More than 15 million people in the U.S. suffer from a potentially lethal combination of fatigue, sleep problems, and overwhelming feelings of guilt, hopelessness and sadness. They have depression, and if left untreated, it could lead to suicide.
That’s because depression is a complex condition with several different causes ― not all of which can be improved with pharmaceutical therapy. But because doctors can’t tell which people would benefit from medication, some may spend several years jumping from one treatment to the next ― a complex process that involves tapering off the drugs ― and might feel increasingly frustrated about their disease. All the while, this experimentation takes away valuable time away from treatment that would work better.
“The disability and the real distress of experiencing depression often comes in the trial and error process that can go on for several years,” said Leanne Williams, a professor of psychiatry and behavioral sciences at Stanford University.
Williams hopes to change this with a new test that will predict how effective antidepressants will be. While the test is still in early stages, a recent study she authored found that it was able to predict whether or not an antidepressant would restore a person’s symptoms to healthy levels with 81 percent accuracy.
If the research is validated by future studies that gauge how well other doctors and clinics can use the test, it will not only bring effective treatment to those who need it, but it will do so faster by eliminating the trial and error period.
“My hope would be to improve the outcomes for people and get their treatments right the first time,” Williams said.
Here’s how the test works
The test combines two factors that researchers have determined play a role in whether or not antidepressants work in someone with depression. The first is a well-known measure of negative experiences in childhood called the Early Life Stress survey, which gauges physical, emotional and sexual abuse or neglect in childhood. These experiences can increase a person’s risk for depression.
The second is a brain scan that focuses on the amygdala, a part of the brain that helps process emotions and respond to stress. The researchers presented subjects with photos of people who are happy or afraid, and then measured whether or not the amygdala reacted strongly to those photos.
While both components play a role in one’s risk for depression, the amygdala’s role in regulating emotions means it also plays an important role in determining whether antidepressant therapy will be successful.
In a study of 70 people, Williams and team predicted that treatment with any one of three commonly prescribed antidepressants (Zoloft, Lexapro and Effexor) would work well for those whose amygdalas did not react strongly to happy or fearful faces, and who hadn’t experienced abuse or neglect in childhood. They also predicted that the antidepressant would work for those who had experienced childhood abuse or neglect, but whose amygdalas reacted only to happy faces.
This could be because of the unique effect of childhood trauma on a developing brain. Some kids who are abused might develop a hypersensitive amygdala so they can sense an abusive caregiver’s moods and learn how to dodge harm. But as abused children grow into adults, these hypersensitive amygdalas can either lose their ability to react to happy faces, or retain them. Whether or not the amygdalas retain this sensitivity to happy faces gives researchers a clue about whether antidepressants will be effective. If a person’s amygdala still responds to happy faces, then an antidepressant is more likely to help alleviate their symptoms.
Williams randomly prescribed antidepressants to the study participants and evaluated their mental health after eight weeks, which is around the amount of time doctors like to wait to see if the medication is helping people.
She found that her two-pronged test was able to predict medication would be effective for about one-third of the 70 participants, which aligns with past research on the effectiveness of antidepressants in large population studies. This prediction had an accuracy rate of 81 percent.
When does the public get to use the test?
Williams hopes in the future that this test can be used to identify people who would most likely not respond to antidepressants, to save them wasted time, money and effort and steer them directly into other types of therapy, such as talk therapy, that would help them most.
While the testing model is highly accurate, the tool is not available for public use yet for practical reasons like training and finances.
One complication is logistical. The test requires at least two different kinds of doctors: psychiatrists or primary care doctors to administer the Early Life Stress survey and radiologists to administer and interpret the brain scans. Then, of course, there are questions about how the care is coordinated, how it should be coded for health insurance, and whether or not insurance companies will want to pay for the test.
However, new studies are underway to see just how feasible it is for care providers to coordinate the tests, Williams noted. If the research reveals that coordination is simple and the tests can be administered by trained clinicians, the tool could be available within a few years.
Untreated depression is a heartbreaking mental condition that deeply hurts not only those who have it, but the people who love them. In addition to the human cost of the disease, depression is the leading cause of disability in the U.S. and costs the U.S. an estimated $210 billion a year in treatment, lost work productivity and the cost of suicide.
Other efforts to develop a diagnostic test for suicide risk, depression risk and the effectiveness of different depression treatments are underway around the country, and involve experiments like blood tests to scan for certain RNA markers linked to depression risk or inflammation markers in the body.
“There’s a paradigm shift that’s occurring with precision medicine right now,” said Williams. “How do you really understand the whole person, taking into account their experiences, but have these tests that can help identify, the first time around, what will work best for them?”
Williams’ test is just one part of a larger effort to bring personalized, precision medicine to mental health treatment ― an area where it’s sorely needed, as mental health treatments are generally prescribed on a trial and error basis, and the potential consequences of a treatment working can mean life or death.