Neurological Phenotype and MRI Severity as Predictors of Duloxetine Response in Lumbar Spinal Stenosis: A Retrospective Cohort Study

Background/Objectives: Lumbar spinal canal stenosis (LSS) is a major cause of neurological disability and is frequently accompanied by neuropathic pain (NeP). Duloxetine is widely used for NeP, but its clinical role in LSS and the determinants of treatment response remain unclear. This study aimed to identify predictors of duloxetine efficacy in LSS. Methods: We retrospectively analyzed 145 patients with LSS who received duloxetine for ≥3 months (median dose 40 mg) with at least 1-year follow-up. Patients were classified into those with radicular pain or cauda equina syndrome. Treatment response was assessed at 3 months. Stenosis severity was evaluated using the Schizas classification. Multivariable logistic regression analysis was performed to identify independent predictors of duloxetine response in patients with cauda equina syndrome. Results: Duloxetine was effective in 29.4% vs. 52.3% in radicular pain and cauda equina syndrome, respectively. Among patients with cauda equina syndrome, Schizas Grade D was more frequent in responders than non-responders and independently predicted duloxetine response. Nearly 90% of responders had been unresponsive to other NeP medications. A subset of patients with severe stenosis avoided surgery following duloxetine treatment. Conclusions: Duloxetine showed greater efficacy in cauda equina-dominant LSS compared with radicular pain. Paradoxically, more severe spinal canal stenosis tended to be associated with a higher likelihood of response. These findings suggest that neurological phenotype and radiological severity may influence duloxetine responsiveness and support a symptom- and imaging-guided pharmacological management for LSS, although these findings should be interpreted with caution and considered hypothesis-generating given the retrospective study design.