IEEE Spectrum May, 2008 - 9

cHanging minds: A brain implant for depression is in the works.
photo: st. Jude mediCal

A Difficult Time For
Depression Devices

mood-disorder treatment has eluded the
makers of brain stimulators. will the next
round of research fare better?

B

rain-stimulation
devices for treating
depression have faced
unexpected setbacks. To
serve the 40 million or so sufferers who fail to respond to
antidepressant drugs, a few
companies have tried to treat
the disorder with electronic
implants and electromagnets.
These therapies, however,
have stumbled en route to the
doctor's office.
To take a crack at those
intractable cases, experiments exploring five device
therapies will start this
year. In total, nine different
technologies are now under
14

investigation in at least
27 human trials.
The largest new study,
done by St. Jude Medical, in
St. Paul, Minn., will be the first
major human trial of one brain
implant that showed dramatic
early results. A device inserted
near the collarbone sends
pulses of current to electrodes
placed inside the brain. At
the other end of the spectrum,
Northstar Neuroscience, in
Seattle, will enroll patients
in a small, exploratory study.
Northstar's technique involves
implanting a postage-stampsize electrode on the surface of
the brain.

Na * IEEE SpEctruM * May 2008

But if history serves as
a guide, the path will not be
easy for either company. In
the United States, which has
both a large market and tough
approval standards, only
two depression devices are
now in clinics. One is electroconvulsive therapy, which precedes the U.S. Food and Drug
Administration's governance.
The other is Houston-based
Cyberonics' vagus nerve stimulator. Here, a pulse generator
in the chest sends current to
an electrode coiled around a
nerve in the neck to indirectly
alter brain regions believed to
control mood.
A factious debate leading
up to the device's approval
pitted the FDA's management against scientists
and was a sign of worse
things to come: the United
States' main governmentfunded health insurers soon
decided that the device was
not useful enough to earn
reimbursement. Private
insurers generally follow the
lead of those agencies, so for
the US $25 000 procedure,
the news was crippling.
The approval process
has not been any smoother
for Malvern, Pa.-based
Neuronetics, whose device
transmits a magnetic field into
the brain from an external coil.
This induces a current that
also seems to assuage depression. Unlike the others, this
method involves no surgery,
which makes it safer and more
palatable to the patient. Even
so, in January 2007 an influential FDA advisory panel gave
it an unfavorable review, again
claiming that its benefit to
patients is unproven.
Northstar, too, has been
knocked off course-and
before it really got started.
A trial of its stimulation
device failed to prove that it

surpassed an existing alternative. The goal was stroke
rehabilitation, but the outcome will likely impinge on
the depression investigation anyway: Northstar cut
one-third of its workforce
in response. Helen Mayberg,
a neurologist at Emory
University who invented the
deep-brain stimulation technique that St. Jude is now
testing, wonders if the companies' troubles will haunt
the next round of research.
"You have to ask, where did
they go wrong?" she says.
The basic problem is
that the changes induced
in a stimulated brain are
poorly understood, in part
because depression itself is
exceedingly complex. Linda
Carpenter, a psychiatrist at
Brown University, explains
that 100 patients might
exhibit 20 different sets of
symptoms.
Furthermore, crafting the
perfect pulse is beyond the
reach of today's psychiatry. A
pill has one main parameter-
dosage. These devices have
at least five: the intensity and
frequency of stimulation, the
duration of each pulse and
the intervals between them,
and the spot being stimulated.
Checking every parameter in hundreds of patients
would bankrupt most
medical-device makers.
"There are no deep pockets
in this game," says Eric
Wasserman, a clinician in the
National Institutes of Health
brain-stimulation unit.
As Mayberg sees it, "We
may look back in 10, 15 years
and say, we did what to the
brain? But it's a definite paradigm shift." In the meantime,
St. Jude and Northstar hope
to avoid the pitfalls of their
predecessors.
-Sandra Upson
www.spectrum.ieee.org
http://www.spectrum.ieee.org
Table of Contents for the Digital Edition of IEEE Spectrum May, 2008
