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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 46. This is the beginning of the thread.
Posted by SLS on February 6, 2012, at 8:25:54
http://www.ncbi.nlm.nih.gov/pubmed/22297150
Biol Psychiatry. 2012 Jan 30. [Epub ahead of print]
Replication of Ketamine's Antidepressant Efficacy in Bipolar Depression: A Randomized Controlled Add-On Trial.
Zarate CA Jr, Brutsche NE, Ibrahim L, Franco-Chaves J, Diazgranados N, Cravchik A, Selter J, Marquardt CA, Liberty V, Luckenbaugh DA.
Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services, Bethesda, Maryland.
AbstractBACKGROUND:
Currently, no pharmacological treatments for bipolar depression exist that exert rapid (within hours) antidepressant or antisuicidal effects. We previously reported that intravenous administration of the N-methyl-D-aspartate antagonist ketamine produced rapid antidepressant effects in patients with treatment-resistant bipolar depression. The present study sought to replicate this finding in an independent sample.
METHODS:
In this double-blind, randomized, crossover, placebo-controlled study, 15 subjects with DSM-IV bipolar I or II depression maintained on therapeutic levels of lithium or valproate received a single intravenous infusion of either ketamine hydrochloride (.5 mg/kg) or placebo on 2 test days 2 weeks apart. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale, which was used to rate overall depressive symptoms at baseline; at 40, 80, 110, and 230 minutes postinfusion; and on days 1, 2, 3, 7, 10, and 14 postinfusion.
RESULTS:
Within 40 minutes, depressive symptoms, as well as suicidal ideation, significantly improved in subjects receiving ketamine compared with placebo (d = .89, 95% confidence interval = .61-1.16, and .98, 95% confidence interval = .64-1.33, respectively); this improvement remained significant through day 3. Seventy-nine percent of subjects responded to ketamine and 0% responded to placebo at some point during the trial. The most common side effect was dissociative symptoms, which occurred only at the 40-minute time point.
CONCLUSIONS:
This study replicated our previous finding that patients with bipolar depression who received a single ketamine infusion experienced a rapid and robust antidepressant response. In addition, we found that ketamine rapidly improved suicidal ideation in these patients.
Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
PMID:
22297150
[PubMed - as supplied by publisher]
Posted by Phillipa on February 6, 2012, at 9:53:17
In reply to Ketamine: Replication of previous studies., posted by SLS on February 6, 2012, at 8:25:54
So it does work. Work you consider this treatment? Phillipa
Posted by jono_in_adelaide on February 6, 2012, at 16:22:17
In reply to Re: Ketamine: Replication of previous studies. » SLS, posted by Phillipa on February 6, 2012, at 9:53:17
I'd consider it if nothing else had helped, I'd rather try ketamine than submit to ECT for example.
I know that when used as an anaesthetic it produced side effects (bad dreams, halucinations) but the dose in depression would be way lower, and I beleive that benzodiazepines greatly reduced the side effects.
All we need now is a drug company to have the balls to get it to market in pill form.
Posted by Hugh on February 7, 2012, at 16:43:09
In reply to Re: Ketamine: Replication of previous studies., posted by jono_in_adelaide on February 6, 2012, at 16:22:17
> I'd consider it if nothing else had helped, I'd rather try ketamine than submit to ECT for example.
>
> I know that when used as an anaesthetic it produced side effects (bad dreams, halucinations) but the dose in depression would be way lower, and I beleive that benzodiazepines greatly reduced the side effects.
>
> All we need now is a drug company to have the balls to get it to market in pill form.There are at least two ketamine-like antidepressants without ketamine-like side effects that are currently being tested. AstraZeneca is working on an NMDA antagonist called AZD6765. It's in phase II trials. Naurex is conducing a phase II trial of GLYX-13, a glycine-site functional partial agonist (GFPA) selective modulator of the NMDA receptor (NMDAR). Magnesium is an NMDA antagonist, but it has a hard time crossing the blood-brain barrier. MIT recently developed a new form of magnesium called magnesium l-threonate that's much better at crossing the blood-brain barrier. It only became available last year. I haven't tried it yet, but I will soon.
Posted by linkadge on February 7, 2012, at 17:18:53
In reply to Re: Ketamine: Replication of previous studies., posted by Hugh on February 7, 2012, at 16:43:09
Yeah, zinc also plays an important role in depression. Zinc plus AD is useful to boost efficacy, lower effective dose and speed onset of action.
Linkadge
Posted by Twinleaf on February 7, 2012, at 17:36:04
In reply to Re: Ketamine: Replication of previous studies., posted by linkadge on February 7, 2012, at 17:18:53
My pdoc told me yesterday that he had a compounding pharmacy formulate ketamine pills for a severely treatment- resistant bipolar patient, and that it was the first thing which had ever worked!
Posted by phidippus on February 8, 2012, at 17:04:31
In reply to Ketamine: Replication of previous studies., posted by SLS on February 6, 2012, at 8:25:54
The disasociative symptoms are a little difficult.
Eric
Posted by linkadge on February 8, 2012, at 19:13:12
In reply to Re: Ketamine: Replication of previous studies. » SLS, posted by phidippus on February 8, 2012, at 17:04:31
>The disasociative symptoms are a little >difficult.
There might be a threshold effect whereby mild halucination correlates with the effect. You know, like a buzz.
The fact that it doesn't need to be taken every day would make this effect manageable.
Linkadge
Posted by SLS on February 9, 2012, at 5:37:08
In reply to Re: Ketamine: Replication of previous studies., posted by linkadge on February 8, 2012, at 19:13:12
> >The disasociative symptoms are a little >difficult.
>
> There might be a threshold effect whereby mild halucination correlates with the effect. You know, like a buzz.
>
> The fact that it doesn't need to be taken every day would make this effect manageable.
>
> Linkadge
>The goal is, of course, being able to synthesize a new drug that offers antidepressant efficacy similar to ketamine, but without the side effects. The NIH is working to identify what mechanisms are responsible for the antidepressant effect of ketamine. There is some thought that there are downstream events that can be exploited, thus obviating the need for a ketamine-like drug.
- Scott
Posted by Roslynn on February 9, 2012, at 14:28:22
In reply to Re: Ketamine: Replication of previous studies., posted by SLS on February 9, 2012, at 5:37:08
Hi,
Did anyone see the guy who was profiled last week on the news w/Diane Sawyer? He responded to Ketamine and now is taking another experimental drug that is also working for him.
Does anyone know the name of the experimental drug he is now taking? I could not find this information.
Thank you for any help!
Roslynn
Posted by Hugh on February 9, 2012, at 17:18:07
In reply to Re: Ketamine: Replication of previous studies., posted by Roslynn on February 9, 2012, at 14:28:22
> Did anyone see the guy who was profiled last week on the news w/Diane Sawyer? He responded to Ketamine and now is taking another experimental drug that is also working for him.
>
> Does anyone know the name of the experimental drug he is now taking? I could not find this information.Riluzole. It's been used for over fifteen years to treat ALS, and is extremely expensive. Sun Pharma received tentative approval from the FDA to manufacture a generic version, which would be much cheaper. That was over a year ago, but generic riluzole still isn't available.
Posted by linkadge on February 9, 2012, at 18:15:00
In reply to Re: Ketamine: Replication of previous studies., posted by SLS on February 9, 2012, at 5:37:08
>The goal is, of course, being able to synthesize >a new drug that offers antidepressant efficacy >similar to ketamine, but without the side >effects.
To be honest, I don't really think that the so called "side effects" are much to be worried about. After all, people take the drug cause it gets them high! I would assume that if it does cause such "side effects", most users wouldn't be too bothered. They might find it enjoyable. I would also expect that major adverse reactions would be low at such doses.
Some of the side effects i.e. grandiosity, feeling "out of body", euphoria, feelings of power etc. are the opposite of depression. Think of it, the depresed person feels worthless, that life has no meaning, that there is no larger picture, that they are trapped in their body and mind, dysphoria etc.
The problem is that psychiatry is still looking for this amazing antidepressant that does not cause euphoria. Its not possible in my opinion.
Depression --> euphoria is a spectrum. The drug simply pushes you a little further along this. I don't think they are going to be able to tease apart the theraputic and so called "side effects".
Linkadge
Posted by linkadge on February 9, 2012, at 18:17:57
In reply to Re: Ketamine: Replication of previous studies., posted by Hugh on February 9, 2012, at 17:18:07
I think that ketamine should be tested beside (or in combination with zinc).
People don't care about zinc because its cheap and readily available. Therefore, all this energy will go towards scarce, expensive and exotic medications like ketamine and riluzole.
Zinc activates the mTOR neurogenic pathway just as ketamine.
Posted by SLS on February 9, 2012, at 18:56:39
In reply to Re: Ketamine: Replication of previous studies., posted by linkadge on February 9, 2012, at 18:17:57
> Zinc activates the mTOR neurogenic pathway just as ketamine.
What does this indicate to you?- Scott
Posted by SLS on February 9, 2012, at 19:05:22
In reply to Re: Ketamine: Replication of previous studies. » SLS, posted by linkadge on February 9, 2012, at 18:15:00
> Depression --> euphoria is a spectrum.
>
> The drug simply pushes you a little further along this.This is simple, to be sure.
> I don't think they are going to be able to tease apart the theraputic and so called "side effects".
Let's just say for now that psyshosis is a side effect. If you would enjoy being psychotic, then perhaps this is the right drug for you.
http://www.ketamine.com/schizohypoth.html
"In healthy subjects, ketamine produces: 1) positive symptoms of psychosis, such as illusions, thought disorder and delusions; 2) negative symptoms similar to those associated with schizophrenia including blunted emotional responses, emotional detachment, and psychomotor retardation; 3) cognitive impairments, in particular impairments on tests of frontal cortical function including increased distractibility, reduced verbal fluency and poorer performance on the Wisconsin Card Sorting Test. "
- Scott
Posted by Twinleaf on February 9, 2012, at 19:19:47
In reply to Re: Ketamine: Replication of previous studies. » linkadge, posted by SLS on February 9, 2012, at 19:05:22
According to my pdoc, the side effects you describe are associated with IV use; he is not seeing them with a low oral dose.
Posted by SLS on February 9, 2012, at 19:40:29
In reply to Re: Ketamine: Replication of previous studies., posted by Twinleaf on February 9, 2012, at 19:19:47
> According to my pdoc, the side effects you describe are associated with IV use; he is not seeing them with a low oral dose.
Ah. That is indeed encouraging.
Would you happen to know what dose he is using?
Is oral ketamine available from pharmacies?
- Scott
Posted by SLS on February 9, 2012, at 20:33:23
In reply to Re: Ketamine: Replication of previous studies. » linkadge, posted by SLS on February 9, 2012, at 19:05:22
> Let's just say for now that psyshosis is a side effect. If you would enjoy being psychotic, then perhaps this is the right drug for you.
My apologies. I was wrong.
- Scott
Posted by Twinleaf on February 9, 2012, at 20:57:43
In reply to Re: Ketamine: Replication of previous studies. » Twinleaf, posted by SLS on February 9, 2012, at 19:40:29
I will ask him about the dosage when I see him next.
He has a compounding pharmacy make the ketamine pills in the dosage he chooses. I asked him if he had to have any kind of special license or permission to prescribe it and he said he didn't
Posted by SLS on February 10, 2012, at 6:15:46
In reply to Re: Ketamine: Replication of previous studies. » linkadge, posted by SLS on February 9, 2012, at 19:05:22
Hi Linkadge.
Just in case you didn't see my other post, I would like to apologize for my having posted the following:
> Let's just say for now that psyshosis is a side effect. If you would enjoy being psychotic, then perhaps this is the right drug for you.
Sorry.
- Scott
Posted by SLS on February 10, 2012, at 6:17:30
In reply to Re: Ketamine: Replication of previous studies., posted by linkadge on February 9, 2012, at 18:17:57
Posted by Twinleaf on February 10, 2012, at 11:33:12
In reply to Re: Ketamine: Replication of previous studies. » Twinleaf, posted by SLS on February 9, 2012, at 19:40:29
The: dosage of ketamine was 100 mg. once daily in the AM initially; he is now maintained on 200 mg. daily. On this dosage he feels slightly high and spacey for about an hour ( no dissociation), and then settles into feeling normal for the rest of the day.
Posted by Roslynn on February 10, 2012, at 12:49:30
In reply to Re: Ketamine: Replication of previous studies., posted by Hugh on February 9, 2012, at 17:18:07
Thank you so much for giving me this info!
Roslynn
>
> Riluzole. It's been used for over fifteen years to treat ALS, and is extremely expensive. Sun Pharma received tentative approval from the FDA to manufacture a generic version, which would be much cheaper. That was over a year ago, but generic riluzole still isn't available.
>
>
Posted by phidippus on February 10, 2012, at 12:53:11
In reply to Re: Ketamine: Replication of previous studies., posted by SLS on February 9, 2012, at 5:37:08
I was on a Ketamine infusion
0.5mg/kg IV over 40 minutes.I exeprienced no psychosis or otherwise undesriable cognitive effects. Just this slight derealization.
Eric
Posted by SLS on February 10, 2012, at 13:10:20
In reply to Re: Ketamine: Replication of previous studies., posted by Twinleaf on February 10, 2012, at 11:33:12
> The: dosage of ketamine was 100 mg. once daily in the AM initially; he is now maintained on 200 mg. daily. On this dosage he feels slightly high and spacey for about an hour ( no dissociation), and then settles into feeling normal for the rest of the day.
Thank you for looking into this.
- Scott
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