An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline.
Level 2 - randomized trial
Multicenter open-label randomized controlled trial evaluating biomarker-drug interaction
PubMed 25017001 · doi:10.1176/appi.ajp.2014.14010094
What was done
In the Genome-Based Therapeutic Drugs for Depression (GENDEP) multicenter open-label randomized trial, baseline serum high-sensitivity C-reactive protein (CRP) was measured in 241 adults with major depressive disorder. Participants were randomized to 12 weeks of treatment with either escitalopram (n=115) or nortriptyline (n=126). The primary outcome was weekly depression severity scored on the Montgomery-Åsberg Depression Rating Scale (MADRS).
What was found
Baseline CRP differentially predicted response across the two drugs (CRP-drug interaction: β=3.27, 95% CI=1.65 to 4.89). For patients with low baseline CRP (<1 mg/L), MADRS improvement was 3 points higher with escitalopram than with nortriptyline. For patients with higher CRP levels, MADRS improvement was 3 points higher with nortriptyline than with escitalopram. CRP and its drug interaction explained more than 10% of individual-level variance in treatment outcome.
Why it matters
Baseline serum CRP may serve as an accessible peripheral biomarker to stratify major depressive disorder patients between serotonergic and noradrenergic antidepressants.
Limits
The trial used an open-label design rather than double-blind controls. The sample size was modest (241 participants across two active arms), and replication in prospective biomarker-stratified trials is needed.