Ketamine is an anesthetic used in human and veterinary
medicine, and its ability to rapidly reduce depressive symptoms in people who
have responded insufficiently to antidepressants has generated great interest
in the scientific and clinical communities. A study of 72 patients, presented in
2013 at the American Psychiatric Association annual meeting, found that more
than half reported fewer symptoms after one intravenous dose of ketamine.
Ketamine, a drug, which has not been federally approved yet
to treat depression, not only works quickly but its effects also can last three
to five days or more, said Dr. Carlos Zarate, chief of the section on the
neurobiology and treatment of mood disorders at the National Institute of
Mental Health.
Those qualities mean it could be useful for patients in
danger of committing suicide, Zarate said.
The clinical effectiveness of Ketamine in the latest
scientific reports sounds too good to be true, particularly when compared with
anything else on the market. The effects take hold within days (if not hours,
compared with weeks to months for SSRIs), they seem to work for most people, there
seem to be few discernible side effects, and it seems to be equally effective
in the treatment of bipolar depression (which is notoriously hard to treat).
Main Facts about
Ketamine
* Ketamine acts fast. About 25% of the all recipients
claim to start feeling better in just an hour or in a couple of hours. Another
50% of people claim to feel substantially better by the next day.
* Few FDA approved drugs have a reputation as
controversial as Ketamine. This reputation is well earned. Originally developed
in the 1960s as a short-acting anesthetic for battlefield use, in recent
decades it has become notorious as a date-rape drug (‘Special K’), a club drug
(‘Vitamin K’) and for its use in veterinary medicine (‘horse tranquilizer’).
So, Ketamine is not, as many believe, just a horse tranquilizer. That is a line
from the movies that has become an urban legend. Ketamine is an anesthetic,
developed over 50 years ago and used safely in tens of millions of medical
procedures a year since then. When used under medical supervision, it is a very
safe drug. It is listed by the World Health Organization as one of the world’s
essential medications.
* When Ketamine was used as a battlefield anesthetic in
Vietnam and the first Gulf war, it was anecdotally noted that wounded soldiers
such treated developed far fewer cases of PTSD than soldiers with similar
injuries that were treated with other anesthetics.
* The effects and side effects of Ketamine are very dose
dependent – the more drug you get, the greater the effects. At low dosages,
Ketamine repairs nerve cells in the brain damaged by depression. At moderate
dosages, Ketamine causes extreme drowsiness and is useful as an anesthetic in
surgical procedures – you may well have already had Ketamine in some point of
your life before. At high dosages, Ketamine is abused on the street and has
several dangerous side effects that do not happen at lower dosages. As a street
drug, abusers snort in one day the full ten-year dose for depression, causing
severe hallucinations - doing that is not going to have a happy ending.
* Ketamine must be given via IV to be effective. Dose
control is critical to achieving the anti-depressant effect, and other modes of
administration are not capable of achieving the needed precision.
Low-dose Ketamine
Treatment
The respectable researchers at Mayo Clinic have also found
that Ketamine is very effective at treating depression when administered over a
long period. The study, published in the Journal of Psychopharmacology,
revealed that prolonged, low-dose intravenous infusions of Ketamine, have
excellent potential in reducing the symptoms of severe depression.
About ten years ago researchers identified that Ketamine
has properties that can help alleviate depression. However, given the serious
psychiatric side effects of the drug, experts have been looking for the safest
ways to use it.
Co-author Timothy Lineberry, M.D., a Mayo Clinic psychiatrist,
said: "It's surprising both that it works and how rapidly it has effects. It
sometimes can work in hours to reduce depressive symptoms and suicidal
ideation. Our goal is to begin to determine how the drug can be administered
safely in routine treatment."
A total of 10 patients with either a major depressive
disorder or type of bipolar disorder were included in the study. All of the
participants failed to respond to anti-depressant medications. The patients
were all treated with low-dose ketamine infusions (0.5 mg/kg total dose), up to
twice a week, until their symptoms of depression went away.
Ketamine proved to be very effective at helping the
patients recover. In addition, the authors found that ketamine infusions at low
rates worked just as well as higher infusion rates.
Dr. Lineberry concluded: "While patients and
clinicians are excited about ketamine's potential, we know that much more
research lies ahead before we know which depressive conditions can be addressed
with ketamine safely by clinicians in routine clinical practice."
The researchers evaluated the side effects of the drug
with two different psychiatric scales: "the Young Mania Rating Scale"
and the "Brief Psychiatric Rating Scale". Eighty percent of the
participants showed signs of significant improvement. During the study five
patients had no depression symptoms at all, four weeks after the study was
completed two of them were still in remission.
Researchers monitored side effects with two psychiatric
scales, the Young Mania Rating Scale and the Brief Psychiatric Rating Scale.
Eight of 10 patients showed at least 50 percent improvement.
Side effects of the drug included:
* Brief and limited hallucinations
* Drowsiness
* Dizziness
Further Research
The evidence for the antidepressant effectiveness of
Ketamine is so overwhelming that quite a few pharmaceutical companies are
feverishly working on Ketamine analogues and delivery methods (e.g. nasal
sprays) as well as alternative NMDA modulators that can be patented and thus
would be worthwhile to put through the highly demanding FDA approval process.
Preliminary results are so promising that one can reasonably hope to have truly
effective antidepressants available within another decade or so. If this
happens, a mental health revolution will be at hand. And it will be sorely
needed. Having rapidly acting and unequivocally effective antidepressants
widely available and covered by insurance (akin to antibiotics) will make all
the difference.
HNK as an
Alternative
One of the latest researches discovered that the Hydroxynorketamine
(HNK), a by-product of the psychoactive drug ketamine, may treat symptoms of
depression just well as ketamine without the unwanted side effects.
"We found that the HNK compound significantly
contributes to the antidepressive effects of ketamine in animals but doesn't
produce the sedation or anesthesia, which makes HNK an attractive alternative
as an antidepressant in humans”, noticed Irving Wainer, PhD, senior
investigator with the Intramural Research Program at the National Institute on
Aging, in Baltimore, Maryland. Dr. Wainer is listed as a coinventor on a patent
application for the use of ketamine metabolites in the treatment of bipolar
disorder and major depression. He suggests that HNK, like ketamine, not only
produced potent and rapid antidepressant effects but also stimulated
neuroregenerative pathways and initiated the regrowth of neurons in rats'
brains.
Obviousely, more clinical research is required before
offering the NHK administration to overcome depression in humans, however, the
preliminary results are quite promising.
Ketamine Self-Administration
Commonly used as an anesthetic for both humans and
animals, ketamine is described by the U.S. Drug Enforcement Administration as a
dissociative anesthetic with hallucinogenic properties. Some users say that,
when taken at high enough doses, the drug can induce a terrifying out-of-body
experience known commonly as a "K-hole." The drug is also known to
cause anxiety, amnesia and cognitive difficulties.
Medical experts have strictly warned against
self-medicating with ketamine. In clinical studies, the drug is typically
administered only in small doses, and patients are always supervised closely.
While that might be very tempting to try it to relieve
your depression symptoms, we would warn you against such attempts. As you will
not be able to determine the proper dosage, the potential positive effect might
be overpowered by the unexpected side effects from the drug consumption.
Sources and
Additional Information:
Updates 08-22-16
Aug. 18, 2016 -- The experimental drug esketamine (also
known as ketamine) has been placed on the fast track for U.S. Food and Drug
Administration approval for treating major depression, according to Janssen
Pharmaceutical.
Ketamine -- perhaps best known as a street drug -- is
listed by the World Health Organization as an important anesthetic and has been
used off-label for pain, anxiety, depression and post-traumatic stress
disorder, CNN reported.
In 1970, the drug received FDA approval for use in people
and was used on American soldiers in Vietnam as an analgesic and sedative.
However, doctors became reluctant to use it because it caused minor
hallucinogenic side effects.
Depression causes damage to nerves and their transmission
pathways, and research leads scientists to believe ketamine remodels those
nerves, triggering neuroplastic processes that make new connections among brain
cells, Dr. Dan Iosifescu of the Icahn School of Medicine at Mount Sinai in New
York City told CNN. "What's unique about ketamine is, this happens in
hours or days, while with other depression medications, this happens in weeks
to months," he said.
