Clinical trial for GAD treatment underway

Researchers at Connecticut’s Hartford Hospital Institute of Living are conducting a clinical trial to investigate the use of neuronavigation in combination with transcranial magnetic stimulation (TMS) to treat generalized anxiety disorder (GAD).

TMS – an FDA-approved treatment for depression – delivers magnetic pulses to the surface of a patient’s scalp. Typically, a standardized measurement is used to figure out where to place the magnetic coil; but with neuronavigation, the Institute of Living is determining the location to administer treatment by using each person’s unique brain scan. “The neuronavigation uses the patient’s MRI, so we can actually say, ‘Here’s the area we want to stimulate,’ and the neuronavigation ‘talks’ to the TMS machine to get the placement in a more precise way onto that target,” says Gretchen Diefenbach, Ph.D., senior scientist at the Institute’s Anxiety Disorders Center, a licensed clinical psychologist and the study’s principal investigator.

Diefenbach says only one other study – a 10-person open trial at UCLA – has been conducted using this specialized treatment for GAD.

“After using neuronavigation, six of those patients were classified as responders to the treatment and scored below the clinical cutoff of what would be clinically significant anxiety,” Diefenbach says. “At the end of the trial, their symptoms were quite low.”

Diefenbach says those numbers are promising because GAD is typically more difficult to treat with traditional therapies than other disorders. “So it’s a really important disorder to be looking at innovative, novel approaches to help people get a better treatment response than with what is currently available,” she says. “This is a very chronic problem. GAD typically has a very early age of onset and people usually have a high level of worry and anxiety throughout their lives.”

The Institute’s clinical trial is a double-blind study. In it, 20 participants ages 18 and older with a primary diagnosis of GAD will receive the same treatment, but 10 will receive a therapeutic level of the pulse that is believed to be clinically meaningful. The other 10 will receive a pulse that is so low that it’s considered a placebo, Diefenbach says. Treatment, which is underway for some participants, will be administered five days per week for six weeks.

“One of the questions we’ll be hoping to answer over time is what is the necessary kind of dose of TMS that people will need because this is just the second trial and it’s so very new,” Diefenbach says. She says the five-day-per week, six-week schedule is being used because that is the FDA-approved dosing schedule for treating depression.

Diefenbach says an additional study is being done to learn more about brain activation in patients with GAD versus those without GAD, which may help refine where to put the magnetic pulse to treat GAD.

Diefenbach’s collaborators are Michal Assaf, M.D., director, Autism and Functional Mapping laboratory, Olin Neuropsychiatry Research Center, IOL; John Goethe, M.D., director, Burlingame Center for Psychiatric Research and Education, IOL; and David Tolin, Ph.D., director, Anxiety Disorders Center, IOL.