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Patients, be patient: Brain images suggest new therapy for severe depression can take months to work

May 26, 2006

Saint Louis University study on vagal nerve stimulation shows brain changes come slowly

It takes time - between three and 12 months - before a new type of therapy for treatment-resistant depression starts to benefit patients, according to new preliminary brain scan research that confirms earlier observations by psychiatrists about vagal nerve stimulation.

Saint Louis University, working in collaboration with Washington University School of Medicine, conducted a pilot study of brain scans of a small group of depressed patients who received vagal nerve stimulation after failing other therapies.

Positron emission tomography (PET) scans showed significant changes in brain activity starting three months after vagal nerve stimulation treatment began. These changes continued to evolve over the course of the next 21 months.

These changes in brain scans appear to "roughly parallel" the significantly delayed effects that psychiatrists observed in improvement in mood.

"The effects come after a significant period of treatment time," said Charles Conway, M.D., an assistant professor of psychiatry at Saint Louis University School of Medicine and the lead investigator of a vagal nerve stimulation research project conducted between 2000 and 2004.

Psychiatrists are not used to such a long time lag before a treatment begins to be effective, he added.

"This is very different from the delays we see with existing treatments for depression, including pharmacotherapy and electroconvulsive therapy (ECT)," Dr. Conway said. "The biggest changes in the brain that we're noting occur between 12 and 24 months after patients began receiving vagal nerve stimulation. In psychiatry, we're used to seeing results after six to 12 weeks."

Dr. Conway cautioned the findings are preliminary and need replication.

"But they suggest that in this type of therapy, the brain takes a relatively long time to change, perhaps as long as a year or more. In this sense, vagal nerve stimulation may represent a paradigm shift in the way we view depression treatment. Patients may have to be instructed to 'be patient,' with the expectations that the antidepressant effects will be slow to come."

The good news, however, seems to be that those who benefit from the treatment stay better.

"The existing evidence suggests that about 70 percent of patients who get better from vagal nerve stimulation at one year, stay better at two years," Dr. Conway said. "That is unheard of in a depressed population this severe, and suggests that the brain changes induced by this treatment appear to be long-lasting."

Dr. Conway examined the brain scans of patients at three, six, 12 and 24 months intervals after they began receiving vagal nerve stimulation. Eight patients participated in the study for the three and six month scans, six patients at 12 months and four patients at 24 months. The size of the study group grew smaller during the two year investigation.

"This is admittedly a very tiny population and the findings of this study are very preliminary. We need to do more research with a larger group of patients," Dr. Conway said. "That said, I think the findings are real and promising and beg more research."

Vagal nerve stimulation was approved in 2005 by the U.S. Food and Drug Administration to treat severe treatment-resistant depression. A vagal nerve stimulator is similar to a cardiac pacemaker and is implanted in the chest with leads that run under the skin to the vagal nerve in the neck. The device emits electrical pulses to simulate the brain, and also is used to treat epilepsy.

Doctors don't know exactly why vagal nerve therapy works, but Dr. Conway says his new research gives some clues.

When Dr. Conway examined the neuroimages of four patients 24 months after they began receiving vagal nerve stimulation, he found brain activity that was similar to what doctors see in patients who have received ECT.

"There actually appears to be decreased activity in regions of the prefrontal cortex, which is very much parallel to the findings of treatment response in ECT, and the opposite of findings seen in medication-response to depression."

He found unexpected action in the prefrontal cortex of the brain that is similar to brain activity in depressed patients immediately after they have received ECT and before its effect wears off.

"No one knows exactly how vagal nerve stimulation works. This suggests that one way in which it works may parallel ECT," Dr. Conway said.

"ECT had been considered to be the best therapy for treatment-resistant depression, but unfortunately the effects are not long-lasting. The data so far shows that one-third of the depressed patients who are treatment resistant are responsive to vagal nerve simulations and those who respond stay well."

Saint Louis University