When doctors determine the best medication for a person with depression, they generally rely upon little more than guesswork and patient self-reports, due to insufficient medical evidence. Research out of UT Southwestern Medical Center (UTSMC) previously suggested that such practices were insufficient, and a new study, published in Psychoneuroendocrinology, provides additional diagnostic information that may change the way depression is treated.

The research team drew upon a large body of research that links low levels of inflammation in the body with depression. They say a blood test for an inflammatory biomarker, known as C-reactive protein (CRP), can significantly improve the success rate of two common antidepressants for depressed patients.

Lead author Madhukar Trivedi, a professor of psychiatry at UTSMC and director of the Center for Depression Research and Clinical Care, says doctors typically pick an antidepressant for their patients in one of three ways: personal experience; matching the perceived benefits of one drug with a certain type of patient’s needs; or having the patient pick a drug by ruling out the unwanted side effects of other drugs. “There isn’t a strong evidence base to support one way [of choosing an antidepressant] over another,” he tells mental_floss.

Trivedi says that because many doctors are pressed for time and overloaded with patients, they don't thoroughly address a depressed patient’s needs. “If you have diabetes, the doctor spends a lot of time explaining that it’s a serious illness—there are consequences for ignoring it, and there are treatments you need to do. In depression, that does not happen as much. Patient engagement is not that strong,” he says.

Trivedi led a landmark study more than a decade ago that revealed how serious the medication problem is: Up to one-third of depressed patients don’t see an improvement in their first month of medication, and approximately 40 percent of people who take antidepressants quit within the first three months.

This failure rate is exacerbated by the lingering social stigma accompanying the illness. “It is not fashionable to say, ‘I have depression,’ so people around you may put in their uninformed advice … 'Just go for a walk,' or 'Why are you depressed?'” says Trivedi.

The CRP blood test is traditionally used as a measure of inflammation for such diseases as cardiovascular disease, diabetes, and rheumatoid arthritis, among others, where doctors are looking for high levels of C-reactive protein—approximately 3 to 5 milligrams per blood liter. In the new study, which Trivedi refers to as a “secondary analysis” of a study he led in 2011 (the Co-MED trial), he says, “Our hypothesis was that for depression there may be stress related inflammation in lower levels.”

Trivedi’s lab measured depression remission rates of 106 patients, culled from 440 patients involved in the 2011 study, each of whom had given blood samples. Fifty-one of them had been prescribed only escitalopram (Lexapro), while 55 of them had been prescribed escitalopram plus bupriopion (Wellbutrin), both commonly prescribed SSRI antidepressant drugs.

After analyzing blood samples, the researchers found that for patients whose CRP levels were less than 1 milligram per liter of blood, escitalopram alone was more effective—patients experienced a 57 percent remission rate of their depression versus 30 percent on the other drug. For patients with higher CRP levels, escitalopram plus bupropion was more effective. These patients experienced a 51 percent remission rate, compared to 33 percent on only escitalopram.

Not only do these SSRI antidepressant drugs promote higher levels of retention of the “feel good” neurotransmitters serotonin and dopamine, they trigger an immune response that blocks inflammatory molecules called cytokines.

“The magnitude of the effect was really thrilling,” Trivedi says. “The bottom line in depression is we have not had objective tests that help us with any component of diagnosis or treatment matching—and this is a very solid first step.”

His next step will be to do a clinical trial in which researchers will go to primary care practices and randomize patients, so that half of the participants will get “the best care the provider is willing to do,” he says, and the other half will do the blood test and then get matched with one of the two drug approaches. “We want to show that if you have the treatment matching based on the blood tests, that group of patients will have significantly better outcomes than those who do usual care.”

He hopes that other studies will use the CRP test with other antidepressant drugs, as well. “It’s not a perfect solution for 100 percent of patients, but it helps.”