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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 18 of 18. This is the beginning of the thread.
Posted by FredPotter on July 10, 2007, at 19:52:56
In the latest edition of Scientific American: MIND, there's a story about Ketamine as a cure for depression. It seems all our theories about serotonin, norepinephrine and even neuron regeneration may have been wrong. It was found that 71% of a group of treatment resistant depressives responded in an hour or two and the effect lasted for days. It's thought the effect is to do with NMDA and glutamate and is independent of the temporary hallucinogenic effects. The main problem now is how to make a drug that has the anti-depressant effect without the psychotic effect. It looks very promising - and fast. Our troubles may all be over in a a few years
Fred
Posted by Phillipa on July 10, 2007, at 22:18:01
In reply to Ketamine, posted by FredPotter on July 10, 2007, at 19:52:56
Fred as we hobble around on our canes. Love Phillipa didn't Quintal have a recent discussion on ketamine?
Posted by deniseuk190466 on July 11, 2007, at 15:38:46
In reply to Ketamine, posted by FredPotter on July 10, 2007, at 19:52:56
Fred,
That sounds wonderful but then why do SSRIs etc work so well for some people (like they used to do for me)?
Also, I can't see how taking Ketamine once every seven days could be seen as a cure it's not making any permanent beneficial changes in the brain.
And I thought lamcital was supposed to affect glutamate, how come that often doesn't work?
Having said that, I think Ketamine sounds really promising but would just like to know a bit more about it.
Denise
Posted by FredPotter on July 11, 2007, at 20:41:44
In reply to Re: Ketamine, posted by deniseuk190466 on July 11, 2007, at 15:38:46
I see you've seen the thread. I think the idea is whatever works as a drug can be translated into some permanent change worked by gene therapy. Anyway once every 7 days sounds fine to me. I take a blood pressure pill every day
Fred
Posted by linkadge on July 12, 2007, at 9:46:44
In reply to Re: Ketamine » deniseuk190466, posted by FredPotter on July 11, 2007, at 20:41:44
Not sure what to say. I definately think there need to be more studies conducted. Ketamine might posess additional activities that give it its antidepressant effect.
Its also too early to throw out monoaminergic theories / neurotrophic theories on depression based upon this.
I still don't see solid proof that it is truely an antidepressant effect and not just a drug induced temprorary improvement. A lot of illegal drugs can improve depression very rapidly.
Growth factors, BDNF, NT-3 etc, when injected directly into the brain, can produce rapid antidepressant effects that last as long as two weeks. In such cases, it is impossable to separate the antidepressant effect from the induction of growth of new brain cells, as the grwoth factor seems to induce both at the same time. BDNF for instance, increases the sensitivity of the d3 receptors in reward areas of the brain, in addition to growing new brain cells. So it may not be the question of whether lack of new brain cells cause depression, or depression causes lack of new brain cells. It could be that the brain lacks substances that posess both mood elevating and neurotrophic effects.
It is possable that Ketamine is producing a rapid increase in trophic factors, which is possable since some other NMDA antagonists have a similar ability to produce rapid elevations of such substances.
Zinc, for intance, produces a rapid antidepressant effect in mouse swim tests, it also produces a rapid increase in BDNF.
Although, I don't know what kind of effect long term administration of such substances would have on the depressive state.
The problem with saying that the neurotrophic model is bunk is that there would still be real differences in the brains of the depressed patient. Hippocampal volumes would still remain atrophied etc.
I personally think without any induction of new brain cells, that this antidepressant response could "kick out" as rapidly as it kicks in.
The plight of depression has been continually riddled with fast acting depression cures, so I think that follow up studies are neccesary to determine the nature of the effect.
Linkadge
Posted by rovers95 on July 12, 2007, at 13:29:15
In reply to Re: Ketamine, posted by deniseuk190466 on July 11, 2007, at 15:38:46
> Fred,
>
> That sounds wonderful but then why do SSRIs etc work so well for some people (like they used to do for me)?
>
> Also, I can't see how taking Ketamine once every seven days could be seen as a cure it's not making any permanent beneficial changes in the brain.
>
> And I thought lamcital was supposed to affect glutamate, how come that often doesn't work?
>
> Having said that, I think Ketamine sounds really promising but would just like to know a bit more about it.
>
>Lamictal works at sodium-sensitive voltage channels, wehereas ketamine inhibits glutamate at the NMDA receptors. The idea is the blockage of "neurotoxic" glutamate at NMDA enables the brain to recover to its pre-depressed state, allowing GABA and dopaminergenic terminals to work more effectively, it also lowers the HPA axis. I also suspect it promotes BDNF etc.
rover
> Denise
Posted by linkadge on July 12, 2007, at 15:39:20
In reply to Re: Ketamine, posted by rovers95 on July 12, 2007, at 13:29:15
Not all NDMA antagonists are have the same effects on growth factors.
Zinc increases BDNF, but magnesium quickly decreases BDNF.
Linkadge
Posted by Iansf on July 13, 2007, at 1:17:32
In reply to Re: Ketamine, posted by linkadge on July 12, 2007, at 9:46:44
> I personally think without any induction of new brain cells, that this antidepressant response could "kick out" as rapidly as it kicks in.
>
> The plight of depression has been continually riddled with fast acting depression cures, so I think that follow up studies are neccesary to determine the nature of the effect.
>
>Even if ketamine proves not to be an effective long-term antidepressant, it could prove very useful for getting people through crises while waiting for a long-term antidepressant to kick in. How much pain could be avoided, and how many lives saved, with something that could turn depression around overnight. Even if its effectiveness petered out after a few weeks, that could be exactly the time needed to get the effect out of a standard med.
Ian
Posted by linkadge on July 13, 2007, at 6:57:24
In reply to Re: Ketamine » linkadge, posted by Iansf on July 13, 2007, at 1:17:32
Yes, but people have been experimenting with other meds for these purposes for a long time. Ritalin is often used as a initial helper to try and boost AD effect untill an SSRI kicks in.
But I'd be afraid people migh remit to the good drug, yet relapse when it is discontinued.
Linkadge
Posted by stargazer2 on July 13, 2007, at 9:40:56
In reply to Re: Ketamine, posted by linkadge on July 13, 2007, at 6:57:24
Here is an abstract for use of Ketamine in Depressed Pts, hope this is the correct link...Stargazer
Posted by Deniseuk190466 on July 15, 2007, at 13:32:49
In reply to Re: Ketamine » deniseuk190466, posted by FredPotter on July 11, 2007, at 20:41:44
Fred,
Yes I agree anything that helps is worth taking (as long as it doesn't make your condition worst in the long run).
I just wish it could be a cure rather than something you have to keep taking in order to feel better.
Denise
Posted by Deniseuk190466 on July 15, 2007, at 13:33:41
In reply to Re: Ketamine, posted by rovers95 on July 12, 2007, at 13:29:15
.
Posted by Deniseuk190466 on July 15, 2007, at 13:35:22
In reply to Re: Ketamine, posted by linkadge on July 12, 2007, at 9:46:44
Hi Linkadge,
I know we are all different but I tried taking zinc and felt no affects either way (good or bad) and I also had magnesium shots and felt no benefits or adverse affects.
Denise
Posted by linkadge on July 15, 2007, at 14:19:19
In reply to Re: Ketamine - To Linkadge, posted by Deniseuk190466 on July 15, 2007, at 13:35:22
Well thats the thing. Some people may not benifit from NMDA antagonists.
I know there is a drug called riluzole that (for some people) has a rapid antidepressant effect. It is either a NMDA antagonist or modulates glutamate in some way.
Anyhow, I remember Scott (SLS) said he tried it with no benifit.
Linkadge
Posted by FredPotter on July 15, 2007, at 16:08:22
In reply to Re: Ketamine - To Linkadge » Deniseuk190466, posted by linkadge on July 15, 2007, at 14:19:19
Linkadge I admire your healthy scepticism, but sometimes you seem difficult to please ;) I can recommend Scientific American: MIND BTW
Posted by linkadge on July 16, 2007, at 9:07:37
In reply to Re: Ketamine - To Linkadge » linkadge, posted by FredPotter on July 15, 2007, at 16:08:22
Its not that I don't think these aren't good leads, I just don't think it is a good idea to throw out all previous work in depression research based upon a few short trials.
For instance, with the advent of the use of RU-386 for psychotic depressive episodes, this was the new cure. All depressives must have high cortisol. But not all do, some actually have low cortisol, and would likely not benifit from RU-486.
Anyhow, all I am saying is that only time will tell what type of impact this drug will uptimately have.Linkadge
Posted by deniseuk190466 on August 11, 2007, at 6:07:28
In reply to Re: Ketamine - To Linkadge » FredPotter, posted by linkadge on July 16, 2007, at 9:07:37
I was reading up on Ketamine for depression and it sounds so promising.
But I was wondering if Ketamine gets to the same targets as other antidepressants do but does so quicker then how would it work on these very treatment resistant people who had already tried 6 other medications.
Surely if it ultimately reaches the same targets as drugs that haven't worked then it wouldn't work at all?
Anybody got any ideas?
Thanks.......Denise
Posted by jhj on August 11, 2007, at 7:17:17
In reply to Another question on Ketamine, posted by deniseuk190466 on August 11, 2007, at 6:07:28
I am quite surprised to read this thread on Ketamine.I am from India and when i mentioned rapid antidepressant effect of Ketamine to my pdoctor,he warned me against talking about illegal drugs.Is not it controlled substance in US or Europe? How much time a drug company needs to take if it decides to develop antidepressant on the basis of Ketamine mechanism?
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