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Dr. Bob is Robert Hsiung, MD,
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Posted by phillipa on October 12, 2012, at 18:35:28
Question is ketamine a viable option for treatment resistant depression? Phillipa
From Medscape Medical News > PsychiatryKetamine a Viable Option for Severe Depression?
Megan Brooks
Authors and Disclosures
October 11, 2012 The discovery that ketamine produces rapid antidepressant effects in patients with severe treatment-resistant depression is fueling basic neuroscience research, leading to a greater understanding of the neurobiology of depression and maybe more effective treatments, a new review suggests.
Ketamine, an N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, is best known in medicine as an anesthetic but also has some notoriety as a street drug, sometimes dubbed "Special K," and is taken illicitly for its psychedelic effects.
However, recently ketamine has gained interest among researchers for its potential as a unique, rapid-acting antidepressant.
Typical antidepressants such as the serotonin selective reuptake inhibitors (SSRIs) take weeks to months to have an effect and are only moderately effective, leaving more than one third of depressed patients resistant to drug therapy.
"The rapid therapeutic response of ketamine in treatment-resistant patients is the biggest breakthrough in depression research in half a century," review author Ronald Duman, PhD, professor of psychiatry and neurobiology at Yale University in New Haven, Connecticut, said in a statement.
However, Dr. Dunham told Medscape Medical News, although clearly promising for depression, ketamine does have some roadblocks.
"It produces transient side effects [for about 1 hour], including mild hallucinations and dissociative effects in some patients, subsequent to the antidepressant response. Ketamine is also a drug of abuse, so caution is needed when considering widespread use of this agent."
"Nevertheless, there are millions of depressed patients who do not respond to conventional antidepressants and are in dire need of a drug like ketamine," Dr. Duman added.
With Dr. Duman and coauthor George Aghajanian, MD, professor emeritus of psychiatry at Yale University, the review was published October 5 in Science.
Timely, AuthoritativeCommenting for Medscape Medical News, James W. Murrough, MD, from Mount Sinai School of Medicine's Mood and Anxiety Disorders Program in New York City, described the article as a "timely, well written, and authoritative review by 2 neuroscience researchers who have really done the bulk of the work looking at the biological basis for how ketamine might bring about a rapid antidepressant effect."
The original link between ketamine and relief of depression was made by John Krystal, MD, chair of the Department of Psychiatry at Yale, and Dennis Charney, MD, formerly of Yale, now professor of psychiatry, neuroscience, and pharmacology and dean at Mount Sinai School of Medicine.
In 2000, they published results of a small, double-blinded, placebo-controlled study showing that intravenous infusions of ketamine produced significant and rapid antidepressant effects (Berman et al; Biol Psychiatry, 2000;47:351-354).
"That was the first controlled study that showed that ketamine had sort of an unexpected rapid antidepressant effect in patients," said Dr. Murrough. "We knew it was a glutamate antagonist, but at this time (in 2000), the role of glutamate in depression was not at all on the radar."
That study was followed by an article published in 2006 that also showed rapid (within 2 hours) and significant antidepressant effects after a single infusion of ketamine in 18 patients with treatment-resistant depression (Zarate Jr et al; Arch Gen Psychiatry, 2006;63:856-864).
Since then, a number of studies replicated and extended the findings including a study by Carlos Zarate Jr, MD, and colleagues published in 2010 in Archives of General Psychiatry and reported by Medscape Medical News at the time.
These studies sent neuroscientists on a quest to figure out at a cellular level, using animal models, how ketamine worked and what it could reveal about depression.
Jury Still Out
The literature suggests that depression is caused by disruption of homeostatic mechanisms that control synaptic plasticity, resulting in destabilization and loss of synaptic connections in mood and emotion circuitry, the authors note. Ketamine appears to target synaptic dysfunction in depression.
The findings highlight the "central importance of homeostatic control of mood circuit connections and form the basis of a synaptogenic hypothesis of depression and treatment response," the review authors write.
Is ketamine currently used to treat refractory depression?
"A year ago, I would have said no, it's not being used clinically. But in the last year, I've run into patients who've said they had been treated with low-dose ketamine by their psychiatrist, and doctors at national meetings who've said they've used it in their practice, but it's very sparse, it's far from widespread," said Dr. Murrough.
It is important to note, he added, that to date, most of the research has been limited to the effects of a single dose.
At a medical conference in June, as reported byMedscape Medical News, Dr. Murrough and colleagues demonstrated that administration of 6 low-dose infusions of ketamine over 2 weeks improved symptoms in a small study of patients with treatment-resistant depression.
It helped "at least while they were getting the ketamine, then there was a relapse that came in as few as a couple days to several months or longer in a few cases," he said.
Dr. Murrough said he and his colleagues are now "closing out" another study of ketamine that should be published in a couple of months. Other trials are ongoing.
"The jury is still out on whether ketamine itself could be developed into a bona fide treatment. We happen to believe that it can be. We advocate a cautious approach, but we are cautiously optimistic that ketamine could be a treatment option for severe refractory depression," he said.
"The benchmark treatment right now for severe refractory depression is electroconvulsive therapy [ECT]," Dr. Murrough pointed out, "so you'd have to believe that ketamine has a worse risk-benefit profile than ECT, and so far, we don't see that; it appears to be very well tolerated."
Dr. Duman and Dr. Aghajanian have disclosed no relevant financial relationships. In the past 2 years, Dr. Murrough has received research support from Evotec Neurosciences and Janssen Research & Development. Dr. Charney has been named as an inventor on a use patent of ketamine for the treatment of depression. If ketamine were shown to be effective in the treatment of depression and received approval from the US Food and Drug Administration for this indication, Dr. Charney and Mount Sinai School of Medicine could benefit financially.
Posted by ChicagoKat on October 12, 2012, at 20:40:55
In reply to Ketamine Viable Option For TX Resistant Depression, posted by phillipa on October 12, 2012, at 18:35:28
I was excited when I first heard of Ketamine, but when I asked my pdoc about it, he said unfortunately it didn't look like it was gonna go anywhere, that he had a colleague who had been involved in a study of it who said it just didn't seem to be a viable option.
But who knows. They could be wrong. And even if Ketamine doesn't pan out, at least researchers have a different mechanism to treat depression to check out.
Kat
Posted by phillipa on October 12, 2012, at 23:02:47
In reply to Re: Ketamine Viable Option For TX Resistant Depression » phillipa, posted by ChicagoKat on October 12, 2012, at 20:40:55
Kat were you here when JohnLA got ketamine? He hasn't been around in a while hope a good sign. Phillipa
Posted by bennybenzo on October 13, 2012, at 4:39:01
In reply to Re: Ketamine Viable Option For TX Resistant Depression » ChicagoKat, posted by phillipa on October 12, 2012, at 23:02:47
This is on an off topic, 20 years ago a female vetinary in my town killed herself with a massive dose of ketamine. At the time everyone said W.T.F is ketamine, it was so bizzare at the time that someone killed themself on horse meds . Now the kids in ENGLAND take it for a high .
Posted by ChicagoKat on October 13, 2012, at 15:14:26
In reply to Re: Ketamine Viable Option For TX Resistant Depression » ChicagoKat, posted by phillipa on October 12, 2012, at 23:02:47
> Kat were you here when JohnLA got ketamine? He hasn't been around in a while hope a good sign. Phillipa
Nope, don't think I was around for that; at least I don't recall it.
How did the Ketamine work for him?
Kat
Posted by ChicagoKat on October 13, 2012, at 15:15:56
In reply to Re: Ketamine Viable Option For TX Resistant Depression, posted by bennybenzo on October 13, 2012, at 4:39:01
> This is on an off topic, 20 years ago a female vetinary in my town killed herself with a massive dose of ketamine. At the time everyone said W.T.F is ketamine, it was so bizzare at the time that someone killed themself on horse meds . Now the kids in ENGLAND take it for a high .
The kids here in idiot america abuse it too...good ol Special K
Posted by phidippus on October 13, 2012, at 16:23:24
In reply to Ketamine Viable Option For TX Resistant Depression, posted by phillipa on October 12, 2012, at 18:35:28
OH MY GOD YOU HAVE A SQUIRREL FACE! GET AWAY FROM ME!!!
Eric
Posted by phillipa on October 13, 2012, at 23:59:57
In reply to Re: Ketamine Viable Option For TX Resistant Depression » phillipa, posted by phidippus on October 13, 2012, at 16:23:24
I'm assuming this is an hallucination from ketamine? Phillipa
Posted by phidippus on October 14, 2012, at 0:41:21
In reply to Re: Ketamine Viable Option For TX Resistant Depression » phidippus, posted by phillipa on October 13, 2012, at 23:59:57
Yes.
Eric
Posted by phillipa on October 14, 2012, at 10:09:39
In reply to Re: Ketamine Viable Option For TX Resistant Depression » phillipa, posted by phidippus on October 14, 2012, at 0:41:21
Phew for a minute thought a squirrel was on my face or you had lost it!!! Just kidding. Phillipa
Posted by phidippus on October 14, 2012, at 19:09:23
In reply to Re: Ketamine Viable Option For TX Resistant Depression » phidippus, posted by phillipa on October 14, 2012, at 10:09:39
I am losing it!
Eric
Posted by phillipa on October 14, 2012, at 22:05:30
In reply to Re: Ketamine Viable Option For TX Resistant Depression » phillipa, posted by phidippus on October 14, 2012, at 19:09:23
What's happening am I a squirrel face again? Phillipa
Posted by phidippus on October 14, 2012, at 22:30:46
In reply to Re: Ketamine Viable Option For TX Resistant Depression » phidippus, posted by phillipa on October 14, 2012, at 22:05:30
No. You're good. I'm good.
Eric
Posted by iforgotmypassword on October 15, 2012, at 10:35:33
In reply to Ketamine Viable Option For TX Resistant Depression, posted by phillipa on October 12, 2012, at 18:35:28
Posted by iforgotmypassword on October 15, 2012, at 10:39:33
In reply to idgi, what are they patenting? use seems unlikely. (nm), posted by iforgotmypassword on October 15, 2012, at 10:35:33
for "novel uses" of existing rx drugs. it never seems to go anywhere. no one is happy with the money they stand to make i guess, and no doctor is really interested in going that far into off-label therapies. if it's intravenous, it seems unlikely patients can guide prescribing here.
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