Thanks to a blood test, doctors can for the first time determine which medication is more likely to help a patient overcome depression, according to US research that pushes the medical field beyond what has essentially been a guessing game of prescribing antidepressants.
A blood test that measures a certain type of protein level provides an immediate tool for physicians who until now have relied heavily on patient questionnaires to choose a treatment, said Dr Madhukar Trivedi, who led the research at University of Texas Southwestern Medical Centre’s Centre for Depression Research and Clinical Care.
“Currently, our selection of depression medications is not any more superior than flipping a coin, and yet that is what we do. Now we have a biological explanation to guide treatment of depression,” said Trivedi.
The study demonstrated that measuring a patient’s C-reactive protein (CRP) levels through a simple finger-prick blood test can help doctors prescribe a medication that is more likely to work. Utilising this test in clinical visits could lead to a significant boost in the success rate of depressed patients who commonly struggle to find effective treatments.
A major national study Trivedi led more than a decade ago, STAR*D, gives insight into the prevalence of the problem: Up to a third of depressed patients don’t improve during their first medication, and about 40 percent of people who start taking antidepressants stop taking them within three months.
“This outcome happens because they give up,” said Trivedi, whose previous national study established widely accepted treatment guidelines for depressed patients. “Giving up hope is really a central symptom of the disease. However, if treatment selection is tied to a blood test and improves outcomes, patients are more likely to continue the treatment and achieve the benefit.”
The new research measured remission rates of more than 100 depressed patients prescribed either escitalopram alone or escitalopram plus bupropion.
Researchers found a strong correlation between CRP levels and which drug regimen improved their symptoms: for patients whose CRP levels were less than 1 milligram per litre, escitalopram alone was more effective – 57% remission rate compared to less than 30% on the other drug; and for patients with higher CRP levels, escitalopram plus bupropion was more likely to work – 51% remission rate compared to 33% on escitalopram alone.
Trivedi noted that these results could readily apply to other commonly used antidepressants. “These findings provide evidence that a biological test can immediately be used in clinical practice,” he said.
Trivedi identified CRP as a potential marker for depression treatments because it has been an effective measure of inflammation for other disorders such as cardiovascular disease and diabetes.
While previous research to establish CRP as an antidepressant marker used levels three to five times higher than the latest study, “my theory was that you don’t need that high of an inflammation to experience the sickness of depression,” Trivedi said. “Even a little inflammation may be sufficient for the patients to experience some of these symptoms of depression.”
The next step is to conduct larger studies to verify CRP’s role with other antidepressants and find alternative markers where CRP does not prove effective. Trivedi said these studies could lead to additional useful biological tests that can be used in practice.
“Both patients and primary-care providers are very desperately looking for markers that would indicate there is some biology involved in this disease. Otherwise, we are talking about deciding treatments from question-and-answer from the patients, and that is not sufficient,” said Trivedi.
The data reviewed for the study came from the CO-MED trial, which was funded by the National Institute of Mental Health. The work was also supported through UT Southwestern’s Centre for Depression Research and Clinical Care and The Hersh Foundation.
“With advances in technology and our understanding of the biology of depression, our ongoing work with additional biomarkers is likely to yield tests for other subtypes of depression,” said Dr Manish Jha, assistant professor of psychiatry.
Objective: Currently, no valid measures inform treatment selection for depressed patients. Whether C-reactive protein (CRP) in particular and two other acute phase reactants (inflammatory markers) could differentiate between patients responding to either of two treatments with different mechanisms of action was assessed.
Method: Subjects included Combining Medications to Enhance Depression Outcomes (CO-MED) trial participants randomly assigned to either escitalopram plus placebo (SSRI monotherapy, n = 51) or bupropion plus escitalopram combination (bupropion-SSRI combination, n = 55) with baseline plasma samples. CRP, serum amyloid P component, and alpha-2-macroglobulin were measured using the Bioplex Pro™ human acute-phase 4-plex panel. We conducted mixed model analyses of depressive symptom (Quick Inventory of Depressive Symptomatology Self-Report) and side-effect burden (Frequency, Intensity, and Burden of Side-Effects Rating Scale) obtained weekly or every other week over the 12-week acute-phase of CO-MED trial to evaluate the relationship between these outcomes and baseline CRP and other acute-phase reactants.
Results: The treatment arms did not differ in depressive symptom or side effect outcomes. Most participants (69.8%, 74/106) had baseline CRP levels greater than 1 mg/L (indicative of systemic inflammatory activity). Higher baseline CRP levels were associated lower depression severity (correlation coefficient = −0.63) with bupropion-SSRI combination but not with SSRI monotherapy (correlation coefficient = 0.40). The overall remission rate was 41.5%. The estimated remission rate with CRP threshold based assignment (SSRI monotherapy for Conclusions: Baseline CRP levels relate differentially to antidepressant treatment outcomes in persons with major depressive disorder.
Manish K Jha, Abu Minhajuddin, Bharathi S Gadad, Tracy Greer, Bruce Grannemann, Abigail Soyombo, Taryn L Mayes, A John Rush, Madhukar H Trivedi