The future holds more than pills

Some people -- no matter what they take, no matter how many therapy sessions they might attend -- simply do not respond to antidepressants.

For them, a number of other options besides medication are available. Some are still in development; others have been around for years.

Steve, a postal carrier in Texas, has spent most of his life trying desperately to control the agonies that depression exacted. He knew that even as a child he was troubled, that an irreducible darkness skirted around the edges of his mind. But in 1998, after the breakup of a relationship, he “went over the edge” and tried to kill himself.

Thus began a revolving-door experience with medication and psychiatric hospitals, one after another for a year. The cycle was relentless: new medication, a few weeks of fragile hope, then suicidal despair and a hospital trip.

“They changed my medicine, added more, changed what I had again and put me back into the hospital,” recalls the 41-year-old, who didn’t want his full name used.

Of the 18.8 million people who suffer from depression, Steve is one of the 30% whose depression is known as “treatment resistant.” His psychiatrist finally suggested “shock treatment,” technically known as electroconvulsive therapy, or ECT.

Research on the brain as an electrical organ, one that actually responds to magnetic treatments, has led to improvements in such therapies, and their use is on the rise.

In 1980, 30,000 people received ECT; in 2001, nearly 100,000. Although there are still side effects -- headaches and memory problems primarily -- seizures, bitten tongues and broken bones are largely a thing of the past. And the response rate, especially for treatment of drug-resistant depression, is as high as 70%.

Steve still takes “about five or six medications, I can’t even remember all of them” to keep him stabilized after the shock therapy. But he takes them to prevent a rapid deterioration after the more effective therapeutic jolt from the ECT.

And he considers the dry mouth and 40 extra pounds from the medications to be far less debilitating than the fact that, by themselves, the medicine simply didn’t work.

His combination of patience, therapy, medication and ECT -- and sheer grit -- has not only kept him alive, but also propelled him toward a new life. He is now taking online college courses, not only to possibly advance himself, but to occupy a mind that has been so destructively rebellious.

ECT is only the beginning of the depression treatments that doctors and researchers are exploring. The following are some of the most promising:

Rapid transcranial magnetic stimulation: Much like the way a defibrillator works in the heart, this form of stimulation uses a powerful magnet to deliver an electric jolt to the brain. In clinical trials, many patients who failed to respond to several other treatments improved within a week of the first round of RTMS sessions, and the vast majority were significantly better after two weeks of daily 20-minute sessions.

Vagus nerve stimulation: This treatment, originally designed to reduce epileptic seizures, uses constant stimulation via a device surgically inserted under the chest wall, much like a pacemaker. It’s connected to the left vagus nerve in the neck, a nerve that threads throughout the body, including the brain. The electrical impulses that the device sends out stimulate the production of serotonin and other brain chemicals. Some people with chronic, treatment-resistant depression have responded well to the procedure, but the cost is high: The device itself runs about $12,000, and surgery can be nearly $15,000.

Deep brain stimulation: This is the most invasive treatment for depression, requiring an electrode implanted directly into a particular part of the brain. It was originally used to treat movement disorders such as Parkinson’s disease by targeting one area of the brain. But researchers found -- by serendipity -- that if the electrode was slightly misplaced, it could either cause or alleviate the symptoms of depression, including hopelessness and suicidal thinking.

Selegiline patch: This is a new delivery system for an old antidepressant, one of the monoamine oxidase inhibitors. Although an often-effective treatment for depression, the MAOIs required patients to avoid foods and medicines -- such as pickles, wine and decongestants -- that contained high levels of the amino acid tyronine. That substance can interact with the antidepressant and cause a sharp increase in blood pressure that can, potentially, cause a stroke. Often, patients simply got tired of having to be so cautious and discontinued the drugs.

The new patch, however, bypasses the stomach altogether. As the American Journal of Psychiatry reported while the patch was being tested in 2002: It “was an effective and well-tolerated treatment for adult outpatients with major depression. The typical side effects commonly seen with traditional monoamine oxidase inhibitor antidepressants were not observed.” In February, the FDA approved the patch, with the brand name Ensam.

Genetics: Although the future may hold promise for gene therapy in treating mood disorders, psychiatrists generally put it in the category “of blue sky stuff,” says Dr. Fred Goodwin, former head of the National Institute of Mental Health. But some progress is being made in determining the genetic predisposition for a response to antidepressant medications.

In a study that will appear in May in the American Journal of Human Genetics, researchers at the National Institutes of Health discovered that some people have two copies of a gene related to the brain’s mood-regulating system. They are 18% more likely to respond to an antidepressant medication than those who have two copies of another, much more common, gene that is also related to mood regulation.

This means that in the future, it may be possible to target antidepressant treatment to particular patients with the genetic predisposition to respond to those particular medications, thereby reducing the long trial and error period that so compromises depression treatment.

Quantitative electroencephalogram: Figuring out who might respond to what drugs has been a basic problem in depression treatment. Dr. Andrew Leuchter and his colleagues at UCLA are using the QEEG -- a noninvasive and easy to use brain mapping technique -- to tease out the various types of depression and the response to a range of antidepressants.

At nine sites throughout the country, depressed patients are having their brains mapped before treatment, 48 hours after receiving their first dose of an antidepressant and several weeks later. Researchers will then see how the medication works over time and how people describe the progress, and possibly the lifting, of their depression.

The researchers hope to eventually determine within a week if a particular treatment works or not, thereby increasing the likelihood of quickly finding the right medicine.

Future drugs: In the past, antidepressant drugs focused primarily on the neurotransmitters serotonin and norepinephrine, but pharmaceutical companies are now looking at drugs that target other neurotransmitters, such as the stress hormone corticotropin-releasing factor, or CRF.

Depressed people often have abnormally high levels of this stress hormone, and drugs that block it have been found to alter moods.