Beyond Drugs, "Science of the Mind" Series Explores New Depression Treatments

By Jeffrey Norris

This fall, the UCSF Mini Medical School for the public is presenting the series “Science of the Mind.” Tonight’s featured lecturer in the Mini Medical School series, Paul Ekman, PhD, UCSF professor emeritus, is regarded as the world’s leading researcher and expert when it comes to reading faces to detect lies. His talk, titled “Reading Facial Expressions: The Science Behind the Hit TV Show ‘Lie to Me’,” is expected to draw a big turnout to the Parnassus campus.
Descartes Li
Last Tuesday’s session featured UCSF psychiatrist Descartes Li, MD, who described new treatments for difficult-to-treat depression. These procedures, coupled with psychotherapy, may help patients shake off depression when drugs fail, Li says. The brain runs on electrical currents coursing through nerve cells. The four techniques Li discussed all directly affect electrical conditions in the brain, and thereby the transmission of signals by nerve cells.

Deep Brain Stimulation

The most striking and highly experimental depression treatment Li described uses a technique first pioneered to treat Parkinson’s disease patients. It’s called deep brain stimulation. Only patients with chronic major depression for whom drugs and other treatments already have failed are potentially eligible for clinical trials. The surgical treatment requires an MRI examination to precisely identify the site within the brain to stimulate. A wire-thin electrode is threaded into the brain through a small hole drilled in the skull. The patient remains awake during the surgery so that surgeons get feedback on the effects of electrode placement. Although the procedure is invasive, it is adjustable and reversible. Only one study, with 20 patients, has been reported so far. After 12 months, 35 percent of patients were no longer depressed. An additional 25 percent were less depressed. “Given the chronic nature of treatment-resistant depression, this is a remarkable outcome,” Li says. According to Li, UCSF is not yet using deep brain stimulation to treat major depression, but plans are underway to begin research studies. In addition, UCSF psychiatrists and neurosurgeons now are collaborating on a clinical trial in which they are using the technique to treat patients with the most severe cases of obsessive compulsive disorder.

Brain-Mapping Progress

In his lecture, provocatively titled “What Emerging Antidepressant Treatments Tell Us About the Brain,” Li pointed to amazing progress in mapping the brain. Dozens of brain regions now are associated with specific functions. Like real estate tracts, the regions are numbered. And when it comes to thinking about treating the brain, increasingly the name of the game is “location, location, location,” Li says. For instance, the region targeted by deep brain stimulation, called Brodmann area 25, is one that links the frontal cortex, the thinking part of the brain, to a part of the limbic system associated with emotions. Magnetic resonance imaging studies revealed that the area is unusually active in many depressed patients. “Who would have thought that we could go into different parts of the brain with electrodes and make people feel different emotions?” Li says. Still, there is still no biological measure that can predict who among the depressed will respond to particular therapies, although symptom profiles are sometimes helpful, according to Li. He describes depression as a “complex, multi-system phenomenon.”

FDA Approved Techniques

Two other techniques have in recent years been approved by the Food and Drug Administration (FDA). In one, called Vagus nerve stimulation, a small generator is implanted in the left chest wall. Electrodes run under the skin to the site where the Vagus nerve passes the carotid artery on its way to the brain. Li questions the value of this technique based on current scientific evidence. Transcranial Magnetic Stimulation is another FDA approved procedure. Pulsed magnetic fields stimulate electric currents in the brain. Brain areas known as Brodmann areas 9 and 46 are targeted, somewhat imprecisely, for activation with high-frequency pulses. A patient is administered 20 to 30 40-minute treatments over the course of four to six weeks. Li believes that studies to date point to a “modest clinical benefit.”

Electroconvulsive Therapy

Li also described modern approaches to an old treatment, electroconvulsive therapy (ECT). ECT remains somewhat controversial. Li sought to dispel what he described as misperceptions about ECT, a technique he specializes in as co-director of the UCSF Electroconvulsive Therapy Service. ECT was first used in the United States in 1940, after researchers noticed that individuals with both epilepsy and depression often felt better in the aftermath of a seizure. ECT induces this same kind of storm of activity throughout the brain. Originally this was done using electrodes applied to each side of the head. Forced treatment, along with abuses of the procedure at in-patient treatment facilities, combined with a major side effect – memory loss -- left ECT with a bad reputation. Berkeley even attempted to outlaw the treatment in the 1980s, only to have the city’s statute trumped at the state level. Li believes ECT is a valuable option for treatment-resistant major depression. It compares favorably to drug treatment in studies conducted over the past three decades, according to Li. Physicians today apply the treatment to patients under general anesthesia, to only one side of the head, for ten to fifteen minutes. A patient receives six to 12 treatments over three weeks. The protocol is intended to minimize the degree to which patients may suffer memory loss and possibly become unable to recall certain significant episodes from their lives. The UCSF Mini Medical School lecture series convene in Cole Hall on the Parnassus campus. Members of the public are welcome. Admission to individual UCSF Mini Medical School lectures may be purchased on site for $15 before the event. Lectures begin at 7 p.m. Image from Mini Medical School website

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Fall 2009 Classes: UCSF Mini Medical School for the Public UCTV Video Archive: UCSF Mini Medical School for the Public