Efficacy of Pregabalin for Lumbar Radicular Pain: A Systematic Review and Meta-analysis of Randomized Placebo-controlled and Add-on Trials

Abstract Pregabalin is widely prescribed for lumbar radicular pain despite uncertainty regarding its efficacy. Randomized trials have evaluated pregabalin both as monotherapy compared with placebo and as add-on therapy to other analgesics, particularly nonsteroidal anti-inflammatory drugs (NSAIDs), addressing different clinical questions. To systematically review and synthesize evidence from randomized controlled trials evaluating pregabalin for lumbar radicular pain, with separate analyses for placebo-controlled and add-on trial designs. Electronic databases and clinical trial registries were searched from inception to 2026 for randomized controlled trials evaluating pregabalin in adults with lumbar radicular pain or sciatica. Trials were categorized as (1) placebo-controlled trials of pregabalin monotherapy, or (2) add-on trials evaluating pregabalin in combination with another active agent. Placebo-controlled trials were pooled quantitatively using random-effects meta-analysis. Add-on trials were analyzed separately due to differences in the comparator and estimand. Risk of bias was assessed using the Cochrane Risk of Bias tool. Two placebo-controlled randomized trials were included in the primary meta-analysis. Pooled analysis demonstrated no significant reduction in pain intensity with pregabalin compared with placebo, with the direction of effect favoring placebo. Three randomized add-on trials compared pregabalin plus NSAIDs with NSAID therapy alone. An exploratory pooled analysis of these trials showed no consistent or clinically meaningful additional benefit of pregabalin for pain reduction. Trials evaluating pregabalin combined with non-NSAID agents were heterogeneous and were summarized narratively. Pregabalin was associated with a higher incidence of adverse effects, particularly dizziness and somnolence. Current evidence from a limited number of randomized trials does not demonstrate a clinically meaningful benefit of pregabalin for lumbar radicular pain, either as monotherapy or as add-on therapy. Pregabalin was consistently associated with increased adverse effects. Given the small number of included trials, these findings should be interpreted cautiously, and further high-quality randomized controlled trials are required to strengthen the evidence base before definitive clinical recommendations can be made.