The treatment, called vagus nerve stimulation, involves sending tiny electric shocks into the vagus nerve in the neck, where it then relays messages deep into brain.
A generator the size of a pocket watch is implanted into the chest. Wires snake up the neck to zap the nerve every few minutes.
It works by stimulating a mysterious region of the brain that governs emotion, scientists say.
The device is still experimental, but a pilot study with patients who failed every other antidepressant proved promising. Other studies suggest this gateway into the brain could be used to enhance memory or curb appetite as well.
About half of the 30 depressed patients treated in a pilot study - people who had failed every other treatment - "got a very good response," Dr. Mark George of the Medical University of South Carolina, who performed the experimental implant.
In one case, a former shipbuilder had severe depression unrelieved by any current therapies, and he was so sick that he had trouble even leaving his house. Doctors implanted the pacemaker-style device to stimulate a part of his brain thought to be important for mood - and that very day the man laughed.
"It was remarkable," George said in an interview. "I said, 'Are you being forced to laugh or do you feel good inside?' He said, 'Both.'"
Stimulating a nerve that runs from the neck into one of the brain's most mysterious regions appears promising enough that the U.S. government just granted permission for a study at 15 hospitals around the country.
The results are not definitive, he cautioned. But he added, "stimulating there really is a wonderful portal into the base of the brain."
Indeed, scientists think stimulating this nerve could have even more far-reaching effects, such as enhancing memory or treating obesity by curbing appetite.
The FDA recently approved a larger trial to start next year and include about 200 patients.
That's because the vagus nerve is what Dr. Mitchell Roslin of Brooklyn's Maimonedes Medical Center calls "one of the information superhighways" between the brain and other organs. It relays messages, such as signals to regulate heartbeat, and sends messages back to the brain, such as when the stomach is full.
The nerve also reaches deep into brain regions thought to regulate mood and emotion, said Dr. John Rush of the University of Texas Southwestern Medical Center, who heads the pilot depression study.
If the implant truly signals the depressed brain circuits to act more normally, it could prove important for some of the estimated 1 million Americans with depression not eased by conventional therapy.
Two years ago, the Food and Drug Administration approved the implant o treat severe epilepsy, a way to signal the brain to reduce seizures.
Depression often accompanies epilepsy. Soon after the implants began selling, doctors began reporting epilepsy patients who felt happier even if the implant failed to reduce their seizures.