Can specific biological and genetic markers predict the antidepressant efficacy of adjunctive L-methylfolate 15 mg in depressed patients who have not adequately responded to SSRIs?
J Clin Psychiatry · 2014 · PMID 24813065 · DOI 10.4088/JCP.13m08947
Certain biological and genetic markers may identify depressed patients who are more likely to respond to adjunctive L-methylfolate when SSRIs are insufficient.
The question
Can specific biological and genetic markers predict the antidepressant efficacy of adjunctive L-methylfolate 15 mg in depressed patients who have not adequately responded to SSRIs?
What they tested
The study hypothesized that specific biological and genetic markers would influence the antidepressant efficacy of adjunctive L-methylfolate 15 mg compared to placebo in patients with SSRI-resistant major depressive disorder.
How they did it
This was a double-blind, randomized, placebo-controlled trial using a sequential parallel comparison design. Outpatients with SSRI-resistant MDD received L-methylfolate 15 mg/d for 60 days, or placebo for 30 days followed by L-methylfolate 15 mg/d for 30 days, or placebo for 60 days. The primary response measure was the 28-Item Hamilton Depression Rating Scale (HDRS-28), and the effects of baseline biological and genetic markers on treatment response were evaluated.
What they found
Seventy-five patients were enrolled. Patients with specific biological markers (BMI ">=" 30 kg/m², elevated high-sensitivity C-reactive protein or 4-hydroxy-2-nonenal, low S-adenosylmethionine/S-adenosylhomocysteine ratio) and genetic markers at baseline showed significantly greater pooled mean change from baseline on the HDRS-28 with L-methylfolate versus placebo. Most combinations of baseline biological and genetic markers also predicted significantly greater reductions in pooled mean change from baseline in HDRS-28 scores with L-methylfolate versus placebo.
What it means
Biomarkers related to inflammation or metabolism and genomic markers associated with L-methylfolate synthesis and metabolism may help identify patients with SSRI-resistant depression who could benefit from adjunctive L-methylfolate 15 mg therapy.
Limitations
This was a post hoc analysis, and confirmatory studies are needed to validate these findings.
The paper at a glance
| Title | Effect of adjunctive L-methylfolate 15 mg among inadequate responders to SSRIs in depressed patients |
|---|---|
| Journal | J Clin Psychiatry |
| Year | 2014 |
| PMID | 24813065 ↗ |
| DOI | 10.4088/JCP.13m08947 ↗ |
| Topic | Brain, cognition & mood |
Read the source: PubMed record (authors, abstract, full citation) ↗ · Publisher via doi.org ↗
Where Magellan uses this paper
This citation sits behind the evidence grade on the pages below. Grades are set from the research and are independent of affiliate commissions.
L-Methylfolate (5-MTHF)
In human trials, both L-5-MTHF and folic acid raise blood folate and lower total homocysteine, an amino acid whose elevation is linked to cardiovascular and cognitive risk; head-to-head studies find L-5-MTHF at least as effective as folic acid, and sometimes better, at improving folate status.
L-Methylfolate (also called 5-methyltetrahydrofolate, 5-MTHF, or levomefolic acid) is the biologically…
Research describes the compound or intervention studied. It is not a claim about any specific product.
Molecules & mechanisms in this paper
Each of these is named in the paper’s own words above. Open the monograph for the full mechanism and its other citations.
Cite this page
These citations point at this summary. To cite the original paper with its full author list, use the PubMed record or doi.org.
Magellan Longevity. (2026). Can specific biological and genetic markers predict the antidepressant efficacy of adjunctive L-methylfolate 15 mg in depressed patients who have not adequately responded to SSRIs? [Plain-English summary of J Clin Psychiatry 2014, PMID 24813065, DOI 10.4088/JCP.13m08947]. Magellan Longevity. https://magellanlongevity.com/study/d24813065.html@misc{magellan_d24813065,
title = {Can specific biological and genetic markers predict the antidepressant efficacy of adjunctive L-methylfolate 15 mg in depressed patients who have not adequately responded to SSRIs?},
author = {{Magellan Longevity}},
year = {2026},
howpublished = {\url{https://magellanlongevity.com/study/d24813065.html}},
note = {Plain-English summary of PubMed PMID 24813065; DOI 10.4088/JCP.13m08947; J Clin Psychiatry 2014. Reviewed by Gabriel Radu, DO},
urldate = {2026-08-11}
}https://magellanlongevity.com/study/d24813065.htmlRelated studies in the Magellan library
- The study investigated the efficacy of folinic acid versus l-methylfolate in lowering total…Clin Nutr ESPEN · 2023 · PMID 38056998
- Acetyl-L-carnitine Slows the Progression from Prefrailty to Frailty in Older SubjectsCurr Pharm Des · 2022 · PMID 36043711
- Citrus polyphenol hesperidin stimulates nitric oxide production while improving endothelial…J Clin Endocrinol Metab · 2011 · PMID 21346065
- Does curcumin supplementation effectively reduce systemic inflammatory mediators in humans?Nutr Rev · 2021 · PMID 34378053
- Does high-resistance inspiratory muscle strength training (IMST) improve blood pressure…J Am Heart Assoc · 2021 · PMID 34184544
- Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older…JAMA Netw Open · 2022 · PMID 35050355
Prefer the interactive version? Open this summary in the Magellan app → · Browse all 314 study summaries →