Multi-pronged war on depression

On an antidepressant and still depressed? Techniques new and old may help.

The landmark STAR*D study, published in the November 2006 issue of the American Journal of Psychiatry, demonstrated that depression is more likely to yield -- and less likely to recur -- when a patient is treated with both an antidepressant and cognitive therapy, a form of talk therapy aimed at correcting negative thought patterns. A second look at the STAR*D data, published in May 2007, found that for patients who failed to respond to a first round of antidepressant therapy, either switching to or adding a short and highly directed course of cognitive therapy is as likely to bring about remission as a switch to or the addition of another drug (though remission might take longer to achieve).

But compared with dispensing medications, talk therapy is time consuming, costly and, according to a 2008 study in the Archives of General Psychiatry, increasingly difficult for patients to find. Because of changes in the field, as well as insurers' growing unwillingness to reimburse for talk therapy, the practice of psychotherapy, and the number of psychiatrists who practice it -- has declined dramatically.

And despite bombardment with drugs and talk therapy, many cases of depression stubbornly refuse to budge.

"In the treatment of depression there is very much an effectiveness vacuum," says North Carolina psychiatrist Neil Scheurich, who writes at the blog Ars Psychiatrica. "Patients urgently want help, and psychiatrists urgently want to help them. . . . Neither patient nor psychiatrist wants to hear, or to say, 'There is nothing more I can do.' "

That, Scheurich says, has helped drive the growth of the atypical antipsychotics. But for patients whose depression fails to yield to a course of one or more antidepressant medications, this class of medication is not the only recourse.

Following are a few techniques -- some more costly and invasive than others -- that might provide relief for treatment-resistant depression:

Light therapy

First used as a treatment for seasonal affective disorder, light therapy has grown among patients who either prefer to avoid antidepressants or have tried them without success. By sitting in front of or near a box that emits light equivalent in intensity to outdoor light, patients are able to better regulate their production of melatonin, a natural hormone that helps govern sleep patterns and influence mood.

Because evidence of light therapy's effectiveness has been inconclusive, the Food and Drug Administration has not cleared any device as a light therapy product. Costs of lamps marketed for light therapy can run from $200 to $500, and it's difficult for consumers to know what levels of light intensity and what safety features are best. (Some good tips are available from the Mayo Clinic.)

EEG monitoring

Some antidepressants work better than others for different individuals. Using an EEG, doctors might be able to monitor the brain's electrical response to an antidepressant in the first week a patient is on it, taking the trial-and-error out of antidepressant prescribing. Currently, a physician relies on a patient's report of improvement in mood -- a response that can take six weeks -- to decide whether an antidepressant seems to be working or should be abandoned for another choice. UCLA psychiatrist Dr. Andrew Leuchter, who is leading a national clinical trial of the EEG-guided technique's effectiveness, says the method predicts (with 70% to 80% reliability) whether an antidepressant will work, speeding the path to finding the right drug for a patient.

Brain stimulation

Magnetic brain stimulation, used by researchers to activate brain regions in an effort to identify what they do, builds on some of those findings when used for treatment-resistant depression.

A device called the Neurostar TMS Therapy System won FDA approval in 2006 for use on adults who have not been helped by at least one antidepressant. The device's magnetic field is trained on the brain's prefrontal cortex, where it sets off a secondary flurry of electrical activity. Resulting chemical changes are thought to take place in regions involved in depression.

This alternative isn't fast or easy, and there are risks. The daily 40-minute treatments, administered over four to six weeks in a psychiatric office or hospital, can cause headaches, and there is a risk of seizures. But a 2002 study found that the device's success in treating persistent major depression was on a par with electroshock therapy -- the 70-year-old technique now called electroconvulsive therapy, which is still in broad use for the most seriously depressed and for treatment-resistant patients. Magnetic brain stimulation is a far gentler technique that some proponents call the equivalent of hitting the "reset" button on the brain's mood centers.

Nerve 'pacemakers'

For some patients with chronic depression who have failed to respond to other treatments, physicians are now trying implantable "pacemakers" that can send either steady or episodic currents of electricity to parts of the nervous system that influence mood.

Deep brain stimulation, which has been used for many years to reduce the involuntary movement of Parkinson's disease patients, relies on a pacemaker implanted under the skin in the chest to deliver electrical currents to the brain via a wire and electrodes. A device made by Medtronic won FDA approval in late February for its first psychiatric use -- to treat patients with severe and unremitting obsessive-compulsive disorder. As a treatment for depression, it is still both experimental and controversial, because the procedure and the device are costly and invasive.

In vagus nerve stimulation, approved by the FDA in 1997 for certain epilepsy patients, an implanted pacemaker device delivers electrical current at the base of the neck to the vagus nerve, which carries signals from the body into the brain's limbic system -- a region that influences mood, sleep, appetite and motivation. In July 2005, the FDA approved the use of the surgical implant used to treat epilepsy -- made by Cyberonics of Houston -- to treat major treatment-resistant depression. The device is about $18,000, and the surgery to implant it can cost almost as much. According to studies presented to the FDA, 21% to 30% of subjects improved with the vagus nerve stimulator; 16% to 17% achieved remission.

Gene testing

Further out on the horizon lies the possibility that genetic tests may be able to guide decisions about which among dozens of medications prescribed for depression is most likely to work. Writing in the Jan. 24 issue of Neuron, researchers at the Max Planck Institute of Psychiatry in Germany reported they had identified 11 subtle genetic variations in the genomes of 443 subjects that could help predict their individual responses to a variety of neurological medications.

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