Celecoxib Accelerates OCD Response

It’s the second trial to support an antinflammatory in OCD

STUDY: Singh S et al, Journal of Psychopharmacology 2026

STUDY TYPE: Randomized, double-blind, placebo-controlled trial

FUNDING: Independent

Background

OCD is linked to low-grade brain inflammation, with elevated interleukin-6 (IL-6) among the more consistent findings. An earlier trial found success with the anti-inflammatory naproxen in 104 patients with OCD, and this is one tests celecoxib, an NSAID and COX-2 inhibitor with over a dozen trials in depression.

The Study

• 44 drug-naive adults, ages 18-50, with moderate to severe OCD (YBOCS score 21 or higher), at a single center in India.
• They started fluoxetine (titrated to 80 mg/d) and celecoxib (200 mg qd) at the same time, or were randomized, double-blind to placebo, for 8 weeks.
• YBOCS severity was measured at baseline, 2, 4, and 8 weeks; serum IL-6 and BDNF at baseline and 8 weeks.

Results

The celecoxib group improved substantially more than placebo (mean YBOCS drop 11.0 vs 6.6 points, large effect size of 1.92), with a difference emerging by week 2. However, large effe

Response, a 35% or greater reduction, was more common with celecoxib (33% vs 11%; number needed to treat 4.2). BDNF rose only with celecoxib, and the drop in IL-6 tracked with symptom improvement only in that group.

Side Effects

No differences (celecoxib is well-tolerated short-term but has a small, long-term risk to kidneys, heart, and GI bleeds).

Limitations

Small trial. Large effect sizes are common in small trials (due in part to publication bias and weaker methodology).

Celecoxib and fluoxetine share metabolic pathways, so higher fluoxetine blood levels in the celecoxib group, which weren’t measured, could partly explain the extra benefit.

Practice Implications

1. I recommend celexocib for treatment-resistant depression with inflammation (hs-CRP at least 3.0). However, with its long-term risks, best to try to taper it off after 6 months of recovery. Learn how to use it.
2. This trial, along with the naproxen data, suggest it has a role in treatment-resistant OCD, particularly when other disorders are present that respond to celecoxib (eg, depression, bipolar, arthritis).