Oral ketamine for treatment-resistant depression

[arctica]

With the specter of ECT looming on the horizon, I'm looking into ketamine for treatment-resistant depression. I met with a doctor who was willing to give me an i.v. infusion every 2 weeks for 5 or 6 sessions at ~$900 per infusion, which is beyond my means. When I asked why he didn't use a less expensive ROA, he said that someone he works with had a patent for intranasal ketamine for treatment-resistant depression; therefore, he couldn't use that ROA. He seemed to think that oral ketamine wouldn't have antidepressant properties because it needed to "get into the arterial blood" which sounds a little bogus to me, as the injection is intravenous, for starters.

My shrink is not averse to giving it a shot, but doesn't have the necessary facilities, equipment, or personnel to do infusions. $30 later, a compounding pharmacy has made up some 25 mg ketamine lozenges which should be delivered to my shrink's office this week. It seems that most oral dosing of ketamine in the literature has to do with pain management rather than treatment-resistant depression. Does anyone have any advice on protocols? Can anyone think of a reason why an intranasal or i.v. ROA would be required to achieve antidepressant effects, or was this guy just trying to make a buck?

Thanks in advance.

 

[sekio]

Oral ketamine has very low bioavailibility, that's why. IM/IV are the "gold standard" - fastest onset of effects, highest bioavailibility.

The experimental protocol I saw for depression was 0.25 mg/kg S-ketamine, or 0.5mg/kg racemic (so about 30mg of the racemate), intravenously over ~40 minutes, six infusions over four weeks. So to mimic that, dissolve either one or two lozenges in your mouth slowly, once every 3-5 days. Buccal absorbtion of ketamine should work pretty good, just be aware it will make your mouth numb.

 

[cj]

With the specter of ECT looming on the horizon, I'm looking into ketamine for treatment-resistant depression. I met with a doctor who was willing to give me an i.v. infusion every 2 weeks for 5 or 6 sessions at ~$900 per infusion, which is beyond my means. When I asked why he didn't use a less expensive ROA, he said that someone he works with had a patent for intranasal ketamine for treatment-resistant depression; therefore, he couldn't use that ROA. He seemed to think that oral ketamine wouldn't have antidepressant properties because it needed to "get into the arterial blood" which sounds a little bogus to me, as the injection is intravenous, for starters.

My shrink is not averse to giving it a shot, but doesn't have the necessary facilities, equipment, or personnel to do infusions. $30 later, a compounding pharmacy has made up some 25 mg ketamine lozenges which should be delivered to my shrink's office this week. It seems that most oral dosing of ketamine in the literature has to do with pain management rather than treatment-resistant depression. Does anyone have any advice on protocols? Can anyone think of a reason why an intranasal or i.v. ROA would be required to achieve antidepressant effects, or was this guy just trying to make a buck?

Thanks in advance.

You have amazing doctors. don't take it for granted.

 

[Toz]

Wait, you can put patents on different ROAs with meds? That's just silly to be honest. Or was it the actual treatment that was patented, as in "intranasal ketamine for treatment resistant depression" only, so if I wanted to I could put my own patent on intranasal ketamine for pain only?

And yea you have an amazing but greedy doctor

What about rectal ketamine? Why is it so unheard of?

 

[ebola?]

localized numbing is not something you want with drugs administered rectally. Other than that, it should work okay. I'd just be wary of anal leakage the first time that you do it. Also, I don't know how easily these lozenges would redissolve in small amounts of water.

ebola

 

[arctica]

You have amazing doctors. don't take it for granted.

Yes, I agree that my current shrink is pretty amazing. I've had to kiss a lot of frogs on my way to finding a prince, though Just to clarify, I had a consult with a doctor who did the i.v. infusions who is part of a private company that does alternative therapies for psychiatric disorders, no insurance accepted, naturally. After hearing the price tag for the i.v. infusions, my regular shrink and I are going to give it a whirl.

It sounded like he had patented the use of intranasal ketamine for the use of treatment-resistant depression. The whole thing seems wildly unethical to me, as ketamine has the potential to save a lot of lives if it lives up to the hype. If it can be administered quickly to those who show up at the ER feeling suicidal and provide immediate relief, as opposed to spending a couple days on a locked ward (until their insurance refuses to pay) and then sent home with a script for an antidepressant that won't kick in for another couple weeks, if it works at all. And as it currently stands, ket is cheap enough to be used in veterinary medicine.

Most of the literature I've seen (and the experiences of the infusion doc) seem to suggest that people get 5-6 treatments and then they're OK. Has anyone heard of ketamine maintenance therapy? It's not something I really want to be taking long-term. I asked the infusion doc about the risk of Olney's lesions, and he said that effect was mostly related to drugs used to cut ketamine, but that medical ket was safe. My bullshit detector started going off again. Is there anything to support this?

 

[arctica]

Oral ketamine has very low bioavailibility, that's why. IM/IV are the "gold standard" - fastest onset of effects, highest bioavailibility.

The experimental protocol I saw for depression was 0.25 mg/kg S-ketamine, or 0.5mg/kg racemic (so about 30mg of the racemate), intravenously over ~40 minutes, six infusions over four weeks. So to mimic that, dissolve either one or two lozenges in your mouth slowly, once every 3-5 days. Buccal absorbtion of ketamine should work pretty good, just be aware it will make your mouth numb.

Can the low oral bioavailability be circumvented by increasing the dose? It sounds like the neurological effects should be similar regardless of ROA, right?

 

[ebola?]

I asked the infusion doc about the risk of Olney's lesions, and he said that effect was mostly related to drugs used to cut ketamine, but that medical ket was safe. My bullshit detector started going off again. Is there anything to support this?

Nope, he's full of shit. However, it's unclear that these lesions occur at all with sub-anaesthetic dosing; it's pretty unlikely that they do, even with chronic use.

ebola

 

[sekio]

It is unclear that Olney's lesions even occur in humans or higher primates.

Can the low oral bioavailability be circumvented by increasing the dose? It sounds like the neurological effects should be similar regardless of ROA, right?

That's the idea, yes.

 

[endotropic]

Can the low oral bioavailability be circumvented by increasing the dose? It sounds like the neurological effects should be similar regardless of ROA, right?

This is something a physician would probably want to avoid though. Some quirk in your metabolism could cause a much higher % of the ketamine reaching your system than in the average person. Dose can be titrated up slowly to avoid that risk, but then you're waiting longer before you can take the full dose.

 

[ketadvocate]

The route and method of administration are critical to achieving the antidepressant effect. The researchers and the doctors who are using it clinically all use the same protocol -- .5mg/kg IV over 40 minutes -- because that's what works. The therapeutic benefit depends on a precise dose delivered at a precise rate, without first-pass metabolism. Too much or too little ketamine and the effect will be greatly diminished. Likewise if it is delivered too fast. Likewise if the liver has a chance to convert it into the metabolyte norketamine, which is useless for depression. IV infusion is the only way to achieve 100% bioavailability, with a very precise dose, with very precise delivery rate. A detailed post comparing the various ROAs will appear on the Ketamine Advocacy Network website within the next few days, www.ketaminenetwork.org.

Oral administration will provide the least benefit -- virtually zero -- because a large % of the drug will be metabolized, and the portion that does reach the brain will do so at a rate vastly different from the therapeutic rate.

Arctica, if you take the lozenges and get no benefit, please don't give up on ketamine. I have been successfully treated with ketamine for depression, and have several friends in the same boat. Between us we have tried IV infusion, intramuscular injection, intranasal, rectal, and sublingual. We've all found the same thing as the research papers indicate: IV infusion provides a vastly superior therapeutic effect compared to other methods Most methods besides IV provide far less relief, if they provide any relief at all. There is a list of US doctors who offer ketamine treatment on the Ketamine Advocacy Network website. The cheapest one I know of is $300 per infusion. This is a brand new procedure for all doctors and there is wide variation in pricing. Perhaps you can find someone near you who is more affordable than the price you were quoted.

 

[ebola?]

The route and method of administration are critical to achieving the antidepressant effect. The researchers and the doctors who are using it clinically all use the same protocol -- .5mg/kg IV over 40 minutes -- because that's what works.

Actually, I've seen little evidence underlying the dosage-schedules employed other than presupposition by researchers.

Oral administration will provide the least benefit -- virtually zero -- because a large % of the drug will be metabolized, and the portion that does reach the brain will do so at a rate vastly different from the therapeutic rate.

But couldn't oral dosing mimic gradual infusion in that way? Oral dosing is like a natural time-release plus first-pass metabolism.

ebola

 

[arctica]

It seems that most of the literature on ketamine for depression uses an IV ROA, while most of the ketamine pain studies are using an oral/buccal ROA. In a research setting, an IV ROA makes a lot of sense for all the reasons you mentioned, but I'm not sure it's worth the price markup for randoms like me who aren't getting free medication (or placebo) from a drug trial. I know that oral ketamine in glucose syrup is given to children for premedication prior to anesthesia to help with anesthesia induction and to lessen separation anxiety.

My doc is suggesting that I start tomorrow with a single 25 mg lozenge, so oral/buccal administration. She is suggesting that I take it daily, however, rather than one dose every two weeks or so to give it a chance to "build up" in my system. One of her patients is getting infusion therapy, and she is trying to avoid the gradual tapering of the antidepressant effect seen in her other patient. Do you guys have any opinions about daily ket versus every 2 weeks?

Out of curiosity, how much are you paying for your infusions? I asked the infusion doc here if there was a less expensive clinic, and he said there was a place in New York that was doing it less expensively, but they don't offer anything comprehensive, just straightforward get your infusion and leave. That being said, an IV ROA will always be more expensive because of the overhead of the equipment and personnel.

 

[arctica]

Also, some new articles, freely available:

Ketamine for Treatment-Resistant Depression: Ready or Not for Clinical Use?
Rush AJ.
Am J Psychiatry. 2013 Aug 28. doi: 10.1176/appi.ajp.2013.13081034. [Epub ahead of print] No abstract available.
PMID: 23982324
http://ajp.psychiatryonline.org/data/Journals/AJP/0/appi.ajp.2013.13081034.pdf

Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial.
Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CM, Perez AM, Iqbal S, Pillemer S, Foulkes A, Shah A, Charney DS, Mathew SJ.
Am J Psychiatry. 2013 Aug 28. doi: 10.1176/appi.ajp.2013.13030392. [Epub ahead of print]
PMID: 23982301
http://neuroscience.md/wp-content/uploads/2013/08/Antidepressant-Efficacy-of-Ketamine-in-Treatment-Resistant-Major-Depression-A-Two-Site-Randomized-Controlled-Trial-James-W.-Murrough.pdf

From Club to Clinic: Physicians Push Off-Label Ketamine as Rapid Depression Treatment, Part 1

 

[arctica]

This is really the crux of what I'm trying to understand here. Ketadvocate, where did you get this information from? I understand that the bioavailability is diminished with oral administration, but ketamine is a cheap drug (cheap enough to use in veterinary medicine), and I can buy a mountain of lozenges for the same price as a single infusion. I'm not worried about "wasting" a few extra mgs of ketamine that I could have had by a different ROA, and I'm not that concerned about additional side effects caused by a slightly larger oral dose, at least at the dosages I would be taking. I don't understand why the dosage is so critical to the antidepressant effect. Can anyone help me out here?

The route and method of administration are critical to achieving the antidepressant effect. The researchers and the doctors who are using it clinically all use the same protocol -- .5mg/kg IV over 40 minutes -- because that's what works. The therapeutic benefit depends on a precise dose delivered at a precise rate, without first-pass metabolism. Too much or too little ketamine and the effect will be greatly diminished. Likewise if it is delivered too fast. Likewise if the liver has a chance to convert it into the metabolyte norketamine, which is useless for depression. IV infusion is the only way to achieve 100% bioavailability, with a very precise dose, with very precise delivery rate. A detailed post comparing the various ROAs will appear on the Ketamine Advocacy Network website within the next few days, www.ketaminenetwork.org.

Oral administration will provide the least benefit -- virtually zero -- because a large % of the drug will be metabolized, and the portion that does reach the brain will do so at a rate vastly different from the therapeutic rate.

 

[ebola?]

i found nasal use fine as an anti-depressant.

 

[arctica]

i found nasal use fine as an anti-depressant.

What kind of dosages were you using, ebola? How long did the anti-depressant effect last for you? Or was this in a more recreational capacity?

 

[ebola?]

I used a procedure developed by Jamshyd, discovered through limited trial and error, so I don't know if it is ideal. I tried to maintain threshold dosing for 2-4 days. This began at ~10 mg per hour, gradually moving to 12. You can kind of feel out what is the appropriate level for you. Aim for ever so slightly noticeable effects, with the impairment of maybe 1 beer. As I accrued tolerance during the procedure, the effects faded (declining from a threshold feeling to unnoticeable). Once the K stopped doing much, I stopped dosing. I felt so much better, simply not depressed and with a natural feeling of happiness for 2-3 weeks following (I've done this a couple of times). The tenuously supported idea is to induce downstream changes, first involving upregulation of glutaminergic AMPA receptors, then inducing a cascade that increases neuroplasticity in the hippocampus and PFC and according synthesis of BDNF. Because the target is to increase AMPAnergic activity, the ketamine is dosed chronically, extending over a much longer period than the procedures used in clinical studies. But I don't think that anyone knows what dosing regimen would be ideal.

You might have noticed that this doesn't resemble recreational dosing at all. However, if you hit some recreation briefly, it doesn't seem to ruin things...It would ruin things if you fall into dosing recreationally over a protracted period though. Be careful if you're prone to compulsion with recreational use of K.

ebola

 

[dopamimetic]

You have amazing doctors. don't take it for granted.

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..

Anyone tried this method with Methoxetamine or N-Ethyl-Norketamine? The first one I guess I've never dosed low enough, if it is active this way at all. Then I do remember my old days when experimenting with Dextromethorphan ... I would say this one does have strong and unique antidepressant action, that lasted sometimes for a week or so- but only after taking >100mg, and the SNRI action from DXM itself is more interfering than helpful.. would still like to give pure Dextrorphan a try.

 

[Foreigner]

I've used ketamine IM to treat my depression. There's a whole thread about it here.

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.

$900 for one infusion is totally outrageous. Even from the perspective of the HMOs that would be unjustified. The cost of one dose of ketamine is not that large, and neither is the effort to actually do it -- unless you're going to be hooked up to some kind of monitoring devices? I just can't believe that cost, it's over the top.

Again, harm reduction tells me to defer to the doctor, but given the variables you are better off doing this on your own.