Depressive illness was described by
Hippocrates in ancient Greece, but
effective therapeutic agents did not
emerge until the 1950s. Today, almost
all antidepressant drugs in clinical use
increase levels of certain
neurotransmitters in the brain, in
particular norepinephrine and
Although these medications are
beneficial, a sizeable minority of
patients remain resistant to their
therapeutic effects. Moreover, in most
patients, there is a delay of weeks to
months before the drugs take full
effect. As a result, there is an urgent
need to develop faster-acting drugs.

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.

So Dr Ronald Duman, professor of
psychiatry and pharmacology at Yale
and colleagues decided to investigate
the effect of ketamine on the brain to
see if it might reveal suitable targets
for other safer and easier to administer

They found that ketamine acts on a
pathway that controls the formation of
new synaptic links between neurons,
encouraging synaptogenesis; they
wrote that they observed:

We observed that ketamine rapidly
activated the mammalian target of
rapamycin (mTOR) pathway, leading to
increased synaptic signaling proteins
and increased number and function of
new spine synapses in the prefrontal
cortex of rats.
Moreover, blockade of mTOR signaling
completely blocked ketamine induction
of synaptogenesis and behavioral
responses in models of depression.
Our results demonstrate that these
effects of ketamine are opposite to the
synaptic deficits that result from
exposure to stress and could
contribute to the fast antidepressant
actions of ketamine.

Current blockbuster drugs: bipolar
disorder drug Seroquel, made by

Eli Lilly &  Co.'s Zyprexa for treating
bipolar disorder and schizophrenia;

Potential blockbusters: paliperidone
palmitate for treating schizophrenia, is
being developed by Johnson &  
Johnson, with NanoCrystal technology
from Elan Corp,