Evidence map›Paper›PMID 42205644›Full record

ReviewCureus2026

The Role of Inflammatory Markers as Predictors of Response to Antidepressants in Major Depressive Disorder: A Meta-Analysis.

Hytham Hummad, Pulkit Gairola, Dilyaver Matakhov, Shivani Shah, Hannah Jeyakkodi, Newton Rahming, Chetachukwu Eze, Michael Yassa, Ulrica S Armbrister, Shashawna S Drum Christie and 1 more

Abstract readReview
In one paragraph

Review in Cureus, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Hytham HummadAnesthesia and Critical Care, College of Applied Medical Sciences, Khamis Mushait, King Khalid University, Abha, SAU.
Pulkit GairolaGeneral Medicine, University of Tennessee Health Science Center College of Medicine, Knoxville, Knoxville, USA.
Dilyaver MatakhovFamily Medicine, Mehtercesme Family Medicine Center, Istanbul, TUR.
Shivani ShahMedicine, Caribbean Medical University School of Medicine, Willemstad, CUW.
Hannah JeyakkodiPsychiatry, Universidad Iberoamericana (UNIBE), Santo Domingo, DOM.
Newton RahmingSurgery, Caribbean Medical University, Willemstad, CUW.
Chetachukwu EzeMedicine, St. George's University School of Medicine, St. George's, GRD.
Michael YassaMedicine, St. George's University School of Medicine, St. George's, GRD.
Ulrica S ArmbristerSurgery, Windsor University School of Medicine, Cayon, KNA.
Shashawna S Drum ChristieMedicine, St. George's University School of Medicine, St. George's, GRD.
Ufn RizwanullahInternal Medicine, Hayatabad Medical Complex Peshawar, Peshawar, PAK.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Major depressive disorder (MDD) is a leading cause of global disability, with fewer than half of patients achieving remission following first-line antidepressant treatment. Inflammatory processes have been implicated in MDD, but the extent to which baseline inflammatory markers predict treatment outcomes remains uncertain, particularly given potential confounding and bidirectional relationships. We conducted a systematic review and meta-analysis following the PRISMA 2020 statement, searching PubMed/MEDLINE, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and PsycINFO from January 1995 to December 2025. Eligible studies included adults with MDD who had at least one baseline inflammatory biomarker measured prior to antidepressant treatment and reported response or remission outcomes. Random-effects meta-analysis (DerSimonian-Laird) was used to estimate pooled ORs for nonresponse in individuals with elevated versus normal inflammatory markers. Risk of bias was assessed using Cochrane Risk of Bias 2.0 (RoB 2) and Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tools. Seventeen studies (n = 1,535 participants) were included. Elevated baseline inflammatory markers were associated with increased odds of antidepressant nonresponse (pooled OR = 2.11; 95% CI: 1.84-2.43; p < 0.001; I² = 15%). Subgroup analyses suggested that CRP, particularly at thresholds around ≥3 mg/L, showed the most consistent association (OR = 2.47; 95% CI: 1.96-3.11). However, definitions of "elevated" inflammation varied substantially across studies, and important confounders (e.g., obesity, smoking, and metabolic conditions) were not consistently adjusted for. The evidence base included both randomized and observational studies, and no prospective biomarker-guided treatment trials were identified. Elevated baseline inflammatory markers are associated with a higher likelihood of antidepressant nonresponse in MDD, but this relationship is correlational and may reflect confounding or reverse causality. Current evidence does not support routine clinical use of inflammatory markers for treatment selection. These findings are hypothesis-generating and highlight the need for prospective, biomarker-guided studies to determine whether inflammation can meaningfully inform antidepressant treatment strategies.

Indexed as

antidepressant responsec-reactive proteincytokinesinflammationinterleukin-6major depressive disordermeta-analysistreatment resistance

Identifiers

PMID42205644
PMCPMC13203315

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.