Scientific American Mind-June/July 2007

(perspectives)
Good News about Depression
A surprising discovery could lead to faster-acting and highly effective drugs to treat
this devastating disorder BY WALTER BROWN
WORRISOME SIDE EFFECTS of antidepressants—that
they incite children
and adults to kill themselves—
have made headlines in recent years;
accordingly, the Food and Drug Administration
began to require warnings
on these medications in 2005.
Most experts, however, agree that this
labeling is unwarranted, that the science
in support of it is fl awed and that
the warning itself is detrimental to
public health—reasoning that it is
likely, if anything, to increase suicide
by discouraging treatment of depression.
Prescriptions for antidepressants
have already gone down.
Although it is true that antidepressants
can trigger unpleasant symptoms,
including agitation, sexual dysfunction
and weight gain, these side
effects are not the drugs’ main problem.
Their biggest shortcoming is that
often they do not work very well; fewer
than half the patients who take
them get complete relief, and that effect
takes an unacceptably long time—
two to three weeks—to kick in.
This is why a 2006 study led by
Carlos A. Zarate, chief of the National
Institute of Mental Health’s Mood and
Anxiety Disorders Research Unit, deserves
more than a passing mention: it
showed that a single infusion of ketamine,
a drug already used as a painkiller
and anesthetic, relieves depressive
symptoms in some patients within
hours and that the relief persists for
several days. The fi nding holds out the
possibility of a far more effective new
class of antidepressants.
Not a Fluke
It would be easy to dismiss this report
if it were a one-off observation.
But this is not the fi rst time ketamine
has been shown to be a powerful antidepressant.
A small study in 2000,
which, like the more recent experi-
ment, compared a single ketamine infusion
with a placebo saline infusion,
yielded identical results. And a study
in 2002 that used a very different approach
reached similar conclusions.
Patients with major depression who
underwent orthopedic surgery were
randomly assigned to receive or not
receive ketamine as part of their anesthesia
regimen. Only the group that
received ketamine showed postoperative
relief of depression.
Ketamine binds selectively and
strongly to the N-methyl-d-aspartate
(NMDA) receptor on neurons, blocking
the neurotransmitter glutamate
Corbis
from activating this receptor. Like ketamine’s
illicit chemical cousin, PCP, it
is also used recreationally and has potential
for abuse. It produces short-lived IMAGES.COM
14 SCIENTIFIC AMERICAN MIND June/July 2007
COPYRIGHT 2007 SCIENTIFIC AMERICAN, INC.