Neuromodulation May Offer New Option for Patients With Psychiatric Disorders

While the majority of pharmacotherapies for psychiatric disorders target chemical imbalances in the brain, a growing number of techniques employing neuromodulation—the application of magnetic or electrical energy to the brain to alter neurotransmission—have emerged in recent years.

“One might think that getting energy to the brain noninvasively would be difficult given the skull barrier, but it actually is surprisingly easy,” said Andrew Leuchter, M.D., a professor of psychiatry at the David Geffen School of Medicine at the University of California, Los Angeles, and director of the neuromodulation division at UCLA’s Semel Institute for Neuroscience and Human Behavior.

There are several critical nerves that connect important behavioral centers in the brain to the exterior of the head, chief among them being the trigeminal nerve, which reacts to sensations all across the face.

A little over a decade ago, researchers at UCLA began to experiment with applying low-level current to the trigeminal nerve—via a patch worn on the forehead as a patient sleeps—as a treatment option for patients with drug-resistant epilepsy. They found that this external trigeminal nerve stimulation (eTNS) not only reduced symptoms of epilepsy in patients but was also associated with improvements in mood.

“It made sense, as the trigeminal nerve feeds into the major centers for mood and anxiety in the brain like the amygdala,” Leuchter said. Together with UCLA Professor of Psychiatry Ian Cook, M.D., Leuchter and colleagues began testing eTNS as an add-on therapy for patients with psychiatric disorders in 2009. Since then, they’ve shown positive results in small pilot studies for depression, attention-deficit/hyperactivity disorder, and most recently comorbid depression and posttraumatic stress disorder (PTSD) (Psychiatric News, March 18).

Another neuromodulation technique under exploration is transcutaneous vagus nerve stimulation (tVNS), a method by which electrical current is delivered to the vagus nerve via small clips on the ears.

Transcutaneous VNS is an outgrowth of traditional VNS, which is an FDA-approved electrical therapy for treatment-resistant depression.

Traditional VNS involves placing an electrode directly on the vagus nerve in the neck; however, as with the trigeminal nerve, the vagus nerve also has some more accessible fibers at the ear tips (which has been utilized by acupuncturists for a long time), and several small research studies have found that stimulating this region can produce modest symptom improvements in patients with depression and other psychiatric disorders.

While these two approaches are fundamentally similar (both the vagus and trigeminal nerves project to many of the same brain regions), there are methodological differences between the techniques.

“One critical limitation of tVNS is that the vagus nerve sends signals to the heart, so tVNS stimulation is limited to low frequencies like 30 Hertz or less to avoid potential cardiac problems,” said Cook. “With eTNS you can use higher frequencies, which equates to raising the dose of medication.”

Another difference between the two techniques is that eTNS requires the stimulation to be carried out over multiple hours at a time, whereas tVNS can be completed in daily sessions of 30 to 60 minutes.

“Just as all antidepressants aren’t exactly the same, all neuromodulations aren’t the same either,” Cook said. “Having more arrows in the quiver is never a bad thing.”

As for where these arrows can go in the future, Pedro Shiozawa, M.D., a professor of psychiatry at Santa Casa School of Medicine in Brazil who has carried out clinical studies with both techniques, told Psychiatric News, “I firmly believe that these strategies play a central part in modulating brain activity, not only facilitate the action of medications. Someday eTNS or tVNS alone may determine the clinical amelioration of psychiatric symptoms.”

The results of a recent study comparing the effectiveness of tVNS with sham stimulation in over 100 patients with mild or moderate depression suggests Shiozawa’s prediction may be accurate. Those who received tVNS therapy alone showed greater improvements in their depressive symptoms compared with a subgroup that received sham stimulation, a joint team of researchers at the China Academy of Medical Sciences and Harvard Medical School reported.

“The field is definitely growing strong,” said Cook. “We still need to build up an evidence base, but I’m confident that electrical-based therapies will become important standards of care for many patients.” ■