Spine Journal - 2026-08-01 - Journal Article; Systematic Review; Meta-Analysis
Association between antidepressant use and pseudarthrosis following spinal fusion: a systematic review and meta-analysis.
Frappa N, Dillon MR, Chernov D, Troiani Z, Scott MM, Lucasti C, Alben MG
Topics
Key Takeaway
Antidepressant use is associated with a 53% increase in pseudarthrosis odds after spinal fusion (OR 1.53, 95% CI 1.17–2.01), rising to a 2.26-fold increase for serotonergic agents specifically.
Summary Depth
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Summary
This systematic review and meta-analysis asked whether antidepressant use increases pseudarthrosis risk after cervical or lumbar spinal fusion across 5 observational studies. Random-effects pooling showed antidepressants overall increased pseudarthrosis odds (OR 1.53, 95% CI 1.17–2.01), with serotonergic agents driving a stronger signal (OR 2.26, 95% CI 1.18–4.33, n=8,572). Heterogeneity was substantial (I²=75.7%), and directionally consistent effects were seen in both cervical and lumbar subgroups.
Key Limitation
Substantial heterogeneity (I²=75.7%) across only 5 observational studies limits confidence in the pooled estimate and prevents reliable dose- or duration-response conclusions.
Original Abstract
BACKGROUND CONTEXT
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.
PURPOSE
To evaluate the association between antidepressant use and pseudarthrosis following spinal fusion, with prespecified subgroup analyses of serotonergic antidepressants and by spinal region.
STUDY DESIGN/SETTING
Systematic review and meta-analysis.
PATIENT SAMPLE
A total of 37,554 adult patients (≥18 years) undergoing cervical or lumbar spinal fusion across 5 observational studies.
OUTCOME MEASURES
Physiologic measures-radiographic nonunion, clinically diagnosed pseudarthrosis, or revision surgery for pseudarthrosis.
METHODS
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.
RESULTS
A total of 5 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=.002), with substantial heterogeneity (I²=75.7%). In the serotonergic antidepressant subgroup (n=8,572), exposure was associated with more than a 2-fold increase in odds of pseudarthrosis (OR 2.26, 95% CI: 1.18-4.33; p=.014). Directionally consistent associations were observed in both cervical and lumbar fusion cohorts.
CONCLUSIONS
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.