The other day I posted some
convincing arguments against the effectiveness of conventional SSRI antidepressants in treating depression. What that argument comes down to is the lack of evidence that depression is connected to low serotonin levels - what seems more likely is that raising serotonin levels essentially creates a "high" that masks the depression.
However, over the last several years there is increasing evidence that a drug never intended to treat mood disorders may be the most effective antidepressant ever developed. That drug is ketamine, and anesthetic - but it is also a popular (and illegal) club drug known as "Special K."
We have no idea how this drug really works, but it works far better than any current antidepressant developed specifically for that purpose. We suspect, at this point, that ketamine may alter - increase - the communication between neurons. This is far more rapid than the possible outcome from SSRI's, which depends on the creation of new neurons for any possible efficacy.
I've posted research supporting the use and efficacy of ketamine in the past, but there is a new article on NPR's site,
Shots: NPR's Health Blog.
Ketamine
has been used as an anesthetic for decades. It's also a widely popular
but illegal club drug known as "Special K." When administered in low
doses, patients report a rapid reduction in depression symptoms.
There's no quick fix for severe depression.
Although antidepressants like Prozac
have been around since the 1970s, they usually take weeks to make a
difference. And for up to 40 percent of patients, they simply don't
work.
As a result, there are limited options when patients show up in an emergency room with suicidal depression.
The doctors and nurses at Ben Taub General Hospital in Houston say they see this problem every day.
You
can get a sense of what they're up against by visiting the cavernous,
bustling emergency center at Ben Taub, which is part of the massive
Texas Medical Center. More than 100,000 patients a year get emergency
care here, and about 5,000 of them need psychiatric evaluation.
The
hospital's 24-hour Psychiatric Emergency Center gets a steady stream
of people with suicidal depression, says Charlzetta McMurray-Horton, who
is in charge of mental health nursing.
Ben Taub General Hospital
Ben Taub General Hospital in Houston sees 100,000 emergency patients a year, 5,000 of whom need psychiatric evaluation.
"If the police bring them in, they're
going to come through this door," McMurray-Horton says, pointing to one
entrance. "If the ambulance brings them in, they're going to come
through this door," she says, pointing to a different entrance.
And
one of the challenges in treating these severely depressed patients is
that there simply isn't any drug that provides quick relief, says Anu
Matorin, medical director of the Psychiatric Emergency Center.
Matorin
talks about one recent patient. The woman had suffered bouts of
depression since college, Matorin says. But after she had a baby, it
became severe. She stopped eating and sleeping. She began to think about
suicide.
Finally, the woman made a desperate call to her mother, Matorin says.
"She
was very emotional, very tearful, not making sense," Matorin says. "She
says, 'I just can't take it anymore. I don't know how to feed the
child.' The mother could hear the infant crying in the background."
The
family called 911, and the woman arrived at the hospital with a police
escort. Matorin says she evaluated the woman and put her on
antidepressants.
Then came the hard
part, Matorin says. She knew the drugs might help the woman eventually.
But they weren't going to do anything about her suicidal thoughts during
the next few critical days.
So Matorin did the only thing she could for her patient. She admitted her to the hospital's locked inpatient unit.
I ask to see the facility, so McMurray-Horton takes me there.
'Keep Them Safe, Keep Them Alive'
The
unit can handle 20 patients, and its main room is warmer, softer and
more colorful than you might expect. Think Holiday Inn, without any
sharp objects or hard edges.
But
there's no avoiding the fact that this is a place where safety is
paramount and privacy isn't, says McMurray-Horton. Shatterproof plastic
windows around the nurses' station provide unobstructed sightlines to
pretty much everywhere.
"Patients
don't want to be here," says McMurray-Horton, explaining that about
three-quarters of them are in the unit because they have been deemed a
threat to themselves or someone else.
So it's not surprising that our tour of the unit is interrupted by the loud protests of one enraged patient.
Units
like this are necessary in part because drugs for depression don't work
fast enough to help someone in the early days of a crisis, Matorin
says.
And McMurray-Horton says staff
members here have a simple goal for patients in crisis: "Keep them
safe, keep them alive until they're in a different space."
Counseling
can help, McMurray-Horton says. So can family. And she says most people
in crisis just start to feel better after a few days in a place where
staff make sure that "they stay in, and the world stays out."
That was certainly true of the depressed young mother that Matorin admitted. She got better and went home several days later.
But
that woman probably could have skipped the hospital stay altogether if
the drugs used to treat depression were as quick and effective as, say,
painkillers, Matorin says.
If drugs
were more effective, "I think it would transform psychiatric care and
really eliminate some of the stigma and fear and concern about
treatment," she says.
'A Completely Different Mechanism'
A growing number of scientists think it won't be long before psychiatric care is transformed.
And they are particularly excited about
an experimental drug that is being tried in the NeuroPsychiatric Center
next to Ben Taub hospital.
It's
here that drug researchers are studying a drug that's unlike anything
now used to treat depression. And they're giving it to patients who
haven't done well on existing drugs.
One
of these patients is Heather Merrill, who speaks to me in a small
conference room that is part of the large and very busy outpatient
clinic.
Merill is 41, with three kids and a nice house in the suburbs.
"I've
suffered from depression for most of my adult life," she says. "It got
to the point where I kind of felt like there wasn't going to be anything
that was going to be able to help me."
At
times her depression gets so bad that she can't take care of her family
or even herself, she says.
And that's how she was feeling the day
before, she says, when doctors placed an IV in her arm and began to
administer a drug.
Because it was
part of an experiment, there were two possibilities. The drug could have
been just a sedative. Or it might have been something called ketamine.
Ketamine
has been used for decades as an anesthetic. It also has become a wildly
popular but illegal club drug known as "Special K."
Mental health researchers got interested in ketamine because of reports that it could make depression vanish almost instantly.
In
contrast, drugs like Prozac take weeks or even months. And the
frustrating thing is that depression medications really haven't changed
much since Prozac arrived in the 1970s, says Sanjay Mathew from Baylor College of Medicine, who is in charge of the ketamine study at Ben Taub.
"Everything since then has been essentially incremental," he says. "There have been tweaks of existing molecules."
But ketamine represents much more than a tweak, Mathews says.
"It's
a completely different mechanism," he says. "And the focus is on really
rapidly helping someone get out of a depressive episode."
'No More Fogginess. No More Heaviness.'
Heather Merrill says she's pretty sure it was ketamine that flowed into her veins 24 hours earlier.
"It was almost immediate, the sense of calmness and relaxation," she says.
Some of the doctors think she might be right.
"Her
demeanor has changed tremendously," says Dr. Asim Shah, who directs the
mood disorder program at Ben Taub. "She looks like a happy person who
is genuinely happy, whereas before the study, she looked very down, very
withdrawn, sort of almost tearful."
But
of course, nobody knows whether Merrill actually got ketamine. That
information will be kept secret until the study is done, months from
now.
So I decide to see how Merrill's experience compares with the experiences of people who definitely took ketamine for depression.
I talk to Carlos Zarate,
who does ketamine research at the NIH and has never met Merrill. Zarate
says patients typically say, " 'I feel that something's lifted or feel
that I've never been depressed in my life. I feel I can work. I
feel I can contribute to society.' And it was a different experience
from feeling high. This was feeling that something has been removed."
I
compare this to what Merrill said about her experience: "No more
fogginess. No more heaviness. I feel like I'm a clean slate right now. I
want to go home and see friends or, you know, go to the grocery store
and cook the family dinner."
The similarities are hard to ignore.
And
researchers say the consistent patient reactions have actually made it
more difficult to do good studies of ketamine. The drug's effects are so
powerful and distinctive, they say, it's hard to prevent doctors and
patients in an experiment from figuring out who got the drug and who
didn't.
* * * * * * *
Sidebar: How Ketamine Works To Treat Depression
Traditional
antidepressants like Prozac work on a group of chemical messengers in
the brain called the serotonin system. Researchers once thought that a
lack of serotonin was the cause of depression, and that these drugs
worked simply by boosting serotonin levels.
Recent research suggests a more complicated explanation. Serotonin drugs work by stimulating the birth of new neurons,
which eventually form new connections in the brain. But creating new
neurons takes time — a few weeks, at least — which is thought to explain
the delay in responding to antidepressant medications.
Ketamine,
in contrast, activates a different chemical system in the brain – the
glutamate system. Researcher Ron Duman at Yale thinks ketamine rapidly increases the communication among existing neurons
by creating new connections. This is a quicker process than waiting for
new neurons to form and accomplishes the same goal of enhancing brain
circuit activity.
To study
how ketamine might work, Duman turned to rats. The first image below
shows the neuron of a rat that has received no ketamine treatment. The
small bumps and spots on the side of the neuron are budding connections
between neurons.
Ronald Duman/Yale University
Just
hours after giving the rats doses of ketamine, Duman saw a dramatic
increase in the number of new connections between brain cells. This
increase in neuronal connectivity is thought to relieve depression.
Ronald Duman/Yale University
From the author: The inspiration came from many years of personal research into a range of scientific fields including consciousness and psi research, psychology, biology, cosmology, quantum physics and philosophy of mind.
