Tiny Human Ferret
2006-08-09 02:41:29 UTC
http://www.biopsychiatry.com/ketaminedep.htm
Background: A growing body of preclinical research suggests
that brain glutamate systems may be involved in the
pathophysiology of major depression and the mechanism
of action of antidepressants. This is the first
placebo-controlled, double-blinded trial to assess the
treatment effects of a single dose of an N-methyl-D-aspartate
(NMDA) receptor antagonist in patients with depression.
Methods: Seven subjects with major depression completed
2 test days that involved intravenous treatment with
ketamine hydrochloride (.5 mg/kg) or saline solutions
under randomized, double-blind conditions.
Results: Subjects with depression evidenced
significant improvement in depressive symptoms
within 72 hours after ketamine but
not placebo infusion (i.e., mean 25-item Hamilton
Depression Rating Scale scores decreased by 14 +/- SD
10 points vs. 0 +/- 12 points, respectively during
active and sham treatment).Conclusions: These results
suggest a potential role for NMDA receptor-modulating
drugs in the treatment of depression.
http://www.clinicaltrials.gov/ct/show/NCT00088699
http://abcnews.go.com/Health/Depression/story?id=2282814&page=1
http://www.healthfinder.gov/news/newsstory.asp?docID=534229
MONDAY, Aug. 7 (HealthDay News) -- A single dose of
an anesthesia drug produced relief from depression in
as little as two hours in a small group of patients
for whom several other treatments had failed,
U.S. government researchers report.
The researchers said, however, that the drug, ketamine,
is unlikely to be used in the treatment of depression
because of possible side effects, including psychosis.
But the new finding does signal an important direction
for future research.
Currently available antidepressants can take weeks to work.
"That was similar to the sound barrier. We felt
we couldn't pass it," said Dr. Carlos A. Zarate Jr.,
lead author of the study and chief of the mood disorders
research unit at the National Institute of Mental Health.
He added, "Now the sound barrier is broken. That doesn't
mean you can get on the plane and take off right away,
but it means it's possible that we can come up with
a treatment that works very rapidly. That's down the road."
Ketamine is novel not only for the speed of its effect,
but also because it targets a new system in the brain.
"It's novel because all antidepressants that
are currently available work on neurotransmitters
that are monoamines like dopamine and serotonin.
That's the focus of the current antidepressant armamentarium,"
explained Dr. Richard A. Friedman, director of the
psychopharmacology clinic at Cornell University's
Medical Center in New York City. "Ketamine involves
a particular system of the brain called glutamate.
It's the main excitory neurotransmitter in the brain,"
he said.
Depression is a chronic, disabling condition affecting
almost 15 million Americans -- almost 7 percent of
the adult U.S. population -- in any given year.
Some 4 percent of people with depression will
end their own lives, resulting in 30,000 suicides
each year.
Unfortunately, about half of people with depression
don't receive treatment and, of those who do get treatment,
only about 40 percent get the best, "evidence-based" treatment.
Some people still don't get better even with this
type of treatment, however.
This is one of the first studies in humans to look
at the effect of ketamine on depression, although
previous animal studies had shown promising results.
For the study, which is published in the August issue
of the Archives of General Psychiatry, 18
treatment-resistant patients with depression were
randomly assigned to receive either one intravenous
dose of ketamine or a placebo. Participants had tried
an average of six antidepressant medications
without success in the past.
Depression improved within one day in 71 percent of
participants who received ketamine; 29 percent of those
became nearly symptom-free within one day.
Thirty-five percent of those receiving ketamine
still showed benefits after several weeks. Those
in the placebo group showed no improvement.
One week later, participants were given
the opposite treatment, unless they were still showing a
benefit from the ketamine.
"People had tried six to seven antidepressants on average
and had been ill for 30 years. The current episode was
three years in duration," Zarate said. "All people
who went through this reported a tremendous relief of suffering."
Short-term side effects, including perception disturbances,
went away usually before the antidepressant effect
kicked in. Participants were given a relatively low dose,
so they did not experience the more severe side effects.
Ketamine works by blocking the N-methyl-D-aspartic acid
(NMDA) receptor, which receives signals for glutamate.
Using ketamine to block glutamate's action on the
NMDA receptor also seemed to have a secondary effect
on another brain receptor, the AMPA receptor.
Zarate and his team are now looking at several ways
to use this information for depressed patients.
"We're looking to see if we can refine ketamine
for clinical use by taking care of side effects," he said.
"We're also looking at other drugs."
More information
For more on depression, head to the National Institute of Mental Health.
(SOURCES: Carlos A. Zarate Jr., M.D., chief, mood disorders research
unit, National Institute of Mental Health, Bethesda, Md.; Richard A.
Friedman, M.D., director, psychopharmacology clinic, Cornell
University's Medical Center, New York City; August 2006, Archives of
General Psychiatry)
http://www.nimh.nih.gov/press/ketamine.cfm
Press Release
August 7, 2006
Contact: Susan Cahill
NIMH Press Office
301-443-4536
***@nih.gov
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.
Background: A growing body of preclinical research suggests
that brain glutamate systems may be involved in the
pathophysiology of major depression and the mechanism
of action of antidepressants. This is the first
placebo-controlled, double-blinded trial to assess the
treatment effects of a single dose of an N-methyl-D-aspartate
(NMDA) receptor antagonist in patients with depression.
Methods: Seven subjects with major depression completed
2 test days that involved intravenous treatment with
ketamine hydrochloride (.5 mg/kg) or saline solutions
under randomized, double-blind conditions.
Results: Subjects with depression evidenced
significant improvement in depressive symptoms
within 72 hours after ketamine but
not placebo infusion (i.e., mean 25-item Hamilton
Depression Rating Scale scores decreased by 14 +/- SD
10 points vs. 0 +/- 12 points, respectively during
active and sham treatment).Conclusions: These results
suggest a potential role for NMDA receptor-modulating
drugs in the treatment of depression.
http://www.clinicaltrials.gov/ct/show/NCT00088699
http://abcnews.go.com/Health/Depression/story?id=2282814&page=1
http://www.healthfinder.gov/news/newsstory.asp?docID=534229
MONDAY, Aug. 7 (HealthDay News) -- A single dose of
an anesthesia drug produced relief from depression in
as little as two hours in a small group of patients
for whom several other treatments had failed,
U.S. government researchers report.
The researchers said, however, that the drug, ketamine,
is unlikely to be used in the treatment of depression
because of possible side effects, including psychosis.
But the new finding does signal an important direction
for future research.
Currently available antidepressants can take weeks to work.
"That was similar to the sound barrier. We felt
we couldn't pass it," said Dr. Carlos A. Zarate Jr.,
lead author of the study and chief of the mood disorders
research unit at the National Institute of Mental Health.
He added, "Now the sound barrier is broken. That doesn't
mean you can get on the plane and take off right away,
but it means it's possible that we can come up with
a treatment that works very rapidly. That's down the road."
Ketamine is novel not only for the speed of its effect,
but also because it targets a new system in the brain.
"It's novel because all antidepressants that
are currently available work on neurotransmitters
that are monoamines like dopamine and serotonin.
That's the focus of the current antidepressant armamentarium,"
explained Dr. Richard A. Friedman, director of the
psychopharmacology clinic at Cornell University's
Medical Center in New York City. "Ketamine involves
a particular system of the brain called glutamate.
It's the main excitory neurotransmitter in the brain,"
he said.
Depression is a chronic, disabling condition affecting
almost 15 million Americans -- almost 7 percent of
the adult U.S. population -- in any given year.
Some 4 percent of people with depression will
end their own lives, resulting in 30,000 suicides
each year.
Unfortunately, about half of people with depression
don't receive treatment and, of those who do get treatment,
only about 40 percent get the best, "evidence-based" treatment.
Some people still don't get better even with this
type of treatment, however.
This is one of the first studies in humans to look
at the effect of ketamine on depression, although
previous animal studies had shown promising results.
For the study, which is published in the August issue
of the Archives of General Psychiatry, 18
treatment-resistant patients with depression were
randomly assigned to receive either one intravenous
dose of ketamine or a placebo. Participants had tried
an average of six antidepressant medications
without success in the past.
Depression improved within one day in 71 percent of
participants who received ketamine; 29 percent of those
became nearly symptom-free within one day.
Thirty-five percent of those receiving ketamine
still showed benefits after several weeks. Those
in the placebo group showed no improvement.
One week later, participants were given
the opposite treatment, unless they were still showing a
benefit from the ketamine.
"People had tried six to seven antidepressants on average
and had been ill for 30 years. The current episode was
three years in duration," Zarate said. "All people
who went through this reported a tremendous relief of suffering."
Short-term side effects, including perception disturbances,
went away usually before the antidepressant effect
kicked in. Participants were given a relatively low dose,
so they did not experience the more severe side effects.
Ketamine works by blocking the N-methyl-D-aspartic acid
(NMDA) receptor, which receives signals for glutamate.
Using ketamine to block glutamate's action on the
NMDA receptor also seemed to have a secondary effect
on another brain receptor, the AMPA receptor.
Zarate and his team are now looking at several ways
to use this information for depressed patients.
"We're looking to see if we can refine ketamine
for clinical use by taking care of side effects," he said.
"We're also looking at other drugs."
More information
For more on depression, head to the National Institute of Mental Health.
(SOURCES: Carlos A. Zarate Jr., M.D., chief, mood disorders research
unit, National Institute of Mental Health, Bethesda, Md.; Richard A.
Friedman, M.D., director, psychopharmacology clinic, Cornell
University's Medical Center, New York City; August 2006, Archives of
General Psychiatry)
http://www.nimh.nih.gov/press/ketamine.cfm
Press Release
August 7, 2006
Contact: Susan Cahill
NIMH Press Office
301-443-4536
***@nih.gov
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.
--
nam primi in omnibus proeliis oculi vincuntur.
nam primi in omnibus proeliis oculi vincuntur.