Treating Depression in Primary Care: Are Biomarkers the Key?

Charles P. Vega, MD


November 06, 2014

In This Article

Review Highlights

Uher and colleagues examined the efficacy of escitalopram, a selective serotonin reuptake inhibitor (SSRI), and nortriptyline, a selective norepinephrine reuptake inhibitor, in the context of serum levels of CRP. Depression is clearly linked with higher levels of systemic inflammation, and antidepressant medications have differential effects on immunologic variables. Medications that inhibit norepinephrine reuptake tend to increase the relative importance of humoral immunity, whereas serotonin reuptake inhibitors promote a stronger cellular immune response.

Study participants were adults older than 18 years who had moderate to severe unipolar depression. Patients at high risk for mania or with primary substance use were excluded from the study, which focused exclusively on persons of European descent because researchers were also evaluating genetic factors associated with depression.

A total of 468 participants underwent randomization, and 51.5% (241 participants) provided blood samples for analysis of CRP levels at the outset of the study. Compared with persons who did not provide a blood sample for CRP testing, those who did were less likely to be treated with an antidepressant before randomization and were slightly younger. The average age of the 241 participants was 41 years, and the average Montgomery-Åsberg Depression Rating Scale (MADRS) score at baseline was 29. A majority (62%) of participants were female, and the majority had a baseline CRP level less than 1 mg/L.

The primary study outcome at 12 weeks was total MADRS score. Researchers also followed two other depression scales and measurements of observed mood and neurovegetative symptoms specifically. The current research analyzed whether CRP levels correlated with the severity of depression, as well as whether CRP was predictive of treatment success with escitalopram and nortriptyline.

Baseline CRP level was positively correlated with age and body mass index, but not depression severity. However, higher CRP levels were associated with a worse response to treatment with both escitalopram and nortriptyline.

There was a significant interaction between the degree of systemic inflammation and antidepressant efficacy. Escitalopram was more effective than nortriptyline among participants with lower baseline levels of CRP, whereas nortriptyline was more effective among those with higher CRP levels. Each standard deviation increase in CRP was associated with a 2.7-point decline in MADRS score in the escitalopram group and a 0.6-point increase in the nortriptyline group. This differential response was noted across all three depression assessment instruments and was most profound on the self-reported Beck Depression Inventory, meaning that the differential effects of the antidepressants were noticeable to patients.

An analysis to account for multiple variables that might affect the level of systemic inflammation failed to alter the main study result, and CRP levels explained 10.6% of individual variance in response to treatment as indicated by the MADRS score.


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