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Psych Congress  

Effect of L-Methylfolate on Inflammatory Markers: A Randomized Clinical Trial of Patients With Major Depression

Authors  
Richard Shelton, MD
Stephen Stahl, MD, PhD
George Papakostas, MD
John Zajecka, MD
Teodoro Bottiglieri, PhD
Clair Cassiello, BS
Maurizio Fava, MD
Sponsor  
Pamlab, Covington, LA

Objective: Elevated levels of high sensitivity C-reactive protein (hsCRP) and obesity (body mass index [BMI] ≥30 kg/m2) may be associated with an increased risk of depression and poor antidepressant response. Previous studies have suggested an association between inflammation and response to treatment. The effect of L-methylfolate 15 mg as an adjunct to selective serotonin reuptake inhibitors (SSRIs) on response and correlations with baseline levels of inflammatory biomarkers was examined. 
Methods: 75 inadequate responders to SSRIs were enrolled in a 60-day, multi-center, double-blind, placebo-controlled trial. Patients received L-methylfolate 15 mg/day for 60 days, placebo for 30 days followed by L-methylfolate 15 mg/day for 30 days, or placebo for 60 days. In a post hoc analysis, mean change from baseline to endpoint for HDRS was examined for correlations with baseline BMI, hsCRP, and other inflammatory markers.
Results: Pooled differences in mean change on HDRS-17 and HDRS-28 were significantly greater (p=0.05 and p=0.02, respectively) with L-methylfolate than placebo. Mean improvement in symptoms on HDRS-28 was significantly greater with L-methylfolate vs. placebo (-7.4 ± 7.9 vs. -2.4 ± 5.3) among patients with a BMI ≥30 kg/m2 (95% CI: -7.449, -1.871, p=0.001), and among those with elevated baseline hsCRP ≥median (2.25 mg/L) (-7.7 ± 7.4 vs. -3.7 ± 7.5; 95% CI: -7.227, 0.002, p=0.050).
Conclusions: A robust response was observed with adjunctive L-methylfolate when examined by the presence of baseline inflammation and elevated BMI. The presence of these markers in individuals with depression may enhance the antidepressant effect of adjunctive L-methylfolate. Confirmatory research is needed.  

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