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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 16 of 16. This is the beginning of the thread.
Posted by FredPotter on April 2, 2015, at 12:38:36
I keep reading that a new antidepressant is just round the corner in the form of a ketamine-like drug. Ketamine is cheap and generic therefore drug companies want to create a drug that's like it but more expensive. The idea is that ketamine at low dose lifts depression in 24h with a sustained effect. Sounds wonderful. I think it's an NMDA antagonist. Is it time to rethink the whole serotonin theory?
Fred
Posted by linkadge on April 2, 2015, at 20:14:26
In reply to Ketamine and ketamine-like drugs, posted by FredPotter on April 2, 2015, at 12:38:36
>Is it time to rethink the whole serotonin theory?
Not necessarily. Ketamine also increases serotonin.
Posted by europerep on April 3, 2015, at 7:37:32
In reply to Re: Ketamine and ketamine-like drugs, posted by linkadge on April 2, 2015, at 20:14:26
> Not necessarily. Ketamine also increases serotonin.
That would still leave open the question of the almost instantaneous onset of antidepressant effects of ketamine. So even if its mechanism of action is similar to that of SSRIs (which I doubt), it still does it much better.
It would be interesting to see whether patients who respond to (or even remit on) SSRIs also respond to ketamine.
Posted by ikasug on April 3, 2015, at 10:23:35
In reply to Ketamine and ketamine-like drugs, posted by FredPotter on April 2, 2015, at 12:38:36
I've always understood antidepressant effects as a systemic adjustment to altered levels of neurotransmitters. Ketamine and derived drugs would be another type of a
antidepressant to try, but I can't see them totally replacing current therapies.
Posted by linkadge on April 3, 2015, at 14:39:53
In reply to Re: Ketamine and ketamine-like drugs » linkadge, posted by europerep on April 3, 2015, at 7:37:32
One of the targets of ketamine is GSK3. GSK3 is also inhibited by lithium and zinc, which can have rapid antidepressant effects.
That being said, GSK3 interacts with serotonin. Low serotonin levels dysregulate GSK3 which can be reversed by increasing serotonin (i.e. SSRIs) or GSK3 inhibitors.
What I am getting at, is that it may not be that ketamine has a different target. It may simply by that ketamine affects a target that other antidepressants take longer to regulate.
http://www.sciencedaily.com/releases/2014/01/140107102442.htm
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3200424/
Linkadge
Posted by linkadge on April 3, 2015, at 14:42:47
In reply to Re: Ketamine and ketamine-like drugs, posted by ikasug on April 3, 2015, at 10:23:35
>but I can't see them totally replacing current >therapies.
Current therapies are lacking for large number of patients. I see current therapies for depression, like current chemo for cancer. You may hit the target, but cause a lot of collateral damage in the mean time.
Posted by SLS on April 3, 2015, at 20:22:37
In reply to Re: Ketamine and ketamine-like drugs » linkadge, posted by europerep on April 3, 2015, at 7:37:32
> > Not necessarily. Ketamine also increases serotonin.
>
> That would still leave open the question of the almost instantaneous onset of antidepressant effects of ketamine. So even if its mechanism of action is similar to that of SSRIs (which I doubt), it still does it much better.
>
> It would be interesting to see whether patients who respond to (or even remit on) SSRIs also respond to ketamine.I think it has more to do with glutamate neurotransmission that does not rely upon NMDA receptors. This would leave AMPA or kainate receptors. It may be that any increase or decrease in other neurotransmitter systems are only secondary to an increase in glutamate activity.
- Scott
Posted by Bill82 on April 3, 2015, at 21:50:19
In reply to Re: Ketamine and ketamine-like drugs, posted by SLS on April 3, 2015, at 20:22:37
Interesting on gsk3, had not looked into that before. Dosnt lithium work much better for bipolar than unipolar though? From what I have read about ketamine and glyx13 and nrx1074 they all primarily inhibit the nmda receptor to carrying degrees, with both glyx13 and nrx1074 being partial agonists(like abilify). It would be interesting to see if they have looked into wether as you said it is gsk3 that is true aspect of their effects on mood.
Posted by cadett on April 3, 2015, at 21:59:13
In reply to Re: Ketamine and ketamine-like drugs, posted by Bill82 on April 3, 2015, at 21:50:19
I have been following the research of Ketamine for about 2 years. It seems to be the most promising new drug in quite a long time! Hope it hits the market in my lifetime!
Posted by Jeroen on April 4, 2015, at 12:44:27
In reply to Ketamine and ketamine-like drugs, posted by FredPotter on April 2, 2015, at 12:38:36
take it from me 15 years of psychosis. stable but still not healed. nightmare
DO'S
1. try Seroquel or XR low dose below 100 mg (wonderfull 2 months of my life) it was like 5D living, no paranoia, depression, but pooped out after 2 Months with extreme anxiety and dying feeling when it stopped working.
Don'ts: Minocycline, too dangerous in my situation, can cause lupus, won't go on doxycycline
DO'S: Thinking of Jesus and God, even when struggling very badlyDO'S: Try to find a psychiatrist who doesn't wanna prescribe or drug (medicates) you like a zombie (hard)
DON'TS: go into experimental drug trials (too dangerous) i am naiive... blinded me for couple of years with reasonable eye cramps
sigh
Posted by linkadge on April 5, 2015, at 17:10:14
In reply to Re: Ketamine and ketamine-like drugs, posted by Bill82 on April 3, 2015, at 21:50:19
Lithium has been known to produce rapid antidepressant effects even in unipolar disorder.
However, it also affects other neurotransmitter systems over time that may produce a net stabilization.
For instance, in the short term, lithium inhibits glutamate reuptake. Over time, however, it tends to enhance it.
Linkadge
Posted by linkadge on April 5, 2015, at 17:14:43
In reply to Re: Ketamine and ketamine-like drugs, posted by SLS on April 3, 2015, at 20:22:37
Zinc and magnesium also inhibit NMDA and can produce rapid antidepressant effects (at least in animal models). Zinc has been shown to augment antidepressants and lower the effective dose needed to produce an antidepressant effect in animal models.
I wonder if a combination of zinc and magnesium might augment ketamine and / or lower the effective dose needed.
I have taken magnesium with dextromethorphan (another NMDA antagonist with SNRI, sigma agonist, opiate agonist properties).
Posted by FredPotter on April 5, 2015, at 19:27:12
In reply to Re: Ketamine and ketamine-like drugs, posted by linkadge on April 5, 2015, at 17:14:43
Glyx-13, a drug like ketamine but without hallucinogenic and dissociative side effects, appears to be very effective against depression. It has been fast-tracked by the FDA and is now in stage III clinical trials
http://www.northwestern.edu/newscenter/stories/2012/12/new-antidepressant-acts-very-rapidly-and-is-long-lasting.html
Posted by Lamdage22 on April 6, 2015, at 3:27:11
In reply to ketamine-like drugs eg GLYX-13, posted by FredPotter on April 5, 2015, at 19:27:12
Its called rapastinel now (Glyx-13).
Posted by paulk on November 22, 2015, at 13:10:01
In reply to Re: ketamine-like drugs eg GLYX-13, posted by Lamdage22 on April 6, 2015, at 3:27:11
My take is that depression syndromes may often be inflammatory disease. One of the reasons they use ketamine in surgery is that it reduces inflammation.
If you think of being sick - remove the fever and out ward symptoms - what you have left is indistinguishable to depression. Give interferon (pro inflammation) and you produce depression.
Many of the antidepressants reduce inflammation markers on their own (Nardil, Tricyclics and more ) Could be the effect on catecholamines is just a side effect.
IMO once the medical community realizes this as a paradigm treatment could greatly improve.
My hunch is one can get exposed to some virus and afterwards there is an autoimmune reaction that continues - a post viral syndrome. If you have the wrong genes as well you can end up with life long dysthymia.
Posted by Jeroen on November 22, 2015, at 14:11:03
In reply to Re: ketamine-like drugs eg GLYX-13, posted by paulk on November 22, 2015, at 13:10:01
dysthymia
This is the end of the thread.
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