Review of: Esalatmanesh S et al, Arch Gynecol Obstet 2024;309(4):1429–1439

Study Type: Randomized, double-blind, placebo-controlled trial 

Postpartum depression (PPD) affects 12% of mothers and takes a toll on infant and family health. PPD is typically treated with antidepressants and therapy, or with the newer neurosteroid zuranolone. Inflammation is also thought to contribute to PPD. Celecoxib, a cyclooxygenase-2 inhibitor that reduces pro-inflammatory cytokines, has extensive trials in major depression, and this is the first trial to test it in PPD. 

This randomized, double-blind, placebo-controlled trial enrolled 50 women aged 18–45 years with mild or moderate PPD, as measured by the Hamilton Depression Rating Scale (HDRS). All underwent weekly cognitive behavioral therapy (CBT) with a psychiatrist for six weeks. During that time, half received celecoxib 200 mg twice daily and half received placebo. HDRS was measured at two-week intervals. Inflammatory markers (BDNF, TNF-a, IFN-y, IL-6, ESR, and CRP) were also measured at the beginning and conclusion of the study. The study was funded by a grant from Tehran University of Medical Science, where it was conducted. 

At all time points, the celecoxib group had significantly lower HDRS scores than the placebo group, culminating in about a 10-point drop and a 5-point difference at week 6. Most (96%) of the patients in the celecoxib group had reached remission by week 6, compared to only 36% of patients in the placebo group—a statistically significant difference. Both response times and remission times were significantly shorter in the celecoxib group. At week 6, ESR, CRP, TNF-a, and IL-6 were significantly lower in the celecoxib group. BDNF was higher, which is consistent with other antidepressant trials. No significant adverse events were reported by either group, and all subjects breastfed their babies throughout the study.

CARLAT TAKE
Remarkably, almost every mother in this small study responded to celecoxib and CBT together. The improvements started at two weeks, with no significant side effects or problems breastfeeding. The placebo group also received CBT, but didn’t do as well, suggesting that celecoxib should be helpful on its own—but it would be nice to see that finding replicated in another study.