Depression is a medical illness in
which a person has feelings of
sadness, discouragement, and a lack
of self-worth.
Depression affects an estimated 17.5
million men and women in the United
States of whom 9.2 million have major
or clinical depression.

About ten years ago, scientists at
Connecticut Mental Health Center
found that in lower doses, ketamine,
normally used as a general anasthetic
for children, appeared to relieve
patients with depression.

Since then, other studies have shown
that over two thirds of patients who
don't respond to all other types of anti-
depressants improved hours after
receiving ketamine.

The problem with using ketamine more
widely to treat depression has been
the fact it has to be given
intravenously under medical
supervision, and it can also cause
short-term psychotic symptoms.

Unlike commercially available
antidepressants, which require weeks
or months to take effect, a single dose
of ketamine can overcome depression
in hours, a speed advantage that can
spell the difference between life and
death for suicidal patients.
Researchers at Yale University School
of Medicine have now discovered why
the compound works so fast.

Depression is believed to correlate
with a reduction in the number of
synapses, or connections between
neurons, in the prefrontal cortex of the
brain, notes Ronald S. Duman, who
studies molecular psychiatry and
pharmacology at Yale. Duman's team
now reports that ketamine undoes this
damage by increasing the number of
these synapses in rats within 24 hours
of administration, whereas traditional
treatments do not.

The researchers determined that
ketamine stimulates the mammalian
target of rapamycin (mTOR) signaling
pathway, which is involved in protein
synthesis and synaptic modification in
neurons. Ketamine activates this
pathway by preventing the
neurotransmitter glutamate from
binding to the N-methyl-D-aspartate
(NMDA) class of receptors on neurons.

Drugs that target this pathway would
provide an alternative to the
antidepressants currently on the
market, nearly all of which function by
boosting brain levels of
neurotransmitters such as serotonin
and norepinephrine.

Ketamine itself is unsuitable as a
commercial antidepressant. At doses
higher than required for the
antidepressant effect, it serves as an
anesthetic. It can induce
hallucinations—hence its popularity as
the street drug "Special K"—and it
must be injected. Ketamine can be
administered by a doctor, but this
practice is inconvenient because the
antidepressant effect of a dose wears
off after about a week.
The pharma industry is trying hard to
develop an acceptable version for
general use.
One lead is Ro 25-6981, a compound
originally developed by Roche.
Duman's team showed that the
compound acts on the mTOR pathway,
just as ketamine does. But Ro 25-6981
might avoid ketamine's side effects
because it activates only the NR2B
subclass of NMDA receptors, Duman

Last month, Roche and the drug
discovery and development firm
Evotec announced the start of Phase II
clinical studies of another potential
rapidly acting antidepressant, a
selective NR2B inhibitor called EVT


TMS means Transcranial Magnetic
TMS Therapy uses short pulses of
magnetic fields to stimulate nerve cells
in the area of the brain thought to
control mood. TMS Therapy is
performed in a psychiatrist’s office
under their supervision while you
remain awake and alert.
NeuroStar TMS Therapy from
Neuronetics Inc  is an outpatient
procedure. The typical treatment
course consists of 5 treatments per
week over a 4-6 week period for 20-30
treatments. Each treatment session
lasts approximately 37 minutes.
Relapse rates for patients with
treatment-resistant major depression
were much lower following transcranial
magnetic stimulation (TMS) than is
normally seen with drugs or
electroconvulsive therapy, according
to a recent study.
At the moment one of the major
barriers to TMS in the US  is that,
despite the FDA approval, most
insurers won't pay for it, but that is
slowly changing.
A course of treatment costs about

Dr Mark George, a neurologist at
Medical University of South Carolina  
recently published a study showing
that brief pulses of TMS as surgery
patients roll out of the operating room  
reduce their need for pain relief from a
morphine pump. TMS may speed the
excruciating process of post-stroke
rehabilitation, lower the volume of
auditory hallucinations and ringing in
the ears, and provide a midflight
attention boost to fatigued pilots.
That's drawn the Pentagon's interest.

George sees endless ways to refine
the technology—reducing the number
of treatment sessions, for example, if,
as he suspects, the brain can tolerate
more stimulation over less time.
Meantime, to depressed patients for
whom drugs haven't worked, six weeks
of painless, noninvasive therapy
counts as a vast improvement.

Cyberonics  recently reported results
from a dosing study (D-21) that was
conducted as a condition for gaining
US Food and Drug Administration
(FDA) approval, for Vagus Nerve
Stimulation (VNS) Therapy. This
therapy was approved in July 2005 for
patients suffering from chronic and
recurrent treatment-resistant
depression. It is also approved for the
treatment of refractory epilepsy.

Results from the dosing study showed
a sustained, consistent and clinically
meaningful reduction in depression
symptoms across all treatment groups.
Adjunctive VNS Therapy was found to
provide improving efficacy over time at
all dosage levels. The study found that
long-term (50 weeks) VNS Therapy
improved symptoms of depression
from 32.4% to 42.0%. Meanwhile,
response rates ranged from 26.7% to
53.3%; and remission rates ranged
from 14.6% and 22.5%.

Cyberonics faces strong competition
from players like Medtronic and St.
Jude Medical.

Stewart R. and Hirani V from King's
College London and University College
London Medical School in the United
Kingdom published in the July 1, 2010
issue of Psychosomatic Medicine
saying depressive symptoms in older
people were linked with clinical vitamin
D deficiency defined as having 25(OH)
D levels lower than 10 ng/mL.

Another study led by May H.T. and
colleagues from Intermountain Medical
Center in Murray, UT  and published in
the June 2010 issue of American Heart
Journal shows that vitamin D levels
were associated with incident
depression among people aged 50 or
older who had cardiovascular disease,
but no history of depression.