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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 SLS on August 7, 2006, at 20:02:08
Experimental Medication Kicks Depression in Hours Instead of Weeks
People with treatment-resistant depression experienced symptom relief in as little as two hours with a single intravenous dose of ketamine, a medication usually used in higher doses as an anesthetic in humans and animals, in a preliminary study. Current antidepressants routinely take eight weeks or more to exert their effect in treatment-resistant patients and four to six weeks in more responsive patients — a major drawback of these medications. Some participants in this study, who previously had tried an average of six medications without relief, continued to show benefits over the next seven days after just a single dose of the experimental treatment, according to researchers conducting the study at the National Institutes of Health’s National Institute of Mental Health.
This is among the first studies of humans to examine the effects of ketamine on depression, a debilitating illness that affects 14.8 million people in any given year. Used in very low doses, the medication is important for research, but is unlikely to become a widely used clinical treatment for depression because of potential side effects, including hallucinations and euphoria, at higher doses. However, scientists say this research could point the way toward development of a new class of faster- and -longer-acting medications. None of the patients in this study, all of whom received a low dose, had serious side effects. Study results were published in the August issue of the Archives of General Psychiatry.
“The public health implications of being able to treat major depression this quickly would be enormous,” said NIH Director Elias A. Zerhouni, M.D. “These new findings demonstrate the importance of developing new classes of antidepressants that are not simply variations of existing medications.”
For this study 18 treatment-resistant, depressed patients were randomly assigned to receive either a single intravenous dose of ketamine or a placebo (inactive compound). Depression improved within one day in 71 percent of all those who received ketamine, and 29 percent of these patients became nearly symptom-free within one day. Thirty-five percent of patients who received ketamine still showed benefits seven days later. Participants receiving a placebo infusion showed no improvement. One week later, participants were given the opposite treatment, unless the beneficial effects of the first treatment were still evident. This “crossover” study design strengthens the validity of the results.
“To my knowledge, this is the first report of any medication or other treatment that results in such a pronounced, rapid, prolonged response with a single dose. These were very treatment-resistant patients,” said NIMH Director Thomas R. Insel, M.D.
Ketamine blocks a brain protein called the N-methyl-D-aspartic acid (NMDA) receptor. Previous studies have shown that agents that block the NMDA receptor reduce depression-like behaviors in animals.
NMDA receptors are critical for receiving the signals of glutamate, a brain chemical that enhances the electrical flow among brain cells that is required for normal function. Studies indicate that dysregulation in glutamate could be among the culprits in depression. Using ketamine to block glutamate’s actions on the NMDA receptor appears to improve function of another brain receptor — the AMPA receptor — that also helps regulate brain cells' electrical flow.
Scientists think the reason current antidepressant medications take weeks to work is that they act on targets close to the beginning of a series of biochemical reactions that regulate mood. The medications’ effects then have to trickle down through the rest of the reactions, which takes time. Scientists theorize that ketamine skips much of this route because its target, the NMDA receptor, is closer to the end of the series of reactions in question.
“This may be a key to developing medications that eliminate the weeks or months patients have to wait for antidepressant treatments to kick in,” said lead researcher Carlos A. Zarate Jr., of the NIMH Mood and Anxiety Disorders Program.
The researchers who conducted the study now are zeroing in on other areas of the glutamate system. Specifying which components of the system are affected by compounds such as ketamine may help scientists understand how and why depression occurs, reveal biological markers that may one day aid in diagnosis, and point the way to more precise targets for new medications.
Dr. Zarate was joined in this research by Husseini K. Manji, chief of the NIMH Mood and Anxiety Disorders Program, and colleagues Jaskaran B. Singh, Paul J. Carlson, Nancy E. Brutsche, Rezvan Ameli, David A. Luckenbaugh, and Dennis S. Charney.
Posted by SLS on August 7, 2006, at 20:21:07
In reply to Ketamine used to treat depression - NIMH, posted by SLS on August 7, 2006, at 20:02:08
These same investigators found that memantine, another NMDA receptor antagonist, was ineffective in treating depression. This was my experience as well, although I did experience a brief mild improvement early in treatment at 20mg/day. I don't know what differentiates ketamine from memantine pharmacologically.
---------------------------------------------------------
: Am J Psychiatry. 2006 Jan;163(1):153-5. Related Articles, Links
Click here to read
A double-blind, placebo-controlled study of memantine in the treatment of major depression.Zarate CA Jr, Singh JB, Quiroz JA, De Jesus G, Denicoff KK, Luckenbaugh DA, Manji HK, Charney DS.
Mood and Anxiety Disorders Program, National Institute of Mental Health, Department of Human Health Services, Bethesda, MD, USA. zaratec@mail.nih.gov
OBJECTIVE: This study was designed to assess possible antidepressant effects of memantine, a selective N-methyl-D-aspartate (NMDA) receptor antagonist in humans. METHOD: In a double-blind, placebo-controlled study, 32 subjects with major depression were randomly assigned to receive memantine (5-20 mg/day) (N=16) or placebo (N=16) for 8 weeks. Primary efficacy was assessed by performance on the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: The linear mixed models for total MADRS scores showed no treatment effect. CONCLUSIONS: In an 8-week trial, the low-to-moderate-affinity NMDA antagonist memantine in doses of 5-20 mg/day was not effective in the treatment of major depressive disorder.
Posted by JahL on August 7, 2006, at 20:35:12
In reply to Ketamine used to treat depression - NIMH, posted by SLS on August 7, 2006, at 20:02:08
You beat me to it by a few minutes!
Interesting article.
Later,
J.
Posted by SLS on August 7, 2006, at 20:49:39
In reply to Re: Ketamine used to treat depression - NIMH » SLS, posted by JahL on August 7, 2006, at 20:35:12
Hi J.
The NIMH used to do an interesting thing with procaine. They would infuse it into depressed patients as a challenge to see how they would react. Many people demonstrated an immediate antidepressant response. For some, it was the only time they had felt well in decades. It only lasted for a fraction of an hour.
- Scott
Posted by JahL on August 7, 2006, at 21:08:44
In reply to Re: Ketamine used to treat depression - NIMH » JahL, posted by SLS on August 7, 2006, at 20:49:39
> Hi J.
>
> The NIMH used to do an interesting thing with procaine. They would infuse it into depressed patients as a challenge to see how they would react. Many people demonstrated an immediate antidepressant response.> For some, it was the only time they had felt well in decades.
:-)
> It only lasted for a fraction of an hour.
:-(
It reminds me of an experiment involving self-confessed Cocaine 'connoisseurs'. They were given similar doses of Procaine and Cocaine and guess what? None of them could accurately differentiate between the two, thus going some way to dispelling the notion that Cocaine has 'special', 'unique' properties.
Anyone who knows me will know I hold liberal attitudes towards recreational drugs, but I have somewhat ambivalent feelings towards Coke. It can be pleasant but I see it as something of an 'Ego-Fuel'; users do not stop talking about themselves, their job, their sports car etc.
Anyway, back to Ketamine before Bob redirects.
See ya Scott,
J.
Posted by linkadge on August 7, 2006, at 21:09:16
In reply to Re: Ketamine used to treat depression - NIMH » JahL, posted by SLS on August 7, 2006, at 20:49:39
It still bothers me that a side effect of euphoria, automatically puts the drug into a "unusable" category.
You'd be suprised the number of "cures" have come and gone based on a small potential for abuse. Oh sure they'll try and tweek the molecule, but I hightly doubt they'll find a drug thats as effetive without the "abuse potential"
Linkadge
Posted by SLS on August 7, 2006, at 21:16:27
In reply to Re: Ketamine used to treat depression - NIMH, posted by linkadge on August 7, 2006, at 21:09:16
> You'd be suprised the number of "cures" have come and gone based on a small potential for abuse.
I know. Look at amineptine.
- Scott
Posted by linkadge on August 7, 2006, at 21:25:11
In reply to Re: Ketamine used to treat depression - NIMH » SLS, posted by JahL on August 7, 2006, at 21:08:44
Its all about the 'pleasure principle'. Pleasure and depression just don't mix, they are like oil and water.
Even the meagre antdiepressant effects of the SSRI's and TCA's are dependant on an upregulation of receptors sites involved in hedonic capacity. A couple of studies have shown that for most recovered antidepressant users, a d2 antagonist will abolish the clinical effect.
It is only when you increase hedonic capacity that people will report feeling any better.
Doctors want this silver bullit that just doesn't exist.
I say, if you find something that can sustainably help depression, then who cares if it causes mood improvement in normal people, who cares if a deeply depressed person feels slightly euphoric.
Linkadge
Posted by Phillipa on August 7, 2006, at 22:13:51
In reply to Re: Ketamine used to treat depression - NIMH, posted by linkadge on August 7, 2006, at 21:25:11
Link you know what helped my depression? Percocet just l at night. That was when I broke my elbow. We told the doc and he said "oh you can't take that it's addictive." I got mad and said then I'm going back to drinking it's legal. Love Phillipa You know what I mean I was laughing for the first time in years. No pleasure.
Posted by JahL on August 7, 2006, at 22:23:49
In reply to Re: Ketamine used to treat depression - NIMH, posted by linkadge on August 7, 2006, at 21:25:11
> I say, if you find something that can sustainably help depression, then who cares if it causes mood improvement in normal people, who cares if a deeply depressed person feels slightly euphoric.
I know. It makes me laugh - in an angry, resentful way - when 'euphoria' is labelled as an 'adverse' side effect. So long as a little euphoria doesn't impinge upon normal functioning, what_is_the_problem?
What do the authorities have to fear from people actually feeling *better* than normal (besides the hoary old 'people won't work/consume' chestnut)?
J.
Posted by Jost on August 8, 2006, at 12:29:33
In reply to Re: Ketamine used to treat depression - NIMH, posted by JahL on August 7, 2006, at 22:23:49
Wonder if it's because the PTB are so worried that some users will become addicted to it.
I've noticed on a couple of medications to help people who use pain meds, there've been strange, long hold-ups in the process at the federal level-- it seems possible that it's because they don't want to allow anything that could also help addicts. Even though they sacrifice the welfare of people with intense or chronic pain, etc.
A question of skewed priorities, IMHO.
Jost
Posted by linkadge on August 8, 2006, at 17:14:31
In reply to Re: Ketamine used to treat depression - NIMH » linkadge, posted by Phillipa on August 7, 2006, at 22:13:51
You can't take percocet cause its addictive yet you can take luvox cause its not (????)
It seems strange to me, since you got off percocet but you're still can't get off luvox. (no insult intended just trying to compare what doctors call addictive)
Linkadge
Posted by linkadge on August 8, 2006, at 17:22:23
In reply to Re: Ketamine used to treat depression - NIMH, posted by Jost on August 8, 2006, at 12:29:33
When people say 'addict' they form a certain picture in their mind.
Yet, if somebody missed their 450mg effexor dose they would go into "acute toxic shock delerium freak-out" (no thats not a medical term). If effexor was illegal, they might even rob a bank if thats what it took to prevent the withdrawl.
Yet, they're not addicted to their medications (?)What we need is not more restictions to drug development, but more restrictions to drug dispensing.
Linkadge
Posted by Phillipa on August 8, 2006, at 20:53:05
In reply to Re: Ketamine used to treat depression - NIMH » Phillipa, posted by linkadge on August 8, 2006, at 17:14:31
Believe me Link I understand. Yup up to 50mg of luvox again. I think going from l50mg to 25mg in two weeks was too fast. And I do think I'm an opiod responder. So should I walk the steets and buy pain meds from dealers? Love Phillipa
Posted by Phillipa on August 8, 2006, at 20:57:42
In reply to Re: Ketamine used to treat depression - NIMH » linkadge, posted by Phillipa on August 8, 2006, at 20:53:05
Oh I'm not bailing just slowing down for a couple of weeks. I stopped the lamictal at the same time due to salivation spitting disgusting and itching horribly, and I've changed to klonopin. Too many changes too fast for me. Plus after 3years my husband is starting work for himself tomorrow and the chores he did will be mine. And frankly I'm scared of being alone and doing those things again. So working on the anxiety first. Love Phillipa
Posted by SLS on August 12, 2006, at 7:07:59
In reply to Memantine fails to treat depression - NIMH, posted by SLS on August 7, 2006, at 20:21:07
> These same investigators found that memantine, another NMDA receptor antagonist, was ineffective in treating depression.
Despite this, I know of a reputable psychiatrist who is reporting success using memantine in treatment resistant cases. I imagine there are more. It has been used to treat depression occasionally in Germany for at least ten years.
- Scott---------------------------------------------------------
>
>
> : Am J Psychiatry. 2006 Jan;163(1):153-5. Related Articles, Links
> Click here to read
> A double-blind, placebo-controlled study of memantine in the treatment of major depression.
>
> Zarate CA Jr, Singh JB, Quiroz JA, De Jesus G, Denicoff KK, Luckenbaugh DA, Manji HK, Charney DS.
>
> Mood and Anxiety Disorders Program, National Institute of Mental Health, Department of Human Health Services, Bethesda, MD, USA. zaratec@mail.nih.gov
>
> OBJECTIVE: This study was designed to assess possible antidepressant effects of memantine, a selective N-methyl-D-aspartate (NMDA) receptor antagonist in humans. METHOD: In a double-blind, placebo-controlled study, 32 subjects with major depression were randomly assigned to receive memantine (5-20 mg/day) (N=16) or placebo (N=16) for 8 weeks. Primary efficacy was assessed by performance on the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: The linear mixed models for total MADRS scores showed no treatment effect. CONCLUSIONS: In an 8-week trial, the low-to-moderate-affinity NMDA antagonist memantine in doses of 5-20 mg/day was not effective in the treatment of major depressive disorder.
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