The Body of Knowledge
Finding the proper treatment for depression has often been a hit-or-miss process in which patients must try an array of drugs to see which one will work--a clinical obstacle course that can take weeks or even months.
Everyone has different brain chemistry, so their responses to the same antidepressant can vary widely. Psychiatrists have no good way to determine how a person will react to a drug; the patient must try it and see.
“We do the best matching we can, based on what a person has responded to in the past or what has worked for a family member,” said Dr. Ian Cook, assistant professor of psychiatry at the UCLA Neuropsychiatric Institute.
New research by Cook and his colleagues at UCLA may make this tortuous waiting period obsolete. Using a brain scan called quantitative electroencephalogram, they have developed a technique that can predict whether a patient will respond to a particular drug therapy within a few days.
“The right drug for a person’s brain is like the key that turns the molecular lock,” said Cook, whose findings were published this month in the journal Neuropsychopharmacology.
The technique focuses on activity in the prefrontal cortex, the most forward part of the brain, which is central to many higher mental functions, such as judgment, planning and executing plans.
Dr. Eric Nofzinger, associate professor of psychiatry at the University of Pittsburgh, said the UCLA research is a significant step in the right direction given the lack of reliable biological measures to predict antidepressant responses.
But he said the results are still preliminary and it will take further work on a larger population sample before the technique can become widely applicable.
Clinical depression is one of the most common mental illnesses, afflicting almost 20 million Americans a year. The World Health Organization estimates that in less than 20 years only heart disease will be a greater burden on health-care systems than depression.
Depression is also among the most treatable of mental disorders; the vast majority of people who seek help for depression improve through therapy or medication.
Antidepressants are one of the most commonly prescribed treatments today. They work by adjusting the balance of chemicals in the brain.
Prozac is the best known of these drugs, modulating one of the brain’s most important signaling chemicals: serotonin. Other pharmaceuticals in this class of drugs, known as serotonin reuptake inhibitors, are Paxil and Zoloft.
A new class of antidepressants, including Effexor and Serzone, acts on another important signaling molecule, norepinephrine, as well as serotonin.
There are a variety of factors that can contribute to abnormalities in the brain’s chemical signaling systems: Stress, genetics, gender and other mental illness can all play a role. Because of this complexity, scientists still don’t fully understand how antidepressants can treat depression so effectively.
Add this intricate interplay to the individuality of the human brain and it becomes very difficult to find a suitable antidepressant therapy. In fact, only 60% to 70% of patients respond to the first drug they try. The rest must try another drug, and half of those must try a third.
The trial-and-error process can take months, time in which the patient is suffering and not able to work. “This can have a tremendous human toll,” Cook said.
Ken Steckla was diagnosed with depression almost two years ago, encouraged to seek treatment by friends who noticed some of the typical symptoms of depression. “I was tired and unmotivated. I felt like I couldn’t get out of bed,” Steckla said. “Getting up and going to work was like putting on a show.”
Steckla started counseling and was prescribed Zoloft, going through the typical six- to eight-week waiting period it would take to feel better. Unfortunately, the side effects of the drug were intolerable. “I felt like a zombie,” Steckla said.
He then started another drug, Wellbutrin, which had no effect, then a third. His doctors finally found a combination of the previous drugs that seemed to work.
Cook, who treats patients at UCLA’s Mood Disorders Clinic, believed a better way to find the right drug was to go to the source, to “listen to what the brain is doing” by looking at changes in the electrical activity on the surface of the brain.
During the EEG procedure, which takes about an hour, a bathing cap with wires running through it is placed on a person’s head.
Cook measured the brain activity of people who had just started taking two types of commonly prescribed antidepressants, Prozac and Effexor. They then looked at these brain wave changes to see whether they matched how a person felt several weeks later when the clinical effects of the antidepressant started to kick in.
People who would respond to antidepressants showed a decrease in activity in the prefrontal cortex. Those who showed the greatest decrease in brain activity were the most helped by the antidepressant.
“EEG is unique in that it has a predictive ability,” Cook said.
The technique does seem to have good clinical potential. EEG machines are relatively inexpensive, compared to other MRI and CAT scanning devices. The machines are small enough to be easily placed in clinics and hospitals, and are relatively easy to operate, Cook said.
He plans to further simplify his method so that other depression researchers can test the technique. He expects it can be used clinically within a couple of years.
Depression patients such as Steckla see the benefits of speedier treatment. “I would have had months of my life back,” he said.
