Doctors at Hadassah University Hospital, Ein Karem are performing a radical experimental procedure on severely depressed patients that could offer them hope after years of failed treatments.

The doctors are implanting a device called a brain pacemaker, which sends electrodes into the patients' brains. The Jerusalem hospital is the first one in Israel to employ the treatment, known as Deep Brain Stimulation, as part of an international clinical trial being conducted concurrently in several European countries and Israel. Four Israeli patients are taking part in the trial, and another six are being recruited.

The team of doctors includes the head of the Biological Psychiatric Unit at Hadassah, Prof. Benjamin Lehrer; the hospital's Neurosurgery Department; Dr. Renana Eitan from the Psychiatric Department; and brain researcher Prof. Hagai Bergman, from the Medical Neurobiology Department.

Hope springs eternal

The treatment, which is covered in Israel by medical insurance, is only being conducted on patients who suffer from severe clinical depression that have not responded to drug or behavioral therapy in the past. "A precondition for being accepted into the study is failure of at least three different drug treatments and failure with electro-convulsive therapy," says Lehrer. To gauge their suitability to the trial, prospective patients underwent a battery of tests to assess their mental and functional condition and their recall, as well as an MRI to determine their brain structure.

The participants are all in their 20s and 30s. They were identified by their psychiatrists as being willing to undergo the procedure "after having failed to attain peace of mind by means of other treatments and after living with a great deal of suffering," says Dr. Tzvi Israel, director of the Functional and Restorative Surgery Department at Hadassah, who is also involved in the experiment.

The treatment involves neurosurgery during which patients are fitted with two metal-compound electrodes that are inserted into symmetrical areas of the brain, located in the frontal area, known to affect mood regulation. "There is evidence of increased activity in these areas among the severely depressed. The electric current reduces that activity and gradually affects mood," says Lehrer.

The electrodes are connected to subdermal filaments implanted under the scalp all the way to the chest wall, where the subdural operating unit, consisting of a computer and a battery, is implanted. There are already systems available with batteries that can be charged outside the body, but the system being used in the current clinical trial requires a surgical procedure to replace the batteries every 2-4 years.

The operating unit can be calibrated and its parameters changed externally, such that the electrical stimulation transmitted from the batteries to the brain can be altered. Externally, the electrodes and operating unit leave virtually no marks on the body, apart from scarring on the head where the electrodes are inserted.

While researchers can't explain precisely why the procedure works, they are pleased with the results so far. "The electrical pulses create neuro-modulation. The electrode reads the electrical activity in the target area and responds accordingly by issuing electrical stimulation. We don't know exactly how stimulation of the area affects mood, but the responses of the first patients are encouraging," says Dr. Yigal Shoshan, director of the hospital's Neurosurgery Department.

"So far we have observed that treating the severely depressed with DBS has a 70 percent success rate," says Dr. Israel.

The operation requires only a four-day hospital stay, including both pre- and post-treatment. Patients are sent home two days after the implant. The electrodes remain in the patients' brain for life. Follow-up appointments are originally scheduled every two to three weeks, then every few months, and eventually, twice a year.

According to Lehrer, "Depression is a common disease, affecting about 5 percent of the population. One-third responds less than optimally to drugs. For most patients, the depression passes with time, but a minority of patients has to cope with severe depression for years at a time, and it is for this group that the current treatment is being studied." DBS was first approved by the U.S. Federal Drug Administration in 1997 in research settings. Since 2002, it's been used routinely to treat Parkinson's disease patients who suffer from severe tremors and since 2003 it's been used to treat a neurological movement disorder known as dystonia.

It wasn't until 2009 that the FDA authorized one of the companies manufacturing the electrodes to use the device to treat psychiatric patients suffering from obsessive-compulsive disorder. Experiments with DBS on patients suffering from depression started in Canada and were then done in the United States. In total, 80 patients from the United Kingdom, France, Germany and Italy, have taken parts in experiments.

Look, no hands

Hadassah will soon start another trial involving a new type of brain pacemaker designed to read brain activity in real time throughout the day and night, in order to further refine DBS treatment. According to Israel, "The information we gather should help us to program an internal system controlled by the pacemaker that can regulate the electrical stimulation without the doctor's external intervention."

The innovative treatment is one of several other brain treatments offered in recent years to the severely depressed, including deep transcranial magnetic stimulation, already available in some Israeli medical centers, in which the patient wears a helmet that transmits magnetic charges into the brain from the outside, in a noninvasive manner. Another treatment involves a pacemaker to stimulate the vagus nerve in the cranium, which transmit signals to the brain.

A treatment employed in the past involved electrodes that were used to heat and remove certain parts of patients' brains. This process, known as ablation, created irreversible damage to an active brain center. "The advantage of the new treatment is that it allows the transmission of an electrical current without causing irreversible brain damage," says Shoshan.