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C-Reactive Protein Levels May Predict SSRI Success

Individuals with depression who had high levels of C-reactive protein responded poorly to selected serotonin reuptake inhibitors compared to those with lower CRP levels, based on data from more than 900 patients.

C-reactive protein (CRP) has been shown to predict antidepressant treatment outcomes in depressed patients, but previous studies have been small and under restricted conditions, and data from large, real-world studies are lacking, wrote Yuqian Pan of First Affiliated Hospital of Zhengzhou University, Henan, China, and colleagues.

In a study published in the Journal of Affective Disorders, the researchers identified depressed patients aged 12-60 years who had tested CRP levels. The participants were followed through outpatient visits or telephone interviews to collect information on medication use and assess efficacy based on the Clinical Global Impressions–Improvement scale.

CRP was separated into the low CRP group of 709 patients (CRP < 1 mg/L) and a high CRP group of 209 patients (CRP ≥ 1 mg/L). The primary outcome was efficacy defined as effective and ineffective for high and low CRP levels in patients using different medications: Selected serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors, (SNRIs), melatonin receptor agonists (MTs), and norepinephrinergic and specific serotonergic antidepressants (NaSSAs).

The researchers compared efficacy in different groups according to CRP levels.

Overall, patients with low CRP showed significantly greater efficacy with SSRIs than did those with high CRP (hazard ratio [HR], 1.257, P = .047). SNRIs were more effective than SSRIs for treating patients with high CRP levels (HR, 1.652, P = .037).

A possible reason for the difference in efficacy is the correlation between CRP and body mass index; previous studies have shown that SSRIs may be less effective in obese individuals, the researchers said.

“Another possible explanation is that at high levels of inflammation, neurons, microglia, and macrophages respond to inflammatory challenges at the cellular level by activating metabolic pathways,” they said.

No significant changes in CRP levels were observed before and after starting medication use, which supports the stability of CRP as a biomarker under normal circumstances.

No difference in efficacy appeared between SSRIs and SNRIs in patients with low CRP, “which may indicate that SNRIs have stronger anti-inflammatory effects than SSRIs,” a finding consistent with previous studies, they said.

The study findings were limited by several factors including the small number of patients taking MT and NaSSA, the irregular time intervals for before and after SSRI treatment in 90 patients, the lack of classification by antidepressant type, and the potential for recall bias, the researchers noted.

However, the results suggest that CRP could predict the efficacy of SSRIs in depressed patients in a real-world setting, which may inform treatment decisions, they said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

This article originally appeared on, part of the Medscape Professional Network.

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