Intravenous NMDA receptor antagonists for depression

[Negrodamus]

I'm a bit curious so please forgive my ignorance. Is there a specific reason why NMDA antagonists, like ketamine , are usually trialled intravenously for depression? There is at least anecdotal evidence that dextromethphan, another NMDA antagonist, has similar effects when taken orally. Is it prohibitively expensive to produce a ketamine pill or is it just a money grab by the medical industrial complex? The cynical bastard in me would love to see Robitussin clinical trial for trd.

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[shan564]

Dextromethorphan has a lot of effects other than just NMDA blockade.

I don't think PO ketamine has been studied for depression, but I think the concerns are the effects of the first-pass metabolite (only relevant in oral formulations) and the variable bioavailability. The latter problem would be a big deal for ketamine dosing, since the therapeutic window is pretty narrow.

Also, I think that ketamine has to be given in a controlled setting because of the potential for overdose if you just give somebody a bottle of pills... especially if that somebody has severe depression and is already at high risk for suicide. Plus, it'd be pretty easy to sell those pills on the street.

 

[digitlnoize]

I'm a bit curious so please forgive my ignorance. Is there a specific reason why NMDA antagonists, like ketamine , are usually trialled intravenously for depression? There is at least anecdotal evidence that dextromethphan, another NMDA antagonist, has similar effects when taken orally. Is it prohibitively expensive to produce a ketamine pill or is it just a money grab by the medical industrial complex? The cynical bastard in me would love to see Robitussin clinical trial for trd.

There actually has been research looking into DXM for all kinds of things. The IV ketamine trials that I've heard about have also been largely for suicidality, not depression (a fine distinction).

 

[SmallBird]

There actually has been research looking into DXM for all kinds of things. The IV ketamine trials that I've heard about have also been largely for suicidality, not depression (a fine distinction).

Hey dig, I have to say you are quite wrong about this - several IV ketamine studies at the NIMH and other sites have been done for depression with robust effects. It has also been studies for acute suicidality but definitely not just for this.

There are other oral NMDA antagonists (strong antagonists, thus not counting memantine) being studied in clinical trials currently. As far as I know most of them still have funny names combining letters and numbers

 

[MiddleRoad]

Here's one that's gone beyond the letters and number combination phase to actually garner a name: lanicemine

http://www.clinicalpsychiatrynews.c...ression/511fdc11f3c5d583871b4978791303fb.html

 

[notdeadyet]

Here's one that's gone beyond the letters and number combination phase to actually garner a name: lanicemine

Also IV-only. I have a hunch we'll see ketamine used here sooner than lancemine. I'm already stroking my figurative beard for a few patients at my place and folks are tentatively supportive.

 

[SmallBird]

Also IV-only. I have a hunch we'll see ketamine used here sooner than lancemine. I'm already stroking my figurative beard for a few patients at my place and folks are tentatively supportive.

You are? Even given the very short period of treatment response? Do you intend to give repeated infusions then? Not criticizing, in case it seems that way, just genuinely interested how you see that going. I don't personally think ketamine is ready for use outside of clincial trials in very refractory patients.

 

[notdeadyet]

I'm looking at extremely suicidal patients who are not ECT candidates. The plan would be repeated infusions...

At this point, I would personally consider ketamine more akin to ECT than psychotropics...

 

[notdeadyet]

And I don't want to give the wrong impression here. I'm early in the push for this. It may not go anywhere.

 

[SmallBird]

And I don't want to give the wrong impression here. I'm early in the push for this. It may not go anywhere.

Of course, I think it's an interesting conversation. I wonder if you would then think about referring them to a clinical trial? It's gonna be really important to do quantitative monitoring if you do this, particularly of cognitive function I would think.

 

[notdeadyet]

I wonder if you would then think about referring them to a clinical trial? It's gonna be really important to do quantitative monitoring if you do this, particularly of cognitive function I would think.

That's the plan, knock wood...

 

[splik]

we were using IV ketamine as an augmentation agent in patients who were already receiving ECT (so it was their induction agent instead of Brevital as there/s a study showing if you use both you negative the effect of the ketamine) but it didn't really seem to help much more so we've stopped using in. there are no plans to use ketamine only in treatment-refractory depression either. it is fun to try something new though!

 

[notdeadyet]

we were using IV ketamine as an augmentation agent in patients who were already receiving ECT (so it was their induction agent instead of Brevital as there/s a study showing if you use both you negative the effect of the ketamine) but it didn't really seem to help much more so we've stopped using in. there are no plans to use ketamine only in treatment-refractory depression either. it is fun to try something new though!

Definitely. I'm more interested in seeing the ketamine as standalone treatment than as augmentation for ECT though. Why subject someone to ECT if the ketamine does the job and if the ketamine isn't doing the job, it wouldn't be my go to for induction.

 

[digitlnoize]

Hey dig, I have to say you are quite wrong about this - several IV ketamine studies at the NIMH and other sites have been done for depression with robust effects. It has also been studies for acute suicidality but definitely not just for this.

Ah. Those must be all the studies I hadn't heard about. Will check it out, thanks!