Brain-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 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-stamp-size electrode on the surface of the brain.
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 government-funded 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.