Association Between Antidepressant Use and Pseudarthrosis Following Spinal Fusion: A Systematic Review and Meta-Analysis.

Abstract

Pseudarthrosis remains a clinically important complication following spinal fusion. Antidepressants are commonly prescribed among patients undergoing spinal arthrodesis, and serotonergic signaling plays a recognized role in bone metabolism. Whether antidepressant use influences fusion outcomes remains uncertain. To evaluate the association between antidepressant use and pseudarthrosis following spinal fusion, with prespecified subgroup analyses of serotonergic antidepressants and by spinal region. Systematic review and meta-analysis. A total of 37,554 adult patients (≥18 years) undergoing cervical or lumbar spinal fusion across five observational studies. Physiologic measures-radiographic nonunion, clinically diagnosed pseudarthrosis, or revision surgery for pseudarthrosis. A systematic search of PubMed, Embase, and Web of Science was performed from database inception through the final search date. Eligible studies compared antidepressant-exposed patients with unexposed controls and reported pseudarthrosis or nonunion outcomes. Random-effects meta-analyses were conducted to estimate pooled odds ratios (ORs) with 95% confidence intervals (CIs). Prespecified subgroup analyses were performed by spinal region and serotonergic antidepressant exposure. Five studies met inclusion criteria. In the primary analysis including all antidepressant classes, antidepressant use was associated with increased odds of pseudarthrosis (OR 1.53, 95% CI 1.17-2.01; p = 0.002), with substantial heterogeneity (I² = 75.7%). In the serotonergic antidepressant subgroup (n = 8,572), exposure was associated with more than a two-fold increase in odds of pseudarthrosis (OR 2.26, 95% CI 1.18-4.33; p = 0.014). Directionally consistent associations were observed in both cervical and lumbar fusion cohorts. Antidepressant use is associated with increased odds of pseudarthrosis following spinal fusion, with a stronger association observed among serotonergic agents. These findings support incorporating antidepressant exposure into preoperative risk stratification and patient counseling.