compounding ketamine injections as it's available commercially. The biochemist at the compounding pharmacy told my psychiatrist that IV/SQ routes are harder on your urinary tract than other ROAs, but did not elaborate which ROAs are least damaging to your urinary tract. Is there any truth to this? I've asked for a clarification, but was interested in what you guys thought.

I know that in order to get into your urinary tract, the ketamine must get into your bloodstream first and then get filtered by your kidneys, so I hadn't thought that one ROA would be that much safer than another, simply because it's all coming from the same location, your bloodstream. I would have guessed that an oral route would be hardest on your kidneys (along with other ROAs that have significant first pass metabolism to norketamine) because you are presumably taking a larger dose to compensate for losing some of the ketamine to norketamine. Why would IV/SQ use be more likely to cause urinary tract complications? Thanks.
 
SQ injection fail because....it's a long story. But, Christmas came early this year and I now have an intranasal formulation to try in a metered spray form factor, 20 mg/spray. My shrink and I are in kind of uncharted territory here, so I'm starting low and going slow, but I'm interested to see if I can tell a difference in the antidepressant effect from minimal first pass metabolism versus oral, and will report back.
 
20 mg / spray seems like a bit high of a dose, unless you have opulent prior experience with ketamine, and thus acquired tolerance; I found 10-12 mg / 1-1.3 times / hour ideal for myself (snorting 'bumps'...that nasal spray might be absorbed more rapidly). Remember that the therapeutic IV infusions indicated for depression are 'pushed' over a protracted period. And if you have acquired tolerance to dissociatives, there's learned speculation that suggests that nmda antagonists won't be particularly effective anti-depressants in such cases (but that doesn't seem like the situation you're in, for the most part). Also, take this with a grain of salt: I'm going off of scattered anecdotes, mainly, and my depression was not particularly severe.

ebola
 
When injected it crosses the blood/brain barrier alot faster.....It is used for pain more , but I believe pain and depression are basically the same beast..the lozemges will work, but not as quickly..I beloeve that depression is caused by a lack of natural endorphins........I have been battling depression and pain for most of my life, so I know ketamine will help ur depression as well as ur pain....so hang in there friend...keepp up the good fight....
 
My depression has beem ruthless, and the pain even worse....I drew the genetic short straw, when it came to natural endogenous opiods, endorphins, enkephalins, sorry for the spelling...the drs are really startimg to believe that certain depressions, should be treated with opiods...of course the drug companies got it backwards, ie cymnalta for pain and depression....no opioid. ? What can we do.
 
Not sure if it was opulent or not, but I'm sure I'm developing a tolerance with daily use. A single 20 mg spray seems to be a threshold/light dose for me. 40 mg (20 in each nostril) is a noticeable effect, not too much different from a 50 mg lozenge? I had been expecting a larger reduction in dosage intranasally, but I'm still playing with it.

My Rx says do not exceed 10 sprays/day, but honestly, that seems like a lot. I think (hope) I will be using less than that.

ebola? said:
20 mg / spray seems like a bit high of a dose, unless you have opulent prior experience with ketamine, and thus acquired tolerance; I found 10-12 mg / 1-1.3 times / hour ideal for myself (snorting 'bumps'...that nasal spray might be absorbed more rapidly). Remember that the therapeutic IV infusions indicated for depression are 'pushed' over a protracted period. And if you have acquired tolerance to dissociatives, there's learned speculation that suggests that nmda antagonists won't be particularly effective anti-depressants in such cases (but that doesn't seem like the situation you're in, for the most part). Also, take this with a grain of salt: I'm going off of scattered anecdotes, mainly, and my depression was not particularly severe.

ebola
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