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Re: Ketamine and side effects SLS

Posted by jrbecker76 on February 19, 2013, at 14:21:05

In reply to Re: Ketamine and side effects jrbecker76, posted by SLS on February 19, 2013, at 13:18:01

> Perhaps you would do better with tianeptine. I don't know. You might not be a SSRI responder.
> How did you react to Zoloft?
> What about MAOIs?
> I am seriously considering using deep TMS as a treatment to accelerate my response to medication. I don't think ketamine represents much more than an intriguing and potentially important heuristic observation, much as sleep deprivation is. It can produce a dramatic antidepressant effect transiently, but what do you do with it? If ketamine were observed to work synergistically with other drugs to make them work better and longer, I would agree that it has a clinical application. Do you know of any studies like that?
> From what I have seen, there is a narrow therapeutic window for ketamine administration. One must be brought to the point of delirium without becoming unconscious. This can only be accomplished with the precision offered by infusions. Ketamine does not produce an antidepressant effect when used at dosages that are too high or too low. Injections just don't accomplish this as well as infusions do. I'm looking forward to the development of an oral agent by Naurex that acts as a partial agonist at the glycine binding site of the NMDA receptor / channel. It should have a wider therapeutic window and avoid psychotomimetic side effects. In the meantime, I am hoping that my impressions of ketamine are wrong, and that it does have practical applications to treat depression. I just haven't seen it yet.
> Do you think that adding magnesium to ketamine would be helpful? What about memantine?
> - Scott

Hi Scott.

You bring up a lot of interesting questions.

In terms of my own SSRI response, I would say that I respond to all of them in terms of impacting my mood on some level. When I say that, I mean that I do better on them rather than off of them. Unfortunately, most of them can cause significant side effects ranging from anergia, fatigue, heightened distractability, mild irritability, apathy, not to mention other non-CNS related SEs. As I mentioned, I do quite well on Citalopram, relatively speaking. Zoloft definitely made me the most irritable and anxious, Lexapro fell somewhere in the middle, and Fluoxetine to a less extent. I did a little better on the SNRIs (Cymbalta a little more so than Effexor) but the SNRIs also caused more ruminative behavior. Overall my favorite is still Citalopram. I do well in combo with a very low-dose of Nefazodone in the mix. Although my dx is MDD, I am most likely a soft case of BPII (there is some family history there). So this probably explains my med sensitivities. In terms of other classes, I have not done as well on tricyclics in comparison to the monoaminergic reuptake inhibitors and other newer classes. As for MAOIs, I concur with my pdoc in believing that I could not tolerate them.

As for Ketamine, yes, I would call it an academic's antidepressant. By this, I mean it obviously comes with quite a few barriers for wider treatment implementation (e.g., in-office administration and related costs, addiction potential, short therapeutic window, etc). That being said, some research clinics have had patients on long-term maintenance ketamine quite successfully for a while now (see UCSD for example). Many of these patients, once stabilized, end up only needing maintenance dosing somewhere between 2-3 x a week to only a 1-2x per month. By the way, almost all of the trials have not demonstrated that dissociation are other issues have been a problem - either during the infusion or hours/days afterwards. I do have a bit of skepticism that the ~70% response rate in ketamine trials will end up being confirmed in larger clinical trials (but for now, a meta-analysis of smaller trials has indeed confirmed this high level of response). I think there is definitely a subset of patients (see JohnLA's threads) that will not respond, and maybe even be detrimental to their mood.

so I'm not ready to drink the koolaid on this quite yet, especially since researchers are hyping the ketamine phenomenon as the most exciting thing that has happened to psychopharmacology in the past 50 years. But I would tend to agree with the sentiment that this is quite a seachange for the field Although Ketamine will probably not ever be prescribed to a wide clinically depressed population, the stimulus of the clinical research beyond the monoamines is something that was drastically needed in the virtual standstill of the psychiatric pipeline just a couple of years ago. Now companies like Roche, J&J, Astra-Zeneca and a few others are testing a number of glutamatergic drugs. As you know, some are testing IV-administered "ketamine-like" drugs (e.g., Naurex and AZ), while others are looking towards oral agents (J&J, Roche, Naurex). As I mentioned earlier, I was in a trial for one of Roche's drugs they are testing (a mGlu 2/3 antagonist). I unfortunately was plagued with more SEs than anything else (as a side note though, preliminary feedback from my trial site remarked that subjects are responding). Perhaps this is a sign I won't be a responder to ketamine. Who knows. But since there a few different glutamatergic mechanisms they are testing out it's likely one of the mechanisms of action under investigation will prove worthy.

As for the fate of ketamine iself, will it eventually become more than just a fad? Well, think of it this way, they've showed response in one trial with non-responders to ECT. So imagine the cost-effectiveness of administering ketamine instead of ECT from an insurer's point of view. So yes, I could be convinced that ketamine will eventually find a place in the treatment spectrum, even if it's just as a protocol for inpatient hospitalizations with suicidal ideation or perhaps as another option instead of ECT for TRD individuals. I corresponded with one researcher who has researched the cost-effectiveness of implementing ketamine treatment on a larger scale. She said that it warrants a lot more research which is currently being undertaken. However, she believes that it could be cost-effective if psychiatrists mimicked the way many pain clinics administer infusion drugs to patients. Realize that in most cases, an anesthesiologist is not being used which will help to keep costs down. As for whether other drugs can "extend" the efficacy of ketamine. They are testing riluzole now in a trial to determine that.





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