Trigeminal nerve stimulation a treatment that offers hope

Of all the methods researchers are using to stimulate the brain as a treatment for depression, this may be the simplest.

It’s called trigeminal nerve stimulation, or TNS, and it consists of putting two electrodes on the forehead, attached to an electrical pulse generator pack.

Pioneered by psychiatrist Ian Cook at the University of California at Los Angeles, TNS has shown promising results in an early small trial with depressed patients who had failed several other treatments.

In the study, 11 depressed patients got overnight stimulation from the electrodes for eight weeks. At the end of that period, four had gone into remission.

That one-third remission rate is the same as most patients experience after their first try on an antidepressant medication, but it is more impressive, because all these patients had been resistant to other depression therapies. The participants had tried an average of five medications each without success.

While the study lasted two months, patients who responded got a boost in their mood more quickly than that, reporting two weeks after they started that their spirits had lifted.

Unlike electroshock therapy or deep brain stimulation, which inserts electrodes deep into the brain, TNS does not activate brain neurons directly, Dr. Cook said in an interview.

Instead, it sends its low-strength signals down the trigeminal nerve and into the brainstem, where the signals seem to flow upward into brain areas that have been implicated in depression, including the anterior cingulate cortex, an area at the back of the brain’s frontal area, just above the eyes.

Most people who have heard of the trigeminal nerve associate it with severe facial pain, known as trigeminal neuralgia. But Dr. Cook said that if the nerve is stimulated with just the right frequencies, it does not trigger pain, but does boost mood and reduce the chance of epileptic seizures.

“Our best interpretation of the study is the trigeminal nerve projects to a lot of important areas in the brain and it’s probably useful for survival to have all that information being sensed from the environment,” he said. “So it’s a sensory nerve that is hooked into a lot of brain areas that are important for behavior.”

For those who responded to the treatment, it didn’t just relieve their feelings of lethargy and low self-worth, but allowed them to “re-engage with life,” he said, returning to their jobs, or going out to movies or restaurants.

Before developing TNS, Dr. Cook and his team worked with transcranial magnetic stimulation, or TMS, another experimental treatment for depression.

In TMS, doctors use a paddle held against the skull to send electromagnetic pulses into the brain. One study that compared TMS to a sham version of the treatment showed that those who got the real pulses showed a 15 percent remission rate, compared with 5 percent in the control group.

Others have reported remission rates of close to 30 percent.

Unlike the trigeminal nerve treatment, the magnetic stimulation requires patients to go into a doctor’s office.

Dr. Cook is a co-inventor of the TNS apparatus and is an adviser to the company that markets it, NeuroSigma of Los Angeles. It has already been approved for routine use in Europe and Canada.

When asked to assess the importance of TNS, he says, “bear in mind I’m the inventor, and I think my baby is beautiful.” Still, he said the good early results for TNS and its ease of use suggest it could be a good treatment to add on when people fail to get help from medications or therapy.

It might even be a good treatment to try eventually with people who resist taking pills.

“About 40 percent of people with depression in the U.S. don’t seek treatment,” he said. “If you can find them in primary care, they will say I don’t want to take medication.”

Mark Roth:, 412-263-1130 and on Twitter: @markomar.

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