'Convenient' Biomarker May Predict Antidepressant Response

Nancy A. Melville

August 06, 2014

Serum levels of C-reactive protein (CRP), a common marker of systemic inflammation, may predict how well patients respond to common antidepressants, allowing for a more personalized approach to depression treatment, new research shows.

Investigators at Dalhousie University in Halifax, Canada, found that CRP, an "easily accessible biomarker of systemic inflammation," predicted response to the antidepressants escitalopram (Lexapro, Forest Laboratories, Inc) and nortriptyline.

"While there have been other biomarkers identified [to predict response to antidepressants], CRP has the major advantage of being 'differential' ― it predicts response to one drug in one direction and response to an alternative drug in the opposite direction," lead author Rudolf Uher, MD, PhD, told Medscape Medical News.

"So it tells us which drug will work for whom. This makes it much more useful, and we do not have other biomarkers that do that," Dr. Uher, an associate professor of psychiatry, added.

The study was published online July 14 in the American Journal of Psychiatry.

Low CRP, Better Response

With previous evidence showing an association between systemic inflammation and depression, the researchers wanted to investigate the hypothesis that a similar relationship might exist between CRP and response to treatment for depression, using the 2 different antidepressants ― escitalopram, a selective serotonin reuptake inhibitor, and nortriptyline, a selective norepinephrine reuptake inhibitor.

The study involved 241 adults with major depressive disorder who were enrolled in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study, a multicenter, randomized clinical trial.

Patients were randomly assigned to receive 12 weeks of treatment with escitalopram (N = 115) or nortriptyline (N = 126), and their CRP levels were measured at baseline.

Patients with low levels of CRP (<1 mg/L) had better response to escitalopram, with Montgomery-Åsberg Depression Rating Scale (MADRS) scores, assessed weekly, that were 3 points higher than those with low CRP levels who were taking nortriptyline.

Meanwhile, patients with higher CRP levels had an opposite response, with MADRS scores that were 3 points higher with nortriptyline than with escitalopram.

Convenient Biomarker

CRP is a convenient biomarker for various reasons ― it can be obtained any time of day from a nonfasting, peripheral blood sample, and high-sensitivity CRP assays are routine in most medical laboratories, the researchers note.

An important limitation of the study is that escitalopram, a highly selective serotonin reuptake inhibitor, has no significant effects on other receptors, whereas nortriptyline, a tricyclic antidepressant, also binds several receptors, the authors point out.

"Given the pleiotropy of nortriptyline effects, the present study cannot separate the effects of norepinephrine reuptake blockage from other compound-specific effects or class effects of tricyclic antidepressants," the investigators note.

"It remains to be investigated whether other antidepressants with similar effects on the immune system can substitute for nortriptyline in patients with high levels of systemic inflammation."

The study nevertheless identifies "the strongest differential predictor of response to a serotonin reuptake inhibitor versus a norepinephrine reuptake inhibitor to date," the authors write.

If the results are reproduced, the clinical implications could be significant, Dr. Uher said.

"We still need to see if the differential prediction replicates, and if it is reproducible, the clinical benefits could be tangible," he said.

"In the study, the predictive effect was large enough to make meaningful difference for individual patients."

Clinically Significant

Commenting on the study for Medscape Medical News, Philip R. Muskin, MD, professor of psychiatry at Columbia University Medical Center in New York City, agreed that the difference in responses to the 2 drugs was indeed meaningful.

"Three points on the MADRS is absolutely a real difference," he told Medscape Medical News. "You can certainly see 3 points clinically."

"This is an early study, but it does suggest signs of biological differences in depression that may not look different phenomenologically, and some of these tests may actually allow us to make treatment decisions more efficiently."

"The fact is that all of the drugs for depression work, but they don't work for everybody, and if we had a biological marker to help make that decision, that would help tremendously," Dr. Muskin added.

The authors' disclosures can be found in the original article. Dr. Muskin reports no relevant financial relationships.

Am J Psychiatry. Published online July 17, 2014. Abstract

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