A 2026 systematic review of seven randomized, double-blind trials found a possible improvement in depression scores when celecoxib was added to an antidepressant. But the overall result was highly variable, and the apparent benefit was no longer statistically confirmed after studies judged to have a high risk of bias were removed.
The findings do not establish celecoxib as a routine add-on treatment for major depressive disorder. The review rated confidence in the efficacy result as very low and described celecoxib as a research lead rather than a tested standard option.
What the review found
The seven trials included 365 adults who received either an antidepressant plus celecoxib or the same antidepressant plus placebo. Across all studies, the celecoxib groups had lower depression scores overall. The standardized mean difference was −0.63, with a 95% confidence interval ranging from −1.25 to −0.01.
That pooled result needs careful interpretation. Trial outcomes varied substantially: the I² statistic was 81.3%, and the 95% prediction interval ranged from −2.23 to 0.97. In practical terms, another similar study could show a strong benefit, no benefit, or a result favoring placebo.
Four trials reported a significant advantage for celecoxib, while three did not. When the review excluded three trials rated at high risk of bias, the estimated effect was smaller—an SMD of −0.27 across four trials—and its confidence interval, from −1.10 to 0.56, did not confirm a benefit.
Why the individual trials differed
Most studies used celecoxib at 400 mg per day for six weeks. One used 200 mg per day for eight weeks. The antidepressants and participant groups varied, and the review could not determine whether those differences explained the mixed results or whether the variation was due to chance.
- A 40-person pilot study pairing celecoxib with reboxetine reported greater improvement than reboxetine plus placebo. However, 55% of participants did not complete the six-week assessment.
- In a 119-person trial, 76% of participants had not responded to earlier treatment. Adding celecoxib to vortioxetine did not produce a confirmed advantage.
- A 43-person inpatient trial found no significant improvement in response or remission when celecoxib was added to sertraline.
- A 60-person trial reported lower depression ratings with celecoxib plus escitalopram at weeks four and eight.
A 2023 meta-analysis estimated a larger benefit, with an SMD of −0.85. The newer review included later negative evidence and placed more emphasis on differences between trials and study quality.
Inflammation did not identify likely responders
Celecoxib is a prescription anti-inflammatory drug that blocks cyclooxygenase-2, or COX-2, an enzyme involved in producing inflammatory signaling molecules. This mechanism has prompted interest in whether inflammation might help identify people more likely to benefit.
That possibility was not established in the newer evidence. In the 119-person trial, baseline C-reactive protein, or CRP, did not reliably predict an added antidepressant effect. A possible pattern in a treatment-resistance subgroup came from a single trial and was considered too narrow to guide patient selection.
Routine CRP testing to decide whether someone should receive celecoxib for depression would therefore run ahead of the evidence described in the review.
Safety evidence was limited
The trials mostly lasted six weeks, so they cannot settle the longer-term balance between possible benefit and risk. Five trials involving 265 people contributed to dropout analyses. The risk ratio for dropout from any cause was 0.77, with a 95% confidence interval from 0.14 to 4.07. For dropout due to adverse effects, the risk ratio was 0.83, with a confidence interval from 0.19 to 3.64.
Those estimates were too imprecise to establish tolerability. The US prescribing label warns of serious cardiovascular events, gastrointestinal bleeding or ulcers, and kidney risks with celecoxib. The source also notes that bleeding risk can rise when celecoxib is used with selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors.
What the findings mean for treatment
The studies tested celecoxib alongside an antidepressant, not as a replacement for one. They leave open the possibility of a modest add-on effect, but they do not establish its size, reliability or the people most likely to benefit.
For now, the evidence does not show a repeatable depression benefit strong enough to offset celecoxib’s known risks for routine use. Further, better-quality trials would be needed before the approach could be considered an established add-on strategy.
AI tools were used to assist with the preparation of this article.
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