Pharmacotherapies for Central Post-Stroke Pain: A Systematic Review and Network Meta-Analysis

Abstract

Background. Central post-stroke pain (CPSP) is a common condition. Several pharmacotherapies have been applied in practice. However, the comparative effectiveness among these pharmacotherapies is unknown. Aim. The aim of this study is to study the comparative effectiveness among differential pharmacotherapies for CPSP through a network meta-analysis. Methods. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science from inception to 30 March 2022, without any language restriction. Two reviewers independently screened the retrieved articles, extracted data, and evaluated the risk of bias (RoB). The outcome of interest of the study was the change in the scores of pain intensity scales. We estimated standard mean differences (SMDs) between treatments and calculated corresponding 95% CIs. Results. Thirteen randomized controlled trials (529 participants) were included after a screen of 1774 articles. Compared with placebo, pamidronate (SMD -2.43, 95% CI -3.54 to -1.31; $P-\text{score}=0.93$ ), prednisone (SMD -2.38, 95% CI -3.09 to -1.67; $P-\text{score}=0.92$ ), levetiracetam (SMD -2.11, 95% CI -2.97 to -1.26; $P-\text{score}=0.87$ ), lamotrigine (SMD -1.39, 95% CI -2.21 to -0.58; $P-\text{score}=0.73$ ), etanercept (SMD -0.92, 95% CI -1.8 to -0.03; $P-\text{score}=0.59$ ), and pregabalin (SMD -0.46, 95% CI -0.71 to -0.22; $P-\text{score}=0.41$ ) had significantly better treatment effect. Pamidronate, prednisone, and levetiracetam ranked as the first three most effective treatments. In subgroup analyses, prednisone, levetiracetam, lamotrigine, and pregabalin were more effective than placebo as oral pharmacotherapies, while etanercept was more effective than placebo as injectable pharmacotherapy. Conclusions. Our study confirmed that pamidronate, prednisone, and guideline-recommended anticonvulsants were effective for reducing pain intensity for CPSP. Pamidronate and prednisone showed better effect than other pharmacotherapies, which warrants further investigation.