The effect of pregabalin on pain and function in knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND: Knee osteoarthritis (OA) is a prevalent chronic condition characterized by joint pain and functional impairment. While non-steroidal anti-inflammatory drugs (NSAIDs) remain the cornerstone of pharmacologic management, a subset of patients may experience persistent symptoms due to central sensitization. Pregabalin, a neuromodulator used in neuropathic pain, has been proposed as an adjunctive treatment for OA, but its efficacy remains unclear.

OBJECTIVE: To evaluate the effectiveness and safety of pregabalin in reducing pain and improving function among patients with knee OA through a systematic review and meta-analysis of randomized controlled trials (RCTs).

METHODS: We searched PubMed, Embase, Scopus, and Cochrane CENTRAL from inception to June 2025 for RCTs comparing pregabalin (alone or in combination with NSAIDs) versus control (NSAIDs or placebo) in knee OA patients. Primary outcomes were pain (Visual Analog Scale, VAS) and function (Western Ontario and McMaster Universities Osteoarthritis Index, WOMAC). A random-effects model was used to calculate pooled weighted mean differences (WMDs) with 95% confidence intervals (CIs). Risk of bias was assessed using the Cochrane RoB 2.0 tool.

RESULTS: Three RCTs comprising four treatment arms with 214 patients were included. Pregabalin, when combined with NSAIDs, resulted in significant functional improvement (WMD: - 10.55; 95% CI: - 19.47 to - 1.63) and a non-significant trend toward pain reduction (WMD: - 0.63; 95% CI: - 1.44 to 0.18). Pregabalin monotherapy was less effective than combination therapy. Moderate to high heterogeneity was observed. Adverse events, primarily dizziness and somnolence, were mild and did not lead to discontinuation.

CONCLUSION: Pregabalin may enhance functional outcomes and contribute to pain relief when used as adjunctive therapy with NSAIDs in knee OA patients. Its benefit as monotherapy remains limited. While pregabalin was generally well-tolerated, larger, high-quality trials with longer follow-up are needed to confirm its role and long-term safety.